WorldWideScience

Sample records for meta-analysis identifies metastatic

  1. Feature genes in metastatic breast cancer identified by MetaDE and SVM classifier methods.

    Science.gov (United States)

    Tuo, Youlin; An, Ning; Zhang, Ming

    2018-03-01

    The aim of the present study was to investigate the feature genes in metastatic breast cancer samples. A total of 5 expression profiles of metastatic breast cancer samples were downloaded from the Gene Expression Omnibus database, which were then analyzed using the MetaQC and MetaDE packages in R language. The feature genes between metastasis and non‑metastasis samples were screened under the threshold of PSVM) classifier training and verification. The accuracy of the SVM classifier was then evaluated using another independent dataset from The Cancer Genome Atlas database. Finally, function and pathway enrichment analyses for genes in the SVM classifier were performed. A total of 541 feature genes were identified between metastatic and non‑metastatic samples. The top 10 genes with the highest betweenness centrality values in the PPI network of feature genes were Nuclear RNA Export Factor 1, cyclin‑dependent kinase 2 (CDK2), myelocytomatosis proto‑oncogene protein (MYC), Cullin 5, SHC Adaptor Protein 1, Clathrin heavy chain, Nucleolin, WD repeat domain 1, proteasome 26S subunit non‑ATPase 2 and telomeric repeat binding factor 2. The cyclin‑dependent kinase inhibitor 1A (CDKN1A), E2F transcription factor 1 (E2F1), and MYC interacted with CDK2. The SVM classifier constructed by the top 30 feature genes was able to distinguish metastatic samples from non‑metastatic samples [correct rate, specificity, positive predictive value and negative predictive value >0.89; sensitivity >0.84; area under the receiver operating characteristic curve (AUROC) >0.96]. The verification of the SVM classifier in an independent dataset (35 metastatic samples and 143 non‑metastatic samples) revealed an accuracy of 94.38% and AUROC of 0.958. Cell cycle associated functions and pathways were the most significant terms of the 30 feature genes. A SVM classifier was constructed to assess the possibility of breast cancer metastasis, which presented high accuracy in several

  2. Targeted agents for patients with advanced/metastatic pancreatic cancer: A protocol for systematic review and network meta-analysis.

    Science.gov (United States)

    Di, Baoshan; Pan, Bei; Ge, Long; Ma, Jichun; Wu, Yiting; Guo, Tiankang

    2018-03-01

    Pancreatic cancer (PC) is a devastating malignant tumor. Although surgical resection may offer a good prognosis and prolong survival, approximately 80% patients with PC are always diagnosed as unresectable tumor. National Comprehensive Cancer Network's (NCCN) recommended gemcitabine-based chemotherapy as efficient treatment. While, according to recent studies, targeted agents might be a better available option for advanced or metastatic pancreatic cancer patients. The aim of this systematic review and network meta-analysis will be to examine the differences of different targeted interventions for advanced/metastatic PC patients. We will conduct this systematic review and network meta-analysis using Bayesian method and according to Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P) statement. To identify relevant studies, 6 electronic databases including PubMed, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of science, CNKI (Chinese National Knowledge Infrastructure), and CBM (Chinese Biological Medical Database) will be searched. The risk of bias in included randomized controlled trials (RCTs) will be assessed using the Cochrane Handbook version 5.1.0. And we will use GRADE approach to assess the quality of evidence from network meta-analysis. Data will be analyzed using R 3.4.1 software. To the best of our knowledge, this systematic review and network meta-analysis will firstly use both direct and indirect evidence to compare the differences of different targeted agents and targeted agents plus chemotherapy for advanced/metastatic pancreatic cancer patients. This is a protocol of systematic review and meta-analysis, so the ethical approval and patient consent are not required. We will disseminate the results of this review by submitting to a peer-reviewed journal.

  3. Gene expression meta-analysis identifies metastatic pathways and transcription factors in breast cancer

    International Nuclear Information System (INIS)

    Thomassen, Mads; Tan, Qihua; Kruse, Torben A

    2008-01-01

    Metastasis is believed to progress in several steps including different pathways but the determination and understanding of these mechanisms is still fragmentary. Microarray analysis of gene expression patterns in breast tumors has been used to predict outcome in recent studies. Besides classification of outcome, these global expression patterns may reflect biological mechanisms involved in metastasis of breast cancer. Our purpose has been to investigate pathways and transcription factors involved in metastasis by use of gene expression data sets. We have analyzed 8 publicly available gene expression data sets. A global approach, 'gene set enrichment analysis' as well as an approach focusing on a subset of significantly differently regulated genes, GenMAPP, has been applied to rank pathway gene sets according to differential regulation in metastasizing tumors compared to non-metastasizing tumors. Meta-analysis has been used to determine overrepresentation of pathways and transcription factors targets, concordant deregulated in metastasizing breast tumors, in several data sets. The major findings are up-regulation of cell cycle pathways and a metabolic shift towards glucose metabolism reflected in several pathways in metastasizing tumors. Growth factor pathways seem to play dual roles; EGF and PDGF pathways are decreased, while VEGF and sex-hormone pathways are increased in tumors that metastasize. Furthermore, migration, proteasome, immune system, angiogenesis, DNA repair and several signal transduction pathways are associated to metastasis. Finally several transcription factors e.g. E2F, NFY, and YY1 are identified as being involved in metastasis. By pathway meta-analysis many biological mechanisms beyond major characteristics such as proliferation are identified. Transcription factor analysis identifies a number of key factors that support central pathways. Several previously proposed treatment targets are identified and several new pathways that may

  4. Cell-Free DNA in Metastatic Colorectal Cancer: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Spindler, Karen-Lise G; Boysen, Anders K; Pallisgård, Niels; Johansen, Julia S; Tabernero, Josep; Sørensen, Morten M; Jensen, Benny V; Hansen, Torben F; Sefrioui, David; Andersen, Rikke F; Brandslund, Ivan; Jakobsen, Anders

    2017-09-01

    Circulating DNA can be detected and quantified in the blood of cancer patients and used for detection of tumor-specific genetic alterations. The clinical utility has been intensively investigated for the past 10 years. The majority of reports focus on analyzing the clinical potential of tumor-specific mutations, whereas the use of total cell-free DNA (cfDNA) quantification is somehow controversial and sparsely described in the literature, but holds important clinical information in itself. The purpose of the present report was to present a systematic review and meta-analysis of the prognostic value of total cfDNA in patients with metastatic colorectal cancer (mCRC) treated with chemotherapy. In addition, we report on the overall performance of cfDNA as source for KRAS mutation detection. A systematic literature search of PubMed and Embase was performed by two independent investigators. Eligibility criteria were (a) total cfDNA analysis, (b) mCRC, and (c) prognostic value during palliative treatment. The preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines were followed, and meta-analysis applied on both aggregate data extraction and individual patients' data. Ten eligible cohorts were identified, including a total of 1,076 patients. Seven studies used quantitative polymerase chain reaction methods, two BEAMing [beads, emulsification, amplification, and magnetics] technology, and one study digital droplet polymerase chain reaction. The baseline levels of cfDNA was similar in the presented studies, and all studies reported a clear prognostic value in favor of patients with lowest levels of baseline cfDNA. A meta-analysis revealed a combined estimate of favorable overall survival hazard ratio (HR) in patients with levels below the median cfDNA (HR = 2.39, 95% confidence interval 2.03-2.82, p  meta-analysis. Reliable prognostic markers could help to guide patients and treating physicians regarding the relevance and choice of

  5. Consistent Differential Expression Pattern (CDEP) on microarray to identify genes related to metastatic behavior.

    Science.gov (United States)

    Tsoi, Lam C; Qin, Tingting; Slate, Elizabeth H; Zheng, W Jim

    2011-11-11

    To utilize the large volume of gene expression information generated from different microarray experiments, several meta-analysis techniques have been developed. Despite these efforts, there remain significant challenges to effectively increasing the statistical power and decreasing the Type I error rate while pooling the heterogeneous datasets from public resources. The objective of this study is to develop a novel meta-analysis approach, Consistent Differential Expression Pattern (CDEP), to identify genes with common differential expression patterns across different datasets. We combined False Discovery Rate (FDR) estimation and the non-parametric RankProd approach to estimate the Type I error rate in each microarray dataset of the meta-analysis. These Type I error rates from all datasets were then used to identify genes with common differential expression patterns. Our simulation study showed that CDEP achieved higher statistical power and maintained low Type I error rate when compared with two recently proposed meta-analysis approaches. We applied CDEP to analyze microarray data from different laboratories that compared transcription profiles between metastatic and primary cancer of different types. Many genes identified as differentially expressed consistently across different cancer types are in pathways related to metastatic behavior, such as ECM-receptor interaction, focal adhesion, and blood vessel development. We also identified novel genes such as AMIGO2, Gem, and CXCL11 that have not been shown to associate with, but may play roles in, metastasis. CDEP is a flexible approach that borrows information from each dataset in a meta-analysis in order to identify genes being differentially expressed consistently. We have shown that CDEP can gain higher statistical power than other existing approaches under a variety of settings considered in the simulation study, suggesting its robustness and insensitivity to data variation commonly associated with microarray

  6. A Comparison of Regorafenib and TAS-102 for Metastatic Colorectal Cancer: A Systematic Review and Network Meta-analysis.

    Science.gov (United States)

    Abrahao, Ana B K; Ko, Yoo-Joung; Berry, Scott; Chan, Kelvin K W

    2017-11-21

    Regorafenib and TAS-102 have shown to be superior to placebo in refractory metastatic colorectal cancer. However, no studies have directly compared both drugs. Giving the lack of standard options in this scenario, a systematic review to compare the efficacy and safety of regorafenib and TAS-102 was performed. A systematic review using the PubMed, Medline, Embase, Scopus, and Cochrane databases to identify published and unpublished studies up to November 2015 for randomized controlled trials for patients with metastatic colorectal cancer, involving regorafenib or TAS-102, was performed. Data including overall survival, progression-free survival, and toxicity were extracted. Pairwise direct meta-analyses (regorafenib vs. placebo and TAS-102 vs. placebo) and indirect comparison (regorafenib vs. TAS-102) using network meta-analyses methods to preserve randomization were performed using random effects. Three randomized controlled trials fulfilled eligibility criteria (regorafenib monotherapy for previously treated metastatic colorectal cancer [CORRECT]: an international, multicentre, randomised, pacebo-controlled, phase 3 trial, regorafenib plus best supportive care versus placebo plus best supportive care in Asian patients with previously treated metastatic colorectal cancer [CONCUR]: a randomised, double-blind, placebo-controlled, phase 3 trial, and randomized trial of TAS-102 for refractory metastatic colorectal cancer [RECOURSE] trials) involving 1764 patients (regorafenib, 641; TAS-102, 534; placebo, 589). Subgroups of patients (1659) who had not received prior regorafenib or TAS-102 were used to perform meta-analyses for efficacy. In the indirect comparison, no statistically significant differences were observed between regorafenib and TAS-102 in overall survival (hazard ratio, 0.96; 95% confidence interval [CI], 0.57-1.66; P = .91) or progression-free survival (hazard ratio, 0.85; 95% CI, 0.40-1.81; P = .67). However, regorafenib has statistically more all

  7. Correlation of bevacizumab-induced hypertension and outcomes of metastatic colorectal cancer patients treated with bevacizumab: a systematic review and meta-analysis.

    Science.gov (United States)

    Cai, Jun; Ma, Hong; Huang, Fang; Zhu, Dichao; Bi, Jianping; Ke, Yang; Zhang, Tao

    2013-11-28

    With the wide application of targeted drug therapies, the relevance of prognostic and predictive markers in patient selection has become increasingly important. Bevacizumab is commonly used in combination with chemotherapy in the treatment of metastatic colorectal cancer. However, there are currently no predictive or prognostic biomarkers for bevacizumab. Several clinical studies have evaluated bevacizumab-induced hypertension in patients with metastatic colorectal cancer. This meta-analysis was performed to better determine the association of bevacizumab-induced hypertension with outcome in patients with metastatic colorectal cancer, and to assess whether bevacizumab-induced hypertension can be used as a prognostic factor in these patients. We performed a systematic review and meta-analysis on seven published studies to investigate the relationship between hypertension and outcome of patients with metastatic colorectal cancer treated with bevacizumab. Our primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS) and overall response rate (ORR). Hazard ratios (HRs) for PFS and OS were extracted from each trial, and the log of the relative risk ratio (RR) was estimated for ORR. The occurrence of bevacizumab-induced hypertension in patients was highly associated with improvements in PFS (HR = 0.57, 95% CI: 0.46-0.72; P hypertension. Bevacizumab-induced hypertension may represent a prognostic factor in patients with metastatic colorectal cancer.

  8. A Systematic Review and Meta-analysis of Retrospective Series of Regorafenib for Treatment of Metastatic Colorectal Cancer.

    Science.gov (United States)

    Mercier, Joey; Voutsadakis, Ioannis A

    2017-11-01

    Metastatic colorectal cancer is a common disease encountered in oncology practice and treatment options beyond fluoropyrimidines, irinotecan, oxaliplatin and monoclonal antibodies against epidermal growth factor receptor and vascular endothelium growth factor (VEGF) are limited. Regorafenib, a new drug that targets tyrosine kinases such as VEGF receptor as well as others, has been added recently to the armamentarium for metastatic colorectal cancer. This report analyzes the published experience with this drug in clinical practice outside of clinical trials. A literature search of major databases was performed for the identification of studies of regorafenib in metastatic colorectal cancer. Studies retained for further analysis were in English or French, describing 20 or more patients treated with regorafenib monotherapy and not part of a phase I, II or III trial. Results of the pooled analysis of retrospective studies were compared with results of the published phase III trials and a phase IIIb prospective study. Twelve publications including a total of 702 patients were included in the meta-analysis. Summary response rate was 2% [95% confidence interval (CI) =0.8-3.2%] and the disease control rate 38.14% (95% CI=32.35-43.93%). Summary survival rates were 3.34 months (95% CI=2.71-3.97 months) for progression-free and 7.27 months (95% CI=6.23-8.3 months) for overall survival. These were similar to the phase III and IIIb studies. Most common adverse effects were also consistent with those of the published phase III experience. This systematic review and meta-analysis confirmed a moderate efficacy of regorafenib in later-stage metastatic colorectal cancer in the everyday clinical practice setting outside of clinical trials. Future identification of biomarkers may aid in further tailoring of this treatment in order to obtain maximum clinical benefit. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  9. Meta-analysis of archived DNA microarrays identifies genes regulated by hypoxia and involved in a metastatic phenotype in cancer cells

    International Nuclear Information System (INIS)

    Pierre, Michael; DeHertogh, Benoît; Gaigneaux, Anthoula; DeMeulder, Bertrand; Berger, Fabrice; Bareke, Eric; Michiels, Carine; Depiereux, Eric

    2010-01-01

    Metastasis is a major cancer-related cause of death. Recent studies have described metastasis pathways. However, the exact contribution of each pathway remains unclear. Another key feature of a tumor is the presence of hypoxic areas caused by a lack of oxygen at the center of the tumor. Hypoxia leads to the expression of pro-metastatic genes as well as the repression of anti-metastatic genes. As many Affymetrix datasets about metastasis and hypoxia are publicly available and not fully exploited, this study proposes to re-analyze these datasets to extract new information about the metastatic phenotype induced by hypoxia in different cancer cell lines. Affymetrix datasets about metastasis and/or hypoxia were downloaded from GEO and ArrayExpress. AffyProbeMiner and GCRMA packages were used for pre-processing and the Window Welch t test was used for processing. Three approaches of meta-analysis were eventually used for the selection of genes of interest. Three complementary approaches were used, that eventually selected 183 genes of interest. Out of these 183 genes, 99, among which the well known JUNB, FOS and TP63, have already been described in the literature to be involved in cancer. Moreover, 39 genes of those, such as SERPINE1 and MMP7, are known to regulate metastasis. Twenty-one genes including VEGFA and ID2 have also been described to be involved in the response to hypoxia. Lastly, DAVID classified those 183 genes in 24 different pathways, among which 8 are directly related to cancer while 5 others are related to proliferation and cell motility. A negative control composed of 183 random genes failed to provide such results. Interestingly, 6 pathways retrieved by DAVID with the 183 genes of interest concern pathogen recognition and phagocytosis. The proposed methodology was able to find genes actually known to be involved in cancer, metastasis and hypoxia and, thus, we propose that the other genes selected based on the same methodology are of prime interest in

  10. Gene Expression Meta-Analysis identifies Cytokine Pathways and 5q Aberrations involved in Metastasis of ERBB2 Amplified and Basal Breast Cancer

    DEFF Research Database (Denmark)

    Thomassen, Mads; Tan, Qihua; Burton, Mark

    2013-01-01

    Background: Breast tumors have been described by molecular subtypes characterized by pervasively different gene expression profiles. The subtypes are associated with different clinical parameters and origin of precursor cells. However, the biological pathways and chromosomal aberrations that differ...... the subgroups impact metastasis. Results: We have scrutinized publicly available gene expression datasets and identified molecular subtypes in 1,394 breast tumors with outcome data. By analysis of chromosomal regions and pathways using “Gene set enrichment analysis” followed by a meta-analysis, we identified...... between the subgroups are less well characterized. The molecular subtypes are associated with different risk of metastatic recurrence of the disease. Nevertheless, the performance of these overall patterns to predict outcome is far from optimal, suggesting that biological mechanisms that extend beyond...

  11. Immune checkpoint inhibitors and targeted therapies for metastatic melanoma: A network meta-analysis.

    Science.gov (United States)

    Pasquali, Sandro; Chiarion-Sileni, Vanna; Rossi, Carlo Riccardo; Mocellin, Simone

    2017-03-01

    Immune checkpoint inhibitors and targeted therapies, two new class of drugs for treatment of metastatic melanoma, have not been compared in randomized controlled trials (RCT). We quantitatively summarized the evidence and compared immune and targeted therapies in terms of both efficacy and toxicity. A comprehensive search for RCTs of immune checkpoint inhibitors and targeted therapies was conducted to August 2016. Using a network meta-analysis approach, treatments were compared with each other and ranked based on their effectiveness (as measured by the impact on progression-free survival [PFS]) and acceptability (the inverse of high grade toxicity). Twelve RCTs enrolling 6207 patients were included. Network meta-analysis generated 15 comparisons. Combined BRAF and MEK inhibitors were associated with longer PFS as compared to anti-CTLA4 (HR: 0.22; 95% confidence interval [CI]: 0.12-0.41) and anti-PD1 antibodies alone (HR: 0.38; CI: 0.20-0.72). However, anti-PD1 monoclonal antibodies were less toxic than anti-CTLA4 monoclonal antibodies (RR: 0.65; CI: 0.40-0.78) and their combination significantly increased toxicity compared to either single agent anti-CTLA4 (RR: 2.06; CI: 1.45-2.93) or anti-PD1 monoclonal antibodies (RR: 3.67; CI: 2.27-5.96). Consistently, ranking analysis suggested that the combination of targeted therapies is the most effective strategy, whereas single agent anti-PD1 antibodies have the best acceptability. The GRADE level of evidence quality for these findings was moderate to low. The simultaneous inhibition of BRAF and MEK appears the most effective treatment for melanomas harboring BRAF V600 mutation, although anti-PD1 antibodies appear to be less toxic. Further research is needed to increase the quality of evidence. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Prostate specific antigen (PSA) kinetic as a prognostic factor in metastatic prostate cancer receiving androgen deprivation therapy: systematic review and meta-analysis.

    Science.gov (United States)

    Afriansyah, Andika; Hamid, Agus Rizal Ardy Hariandy; Mochtar, Chaidir Arif; Umbas, Rainy

    2018-01-01

    Aim: Metastatic prostate cancer (mPCa) has a poor outcome with median survival of two to five years. The use of androgen deprivation therapy (ADT) is a gold standard in management of this stage.  Aim of this study is to analyze the prognostic value of PSA kinetics of patient treated with hormonal therapy related to survival from several published studies Method: Systematic review and meta-analysis was performed using literature searching in the electronic databases of MEDLINE, Science Direct, and Cochrane Library. Inclusion criteria were mPCa receiving ADT, a study analyzing Progression Free Survival (PFS), Overall Survival (OS), or Cancer Specific Survival (CSS) and prognostic factor of survival related to PSA kinetics (initial PSA, PSA nadir, and time to achieve nadir (TTN)). The exclusion criteria were metastatic castration resistant of prostate cancer (mCRPC) and non-metastatic disease. Generic inverse variance method was used to combine hazard ratio (HR) within the studies. Meta-analysis was performed using Review Manager 5.2 and a p-value PSA and PFS. In addition, there was no association between initial PSA and CSS/ OS. We found association of reduced PFS (HR 2.22; 95% CI 1.82 to 2.70) and OS/ CSS (HR 3.31; 95% CI 2.01-5.43) of patient with high PSA nadir. Shorter TTN was correlated with poor result of survival either PFS (HR 2.41; 95% CI 1.19 - 4.86) or CSS/ OS (HR 1.80; 95%CI  1.42 - 2.30) Conclusion: Initial PSA before starting ADT do not associated with survival in mPCa.  There is association of PSA nadir and TTN with survival.

  13. Contrast-enhanced ultrasonography in qualitative diagnosis of sentinel lymph node metastasis in breast cancer: A meta-analysis

    Directory of Open Access Journals (Sweden)

    Yi-Xia Zhang

    2015-01-01

    Conclusions: Our meta-analysis suggests that CEUS may have high a diagnostic accuracy in testing for metastatic SLN in breast cancer. Thus, CEUS may be a good tool for differential diagnosis between metastatic and non-metastatic SLN.

  14. Effectiveness of Reirradiation for Painful Bone Metastases: A Systematic Review and Meta-Analysis

    International Nuclear Information System (INIS)

    Huisman, Merel; Bosch, Maurice A.A.J. van den; Wijlemans, Joost W.; Vulpen, Marco van; Linden, Yvette M. van der; Verkooijen, Helena M.

    2012-01-01

    Purpose: Reirradiation of painful bone metastases in nonresponders or patients with recurrent pain after initial response is performed in up to 42% of patients initially treated with radiotherapy. Literature on the effect of reirradiation for pain control in those patients is scarce. In this systematic review and meta-analysis, we quantify the effectiveness of reirradiation for achieving pain control in patients with painful bone metastases. Methods and Materials: A free text search was performed to identify eligible studies using the MEDLINE, EMBASE, and the Cochrane Collaboration library electronic databases. After study selection and quality assessment, a pooled estimate was calculated for overall pain response for reirradiation of metastatic bone pain. Results: Our literature search identified 707 titles, of which 10 articles were selected for systematic review and seven entered the meta-analysis. Overall study quality was mediocre. Of the 2,694 patients initially treated for metastatic bone pain, 527 (20%) patients underwent reirradiation. Overall, a pain response after reirradiation was achieved in 58% of patients (pooled overall response rate 0.58, 95% confidence interval = 0.49–0.67). There was a substantial between-study heterogeneity (I 2 = 63.3%, p = 0.01) because of clinical and methodological differences between studies. Conclusions: Reirradiation of painful bone metastases is effective in terms of pain relief for a small majority of patients; approximately 40% of patients do not benefit from reirradiation. Although the validity of results is limited, this meta-analysis provides a comprehensive overview and the most quantitative estimate of reirradiation effectiveness to date.

  15. Quantitative Secretomic Analysis Identifies Extracellular Protein Factors That Modulate the Metastatic Phenotype of Non-Small Cell Lung Cancer.

    Science.gov (United States)

    Hu, Rongkuan; Huffman, Kenneth E; Chu, Michael; Zhang, Yajie; Minna, John D; Yu, Yonghao

    2016-02-05

    Lung cancer is the leading cause of cancer-related deaths for men and women in the United States, with non-small cell lung cancer (NSCLC) representing 85% of all diagnoses. Late stage detection, metastatic disease and lack of actionable biomarkers contribute to the high mortality rate. Proteins in the extracellular space are known to be critically involved in regulating every stage of the pathogenesis of lung cancer. To investigate the mechanism by which secreted proteins contribute to the pathogenesis of NSCLC, we performed quantitative secretomic analysis of two isogenic NSCLC cell lines (NCI-H1993 and NCI-H2073) and an immortalized human bronchial epithelial cell line (HBEC3-KT) as control. H1993 was derived from a chemo-naïve metastatic tumor, while H2073 was derived from the primary tumor after etoposide/cisplatin therapy. From the conditioned media of these three cell lines, we identified and quantified 2713 proteins, including a series of proteins involved in regulating inflammatory response, programmed cell death and cell motion. Gene Ontology (GO) analysis indicates that a number of proteins overexpressed in H1993 media are involved in biological processes related to cancer metastasis, including cell motion, cell-cell adhesion and cell migration. RNA interference (RNAi)-mediated knock down of a number of these proteins, including SULT2B1, CEACAM5, SPRR3, AGR2, S100P, and S100A14, leads to dramatically reduced migration of these cells. In addition, meta-analysis of survival data indicates NSCLC patients whose tumors express higher levels of several of these secreted proteins, including SULT2B1, CEACAM5, SPRR3, S100P, and S100A14, have a worse prognosis. Collectively, our results provide a potential molecular link between deregulated secretome and NSCLC cell migration/metastasis. In addition, the identification of these aberrantly secreted proteins might facilitate the development of biomarkers for early detection of this devastating disease.

  16. Treatment with Antiangiogenic Drugs in Multiple Lines in Patients with Metastatic Colorectal Cancer: Meta-Analysis of Randomized Trials

    Directory of Open Access Journals (Sweden)

    R.-D. Hofheinz

    2016-01-01

    Full Text Available Background. In metastatic colorectal cancer (mCRC, continuing antiangiogenic drugs beyond progression might provide clinical benefit. We synthesized the available evidence in a meta-analysis. Patients and Methods. We conducted a meta-analysis of studies investigating the use of antiangiogenic drugs beyond progression. Eligible studies were randomized phase II/III trials. Primary endpoints were overall survival (OS and progression-free survival (PFS. Secondary endpoints were the impact of continuing antiangiogenic drugs (i in subgroups, (ii in different types of compounds targeting the VEGF-axis (monoclonal antibodies versus tyrosine kinase inhibitors, and (iii on remission rates and prevention of progression. Results. Eight studies (3,668 patients were included. Continuing antiangiogenic treatment beyond progression significantly improved PFS (HR 0.64; 95%-CI, 0.55–0.75 and OS (HR 0.83; 95%-CI, 0.76–0.89. PFS was significantly improved in all subgroups with comparable HR. OS was improved in all subgroups stratified by age, gender, and ECOG status. The rate of patients achieving at least stable disease was improved with an OR of 2.25 (95%-CI, 1.41–3.58. Conclusions. This analysis shows a significant PFS and OS benefit as well as a benefit regarding disease stabilization when using antiangiogenic drugs beyond progression in mCRC. Future studies should focus on the optimal sequence of administering antiangiogenic drugs.

  17. Transcriptomic meta-analysis identifies gene expression characteristics in various samples of HIV-infected patients with nonprogressive disease.

    Science.gov (United States)

    Zhang, Le-Le; Zhang, Zi-Ning; Wu, Xian; Jiang, Yong-Jun; Fu, Ya-Jing; Shang, Hong

    2017-09-12

    A small proportion of HIV-infected patients remain clinically and/or immunologically stable for years, including elite controllers (ECs) who have undetectable viremia (10 years). However, the mechanism of nonprogression needs to be further resolved. In this study, a transcriptome meta-analysis was performed on nonprogressor and progressor microarray data to identify differential transcriptome pathways and potential biomarkers. Using the INMEX (integrative meta-analysis of expression data) program, we performed the meta-analysis to identify consistently differentially expressed genes (DEGs) in nonprogressors and further performed functional interpretation (gene ontology analysis and pathway analysis) of the DEGs identified in the meta-analysis. Five microarray datasets (81 cases and 98 controls in total), including whole blood, CD4 + and CD8 + T cells, were collected for meta-analysis. We determined that nonprogressors have reduced expression of important interferon-stimulated genes (ISGs), CD38, lymphocyte activation gene 3 (LAG-3) in whole blood, CD4 + and CD8 + T cells. Gene ontology (GO) analysis showed a significant enrichment in DEGs that function in the type I interferon signaling pathway. Upregulated pathways, including the PI3K-Akt signaling pathway in whole blood, cytokine-cytokine receptor interaction in CD4 + T cells and the MAPK signaling pathway in CD8 + T cells, were identified in nonprogressors compared with progressors. In each metabolic functional category, the number of downregulated DEGs was more than the upregulated DEGs, and almost all genes were downregulated DEGs in the oxidative phosphorylation (OXPHOS) and tricarboxylic acid (TCA) cycle in the three types of samples. Our transcriptomic meta-analysis provides a comprehensive evaluation of the gene expression profiles in major blood types of nonprogressors, providing new insights in the understanding of HIV pathogenesis and developing strategies to delay HIV disease progression.

  18. A meta-analysis of genome-wide association studies identifies novel variants associated with osteoarthritis of the hip

    DEFF Research Database (Denmark)

    Evangelou, Evangelos; Kerkhof, Hanneke J; Styrkarsdottir, Unnur

    2014-01-01

    Osteoarthritis (OA) is the most common form of arthritis with a clear genetic component. To identify novel loci associated with hip OA we performed a meta-analysis of genome-wide association studies (GWAS) on European subjects.......Osteoarthritis (OA) is the most common form of arthritis with a clear genetic component. To identify novel loci associated with hip OA we performed a meta-analysis of genome-wide association studies (GWAS) on European subjects....

  19. Comparison of palbociclib in combination with letrozole or fulvestrant with endocrine therapies for advanced/metastatic breast cancer: network meta-analysis.

    Science.gov (United States)

    Chirila, Costel; Mitra, Debanjali; Colosia, Ann; Ling, Caroline; Odom, Dawn; Iyer, Shrividya; Kaye, James A

    2017-08-01

    Palbociclib is the first cyclin-dependent kinase 4/6 inhibitor approved in the United States for HR+/HER2- advanced/metastatic breast cancer, in combination with letrozole as initial endocrine-based therapy in postmenopausal women or with fulvestrant in women with disease progression following endocrine therapy. We compared progression-free survival (PFS) and discontinuations due to adverse events for palbociclib combinations against other endocrine therapies using a mixed-treatment comparison meta-analysis of randomized, controlled trials. A systematic literature review identified relevant trials. Separate analyses were conducted for each palbociclib combination using a Bayesian approach. Treatment rankings were established using the surface under the cumulative ranking curve (SUCRA). Sixty-five unique studies met inclusion criteria. Palbociclib plus letrozole had the highest SUCRA value (99.9%) and was associated with significantly longer PFS than all comparators in treatment-naïve patients (hazard ratios [HRs] ranged from 0.41 to 0.58). Palbociclib plus fulvestrant had the second highest SUCRA value (93.9%) and, in previously treated patients, yielded significantly longer PFS than most comparators (HRs ranged from 0.26 to 0.46); the exception was everolimus plus exemestane, with similar PFS (HR, 1.04; 95% credible interval [CrI], 0.58-1.76). Palbociclib plus fulvestrant was associated with significantly lower odds of discontinuation due to adverse events than everolimus plus exemestane (odds ratio, 0.14; 95% CrI, 0.05-0.39). The results suggest that the two palbociclib combinations yielded significantly greater PFS than endocrine therapy in treatment-naïve and previously treated patients with advanced/metastatic breast cancer. Palbociclib plus fulvestrant was associated with significantly less toxicity than everolimus plus exemestane.

  20. Meta-analysis identifies common and rare variants influencing blood pressure and overlapping with metabolic trait loci

    NARCIS (Netherlands)

    Liu, C. (Chunyu); A. Kraja (Aldi); J.A. Smith (Jennifer A); J. Brody (Jennifer); N. Franceschini (Nora); J.C. Bis (Joshua); K.M. Rice (Kenneth); A.C. Morrison (Alanna); Y. Lu (Yingchang); Weiss, S. (Stefan); X. Guo (Xiuqing); W. Palmas (Walter); L.W. Martin (Lisa); Y.D. Chen (Y.); Surendran, P. (Praveen); F. Drenos (Fotios); Cook, J.P. (James P.); P. Auer (Paul); A.Y. Chu (Audrey); Giri, A. (Ayush); Zhao, W. (Wei); M. Jakobsdottir (Margret); Lin, L.-A. (Li-An); J.M. Stafford (Jeanette M.); N. Amin (Najaf); Mei, H. (Hao); J. Yao (Jiefen); J.M. Voorman (Jeanine); M.G. Larson (Martin); M.L. Grove (Megan); A.V. Smith (Albert Vernon); S.J. Hwang; H. Chen (Han); T. Huan (Tianxiao); Kosova, G. (Gulum); N.O. Stitziel (Nathan); S. Kathiresan (Sekar); N.J. Samani (Nilesh); H. Schunkert (Heribert); P. Deloukas (Panagiotis); M. Li (Man); C. Fuchsberger (Christian); C. Pattaro (Cristian); M. Gorski (Mathias); C. Kooperberg (Charles); G. Papanicolaou (George); Rossouw, J.E. (Jacques E.); J.D. Faul (Jessica D.); S.L.R. Kardia (Sharon); C. Bouchard (Claude); L.J. Raffel (Leslie); Uitterlinden, A.G. (André G.); O.H. Franco (Oscar); R. Vasan (Ramachandran); C.J. O'Donnell (Christopher); K.D. Taylor (Kent); K.Y. Liu; E.P. Bottinger (Erwin); R.F. Gottesman (Rebecca); E.W. Daw (E. Warwick); F. Giulianini (Franco); S.K. Ganesh (Santhi); E. Salfati (Elias); T.B. Harris (Tamara); Launer, L.J. (Lenore J.); M. Dörr (Marcus); S.B. Felix (Stephan); R. Rettig (Rainer); H. Völzke (Henry); E. Kim (Eric); W.-J. Lee (Wen-Jane); I.T. Lee; Sheu, W.H.-H. (Wayne H.-H.); Tsosie, K.S. (Krystal S.); Edwards, D.R.V. (Digna R. Velez); Y. Liu (YongMei); Correa, A. (Adolfo); D.R. Weir (David); U. Völker (Uwe); P.M. Ridker (Paul); E.A. Boerwinkle (Eric); V. Gudnason (Vilmundur); A. Reiner (Alexander); Van Duijn, C.M. (Cornelia M.); I.B. Borecki (Ingrid); T.L. Edwards (Todd L.); A. Chakravarti (Aravinda); Rotter, J.I. (Jerome I.); B.M. Psaty (Bruce); R.J.F. Loos (Ruth); M. Fornage (Myriam); G.B. Ehret (Georg); C. Newton-Cheh (Christopher); D. Levy (Daniel); D.I. Chasman (Daniel)

    2016-01-01

    textabstractMeta-analyses of association results for blood pressure using exome-centric single-variant and gene-based tests identified 31 new loci in a discovery stage among 146,562 individuals, with follow-up and meta-analysis in 180,726 additional individuals (total n = 327,288). These blood

  1. A meta-analysis of 18F-Fluoride positron emission tomography for assessment of metastatic bone tumor

    International Nuclear Information System (INIS)

    Tateishi, Ukihide; Morita, Satoshi; Taguri, Masataka

    2010-01-01

    The aim of this study was to assess the diagnostic performance of 18 F-Fluoride positron emission tomography (PET) or positron emission tomography/computed tomography (PET/CT) compared with bone scintigraphy (BS) planar or BS planar and single photon emission computed tomography (SPECT) in evaluating patients with metastatic bone tumor. We performed a meta-analysis of all available studies addressing the diagnostic accuracy of 18 F-Fluoride PET, 18 F-Fluoride PET/CT, BS planar, and BS planar and SPECT for detecting the metastatic bone tumor. We determined sensitivities and specificities across studies, calculated positive and negative likelihood ratios, and drew summary receiver operating characteristic curves using hierarchical regression models. We also compared the effective dose and cost-effectiveness estimated by data from the enrolled studies between 18 F-Fluoride PET or PET/CT and BS planar or BS planar and SPECT. When comparing all studies with data on 18 F-Fluoride PET or PET/CT, sensitivity and specificity were 96.2% [95% confidence interval (CI) 93.5-98.9%] and 98.5% (95% CI 97.0-100%), respectively, on a patient basis and 96.9% (95% CI 95.9-98.0%) and 98.0% (95% CI 97.1-98.9%), respectively, on a lesion basis. The Az values of 18 F-Fluoride PET or PET/CT were 0.986 for the patient basis and 0.905 for the lesion basis, whereas those of BS or BS and SPECT were 0.866 for the patient basis and 0.854 for the lesion basis. However, the estimated effective dose and average cost-effective ratio were poorer for 18 F-Fluoride PET or PET/CT than those of BS planar or BS planar and SPECT. 18 F-Fluoride PET or PET/CT has excellent diagnostic performance for the detection of metastatic bone tumor, but the estimated effective dose and average cost-effective ratio are at a disadvantage compared with BS planar or BS planar and SPECT. (author)

  2. Meta-Analysis of Placental Transcriptome Data Identifies a Novel Molecular Pathway Related to Preeclampsia.

    Science.gov (United States)

    van Uitert, Miranda; Moerland, Perry D; Enquobahrie, Daniel A; Laivuori, Hannele; van der Post, Joris A M; Ris-Stalpers, Carrie; Afink, Gijs B

    2015-01-01

    Studies using the placental transcriptome to identify key molecules relevant for preeclampsia are hampered by a relatively small sample size. In addition, they use a variety of bioinformatics and statistical methods, making comparison of findings challenging. To generate a more robust preeclampsia gene expression signature, we performed a meta-analysis on the original data of 11 placenta RNA microarray experiments, representing 139 normotensive and 116 preeclamptic pregnancies. Microarray data were pre-processed and analyzed using standardized bioinformatics and statistical procedures and the effect sizes were combined using an inverse-variance random-effects model. Interactions between genes in the resulting gene expression signature were identified by pathway analysis (Ingenuity Pathway Analysis, Gene Set Enrichment Analysis, Graphite) and protein-protein associations (STRING). This approach has resulted in a comprehensive list of differentially expressed genes that led to a 388-gene meta-signature of preeclamptic placenta. Pathway analysis highlights the involvement of the previously identified hypoxia/HIF1A pathway in the establishment of the preeclamptic gene expression profile, while analysis of protein interaction networks indicates CREBBP/EP300 as a novel element central to the preeclamptic placental transcriptome. In addition, there is an apparent high incidence of preeclampsia in women carrying a child with a mutation in CREBBP/EP300 (Rubinstein-Taybi Syndrome). The 388-gene preeclampsia meta-signature offers a vital starting point for further studies into the relevance of these genes (in particular CREBBP/EP300) and their concomitant pathways as biomarkers or functional molecules in preeclampsia. This will result in a better understanding of the molecular basis of this disease and opens up the opportunity to develop rational therapies targeting the placental dysfunction causal to preeclampsia.

  3. A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer

    DEFF Research Database (Denmark)

    Al Olama, Ali Amin; Kote-Jarai, Zsofia; Berndt, Sonja I

    2014-01-01

    Genome-wide association studies (GWAS) have identified 76 variants associated with prostate cancer risk predominantly in populations of European ancestry. To identify additional susceptibility loci for this common cancer, we conducted a meta-analysis of > 10 million SNPs in 43,303 prostate cancer...

  4. Identifying novel glioma associated pathways based on systems biology level meta-analysis.

    Science.gov (United States)

    Hu, Yangfan; Li, Jinquan; Yan, Wenying; Chen, Jiajia; Li, Yin; Hu, Guang; Shen, Bairong

    2013-01-01

    With recent advances in microarray technology, including genomics, proteomics, and metabolomics, it brings a great challenge for integrating this "-omics" data to analysis complex disease. Glioma is an extremely aggressive and lethal form of brain tumor, and thus the study of the molecule mechanism underlying glioma remains very important. To date, most studies focus on detecting the differentially expressed genes in glioma. However, the meta-analysis for pathway analysis based on multiple microarray datasets has not been systematically pursued. In this study, we therefore developed a systems biology based approach by integrating three types of omics data to identify common pathways in glioma. Firstly, the meta-analysis has been performed to study the overlapping of signatures at different levels based on the microarray gene expression data of glioma. Among these gene expression datasets, 12 pathways were found in GeneGO database that shared by four stages. Then, microRNA expression profiles and ChIP-seq data were integrated for the further pathway enrichment analysis. As a result, we suggest 5 of these pathways could be served as putative pathways in glioma. Among them, the pathway of TGF-beta-dependent induction of EMT via SMAD is of particular importance. Our results demonstrate that the meta-analysis based on systems biology level provide a more useful approach to study the molecule mechanism of complex disease. The integration of different types of omics data, including gene expression microarrays, microRNA and ChIP-seq data, suggest some common pathways correlated with glioma. These findings will offer useful potential candidates for targeted therapeutic intervention of glioma.

  5. Meta-Analysis of Placental Transcriptome Data Identifies a Novel Molecular Pathway Related to Preeclampsia.

    Directory of Open Access Journals (Sweden)

    Miranda van Uitert

    Full Text Available Studies using the placental transcriptome to identify key molecules relevant for preeclampsia are hampered by a relatively small sample size. In addition, they use a variety of bioinformatics and statistical methods, making comparison of findings challenging. To generate a more robust preeclampsia gene expression signature, we performed a meta-analysis on the original data of 11 placenta RNA microarray experiments, representing 139 normotensive and 116 preeclamptic pregnancies. Microarray data were pre-processed and analyzed using standardized bioinformatics and statistical procedures and the effect sizes were combined using an inverse-variance random-effects model. Interactions between genes in the resulting gene expression signature were identified by pathway analysis (Ingenuity Pathway Analysis, Gene Set Enrichment Analysis, Graphite and protein-protein associations (STRING. This approach has resulted in a comprehensive list of differentially expressed genes that led to a 388-gene meta-signature of preeclamptic placenta. Pathway analysis highlights the involvement of the previously identified hypoxia/HIF1A pathway in the establishment of the preeclamptic gene expression profile, while analysis of protein interaction networks indicates CREBBP/EP300 as a novel element central to the preeclamptic placental transcriptome. In addition, there is an apparent high incidence of preeclampsia in women carrying a child with a mutation in CREBBP/EP300 (Rubinstein-Taybi Syndrome. The 388-gene preeclampsia meta-signature offers a vital starting point for further studies into the relevance of these genes (in particular CREBBP/EP300 and their concomitant pathways as biomarkers or functional molecules in preeclampsia. This will result in a better understanding of the molecular basis of this disease and opens up the opportunity to develop rational therapies targeting the placental dysfunction causal to preeclampsia.

  6. Genome-wide meta-analysis identifies new susceptibility loci for migraine.

    Science.gov (United States)

    Anttila, Verneri; Winsvold, Bendik S; Gormley, Padhraig; Kurth, Tobias; Bettella, Francesco; McMahon, George; Kallela, Mikko; Malik, Rainer; de Vries, Boukje; Terwindt, Gisela; Medland, Sarah E; Todt, Unda; McArdle, Wendy L; Quaye, Lydia; Koiranen, Markku; Ikram, M Arfan; Lehtimäki, Terho; Stam, Anine H; Ligthart, Lannie; Wedenoja, Juho; Dunham, Ian; Neale, Benjamin M; Palta, Priit; Hamalainen, Eija; Schürks, Markus; Rose, Lynda M; Buring, Julie E; Ridker, Paul M; Steinberg, Stacy; Stefansson, Hreinn; Jakobsson, Finnbogi; Lawlor, Debbie A; Evans, David M; Ring, Susan M; Färkkilä, Markus; Artto, Ville; Kaunisto, Mari A; Freilinger, Tobias; Schoenen, Jean; Frants, Rune R; Pelzer, Nadine; Weller, Claudia M; Zielman, Ronald; Heath, Andrew C; Madden, Pamela A F; Montgomery, Grant W; Martin, Nicholas G; Borck, Guntram; Göbel, Hartmut; Heinze, Axel; Heinze-Kuhn, Katja; Williams, Frances M K; Hartikainen, Anna-Liisa; Pouta, Anneli; van den Ende, Joyce; Uitterlinden, Andre G; Hofman, Albert; Amin, Najaf; Hottenga, Jouke-Jan; Vink, Jacqueline M; Heikkilä, Kauko; Alexander, Michael; Muller-Myhsok, Bertram; Schreiber, Stefan; Meitinger, Thomas; Wichmann, Heinz Erich; Aromaa, Arpo; Eriksson, Johan G; Traynor, Bryan; Trabzuni, Daniah; Rossin, Elizabeth; Lage, Kasper; Jacobs, Suzanne B R; Gibbs, J Raphael; Birney, Ewan; Kaprio, Jaakko; Penninx, Brenda W; Boomsma, Dorret I; van Duijn, Cornelia; Raitakari, Olli; Jarvelin, Marjo-Riitta; Zwart, John-Anker; Cherkas, Lynn; Strachan, David P; Kubisch, Christian; Ferrari, Michel D; van den Maagdenberg, Arn M J M; Dichgans, Martin; Wessman, Maija; Smith, George Davey; Stefansson, Kari; Daly, Mark J; Nyholt, Dale R; Chasman, Daniel; Palotie, Aarno

    2013-08-01

    Migraine is the most common brain disorder, affecting approximately 14% of the adult population, but its molecular mechanisms are poorly understood. We report the results of a meta-analysis across 29 genome-wide association studies, including a total of 23,285 individuals with migraine (cases) and 95,425 population-matched controls. We identified 12 loci associated with migraine susceptibility (P<5×10(-8)). Five loci are new: near AJAP1 at 1p36, near TSPAN2 at 1p13, within FHL5 at 6q16, within C7orf10 at 7p14 and near MMP16 at 8q21. Three of these loci were identified in disease subgroup analyses. Brain tissue expression quantitative trait locus analysis suggests potential functional candidate genes at four loci: APOA1BP, TBC1D7, FUT9, STAT6 and ATP5B.

  7. Meta-analysis of grain yield QTL identified during agricultural drought in grasses showed consensus.

    Science.gov (United States)

    Swamy, B P Mallikarjuna; Vikram, Prashant; Dixit, Shalabh; Ahmed, H U; Kumar, Arvind

    2011-06-16

    In the last few years, efforts have been made to identify large effect QTL for grain yield under drought in rice. However, identification of most precise and consistent QTL across the environments and genetics backgrounds is essential for their successful use in Marker-assisted Selection. In this study, an attempt was made to locate consistent QTL regions associated with yield increase under drought by applying a genome-wide QTL meta-analysis approach. The integration of 15 maps resulted in a consensus map with 531 markers and a total map length of 1821 cM. Fifty-three yield QTL reported in 15 studies were projected on a consensus map and meta-analysis was performed. Fourteen meta-QTL were obtained on seven chromosomes. MQTL1.2, MQTL1.3, MQTL1.4, and MQTL12.1 were around 700 kb and corresponded to a reasonably small genetic distance of 1.8 to 5 cM and they are suitable for use in marker-assisted selection (MAS). The meta-QTL for grain yield under drought coincided with at least one of the meta-QTL identified for root and leaf morphology traits under drought in earlier reports. Validation of major-effect QTL on a panel of random drought-tolerant lines revealed the presence of at least one major QTL in each line. DTY12.1 was present in 85% of the lines, followed by DTY4.1 in 79% and DTY1.1 in 64% of the lines. Comparative genomics of meta-QTL with other cereals revealed that the homologous regions of MQTL1.4 and MQTL3.2 had QTL for grain yield under drought in maize, wheat, and barley respectively. The genes in the meta-QTL regions were analyzed by a comparative genomics approach and candidate genes were deduced for grain yield under drought. Three groups of genes such as stress-inducible genes, growth and development-related genes, and sugar transport-related genes were found in clusters in most of the meta-QTL. Meta-QTL with small genetic and physical intervals could be useful in Marker-assisted selection individually and in combinations. Validation and comparative

  8. Immunotherapy in advanced melanoma: a network meta-analysis.

    Science.gov (United States)

    Pyo, Jung-Soo; Kang, Guhyun

    2017-05-01

    The aim of this study was to compare the effects of various immunotherapeutic agents and chemotherapy for unresected or metastatic melanomas. We performed a network meta-analysis using a Bayesian statistical model to compare objective response rate (ORR) of various immunotherapies from 12 randomized controlled studies. The estimated ORRs of immunotherapy and chemotherapy were 0.224 and 0.108, respectively. The ORRs of immunotherapy in untreated and pretreated patients were 0.279 and 0.176, respectively. In network meta-analysis, the odds ratios for ORR of nivolumab (1 mg/kg)/ipilmumab (3 mg/kg), pembrolizumab 10 mg/kg and nivolumab 3 mg/kg were 8.54, 5.39 and 4.35, respectively, compared with chemotherapy alone. Our data showed that various immunotherapies had higher ORRs rather than chemotherapy alone.

  9. Genome-wide association scan meta-analysis identifies three loci influencing adiposity and fat distribution

    NARCIS (Netherlands)

    C.M. Lindgren (Cecilia); I.M. Heid (Iris); J.C. Randall (Joshua); C. Lamina (Claudia); V. Steinthorsdottir (Valgerdur); L. Qi (Lu); E.K. Speliotes (Elizabeth); G. Thorleifsson (Gudmar); C.J. Willer (Cristen); B.M. Herrera (Blanca); A.U. Jackson (Anne); N. Lim (Noha); P. Scheet (Paul); N. Soranzo (Nicole); N. Amin (Najaf); Y.S. Aulchenko (Yurii); J.C. Chambers (John); A. Drong (Alexander); J. Luan; H.N. Lyon (Helen); F. Rivadeneira Ramirez (Fernando); S. Sanna (Serena); N.J. Timpson (Nicholas); M.C. Zillikens (Carola); H.Z. Jing; P. Almgren (Peter); S. Bandinelli (Stefania); A.J. Bennett (Amanda); R.N. Bergman (Richard); L.L. Bonnycastle (Lori); S. Bumpstead (Suzannah); S.J. Chanock (Stephen); L. Cherkas (Lynn); P.S. Chines (Peter); L. Coin (Lachlan); C. Cooper (Charles); G. Crawford (Gabe); A. Doering (Angela); A. Dominiczak (Anna); A.S.F. Doney (Alex); S. Ebrahim (Shanil); P. Elliott (Paul); M.R. Erdos (Michael); K. Estrada Gil (Karol); L. Ferrucci (Luigi); G. Fischer (Guido); N.G. Forouhi (Nita); C. Gieger (Christian); H. Grallert (Harald); C.J. Groves (Christopher); S.M. Grundy (Scott); C. Guiducci (Candace); D. Hadley (David); A. Hamsten (Anders); A.S. Havulinna (Aki); A. Hofman (Albert); R. Holle (Rolf); J.W. Holloway (John); T. Illig (Thomas); B. Isomaa (Bo); L.C. Jacobs (Leonie); K. Jameson (Karen); P. Jousilahti (Pekka); F. Karpe (Fredrik); J. Kuusisto (Johanna); J. Laitinen (Jaana); G.M. Lathrop (Mark); D.A. Lawlor (Debbie); M. Mangino (Massimo); W.L. McArdle (Wendy); T. Meitinger (Thomas); M.A. Morken (Mario); A.P. Morris (Andrew); P. Munroe (Patricia); N. Narisu (Narisu); A. Nordström (Anna); B.A. Oostra (Ben); C.N.A. Palmer (Colin); F. Payne (Felicity); J. Peden (John); I. Prokopenko (Inga); F. Renström (Frida); A. Ruokonen (Aimo); V. Salomaa (Veikko); M.S. Sandhu (Manjinder); L.J. Scott (Laura); A. Scuteri (Angelo); K. Silander (Kaisa); K. Song (Kijoung); X. Yuan (Xin); H.M. Stringham (Heather); A.J. Swift (Amy); T. Tuomi (Tiinamaija); M. Uda (Manuela); P. Vollenweider (Peter); G. Waeber (Gérard); C. Wallace (Chris); G.B. Walters (Bragi); M.N. Weedon (Michael); J.C.M. Witteman (Jacqueline); C. Zhang (Cuilin); M. Caulfield (Mark); F.S. Collins (Francis); G.D. Smith; I.N.M. Day (Ian); P.W. Franks (Paul); A.T. Hattersley (Andrew); F.B. Hu (Frank); M.-R. Jarvelin (Marjo-Riitta); A. Kong (Augustine); J.S. Kooner (Jaspal); M. Laakso (Markku); E. Lakatta (Edward); V. Mooser (Vincent); L. Peltonen (Leena Johanna); N.J. Samani (Nilesh); T.D. Spector (Timothy); D.P. Strachan (David); T. Tanaka (Toshiko); J. Tuomilehto (Jaakko); A.G. Uitterlinden (André); P. Tikka-Kleemola (Päivi); N.J. Wareham (Nick); H. Watkins (Hugh); D. Waterworth (Dawn); M. Boehnke (Michael); P. Deloukas (Panagiotis); L. Groop (Leif); D.J. Hunter (David); U. Thorsteinsdottir (Unnur); D. Schlessinger (David); H.E. Wichmann (Erich); T.M. Frayling (Timothy); G.R. Abecasis (Gonçalo); J.N. Hirschhorn (Joel); R.J.F. Loos (Ruth); J-A. Zwart (John-Anker); K.L. Mohlke (Karen); I.E. Barroso (Inês); M.I. McCarthy (Mark)

    2009-01-01

    textabstractTo identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist-hip ratio (WHR). We selected 26 SNPs for follow-up, for which the

  10. Metallothionein - immunohistochemical cancer biomarker: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Jaromir Gumulec

    Full Text Available Metallothionein (MT has been extensively investigated as a molecular marker of various types of cancer. In spite of the fact that numerous reviews have been published in this field, no meta-analytical approach has been performed. Therefore, results of to-date immunohistochemistry-based studies were summarized using meta-analysis in this review. Web of science, PubMed, Embase and CENTRAL databases were searched (up to April 30, 2013 and the eligibility of individual studies and heterogeneity among the studies was assessed. Random and fixed effects model meta-analysis was employed depending on the heterogeneity, and publication bias was evaluated using funnel plots and Egger's tests. A total of 77 studies were included with 8,015 tissue samples (4,631 cases and 3,384 controls. A significantly positive association between MT staining and tumors (vs. healthy tissues was observed in head and neck (odds ratio, OR 9.95; 95% CI 5.82-17.03 and ovarian tumors (OR 7.83; 1.09-56.29, and a negative association was ascertained in liver tumors (OR 0.10; 0.03-0.30. No significant associations were identified in breast, colorectal, prostate, thyroid, stomach, bladder, kidney, gallbladder, and uterine cancers and in melanoma. While no associations were identified between MT and tumor staging, a positive association was identified with the tumor grade (OR 1.58; 1.08-2.30. In particular, strong associations were observed in breast, ovarian, uterine and prostate cancers. Borderline significant association of metastatic status and MT staining were determined (OR 1.59; 1.03-2.46, particularly in esophageal cancer. Additionally, a significant association between the patient prognosis and MT staining was also demonstrated (hazard ratio 2.04; 1.47-2.81. However, a high degree of inconsistence was observed in several tumor types, including colorectal, kidney and prostate cancer. Despite the ambiguity in some tumor types, conclusive results are provided in the tumors of

  11. Differential Expression of Ccn4 and Other Genes Between Metastatic and Non-metastatic EL4 Mouse Lymphoma Cells

    OpenAIRE

    S. CHAHAL, MANPREET; TERESA KU, H.; ZHANG, ZHIHONG; M. LEGASPI, CHRISTIAN; LUO, ANGELA; M. HOPKINS, MANDI; E. MEIER, KATHRYN

    2016-01-01

    Background: Previous work characterized variants of the EL4 murine lymphoma cell line. Some are non-metastatic, and others metastatic, in syngenic mice. In addition, metastatic EL4 cells were stably transfected with phospholipase D2 (PLD2), which further enhanced metastasis. Materials and Methods: Microarray analyses of mRNA expression was performed for non-metastatic, metastatic, and PLD2-expressing metastatic EL4 cells. Results: Many differences were observed between non-metastatic and meta...

  12. Living network meta-analysis compared with pairwise meta-analysis in comparative effectiveness research: empirical study

    Science.gov (United States)

    Nikolakopoulou, Adriani; Mavridis, Dimitris; Furukawa, Toshi A; Cipriani, Andrea; Tricco, Andrea C; Straus, Sharon E; Siontis, George C M; Egger, Matthias

    2018-01-01

    Abstract Objective To examine whether the continuous updating of networks of prospectively planned randomised controlled trials (RCTs) (“living” network meta-analysis) provides strong evidence against the null hypothesis in comparative effectiveness of medical interventions earlier than the updating of conventional, pairwise meta-analysis. Design Empirical study of the accumulating evidence about the comparative effectiveness of clinical interventions. Data sources Database of network meta-analyses of RCTs identified through searches of Medline, Embase, and the Cochrane Database of Systematic Reviews until 14 April 2015. Eligibility criteria for study selection Network meta-analyses published after January 2012 that compared at least five treatments and included at least 20 RCTs. Clinical experts were asked to identify in each network the treatment comparison of greatest clinical interest. Comparisons were excluded for which direct and indirect evidence disagreed, based on side, or node, splitting test (Pmeta-analysis. The frequency and time to strong evidence was compared against the null hypothesis between pairwise and network meta-analyses. Results 49 comparisons of interest from 44 networks were included; most (n=39, 80%) were between active drugs, mainly from the specialties of cardiology, endocrinology, psychiatry, and rheumatology. 29 comparisons were informed by both direct and indirect evidence (59%), 13 by indirect evidence (27%), and 7 by direct evidence (14%). Both network and pairwise meta-analysis provided strong evidence against the null hypothesis for seven comparisons, but for an additional 10 comparisons only network meta-analysis provided strong evidence against the null hypothesis (P=0.002). The median time to strong evidence against the null hypothesis was 19 years with living network meta-analysis and 23 years with living pairwise meta-analysis (hazard ratio 2.78, 95% confidence interval 1.00 to 7.72, P=0.05). Studies directly comparing

  13. Computer tomography, magnetic resonance imaging, and positron emission tomography or positron emission tomography/computer tomography for detection of metastatic lymph nodes in patients with ovarian cancer: A meta-analysis

    International Nuclear Information System (INIS)

    Yuan Ying; Gu Zhaoxiang; Tao Xiaofeng; Liu Shiyuan

    2012-01-01

    Objectives: To compare the diagnostic performances of computed tomography (CT), magnetic resonance (MR) imaging, and positron emission tomography (PET or PET/CT) for detection of metastatic lymph nodes in patients with ovarian cancer. Methods: Relevant studies were identified with MEDLINE and EMBASE from January 1990 to July 2010. We estimated the weighted summary sensitivities, specificities, OR (odds ratio), and summary receiver operating characteristic (sROC) curves of each imaging technique and conducted pair-wise comparisons using the two-sample Z-test. Meta-regression, subgroup analysis, and funnel plots were also performed to explain the between-study heterogeneity. Results: Eighteen eligible studies were included, with a total of 882 patients. PET or PET/CT was a more accurate modality (sensitivity, 73.2%; specificity, 96.7%; OR [odds ratio], 90.32). No significant difference was detected between CT (sensitivity, 42.6%; specificity, 95.0%; OR, 19.87) and MR imaging (sensitivity, 54.7%; specificity, 88.3%; OR, 12.38). Meta-regression analyses and subgroup analyses revealed no statistical difference. Funnel plots with marked asymmetry suggested a publication bias. Conclusion: FDG-PET or FDG-PET/CT is more accurate than CT and MR imaging in the detection of lymph node metastasis in patients with ovarian cancer.

  14. Application of carbon nanoparticles in lymph node dissection and parathyroid protection during thyroid cancer surgeries: a systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Wang L

    2017-02-01

    Full Text Available Lun Wang, Dong Yang, Jun-Yuan Lv, Dan Yu, Shi-Jie Xin Department of Vascular and Thyroid Surgery, The First Affiliated Hospital, China Medical University, Shenyang, People’s Republic of China Purpose: To investigate whether carbon nanoparticles (CNs are helpful in identifying lymph nodes and metastatic lymph nodes and in parathyroid protection during thyroid cancer surgery. Methods: English and Chinese literature in PubMed, Cochrane Database of Systematic Reviews, EMBASE, ClinicalTrials.gov, China Biology Medicine Database, China National Knowledge Infrastructure, China Master’s and Doctoral Theses Full-Text Database, Wanfang database, and Cqvip database were searched (till March 22, 2016. Randomized controlled trials (RCTs that compared the use of CNs with a blank control in patients undergoing thyroid cancer surgery were included. Quality assessment and data extraction were performed, and a meta-analysis was conducted using RevMan 5.1 software. The primary outcomes were the number of retrieved central lymph nodes and metastatic lymph nodes, and the rate of accidental parathyroid removal. Results: We obtained 149 relevant studies, and only 47 RCTs with 4,605 patients (CN group: n=2,197; blank control group: n=2,408 met the inclusion criteria. Compared with the control group, the CN group was associated with more retrieved lymph nodes/patient (weighted mean difference [WMD]: 3.39, 95% confidence interval [CI]: 2.73–4.05, more retrieved metastatic lymph nodes (WMD: 0.98, 95% CI: 0.61–1.35, lower rate of accidental parathyroid removal, and lower rates of hypoparathyroidism and hypocalcemia. However, the total metastatic rate of the retrieved lymph nodes did not differ between the groups (odds ratio: 1.13, 95% CI: 0.87–1.47, P=0.35. Conclusion: CNs can improve the extent of neck dissection and protect the parathyroid glands during thyroid cancer surgery. And the number of identified metastatic lymph nodes can be simultaneously increased

  15. Microarray Meta-Analysis Identifies Acute Lung Injury Biomarkers in Donor Lungs That Predict Development of Primary Graft Failure in Recipients

    Science.gov (United States)

    Haitsma, Jack J.; Furmli, Suleiman; Masoom, Hussain; Liu, Mingyao; Imai, Yumiko; Slutsky, Arthur S.; Beyene, Joseph; Greenwood, Celia M. T.; dos Santos, Claudia

    2012-01-01

    Objectives To perform a meta-analysis of gene expression microarray data from animal studies of lung injury, and to identify an injury-specific gene expression signature capable of predicting the development of lung injury in humans. Methods We performed a microarray meta-analysis using 77 microarray chips across six platforms, two species and different animal lung injury models exposed to lung injury with or/and without mechanical ventilation. Individual gene chips were classified and grouped based on the strategy used to induce lung injury. Effect size (change in gene expression) was calculated between non-injurious and injurious conditions comparing two main strategies to pool chips: (1) one-hit and (2) two-hit lung injury models. A random effects model was used to integrate individual effect sizes calculated from each experiment. Classification models were built using the gene expression signatures generated by the meta-analysis to predict the development of lung injury in human lung transplant recipients. Results Two injury-specific lists of differentially expressed genes generated from our meta-analysis of lung injury models were validated using external data sets and prospective data from animal models of ventilator-induced lung injury (VILI). Pathway analysis of gene sets revealed that both new and previously implicated VILI-related pathways are enriched with differentially regulated genes. Classification model based on gene expression signatures identified in animal models of lung injury predicted development of primary graft failure (PGF) in lung transplant recipients with larger than 80% accuracy based upon injury profiles from transplant donors. We also found that better classifier performance can be achieved by using meta-analysis to identify differentially-expressed genes than using single study-based differential analysis. Conclusion Taken together, our data suggests that microarray analysis of gene expression data allows for the detection of

  16. Meta-Analysis at Middle Age: A Personal History

    Science.gov (United States)

    Glass, Gene V.

    2015-01-01

    The 40-year history of meta-analysis is traced from the vantage point of one of its originators. Research syntheses leading to the first examples of meta-analysis are identified. Early meta-analyses of the literature on psychotherapy outcomes and school class size are recounted. The influence on the development of meta-analysis of several…

  17. Integrative multi-platform meta-analysis of gene expression profiles in pancreatic ductal adenocarcinoma patients for identifying novel diagnostic biomarkers.

    Science.gov (United States)

    Irigoyen, Antonio; Jimenez-Luna, Cristina; Benavides, Manuel; Caba, Octavio; Gallego, Javier; Ortuño, Francisco Manuel; Guillen-Ponce, Carmen; Rojas, Ignacio; Aranda, Enrique; Torres, Carolina; Prados, Jose

    2018-01-01

    Applying differentially expressed genes (DEGs) to identify feasible biomarkers in diseases can be a hard task when working with heterogeneous datasets. Expression data are strongly influenced by technology, sample preparation processes, and/or labeling methods. The proliferation of different microarray platforms for measuring gene expression increases the need to develop models able to compare their results, especially when different technologies can lead to signal values that vary greatly. Integrative meta-analysis can significantly improve the reliability and robustness of DEG detection. The objective of this work was to develop an integrative approach for identifying potential cancer biomarkers by integrating gene expression data from two different platforms. Pancreatic ductal adenocarcinoma (PDAC), where there is an urgent need to find new biomarkers due its late diagnosis, is an ideal candidate for testing this technology. Expression data from two different datasets, namely Affymetrix and Illumina (18 and 36 PDAC patients, respectively), as well as from 18 healthy controls, was used for this study. A meta-analysis based on an empirical Bayesian methodology (ComBat) was then proposed to integrate these datasets. DEGs were finally identified from the integrated data by using the statistical programming language R. After our integrative meta-analysis, 5 genes were commonly identified within the individual analyses of the independent datasets. Also, 28 novel genes that were not reported by the individual analyses ('gained' genes) were also discovered. Several of these gained genes have been already related to other gastroenterological tumors. The proposed integrative meta-analysis has revealed novel DEGs that may play an important role in PDAC and could be potential biomarkers for diagnosing the disease.

  18. CRISPR-Cas9-Mediated Silencing of CD44 in Human Highly Metastatic Osteosarcoma Cells

    Directory of Open Access Journals (Sweden)

    Tang Liu

    2018-04-01

    Full Text Available Background/Aims: Metastasis is the major cause of death in patients with osteosarcoma. There is an urgent need to identify molecular markers that promote metastasis. Cluster of differentiation 44 is a receptor for hyaluronic acid (HA and HA-binding has been proven to participate in various biological tumor activities, including tumor progression and metastasis. Methods: We performed a meta-analysis to investigate the relationship between CD44 expression, survival, and metastasis in patients with osteosarcoma. We then utilized the CRISPR-Cas9 system to specifically silence CD44 in highly metastatic human osteosarcoma cells (MNNG/HOS and 143B and further determined the functional effects of CD44 knockout in these cells. Results: The meta-analysis demonstrated that a high level of CD44 may predict poor survival and higher potential of metastasis in patients with osteosarcoma. The expression of CD44 in highly metastatic human osteosarcoma cell lines was efficiently blocked by CRISPR-Cas9. When CD44 was silenced, the proliferation and spheroid formation of these osteosarcoma cells was inhibited under 3-D culture conditions. Furthermore, the migratory and invasive functions were also impaired in these highly metastatic osteosarcoma cells. Conclusion: These results suggest that developing new strategies to target CD44 in osteosarcoma may prevent metastasis and improve the clinical outcome of osteosarcoma patients.

  19. Teaching meta-analysis using MetaLight

    Directory of Open Access Journals (Sweden)

    Thomas James

    2012-10-01

    Full Text Available Abstract Background Meta-analysis is a statistical method for combining the results of primary studies. It is often used in systematic reviews and is increasingly a method and topic that appears in student dissertations. MetaLight is a freely available software application that runs simple meta-analyses and contains specific functionality to facilitate the teaching and learning of meta-analysis. While there are many courses and resources for meta-analysis available and numerous software applications to run meta-analyses, there are few pieces of software which are aimed specifically at helping those teaching and learning meta-analysis. Valuable teaching time can be spent learning the mechanics of a new software application, rather than on the principles and practices of meta-analysis. Findings We discuss ways in which the MetaLight tool can be used to present some of the main issues involved in undertaking and interpreting a meta-analysis. Conclusions While there are many software tools available for conducting meta-analysis, in the context of a teaching programme such software can require expenditure both in terms of money and in terms of the time it takes to learn how to use it. MetaLight was developed specifically as a tool to facilitate the teaching and learning of meta-analysis and we have presented here some of the ways it might be used in a training situation.

  20. Diagnostic value of whole-body diffusion-weighted magnetic resonance imaging for detection of primary and metastatic malignancies: A meta-analysis

    Energy Technology Data Exchange (ETDEWEB)

    Li, Bin, E-mail: lllb146@163.com [Department of Radiology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai 200003 (China); Li, Qiong [Department of Radiology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai 200003 (China); Nie, Wei [Department of Respiratory Disease, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai 200003 (China); Liu, Shiyuan, E-mail: lsy20112077@163.com [Department of Radiology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai 200003 (China)

    2014-02-15

    Purpose: To perform a meta-analysis to evaluate the diagnostic performance of whole-body diffusion-weighted magnetic resonance imaging (WB-DWI) technique in detection of primary and metastatic malignancies compared with that of whole-body positron emission tomography/computed tomography (WB-PET/CT). Materials and methods: Search Pubmed, MEDLINE, EMBASE and Cochrane Library database from January 1984 to July 2013 for studies comparing WB-DWI with WB-PET/CT for detection of primary and metastatic malignancies. Methodological quality was assessed by the quality assessment of diagnostic studies (QUADAS) instrument. Sensitivities, specificities, predictive values, diagnostic odds ratio (DOR) and areas under the summary receiver operator characteristic curve (AUC) were calculated. Potential threshold effect, heterogeneity and publication bias were investigated. Result: Thirteen eligible studies were included, with a total of 1067 patients. There was no significant threshold effect. WB-DWI had a similar AUC (0.966 (95% CI, 0.940–0.992) versus 0.984 (95% CI, 0.965–0.999)) with WB-PET/CT. No significant difference was detected between AUC of WB-DWI and WB-PET/CT. WB-DWI had a pooled sensitivity of 0.897 (95% CI, 0.876–0.916) and a pooled specificity of 0.954 (95% CI, 0.944–0.962). WB-PET/CT had a pooled sensitivity of 0.895 (95% CI, 0.865–0.920) and a pooled specificity of 0.975 (95% CI, 0.966–0.981). Heterogeneity was found to stem primarily from data type (per lesion versus per patient), MR sequence (DWIBS only and DWIBS with other sequence), and primary lesion type (single type and multiple type). The Deeks's funnel plots suggested the absence of publication bias. Conclusion: WB-DWI has similar, good diagnostic performance for the detection of primary and metastatic malignancies compared with WB-PET/CT. DWIBS with other MR sequences could further improve the diagnostic performance. More high-quality studies regarding comparison of WB-DWI and WB

  1. Identifying Effective Education Interventions in Sub-Saharan Africa: A Meta-Analysis of Rigorous Impact Evaluations

    Science.gov (United States)

    Conn, Katharine

    2014-01-01

    The aim of this dissertation is to identify effective educational interventions in Sub-Saharan African with an impact on student learning. This is the first meta-analysis in the field of education conducted for Sub-Saharan Africa. This paper takes an in-depth look at twelve different types of education interventions or programs and attempts to not…

  2. Living network meta-analysis compared with pairwise meta-analysis in comparative effectiveness research: empirical study.

    Science.gov (United States)

    Nikolakopoulou, Adriani; Mavridis, Dimitris; Furukawa, Toshi A; Cipriani, Andrea; Tricco, Andrea C; Straus, Sharon E; Siontis, George C M; Egger, Matthias; Salanti, Georgia

    2018-02-28

    To examine whether the continuous updating of networks of prospectively planned randomised controlled trials (RCTs) ("living" network meta-analysis) provides strong evidence against the null hypothesis in comparative effectiveness of medical interventions earlier than the updating of conventional, pairwise meta-analysis. Empirical study of the accumulating evidence about the comparative effectiveness of clinical interventions. Database of network meta-analyses of RCTs identified through searches of Medline, Embase, and the Cochrane Database of Systematic Reviews until 14 April 2015. Network meta-analyses published after January 2012 that compared at least five treatments and included at least 20 RCTs. Clinical experts were asked to identify in each network the treatment comparison of greatest clinical interest. Comparisons were excluded for which direct and indirect evidence disagreed, based on side, or node, splitting test (Pmeta-analyses were performed for each selected comparison. Monitoring boundaries of statistical significance were constructed and the evidence against the null hypothesis was considered to be strong when the monitoring boundaries were crossed. A significance level was defined as α=5%, power of 90% (β=10%), and an anticipated treatment effect to detect equal to the final estimate from the network meta-analysis. The frequency and time to strong evidence was compared against the null hypothesis between pairwise and network meta-analyses. 49 comparisons of interest from 44 networks were included; most (n=39, 80%) were between active drugs, mainly from the specialties of cardiology, endocrinology, psychiatry, and rheumatology. 29 comparisons were informed by both direct and indirect evidence (59%), 13 by indirect evidence (27%), and 7 by direct evidence (14%). Both network and pairwise meta-analysis provided strong evidence against the null hypothesis for seven comparisons, but for an additional 10 comparisons only network meta-analysis provided

  3. Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer’s disease

    Science.gov (United States)

    Lambert, Jean-Charles; Ibrahim-Verbaas, Carla A; Harold, Denise; Naj, Adam C; Sims, Rebecca; Bellenguez, Céline; Jun, Gyungah; DeStefano, Anita L; Bis, Joshua C; Beecham, Gary W; Grenier-Boley, Benjamin; Russo, Giancarlo; Thornton-Wells, Tricia A; Jones, Nicola; Smith, Albert V; Chouraki, Vincent; Thomas, Charlene; Ikram, M Arfan; Zelenika, Diana; Vardarajan, Badri N; Kamatani, Yoichiro; Lin, Chiao-Feng; Gerrish, Amy; Schmidt, Helena; Kunkle, Brian; Dunstan, Melanie L; Ruiz, Agustin; Bihoreau, Marie-Thérèse; Choi, Seung-Hoan; Reitz, Christiane; Pasquier, Florence; Hollingworth, Paul; Ramirez, Alfredo; Hanon, Olivier; Fitzpatrick, Annette L; Buxbaum, Joseph D; Campion, Dominique; Crane, Paul K; Baldwin, Clinton; Becker, Tim; Gudnason, Vilmundur; Cruchaga, Carlos; Craig, David; Amin, Najaf; Berr, Claudine; Lopez, Oscar L; De Jager, Philip L; Deramecourt, Vincent; Johnston, Janet A; Evans, Denis; Lovestone, Simon; Letenneur, Luc; Morón, Francisco J; Rubinsztein, David C; Eiriksdottir, Gudny; Sleegers, Kristel; Goate, Alison M; Fiévet, Nathalie; Huentelman, Matthew J; Gill, Michael; Brown, Kristelle; Kamboh, M Ilyas; Keller, Lina; Barberger-Gateau, Pascale; McGuinness, Bernadette; Larson, Eric B; Green, Robert; Myers, Amanda J; Dufouil, Carole; Todd, Stephen; Wallon, David; Love, Seth; Rogaeva, Ekaterina; Gallacher, John; St George-Hyslop, Peter; Clarimon, Jordi; Lleo, Alberto; Bayer, Anthony; Tsuang, Debby W; Yu, Lei; Tsolaki, Magda; Bossù, Paola; Spalletta, Gianfranco; Proitsi, Petroula; Collinge, John; Sorbi, Sandro; Sanchez-Garcia, Florentino; Fox, Nick C; Hardy, John; Deniz Naranjo, Maria Candida; Bosco, Paolo; Clarke, Robert; Brayne, Carol; Galimberti, Daniela; Mancuso, Michelangelo; Matthews, Fiona; Moebus, Susanne; Mecocci, Patrizia; Zompo, Maria Del; Maier, Wolfgang; Hampel, Harald; Pilotto, Alberto; Bullido, Maria; Panza, Francesco; Caffarra, Paolo; Nacmias, Benedetta; Gilbert, John R; Mayhaus, Manuel; Lannfelt, Lars; Hakonarson, Hakon; Pichler, Sabrina; Carrasquillo, Minerva M; Ingelsson, Martin; Beekly, Duane; Alvarez, Victoria; Zou, Fanggeng; Valladares, Otto; Younkin, Steven G; Coto, Eliecer; Hamilton-Nelson, Kara L; Gu, Wei; Razquin, Cristina; Pastor, Pau; Mateo, Ignacio; Owen, Michael J; Faber, Kelley M; Jonsson, Palmi V; Combarros, Onofre; O’Donovan, Michael C; Cantwell, Laura B; Soininen, Hilkka; Blacker, Deborah; Mead, Simon; Mosley, Thomas H; Bennett, David A; Harris, Tamara B; Fratiglioni, Laura; Holmes, Clive; de Bruijn, Renee F A G; Passmore, Peter; Montine, Thomas J; Bettens, Karolien; Rotter, Jerome I; Brice, Alexis; Morgan, Kevin; Foroud, Tatiana M; Kukull, Walter A; Hannequin, Didier; Powell, John F; Nalls, Michael A; Ritchie, Karen; Lunetta, Kathryn L; Kauwe, John S K; Boerwinkle, Eric; Riemenschneider, Matthias; Boada, Mercè; Hiltunen, Mikko; Martin, Eden R; Schmidt, Reinhold; Rujescu, Dan; Wang, Li-san; Dartigues, Jean-François; Mayeux, Richard; Tzourio, Christophe; Hofman, Albert; Nöthen, Markus M; Graff, Caroline; Psaty, Bruce M; Jones, Lesley; Haines, Jonathan L; Holmans, Peter A; Lathrop, Mark; Pericak-Vance, Margaret A; Launer, Lenore J; Farrer, Lindsay A; van Duijn, Cornelia M; Van Broeckhoven, Christine; Moskvina, Valentina; Seshadri, Sudha; Williams, Julie; Schellenberg, Gerard D; Amouyel, Philippe

    2013-01-01

    Eleven susceptibility loci for late-onset Alzheimer’s disease (LOAD) were identified by previous studies; however, a large portion of the genetic risk for this disease remains unexplained. We conducted a large, two-stage meta-analysis of genome-wide association studies (GWAS) in individuals of European ancestry. In stage 1, we used genotyped and imputed data (7,055,881 SNPs) to perform meta-analysis on 4 previously published GWAS data sets consisting of 17,008 Alzheimer’s disease cases and 37,154 controls. In stage 2,11,632 SNPs were genotyped and tested for association in an independent set of 8,572 Alzheimer’s disease cases and 11,312 controls. In addition to the APOE locus (encoding apolipoprotein E), 19 loci reached genome-wide significance (P < 5 × 10−8) in the combined stage 1 and stage 2 analysis, of which 11 are newly associated with Alzheimer’s disease. PMID:24162737

  4. 18F-FDG-PET and 18F-FDG-PET/CT in the detection of recurrent or metastatic medullary thyroid carcinoma: a systematic review and meta-analysis

    International Nuclear Information System (INIS)

    Cheng, Xu; Bao, Lihua; Xu, Zhaoqiang; Li, Dianfu; Li, Yongjun; Wang, Jie

    2012-01-01

    The aim of this study was to investigate diagnostic performance of 18F-fluorodeoxyglucose position emission tomography (FDG-PET) and PET/computed tomography (PET/CT) for detection of recurrent or metastatic medullary thyroid carcinoma (MTC) in patients after surgery with a meta-analysis. MEDLINE and EMBASE databases were searched for relevant articles. Two investigators independently extracted the data about study characteristics and examination results. Pooled estimates of sensitivity of FDG-PET or FDG-PET/CT were obtained. Fifteen studies met all inclusion criteria. The sensitivity of FDG-PET ranged from 0.47 (95% confidence intervals (CI): 0.21–0.73) to 0.96 (95%CI: 0.86–0.99), the sensitivity of FDG-PET/CT ranger from 0.47 (95% CI: 0.31–0.64) to 0.80 (95% CI: 0.65–0.90). The pooled sensitivities of FDG-PET and PET/CT were 0.68 (95% CI: 0.64–0.72) and 0.69 (95% CI: 0.64–0.74), respectively. There was no statistic significant between FDG-PET and PET/CT. Our results indicate that FDG-PET or FDG-PET/CT has reasonable sensitivity in detecting recurrent or metastatic MTC after primary surgery. However, no single diagnostic technique is able to reliably demonstrate the full extent of disease in patients with recurrent or metastatic MTC, the combination of cross-sectional radiography with FDG-PET or PET/CT is recommended.

  5. High-dose chemotherapy followed by autologous stem cell transplantation for metastatic rhabdomyosarcoma--a systematic review.

    Directory of Open Access Journals (Sweden)

    Frank Peinemann

    Full Text Available INTRODUCTION: Patients with metastatic rhabdomyosarcoma (RMS have a poor prognosis. The aim of this systematic review is to investigate whether high-dose chemotherapy (HDCT followed by autologous hematopoietic stem cell transplantation (HSCT in patients with metastatic RMS has additional benefit or harm compared to standard chemotherapy. METHODS: Systematic literature searches were performed in MEDLINE, EMBASE, and The Cochrane Library. All databases were searched from inception to February 2010. PubMed was searched in June 2010 for a last update. In addition to randomized and non-randomized controlled trials, case series and case reports were included to complement results from scant data. The primary outcome was overall survival. A meta-analysis was performed using the hazard ratio as primary effect measure, which was estimated from Cox proportional hazard models or from summary statistics of Kaplan Meier product-limit estimations. RESULTS: A total of 40 studies with 287 transplant patients with metastatic RMS (age range 0 to 32 years were included in the assessment. We identified 3 non-randomized controlled trials. The 3-year overall survival ranged from 22% to 53% in the transplant groups vs. 18% to 55% in the control groups. Meta-analysis on overall survival in controlled trials showed no difference between treatments. Result of meta-analysis of pooled individual survival data of case series and case reports, and results from uncontrolled studies with aggregate data were in the range of those from controlled data. The risk of bias was high in all studies due to methodological flaws. CONCLUSIONS: HDCT followed by autologous HSCT in patients with RMS remains an experimental treatment. At present, it does not appear justifiable to use this treatment except in appropriately designed controlled trials.

  6. Drivers of wetland conversion: a global meta-analysis.

    Science.gov (United States)

    van Asselen, Sanneke; Verburg, Peter H; Vermaat, Jan E; Janse, Jan H

    2013-01-01

    Meta-analysis of case studies has become an important tool for synthesizing case study findings in land change. Meta-analyses of deforestation, urbanization, desertification and change in shifting cultivation systems have been published. This present study adds to this literature, with an analysis of the proximate causes and underlying forces of wetland conversion at a global scale using two complementary approaches of systematic review. Firstly, a meta-analysis of 105 case-study papers describing wetland conversion was performed, showing that different combinations of multiple-factor proximate causes, and underlying forces, drive wetland conversion. Agricultural development has been the main proximate cause of wetland conversion, and economic growth and population density are the most frequently identified underlying forces. Secondly, to add a more quantitative component to the study, a logistic meta-regression analysis was performed to estimate the likelihood of wetland conversion worldwide, using globally-consistent biophysical and socioeconomic location factor maps. Significant factors explaining wetland conversion, in order of importance, are market influence, total wetland area (lower conversion probability), mean annual temperature and cropland or built-up area. The regression analyses results support the outcomes of the meta-analysis of the processes of conversion mentioned in the individual case studies. In other meta-analyses of land change, similar factors (e.g., agricultural development, population growth, market/economic factors) are also identified as important causes of various types of land change (e.g., deforestation, desertification). Meta-analysis helps to identify commonalities across the various local case studies and identify which variables may lead to individual cases to behave differently. The meta-regression provides maps indicating the likelihood of wetland conversion worldwide based on the location factors that have determined historic

  7. Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies

    NARCIS (Netherlands)

    C.E. Elks (Cathy); J.R.B. Perry (John); P. Sulem (Patrick); D.I. Chasman (Daniel); N. Franceschini (Nora); C. He (Chunyan); K.L. Lunetta (Kathryn); J.A. Visser (Jenny); E.M. Byrne (Enda); D.L. Cousminer (Diana); D.F. Gudbjartsson (Daniel); T. Esko (Tõnu); B. Feenstra (Bjarke); J.J. Hottenga (Jouke Jan); D.L. Koller (Daniel); Z. Kutalik (Zoltán); P. Lin (Peng); M. Mangino (Massimo); M. Marongiu (Mara); P.F. McArdle (Patrick); A.V. Smith (Albert Vernon); L. Stolk (Lisette); S. van Wingerden (Sophie); J.H. Zhao (Jing Hua); E. Albrecht (Eva); T. Corre (Tanguy); E. Ingelsson (Erik); C. Hayward (Caroline); P.K. Magnusson (Patrik); S. Ulivi (Shelia); N.M. Warrington (Nicole); L. Zgaga (Lina); H. Alavere (Helene); N. Amin (Najaf); T. Aspelund (Thor); S. Bandinelli (Stefania); I.E. Barroso (Inês); G. Berenson (Gerald); S.M. Bergmann (Sven); H. Blackburn (Hannah); E.A. Boerwinkle (Eric); J.E. Buring (Julie); F. Busonero; H. Campbell (Harry); S.J. Chanock (Stephen); W. Chen (Wei); M. Cornelis (Marilyn); D.J. Couper (David); A.D. Coviello (Andrea); P. d' Adamo (Pio); U. de Faire (Ulf); E.J.C. de Geus (Eco); P. Deloukas (Panagiotis); A. Döring (Angela); D.F. Easton (Douglas); G. Eiriksdottir (Gudny); V. Emilsson (Valur); J.G. Eriksson (Johan); L. Ferrucci (Luigi); A.R. Folsom (Aaron); T. Foroud (Tatiana); M. Garcia (Melissa); P. Gasparini (Paolo); F. Geller (Frank); C. Gieger (Christian); V. Gudnason (Vilmundur); A.S. Hall (Alistair); S.E. Hankinson (Susan); L. Ferreli (Liana); A.C. Heath (Andrew); D.G. Hernandez (Dena); A. Hofman (Albert); F.B. Hu (Frank); T. Illig (Thomas); M.R. Järvelin; A.D. Johnson (Andrew); D. Karasik (David); K-T. Khaw (Kay-Tee); D.P. Kiel (Douglas); T.O. Kilpelänen (Tuomas); I. Kolcic (Ivana); P. Kraft (Peter); L.J. Launer (Lenore); J.S.E. Laven (Joop); S. Li (Shengxu); J. Liu (Jianjun); D. Levy (Daniel); N.G. Martin (Nicholas); M. Melbye (Mads); V. Mooser (Vincent); J.C. Murray (Jeffrey); M.A. Nalls (Michael); P. Navarro (Pau); M. Nelis (Mari); A.R. Ness (Andrew); K. Northstone (Kate); B.A. Oostra (Ben); M. Peacock (Munro); C. Palmer (Cameron); A. Palotie (Aarno); G. Paré (Guillaume); A.N. Parker (Alex); N.L. Pedersen (Nancy); L. Peltonen (Leena Johanna); C.E. Pennell (Craig); P.D.P. Pharoah (Paul); O. Polasek (Ozren); A.S. Plump (Andrew); A. Pouta (Anneli); E. Porcu (Eleonora); T. Rafnar (Thorunn); J.P. Rice (John); S.M. Ring (Susan); F. Rivadeneira Ramirez (Fernando); I. Rudan (Igor); C. Sala (Cinzia); V. Salomaa (Veikko); S. Sanna (Serena); D. Schlessinger; N.J. Schork (Nicholas); A. Scuteri (Angelo); A.V. Segrè (Ayellet); A.R. Shuldiner (Alan); N. Soranzo (Nicole); U. Sovio (Ulla); S.R. Srinivasan (Sathanur); D.P. Strachan (David); M.L. Tammesoo; E. Tikkanen (Emmi); D. Toniolo (Daniela); K. Tsui (Kim); L. Tryggvadottir (Laufey); J.P. Tyrer (Jonathan); M. Uda (Manuela); R.M. van Dam (Rob); J.B.J. van Meurs (Joyce); P. Vollenweider (Peter); G. Waeber (Gérard); N.J. Wareham (Nick); D. Waterworth (Dawn); H.E. Wichmann (Heinz Erich); G.A.H.M. Willemsen (Gonneke); J.F. Wilson (James); A.F. Wright (Alan); L. Young (Lauren); G. Zhai (Guangju); W.V. Zhuang; L.J. Bierut (Laura); D.I. Boomsma (Dorret); H.A. Boyd (Heather); L. Crisponi (Laura); E.W. Demerath (Ellen); P. Tikka-Kleemola (Päivi); M.J. Econs (Michael); T.B. Harris (Tamara); D. Hunter (David); R.J.F. Loos (Ruth); A. Metspalu (Andres); G.W. Montgomery (Grant); P.M. Ridker (Paul); T.D. Spector (Tim); E.A. Streeten (Elizabeth); K. Stefansson (Kari); U. Thorsteinsdottir (Unnur); A.G. Uitterlinden (André); E. Widen (Elisabeth); J. Murabito (Joanne); K. Ong (Ken); M.N. Weedon (Michael)

    2010-01-01

    textabstractTo identify loci for age at menarche, we performed a meta-analysis of 32 genome-wide association studies in 87,802 women of European descent, with replication in up to 14,731 women. In addition to the known loci at LIN28B (P = 5.4 × 10 -60) and 9q31.2 (P = 2.2 × 10 -33), we identified 30

  8. Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease

    NARCIS (Netherlands)

    Nalls, Mike A.; Pankratz, Nathan; Lill, Christina M.; Do, Chuong B.; Hernandez, Dena G.; Saad, Mohamad; DeStefano, Anita L.; Kara, Eleanna; Bras, Jose; Sharma, Manu; Schulte, Claudia; Keller, Margaux F.; Arepalli, Sampath; Letson, Christopher; Edsall, Connor; Stefansson, Hreinn; Liu, Xinmin; Pliner, Hannah; Lee, Joseph H.; Cheng, Rong; Ikram, M. Arfan; Ioannidis, John P. A.; Hadjigeorgiou, Georgios M.; Bis, Joshua C.; Martinez, Maria; Perlmutter, Joel S.; Goate, Alison; Marder, Karen; Fiske, Brian; Sutherland, Margaret; Xiromerisiou, Georgia; Myers, Richard H.; Clark, Lorraine N.; Stefansson, Kari; Hardy, John A.; Heutink, Peter; Chen, Honglei; Wood, Nicholas W.; Houlden, Henry; Payami, Haydeh; Brice, Alexis; Scott, William K.; Gasser, Thomas; Bertram, Lars; Eriksson, Nicholas; Foroud, Tatiana; Singleton, Andrew B.; Plagnol, Vincent; Sheerin, Una-Marie; Simón-Sánchez, Javier; Lesage, Suzanne; Sveinbjörnsdóttir, Sigurlaug; Barker, Roger; Ben-Shlomo, Yoav; Berendse, Henk W.; Berg, Daniela; Bhatia, Kailash; de Bie, Rob M. A.; Biffi, Alessandro; Bloem, Bas; Bochdanovits, Zoltan; Bonin, Michael; Bras, Jose M.; Brockmann, Kathrin; Brooks, Janet; Burn, David J.; Charlesworth, Gavin; Chinnery, Patrick F.; Chong, Sean; Clarke, Carl E.; Cookson, Mark R.; Cooper, J. Mark; Corvol, Jean Christophe; Counsell, Carl; Damier, Philippe; Dartigues, Jean-François; Deloukas, Panos; Deuschl, Günther; Dexter, David T.; van Dijk, Karin D.; Dillman, Allissa; Durif, Frank; Dürr, Alexandra; Edkins, Sarah; Evans, Jonathan R.; Foltynie, Thomas; Dong, Jing; Gardner, Michelle; Gibbs, J. Raphael; Gray, Emma; Guerreiro, Rita; Harris, Clare; van Hilten, Jacobus J.; Hofman, Albert; Hollenbeck, Albert; Holton, Janice; Hu, Michele; Huang, Xuemei; Wurster, Isabel; Mätzler, Walter; Hudson, Gavin; Hunt, Sarah E.; Huttenlocher, Johanna; Illig, Thomas; Jónsson, Pálmi V.; Lambert, Jean-Charles; Langford, Cordelia; Lees, Andrew; Lichtner, Peter; Limousin, Patricia; Lopez, Grisel; Lorenz, Delia; McNeill, Alisdair; Moorby, Catriona; Moore, Matthew; Morris, Huw R.; Morrison, Karen E.; Mudanohwo, Ese; O'Sullivan, Sean S.; Pearson, Justin; Pétursson, Hjörvar; Pollak, Pierre; Post, Bart; Potter, Simon; Ravina, Bernard; Revesz, Tamas; Riess, Olaf; Rivadeneira, Fernando; Rizzu, Patrizia; Ryten, Mina; Sawcer, Stephen; Schapira, Anthony; Scheffer, Hans; Shaw, Karen; Shoulson, Ira; Sidransky, Ellen; Smith, Colin; Spencer, Chris C. A.; Stefánsson, Hreinn; Bettella, Francesco; Stockton, Joanna D.; Strange, Amy; Talbot, Kevin; Tanner, Carlie M.; Tashakkori-Ghanbaria, Avazeh; Tison, François; Trabzuni, Daniah; Traynor, Bryan J.; Uitterlinden, André G.; Velseboer, Daan; Vidailhet, Marie; Walker, Robert; van de Warrenburg, Bart; Wickremaratchi, Mirdhu; Williams, Nigel; Williams-Gray, Caroline H.; Winder-Rhodes, Sophie; Stefánsson, Kári; Hardy, John; Factor, S.; Higgins, D.; Evans, S.; Shill, H.; Stacy, M.; Danielson, J.; Marlor, L.; Williamson, K.; Jankovic, J.; Hunter, C.; Simon, D.; Ryan, P.; Scollins, L.; Saunders-Pullman, R.; Boyar, K.; Costan-Toth, C.; Ohmann, E.; Sudarsky, L.; Joubert, C.; Friedman, J.; Chou, K.; Fernandez, H.; Lannon, M.; Galvez-Jimenez, N.; Podichetty, A.; Thompson, K.; Lewitt, P.; Deangelis, M.; O'Brien, C.; Seeberger, L.; Dingmann, C.; Judd, D.; Marder, K.; Fraser, J.; Harris, J.; Bertoni, J.; Peterson, C.; Rezak, M.; Medalle, G.; Chouinard, S.; Panisset, M.; Hall, J.; Poiffaut, H.; Calabrese, V.; Roberge, P.; Wojcieszek, J.; Belden, J.; Jennings, D.; Marek, K.; Mendick, S.; Reich, S.; Dunlop, B.; Jog, M.; Horn, C.; Uitti, R.; Turk, M.; Ajax, T.; Mannetter, J.; Sethi, K.; Carpenter, J.; Dill, B.; Hatch, L.; Ligon, K.; Narayan, S.; Blindauer, K.; Abou-Samra, K.; Petit, J.; Elmer, L.; Aiken, E.; Davis, K.; Schell, C.; Wilson, S.; Velickovic, M.; Koller, W.; Phipps, S.; Feigin, A.; Gordon, M.; Hamann, J.; Licari, E.; Marotta-Kollarus, M.; Shannon, B.; Winnick, R.; Simuni, T.; Videnovic, A.; Kaczmarek, A.; Williams, K.; Wolff, M.; Rao, J.; Cook, M.; Fernandez, M.; Kostyk, S.; Hubble, J.; Campbell, A.; Reider, C.; Seward, A.; Camicioli, R.; Carter, J.; Nutt, J.; Andrews, P.; Morehouse, S.; Stone, C.; Mendis, T.; Grimes, D.; Alcorn-Costa, C.; Gray, P.; Haas, K.; Vendette, J.; Sutton, J.; Hutchinson, B.; Young, J.; Rajput, A.; Klassen, L.; Shirley, T.; Manyam, B.; Simpson, P.; Whetteckey, J.; Wulbrecht, B.; Truong, D.; Pathak, M.; Frei, K.; Luong, N.; Tra, T.; Tran, A.; Vo, J.; Lang, A.; Kleiner- Fisman, G.; Nieves, A.; Johnston, L.; So, J.; Podskalny, G.; Giffin, L.; Atchison, P.; Allen, C.; Martin, W.; Wieler, M.; Suchowersky, O.; Furtado, S.; Klimek, M.; Hermanowicz, N.; Niswonger, S.; Shults, C.; Fontaine, D.; Aminoff, M.; Christine, C.; Diminno, M.; Hevezi, J.; Dalvi, A.; Kang, U.; Richman, J.; Uy, S.; Sahay, A.; Gartner, M.; Schwieterman, D.; Hall, D.; Leehey, M.; Culver, S.; Derian, T.; Demarcaida, T.; Thurlow, S.; Rodnitzky, R.; Dobson, J.; Lyons, K.; Pahwa, R.; Gales, T.; Thomas, S.; Shulman, L.; Weiner, W.; Dustin, K.; Singer, C.; Zelaya, L.; Tuite, P.; Hagen, V.; Rolandelli, S.; Schacherer, R.; Kosowicz, J.; Gordon, P.; Werner, J.; Serrano, C.; Roque, S.; Kurlan, R.; Berry, D.; Gardiner, I.; Hauser, R.; Sanchez-Ramos, J.; Zesiewicz, T.; Delgado, H.; Price, K.; Rodriguez, P.; Wolfrath, S.; Pfeiffer, R.; Davis, L.; Pfeiffer, B.; Dewey, R.; Hayward, B.; Johnson, A.; Meacham, M.; Estes, B.; Walker, F.; Hunt, V.; O'Neill, C.; Racette, B.; Swisher, L.; Dijamco, Cheri; Conley, Emily Drabant; Dorfman, Elizabeth; Tung, Joyce Y.; Hinds, David A.; Mountain, Joanna L.; Wojcicki, Anne; Lew, M.; Klein, C.; Golbe, L.; Growdon, J.; Wooten, G. F.; Watts, R.; Guttman, M.; Goldwurm, S.; Saint-Hilaire, M. H.; Baker, K.; Litvan, I.; Nicholson, G.; Nance, M.; Drasby, E.; Isaacson, S.; Burn, D.; Pramstaller, P.; Al-hinti, J.; Moller, A.; Sherman, S.; Roxburgh, R.; Slevin, J.; Perlmutter, J.; Mark, M. H.; Huggins, N.; Pezzoli, G.; Massood, T.; Itin, I.; Corbett, A.; Chinnery, P.; Ostergaard, K.; Snow, B.; Cambi, F.; Kay, D.; Samii, A.; Agarwal, P.; Roberts, J. W.; Higgins, D. S.; Molho, Eric; Rosen, Ami; Montimurro, J.; Martinez, E.; Griffith, A.; Kusel, V.; Yearout, D.; Zabetian, C.; Clark, L. N.; Liu, X.; Lee, J. H.; Taub, R. Cheng; Louis, E. D.; Cote, L. J.; Waters, C.; Ford, B.; Fahn, S.; Vance, Jeffery M.; Beecham, Gary W.; Martin, Eden R.; Nuytemans, Karen; Pericak-Vance, Margaret A.; Haines, Jonathan L.; DeStefano, Anita; Seshadri, Sudha; Choi, Seung Hoan; Frank, Samuel; Psaty, Bruce M.; Rice, Kenneth; Longstreth, W. T.; Ton, Thanh G. N.; Jain, Samay; van Duijn, Cornelia M.; Verlinden, Vincent J.; Koudstaal, Peter J.; Singleton, Andrew; Cookson, Mark; Hernandez, Dena; Nalls, Michael; Zonderman, Alan; Ferrucci, Luigi; Johnson, Robert; Longo, Dan; O'Brien, Richard; Traynor, Bryan; Troncoso, Juan; van der Brug, Marcel; Zielke, Ronald; Weale, Michael; Ramasamy, Adaikalavan; Dardiotis, Efthimios; Tsimourtou, Vana; Spanaki, Cleanthe; Plaitakis, Andreas; Bozi, Maria; Stefanis, Leonidas; Vassilatis, Dimitris; Koutsis, Georgios; Panas, Marios; Lunnon, Katie; Lupton, Michelle; Powell, John; Parkkinen, Laura; Ansorge, Olaf

    2014-01-01

    We conducted a meta-analysis of Parkinson's disease genome-wide association studies using a common set of 7,893,274 variants across 13,708 cases and 95,282 controls. Twenty-six loci were identified as having genome-wide significant association; these and 6 additional previously reported loci were

  9. Identifying effective components of child maltreatment interventions: A meta-analysis

    NARCIS (Netherlands)

    van der Put, C.E.; Assink, M.; Gubbels, J.; Boekhout van Solinge, N.F.

    There is a lack of knowledge about specific components that make interventions effective in preventing or reducing child maltreatment. The aim of the present meta-analysis was to increase this knowledge by summarizing findings on effects of interventions for child maltreatment and by examining

  10. Molecular genetic studies in Saudi population; identified variants from GWAS and meta-analysis in stroke.

    Science.gov (United States)

    Alharbi, Khalid Khalaf; Ali Khan, Imran; Alotaibi, Mohammad Abdullah; Saud Aloyaid, Abdullah; Al-Basheer, Haifa Abdulaziz; Alghamdi, Naelah Abdullah; Al-Baradie, Raid Saleem; Al-Sulaiman, A M

    2018-01-01

    Stroke is a multifactorial and heterogeneous disorder, correlates with heritability and considered as one of the major diseases. The prior reports performed the variable models such as genome-wide association studies (GWAS), replication, case-control, cross-sectional and meta-analysis studies and still, we lack diagnostic marker in the global world. There are limited studies were carried out in Saudi population, and we aim to investigate the molecular association of single nucleotide polymorphisms (SNPs) identified through GWAS and meta-analysis studies in stroke patients in the Saudi population. In this case-control study, we have opted gender equality of 207 cases and 207 controls from the capital city of Saudi Arabia in King Saud University Hospital. The peripheral blood (5 ml) sample will be collected in two different vacutainers, and three mL of the coagulated blood will be used for lipid analysis (biochemical tests) and two mL will be used for DNA analysis (molecular tests). Genomic DNA will be extracted with the collected blood samples, and specific primers will be designed for the opted SNPs ( SORT1 -rs646218 and OLR1 -rs11053646 polymorphisms) and PCR-RFLP will be performed and randomly DNA sequencing will be carried out to cross check the results. The rs646218 and rs11053646 polymorphisms were significantly associated with allele, genotype and dominant models with and without crude odds ratios (OR's) and Multiple logistic regression analysis (p Saudi population. The current results were in the association with the prior study results documented through GWAS and meta-analysis association. However, other ethnic population studies should be performed to rule out in the human hereditary diseases.

  11. mTOR inhibitors, a new era for metastatic luminal HER2-negative breast cancer? A systematic review and a meta-analysis of randomized trials.

    Science.gov (United States)

    Rotundo, Maria Saveria; Galeano, Teresa; Tassone, Pierfrancesco; Tagliaferri, Pierosandro

    2016-05-10

    We evaluated if standard hormonal therapy (HT) could be improved by the addition of mammalian target of rapamycin inhibitors (mTOR-I) in metastatic luminal breast cancer. A meta-analysis on 4 phase II-III randomized clinical trials was performed. Pooled hazard ratio (HR) for progression free survival (PFS)/ time to progression (TTP) was 0.62 in favor of mTOR-I+HT arm (95% confidence interval [CI] 0.55-0.70; p<0.0001). There was significant heterogeneity for PFS/TTP (Cochran's Q 32, p<0.0001, I2 index 90.6%). Pooled HR for overall survival (OS) was 0.84 in favor of the combination arm (95% CI 0.71-0.99; p=0.04). Heterogeneity was not significant (Cochran's Q 4.47, p=0.1, I2 index 55.3%). Pooled risk ratio (RR) for objective response rate (ORR) was 0.88 in favor of experimental arm (95% CI 0.85-0.91; p<0.0001). Heterogeneity was not significant (Cochran's Q 2.11, p=0.3, I2 index 5.2%). Adverse events (AEs), in particular those of grade 3-4, mostly occurred in mTOR-I+HT arm. Combination therapy of HT plus mTOR-I improves the outcome of metastatic luminal breast cancer patients. Our results provide evidence of a class-effect of these targeting molecules.

  12. Genome-wide meta-analysis identifies new susceptibility loci for migraine

    NARCIS (Netherlands)

    Anttila, Verneri; Winsvold, Bendik S.; Gormley, Padhraig; Kurth, Tobias; Bettella, Francesco; McMahon, George; Kallela, Mikko; Malik, Rainer; de Vries, Boukje; Terwindt, Gisela; Medland, Sarah E.; Todt, Unda; McArdle, Wendy L.; Quaye, Lydia; Koiranen, Markku; Ikram, M. Arfan; Lehtimaki, Terho; Stam, Anine H.; Ligthart, Lannie; Wedenoja, Juho; Dunham, Ian; Neale, Benjamin M.; Palta, Priit; Hamalainen, Eija; Schuerks, Markus; Rose, Lynda M.; Buring, Julie E.; Ridker, Paul M.; Steinberg, Stacy; Stefansson, Hreinn; Jakobsson, Finnbogi; Lawlor, Debbie A.; Evans, David M.; Ring, Susan M.; Farkkila, Markus; Artto, Ville; Kaunisto, Mari A.; Freilinger, Tobias; Schoenen, Jean; Frants, Rune R.; Pelzer, Nadine; Weller, Claudia M.; Zielman, Ronald; Heath, Andrew C.; Madden, Pamela A. F.; Montgomery, Grant W.; Martin, Nicholas G.; Borck, Guntram; Goebel, Hartmut; Heinze, Axel

    Migraine is the most common brain disorder, affecting approximately 14% of the adult population, but its molecular mechanisms are poorly understood. We report the results of a meta-analysis across 29 genome-wide association studies, including a total of 23,285 individuals with migraine (cases) and

  13. Genome-wide meta-analysis identifies new susceptibility loci for migraine

    NARCIS (Netherlands)

    Anttila, V.; Winsvold, B.S.; Gormley, P.; Kurth, T.; Bettella, F.; McMahon, G.; Kallela, M.; Malik, R.; de Vries, B.; Terwindt, G.; Medland, S.E.; Todt, U.; McArdle, W.L.; Quaye, L.; Koiranen, M.; Ikram, M.A.; Lehtimäki, T.; Stam, A.H.; Ligthart, R.S.L.; Wedenoja, J.; Dunham, I.; Neale, B. M.; Palta, P.; Hamalainen, E.; Schürks, M.; Rose, L.M.; Buring, J.E.; Ridker, P.M.; Steinberg, S.; Stefansson, H.; Jakobsson, F.; Lawlor, D.A.; Evans, D.M.; Ring, S.M.; Färkkilä, M.; Artto, V.; Kaunisto, M.A.; Freilinger, T.; Schoenen, J.; Frants, R.R.; Pelzer, N.; Weller, C.M.; Zielman, R.; Heath, A.C.; Madden, P.A.F.; Montgomery, G.W.; Martin, N.G.; Borck, G.; Göbel, H.; Heinze, A.; Heinze-Kuhn, K.; Williams, F.M.; Hartikainen, A.-L.; Pouta, A.; van den Ende, J..; Uitterlinden, A.G.; Hofman, A.; Amin, N.; Hottenga, J.J.; Vink, J.M.; Heikkilä, K.; Alexander, M.; Muller-Myhsok, B.; Schreiber, S; Meitinger, T.; Wichmann, H. E.; Aromaa, A.; Eriksson, J.G.; Traynor, B.J.; Trabzuni, D.; Rossin, E.; Lage, K.; Jacobs, S.B.; Gibbs, J.R.; Birney, E.; Kaprio, J.; Penninx, B.W.J.H.; Boomsma, D.I.; van Duijn, C.M.; Raitakari, O.; Jarvelin, M.-R.; Zwart, J.A.; Cherkas, L.; Strachan, D.P.; Kubisch, C.; Ferrari, M.D.; van den Maagdenberg, A.M.J.M.; Dichgans, M.; Wessman, M.; Smith, G.D.; Stefansson, K.; Daly, M.J.; Nyholt, DR; Chasman, D.I.; Palotie, A.

    2013-01-01

    Migraine is the most common brain disorder, affecting approximately 14% of the adult population, but its molecular mechanisms are poorly understood. We report the results of a meta-analysis across 29 genome-wide association studies, including a total of 23,285 individuals with migraine (cases) and

  14. Genome-wide meta-analysis identifies new susceptibility loci for migraine

    DEFF Research Database (Denmark)

    Anttila, Verneri; Winsvold, Bendik S; Gormley, Padhraig

    2013-01-01

    Migraine is the most common brain disorder, affecting approximately 14% of the adult population, but its molecular mechanisms are poorly understood. We report the results of a meta-analysis across 29 genome-wide association studies, including a total of 23,285 individuals with migraine (cases) an...

  15. Integration of machine learning and meta-analysis identifies the transcriptomic bio-signature of mastitis disease in cattle.

    Science.gov (United States)

    Sharifi, Somayeh; Pakdel, Abbas; Ebrahimi, Mansour; Reecy, James M; Fazeli Farsani, Samaneh; Ebrahimie, Esmaeil

    2018-01-01

    Gram-negative bacteria such as Escherichia coli (E. coli) are assumed to be among the main agents that cause severe mastitis disease with clinical signs in dairy cattle. Rapid detection of this disease is so important in order to prevent transmission to other cows and helps to reduce inappropriate use of antibiotics. With the rapid progress in high-throughput technologies, and accumulation of various kinds of '-omics' data in public repositories, there is an opportunity to retrieve, integrate, and reanalyze these resources to improve the diagnosis and treatment of different diseases and to provide mechanistic insights into host resistance in an efficient way. Meta-analysis is a relatively inexpensive option with good potential to increase the statistical power and generalizability of single-study analysis. In the current meta-analysis research, six microarray-based studies that investigate the transcriptome profile of mammary gland tissue after induced mastitis by E. coli infection were used. This meta-analysis not only reinforced the findings in individual studies, but also several novel terms including responses to hypoxia, response to drug, anti-apoptosis and positive regulation of transcription from RNA polymerase II promoter enriched by up-regulated genes. Finally, in order to identify the small sets of genes that are sufficiently informative in E. coli mastitis, the differentially expressed gene introduced by meta-analysis were prioritized by using ten different attribute weighting algorithms. Twelve meta-genes were detected by the majority of attribute weighting algorithms (with weight above 0.7) as most informative genes including CXCL8 (IL8), NFKBIZ, HP, ZC3H12A, PDE4B, CASP4, CXCL2, CCL20, GRO1(CXCL1), CFB, S100A9, and S100A8. Interestingly, the results have been demonstrated that all of these genes are the key genes in the immune response, inflammation or mastitis. The Decision tree models efficiently discovered the best combination of the meta-genes as

  16. Identifying psychosocial predictors of medication non-adherence following acute coronary syndrome: A systematic review and meta-analysis.

    Science.gov (United States)

    Crawshaw, Jacob; Auyeung, Vivian; Norton, Sam; Weinman, John

    2016-11-01

    Medication non-adherence following acute coronary syndrome (ACS) is associated with poor clinical outcomes. A systematic review and meta-analysis were undertaken to identify psychosocial factors associated with medication adherence in patients with ACS. A search of electronic databases (Cochrane Library, Medline, EMBASE, PsycINFO, Web of Science, International Pharmaceutical Abstracts, CINAHL, ASSIA, OpenGrey, EthOS and WorldCat) was undertaken to identify relevant articles published in English between 2000 and 2014. Articles were screened against our inclusion criteria and data on study design, sample characteristics, predictors, outcomes, analyses, key findings and study limitations were abstracted. Our search identified 3609 records, of which 17 articles met our inclusion criteria (15 independent studies). Eight out of ten studies found an association between depression and non-adherence. A meta-analysis revealed that depressed patients were twice as likely to be non-adherent compared to patients without depression (OR=2.00, 95% CI 1.57-3.33, p=0.015). Type D personality was found to predict non-adherence in both studies in which it was measured. Three out of three studies reported that treatment beliefs based on the Necessity-Concerns Framework predicted medication non-adherence and there was some evidence that social support was associated with better adherence. There was insufficient data to meta-analyse all other psychosocial factors identified. There was some evidence that psychosocial factors, particularly depression, were associated with medication adherence following ACS. Targeting depressive symptoms, screening for Type D personality, challenging maladaptive treatment beliefs, and providing better social support for patients may be useful strategies to improve medication adherence. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

  17. MicroRNA meta-signature of oral cancer: evidence from a meta-analysis.

    Science.gov (United States)

    Zeljic, Katarina; Jovanovic, Ivan; Jovanovic, Jasmina; Magic, Zvonko; Stankovic, Aleksandra; Supic, Gordana

    2018-03-01

    It was the aim of the study to identify commonly deregulated miRNAs in oral cancer patients by performing a meta-analysis of previously published miRNA expression profiles in cancer and matched normal non-cancerous tissue in such patients. Meta-analysis included seven independent studies analyzed by a vote-counting method followed by bioinformatic enrichment analysis. Amongst seven independent studies included in the meta-analysis, 20 miRNAs were found to be deregulated in oral cancer when compared with non-cancerous tissue. Eleven miRNAs were consistently up-regulated in three or more studies (miR-21-5p, miR-31-5p, miR-135b-5p, miR-31-3p, miR-93-5p, miR-34b-5p, miR-424-5p, miR-18a-5p, miR-455-3p, miR-450a-5p, miR-21-3p), and nine were down-regulated (miR-139-5p, miR-30a-3p, miR-376c-3p, miR-885-5p, miR-375, miR-486-5p, miR-411-5p, miR-133a-3p, miR-30a-5p). The meta-signature of identified miRNAs was functionally characterized by KEGG enrichment analysis. Twenty-four KEGG pathways were significantly enriched, and TGF-beta signaling was the most enriched signaling pathway. The highest number of meta-signature miRNAs was involved in the sphingolipid signaling pathway. Natural killer cell-mediated cytotoxicity was the pathway with most genes regulated by identified miRNAs. The rest of the enriched pathways in our miRNA list describe different malignancies and signaling. The identified miRNA meta-signature might be considered as a potential battery of biomarkers when distinguishing oral cancer tissue from normal, non-cancerous tissue. Further mechanistic studies are warranted in order to confirm and fully elucidate the role of deregulated miRNAs in oral cancer.

  18. Genome-wide association study to identify common variants associated with brachial circumference: a meta-analysis of 14 cohorts.

    Directory of Open Access Journals (Sweden)

    Vesna Boraska

    Full Text Available Brachial circumference (BC, also known as upper arm or mid arm circumference, can be used as an indicator of muscle mass and fat tissue, which are distributed differently in men and women. Analysis of anthropometric measures of peripheral fat distribution such as BC could help in understanding the complex pathophysiology behind overweight and obesity. The purpose of this study is to identify genetic variants associated with BC through a large-scale genome-wide association scan (GWAS meta-analysis. We used fixed-effects meta-analysis to synthesise summary results across 14 GWAS discovery and 4 replication cohorts comprising overall 22,376 individuals (12,031 women and 10,345 men of European ancestry. Individual analyses were carried out for men, women, and combined across sexes using linear regression and an additive genetic model: adjusted for age and adjusted for age and BMI. We prioritised signals for follow-up in two-stages. We did not detect any signals reaching genome-wide significance. The FTO rs9939609 SNP showed nominal evidence for association (p<0.05 in the age-adjusted strata for men and across both sexes. In this first GWAS meta-analysis for BC to date, we have not identified any genome-wide significant signals and do not observe robust association of previously established obesity loci with BC. Large-scale collaborations will be necessary to achieve higher power to detect loci underlying BC.

  19. Meta-analysis of five genome-wide association studies identifies multiple new loci associated with testicular germ cell tumor

    DEFF Research Database (Denmark)

    Wang, Zhaoming; McGlynn, Katherine A.; Rajpert-De Meyts, Ewa

    2017-01-01

    The international Testicular Cancer Consortium (TECAC) combined five published genome-wide association studies of testicular germ cell tumor (TGCT; 3,558 cases and 13,970 controls) to identify new susceptibility loci. We conducted a fixed-effects meta-analysis, including, to our knowledge, the fi...

  20. Periostin is identified as a putative metastatic marker in breast cancer-derived exosomes.

    Science.gov (United States)

    Vardaki, Ioulia; Ceder, Sophia; Rutishauser, Dorothea; Baltatzis, George; Foukakis, Theodoros; Panaretakis, Theocharis

    2016-11-15

    Breast cancer (BrCa) is the most frequent cancer type in women and a leading cause of cancer related deaths in the world. Despite the decrease in mortality due to better diagnostics and palliative care, there is a lack of prognostic markers of metastasis. Recently, the exploitation of liquid biopsies and in particular of the extracellular vesicles has shown promise in the identification of such prognostic markers. In this study we compared the proteomic content of exosomes derived from metastatic and non-metastatic human (MCF7 and MDA-MB-231) and mouse (67NR and 4T1) cell lines. We found significant differences not only in the amount of secreted exosomes but most importantly in the protein content of exosomes secreted from metastatic versus non-metastatic ones. We identified periostin as a protein that is enriched in exosomes secreted by metastatic cells and validated its presence in a pilot cohort of breast cancer patient samples with localized disease or lymph node (LN) metastasis.

  1. Kinase Gene Expression Profiling of Metastatic Clear Cell Renal Cell Carcinoma Tissue Identifies Potential New Therapeutic Targets.

    Directory of Open Access Journals (Sweden)

    Pooja Ghatalia

    Full Text Available Kinases are therapeutically actionable targets. Kinase inhibitors targeting vascular endothelial growth factor receptors (VEGFR and mammalian target of rapamycin (mTOR improve outcomes in metastatic clear cell renal cell carcinoma (ccRCC, but are not curative. Metastatic tumor tissue has not been comprehensively studied for kinase gene expression. Paired intra-patient kinase gene expression analysis in primary tumor (T, matched normal kidney (N and metastatic tumor tissue (M may assist in identifying drivers of metastasis and prioritizing therapeutic targets. We compared the expression of 519 kinase genes using NanoString in T, N and M in 35 patients to discover genes over-expressed in M compared to T and N tissue. RNA-seq data derived from ccRCC tumors in The Cancer Genome Atlas (TCGA were used to demonstrate differential expression of genes in primary tumor tissue from patients that had metastasis at baseline (n = 79 compared to those that did not develop metastasis for at least 2 years (n = 187. Functional analysis was conducted to identify key signaling pathways by using Ingenuity Pathway Analysis. Of 10 kinase genes overexpressed in metastases compared to primary tumor in the discovery cohort, 9 genes were also differentially expressed in TCGA primary tumors with metastasis at baseline compared to primary tumors without metastasis for at least 2 years: EPHB2, AURKA, GSG2, IKBKE, MELK, CSK, CHEK2, CDC7 and MAP3K8; p<0.001. The top pathways overexpressed in M tissue were pyridoxal 5'-phosphate salvage, salvage pathways of pyrimidine ribonucleotides, NF-kB signaling, NGF signaling and cell cycle control of chromosomal replication. The 9 kinase genes validated to be over-expressed in metastatic ccRCC may represent currently unrecognized but potentially actionable therapeutic targets that warrant functional validation.

  2. Meta-analytic framework for sparse K-means to identify disease subtypes in multiple transcriptomic studies.

    Science.gov (United States)

    Huo, Zhiguang; Ding, Ying; Liu, Silvia; Oesterreich, Steffi; Tseng, George

    Disease phenotyping by omics data has become a popular approach that potentially can lead to better personalized treatment. Identifying disease subtypes via unsupervised machine learning is the first step towards this goal. In this paper, we extend a sparse K -means method towards a meta-analytic framework to identify novel disease subtypes when expression profiles of multiple cohorts are available. The lasso regularization and meta-analysis identify a unique set of gene features for subtype characterization. An additional pattern matching reward function guarantees consistent subtype signatures across studies. The method was evaluated by simulations and leukemia and breast cancer data sets. The identified disease subtypes from meta-analysis were characterized with improved accuracy and stability compared to single study analysis. The breast cancer model was applied to an independent METABRIC dataset and generated improved survival difference between subtypes. These results provide a basis for diagnosis and development of targeted treatments for disease subgroups.

  3. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC) : an update on 93 randomised trials and 17,346 patients

    NARCIS (Netherlands)

    Pignon, Jean-Pierre; le Maître, Aurélie; Maillard, Emilie; Bourhis, Jean; Widder, Joachim

    BACKGROUND: Our previous individual patient data (IPD) meta-analysis showed that chemotherapy improved survival in patients curatively treated for non-metastatic head and neck squamous cell carcinoma (HNSCC), with a higher benefit with concomitant chemotherapy. However the heterogeneity of the

  4. Meta-analysis with R

    CERN Document Server

    Schwarzer, Guido; Rücker, Gerta

    2015-01-01

    This book provides a comprehensive introduction to performing meta-analysis using the statistical software R. It is intended for quantitative researchers and students in the medical and social sciences who wish to learn how to perform meta-analysis with R. As such, the book introduces the key concepts and models used in meta-analysis. It also includes chapters on the following advanced topics: publication bias and small study effects; missing data; multivariate meta-analysis, network meta-analysis; and meta-analysis of diagnostic studies.  .

  5. A two-stage meta-analysis identifies several new loci for Parkinson's disease.

    NARCIS (Netherlands)

    Plagnol, V.; Nalls, M.A.; Bras, J.M.; Hernandez, D.; Sharma, M.; Sheerin, U.M.; Saad, M.; Simon-Sanchez, J.; Schulte, C.; Lesage, S.; Sveinbjornsdottir, S.; Amouyel, P.; Arepalli, S.; Band, G.; Barker, R.A.; Bellinguez, C.; Ben-Shlomo, Y.; Berendse, H.W.; Berg, D; Bhatia, K.P.; Bie, R.M. de; Biffi, A.; Bloem, B.R.; Bochdanovits, Z.; Bonin, M.; Brockmann, K.; Brooks, J.; Burn, D.J.; Charlesworth, G.; Chen, H.; Chinnery, P.F.; Chong, S.; Clarke, C.E.; Cookson, M.R.; Cooper, J.M.; Corvol, J.C.; Counsell, J.; Damier, P.; Dartigues, J.F.; Deloukas, P.; Deuschl, G.; Dexter, D.T.; Dijk, K.D. van; Dillman, A.; Durif, F.; Durr, A.; Edkins, S.; Evans, J.R.; Foltynie, T.; Freeman, C.; Gao, J.; Gardner, M.; Gibbs, J.R.; Goate, A.; Gray, E.; Guerreiro, R.; Gustafsson, O.; Harris, C.; Hellenthal, G.; Hilten, J.J. van; Hofman, A.; Hollenbeck, A.; Holton, J.L.; Hu, M.; Huang, X.; Huber, H; Hudson, G.; Hunt, S.E.; Huttenlocher, J.; Illig, T.; Jonsson, P.V.; Langford, C.; Lees, A.J.; Lichtner, P.; Limousin, P.; Lopez, G.; McNeill, A.; Moorby, C.; Moore, M.; Morris, H.A.; Morrison, K.E.; Mudanohwo, E.; O'Sullivan, S.S; Pearson, J.; Pearson, R.; Perlmutter, J.; Petursson, H.; Pirinen, M.; Polnak, P.; Post, B.; Potter, S.C.; Ravina, B.; Revesz, T.; Riess, O.; Rivadeneira, F.; Rizzu, P.; Ryten, M.; Sawcer, S.J.; Schapira, A.; Scheffer, H.; Shaw, K.; Shoulson, I.; Sidransky, E.; Silva, R. de; Smith, C.; Spencer, C.C.; Stefansson, H.; Steinberg, S.; Stockton, J.D.; Strange, A.; Su, Z.; Talbot, K.; Tanner, C.M.; Tashakkori-Ghanbaria, A.; Tison, F.; Trabzuni, D.; Traynor, B.J.; Uitterlinden, A.G.; Vandrovcova, J.; Velseboer, D.; Vidailhet, M.; Vukcevic, D.; Walker, R.; Warrenburg, B.P.C. van de; Weale, M.E.; Wickremaratchi, M.; Williams, N.; Williams-Gray, C.H.; Winder-Rhodes, S.; Stefansson, K.; Martinez, M.; Donnelly, P.; Singleton, A.B.; Hardy, J.; Heutink, P.; Brice, A.; Gasser, T.; Wood, N.W.

    2011-01-01

    A previous genome-wide association (GWA) meta-analysis of 12,386 PD cases and 21,026 controls conducted by the International Parkinson's Disease Genomics Consortium (IPDGC) discovered or confirmed 11 Parkinson's disease (PD) loci. This first analysis of the two-stage IPDGC study

  6. Marital status integration and suicide: A meta-analysis and meta-regression.

    Science.gov (United States)

    Kyung-Sook, Woo; SangSoo, Shin; Sangjin, Shin; Young-Jeon, Shin

    2018-01-01

    Marital status is an index of the phenomenon of social integration within social structures and has long been identified as an important predictor suicide. However, previous meta-analyses have focused only on a particular marital status, or not sufficiently explored moderators. A meta-analysis of observational studies was conducted to explore the relationships between marital status and suicide and to understand the important moderating factors in this association. Electronic databases were searched to identify studies conducted between January 1, 2000 and June 30, 2016. We performed a meta-analysis, subgroup analysis, and meta-regression of 170 suicide risk estimates from 36 publications. Using random effects model with adjustment for covariates, the study found that the suicide risk for non-married versus married was OR = 1.92 (95% CI: 1.75-2.12). The suicide risk was higher for non-married individuals aged analysis by gender, non-married men exhibited a greater risk of suicide than their married counterparts in all sub-analyses, but women aged 65 years or older showed no significant association between marital status and suicide. The suicide risk in divorced individuals was higher than for non-married individuals in both men and women. The meta-regression showed that gender, age, and sample size affected between-study variation. The results of the study indicated that non-married individuals have an aggregate higher suicide risk than married ones. In addition, gender and age were confirmed as important moderating factors in the relationship between marital status and suicide. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Efficacy of anthropometric measures for identifying cardiovascular disease risk in adolescents: review and meta-analysis.

    Science.gov (United States)

    Lichtenauer, Michael; Wheatley, Sean D; Martyn-St James, Marrissa; Duncan, Michael J; Cobayashi, Fernanda; Berg, Gabriela; Musso, Carla; Graffigna, Mabel; Soutelo, Jimena; Bovet, Pascal; Kollias, Anastasios; Stergiou, George S; Grammatikos, Evangelos; Griffiths, Claire; Ingle, Lee; Jung, Christian

    2018-04-12

    To compare the ability of body mass index (BMI), waist circumference (WC) and waist to height ratio (WHtR) to estimate cardiovascular disease (CVD) risk levels in adolescents. A systematic review and meta-analysis was performed after a database search for relevant literature (Cochrane, Centre for Review and Dissemination, PubMed, British Nursing Index, CINAHL, BIOSIS citation index, ChildData, metaRegister). 117 records representing 96 studies with 994,595 participants were included in the systematic review, 14 of which (13 studies, n=14,610) were eligible for the meta-analysis. The results of the meta-analysis showed that BMI was a strong indicator of systolic blood pressure, diastolic blood pressure, triglycerides, high-density lipoprotein cholesterol and insulin; but not total cholesterol, low-density lipoprotein or glucose. Few studies were eligible for inclusion in the meta-analysis considering WC or WHtR (n≤2). The narrative synthesis found measures of central adiposity to be consistently valid indicators of the same risk factors as BMI. BMI was an indicator of CVD risk. WC and WHtR were efficacious for indicating the same risk factors BMI performed strongly for, though there was insufficient evidence to judge the relative strength of each measure possibly due to heterogeneity in the methods for measuring and classifying WC.

  8. A meta-analysis of genome-wide association studies to identify prostate cancer susceptibility loci associated with aggressive and non-aggressive disease

    DEFF Research Database (Denmark)

    Amin Al Olama, Ali; Kote-Jarai, Zsofia; Schumacher, Fredrick R

    2013-01-01

    Genome-wide association studies (GWAS) have identified multiple common genetic variants associated with an increased risk of prostate cancer (PrCa), but these explain less than one-third of the heritability. To identify further susceptibility alleles, we conducted a meta-analysis of four GWAS inc...

  9. A Two-Stage Meta-Analysis Identifies Several New Loci for Parkinson's Disease

    NARCIS (Netherlands)

    Plagnol, Vincent; Nalls, Michael A.; Bras, Jose M.; Hernandez, Dena G.; Sharma, Manu; Sheerin, Una-Marie; Saad, Mohamad; Simon-Sanchez, Javier; Schulte, Claudia; Lesage, Suzanne; Sveinbjornsdottir, Sigurlaug; Amouyel, Philippe; Arepalli, Sampath; Band, Gavin; Barker, Roger A.; Bellinguez, Celine; Ben-Shlomo, Yoav; Berendse, Henk W.; Berg, Daniela; Bhatia, Kailash; de Bie, Rob M. A.; Biffi, Alessandro; Bloem, Bas; Bochdanovits, Zoltan; Bonin, Michael; Brockmann, Kathrin; Brooks, Janet; Burn, David J.; Charlesworth, Gavin; Chen, Honglei; Chinnery, Patrick F.; Chong, Sean; Clarke, Carl E.; Cookson, Mark R.; Cooper, J. Mark; Corvol, Jean Christophe; Counsell, Carl; Damier, Philippe; Dartigues, Jean-Francois; Deloukas, Panos; Deuschl, Guenther; Dexter, David T.; van Dijk, Karin D.; Dillman, Allissa; Durif, Frank; Duerr, Alexandra; Edkins, Sarah; Evans, Jonathan R.; Foltynie, Thomas; Freeman, Colin; Gao, Jianjun; Gardner, Michelle; Gibbs, J. Raphael; Goate, Alison; Gray, Emma; Guerreiro, Rita; Gustafsson, Omar; Harris, Clare; Hellenthal, Garrett; van Hilten, Jacobus J.; Hofman, Albert; Hollenbeck, Albert; Holton, Janice; Hu, Michele; Huang, Xuemei; Huber, Heiko; Hudson, Gavin; Hunt, Sarah E.; Huttenlocher, Johanna; Illig, Thomas; Jonsson, Palmi V.; Langford, Cordelia; Lees, Andrew; Lichtner, Peter; Limousin, Patricia; Lopez, Grisel; Lorenz, Delia; McNeill, Alisdair; Moorby, Catriona; Moore, Matthew; Morris, Huw; Morrison, Karen E.; Mudanohwo, Ese; O'Sullivan, Sean S.; Pearson, Justin; Pearson, Richard; Perlmutter, Joel S.; Petursson, Hjoervar; Pirinen, Matti; Pollak, Pierre; Post, Bart; Potter, Simon; Ravina, Bernard; Revesz, Tamas; Riess, Olaf; Rivadeneira, Fernando; Rizzu, Patrizia; Ryten, Mina; Sawcer, Stephen; Schapira, Anthony; Scheffer, Hans; Shaw, Karen; Shoulson, Ira; Sidransky, Ellen; de Silva, Rohan; Smith, Colin; Spencer, Chris C. A.; Stefansson, Hreinn; Steinberg, Stacy; Stockton, Joanna D.; Strange, Amy; Su, Zhan; Talbot, Kevin; Tanner, Carlie M.; Tashakkori-Ghanbaria, Avazeh; Tison, Francois; Trabzuni, Daniah; Traynor, Bryan J.; Uitterlinden, Andre G.; Vandrovcova, Jana; Velseboer, Daan; Vidailhet, Marie; Vukcevic, Damjan; Walker, Robert; van de Warrenburg, Bart; Weale, Michael E.; Wickremaratchi, Mirdhu; Williams, Nigel; Williams-Gray, Caroline H.; Winder-Rhodes, Sophie; Stefansson, Kari; Martinez, Maria; Donnelly, Peter; Singleton, Andrew B.; Hardy, John; Heutink, Peter; Brice, Alexis; Gasser, Thomas; Wood, Nicholas W.

    2011-01-01

    A previous genome-wide association (GWA) meta-analysis of 12,386 PD cases and 21,026 controls conducted by the International Parkinson's Disease Genomics Consortium (IPDGC) discovered or confirmed 11 Parkinson's disease (PD) loci. This first analysis of the two-stage IPDGC study focused on the set

  10. A genome-wide association meta-analysis identifies new childhood obesity loci

    NARCIS (Netherlands)

    Bradfield, Jonathan P.; Taal, H. Rob; Timpson, Nicholas J.; Scherag, Andre; Lecoeur, Cecile; Warrington, Nicole M.; Hypponen, Elina; Holst, Claus; Valcarcel, Beatriz; Thiering, Elisabeth; Salem, Rany M.; Schumacher, Fredrick R.; Cousminer, Diana L.; Sleiman, Patrick M. A.; Zhao, Jianhua; Berkowitz, Robert I.; Vimaleswaran, Karani S.; Jarick, Ivonne; Pennell, Craig E.; Evans, David M.; St Pourcain, Beate; Berry, Diane J.; Mook-Kanamori, Dennis O.; Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, Andre G.; van Duijn, Cornelia M.; van der Valk, Ralf J. P.; de Jongste, Johan C.; Postma, Dirkje S.; Boomsma, Dorret I.; Gauderman, W. James; Hassanein, Mohamed T.; Lindgren, Cecilia M.; Magi, Reedik; Boreham, Colin A. G.; Neville, Charlotte E.; Moreno, Luis A.; Elliott, Paul; Pouta, Anneli; Hartikainen, Anna-Liisa; Li, Mingyao; Raitakari, Olli; Lehtimaki, Terho; Eriksson, Johan G.; Palotie, Aarno; Dallongeville, Jean; Das, Shikta; Deloukas, Panos; McMahon, George

    Multiple genetic variants have been associated with adult obesity and a few with severe obesity in childhood; however, less progress has been made in establishing genetic influences on common early-onset obesity. We performed a North American, Australian and European collaborative meta-analysis of

  11. A genome-wide association meta-analysis identifies new childhood obesity loci

    NARCIS (Netherlands)

    Bradfield, J.P.; Taal, H.R.; Timpson, N.J.; Scherag, A.; Lecoeur, C.; Warrington, N.M.; Hypponen, E.; Holst, C.; Valcarcel, B.; Thiering, E.; Salem, R.M.; Schumacher, F.R.; Cousminer, D.L.; Sleiman, P.M.A.; Zhao, J.; Berkowitz, R.I.; Vimaleswaran, K.S.; Jarick, I.; Pennell, C.E.; Evans, D.M.; St Pourcain, B.; Berry, D.J.; Mook-Kanamori, D.O.; Hofman, A.; Rivadeneira, F.; Uitterlinden, A.G.; van Duijn, C.M.; van der Valk, R.J.P.; de Jongste, J.C.; Postma, D.S.; Boomsma, D.I.; Gauderman, W.J.; Hassanein, M.T.; Lindgren, C.M.; Mägi, R.; Boreham, C.A.G.; Neville, C.E.; Moreno, L.A.; Elliott, P.; Pouta, A.; Hartikainen, A.-L.; Li, M.; Raitakari, O.; Lehtimäki, T.; Eriksson, J.G.; Palotie, A.; Dallongeville, J.; Das, S.; Deloukas, P.; McMahon, G.; Ring, S.M.; Kemp, J.P.; Buxton, J.L.; Blakemore, A.I.F.; Bustamante, M.; Guxens, M.; Hirschhorn, J.N.; Gillman, M.W.; Kreiner-Møller, E.; Bisgaard, H.; Gilliland, F.D.; Heinrich, J.; Wheeler, E.; Barroso, I.; O'Rahilly, S.; Meirhaeghe, A.; Sørensen, T.I.A.; Power, C.; Palmer, L.J.; Hinney, A.; Widen, E.; Farooqi, I.S.; McCarthy, M.I.; Froguel, P.; Meyre, D.; Hebebrand, J.; Järvelin, M.J.; Jaddoe, V.W.V.; Smith, G.D.; Hakonarson, H.; Grant, S.F.A.

    2012-01-01

    Multiple genetic variants have been associated with adult obesity and a few with severe obesity in childhood; however, less progress has been made in establishing genetic influences on common early-onset obesity. We performed a North American, Australian and European collaborative meta-analysis of

  12. Proteomic analysis of cerebrospinal fluid from children with central nervous system tumors identifies candidate proteins relating to tumor metastatic spread.

    Science.gov (United States)

    Spreafico, Filippo; Bongarzone, Italia; Pizzamiglio, Sara; Magni, Ruben; Taverna, Elena; De Bortoli, Maida; Ciniselli, Chiara M; Barzanò, Elena; Biassoni, Veronica; Luchini, Alessandra; Liotta, Lance A; Zhou, Weidong; Signore, Michele; Verderio, Paolo; Massimino, Maura

    2017-07-11

    Central nervous system (CNS) tumors are the most common solid tumors in childhood. Since the sensitivity of combined cerebrospinal fluid (CSF) cytology and radiological neuroimaging in detecting meningeal metastases remains relatively low, we sought to characterize the CSF proteome of patients with CSF tumors to identify biomarkers predictive of metastatic spread. CSF samples from 27 children with brain tumors and 13 controls (extra-CNS non-Hodgkin lymphoma) were processed using core-shell hydrogel nanoparticles, and analyzed with reverse-phase liquid chromatography/electrospray tandem mass spectrometry (LC-MS/MS). Candidate proteins were identified with Fisher's exact test and/or a univariate logistic regression model. Reverse phase protein array (RPPA), Western blot (WB), and ELISA were used in the training set and in an independent set of CFS samples (60 cases, 14 controls) to validate our discovery findings. Among the 558 non-redundant proteins identified by LC-MS/MS, 147 were missing from the CSF database at http://www.biosino.org. Fourteen of the 26 final top-candidate proteins were chosen for validation with WB, RPPA and ELISA methods. Six proteins (type 1 collagen, insulin-like growth factor binding protein 4, procollagen C-endopeptidase enhancer 1, glial cell-line derived neurotrophic factor receptor α2, inter-alpha-trypsin inhibitor heavy chain 4, neural proliferation and differentiation control protein-1) revealed the ability to discriminate metastatic cases from controls. Combining a unique dataset of CSFs from pediatric CNS tumors with a novel enabling nanotechnology led us to identify CSF proteins potentially related to metastatic status.

  13. Formalizing the definition of meta-analysis in Molecular Ecology.

    Science.gov (United States)

    ArchMiller, Althea A; Bauer, Eric F; Koch, Rebecca E; Wijayawardena, Bhagya K; Anil, Ammu; Kottwitz, Jack J; Munsterman, Amelia S; Wilson, Alan E

    2015-08-01

    Meta-analysis, the statistical synthesis of pertinent literature to develop evidence-based conclusions, is relatively new to the field of molecular ecology, with the first meta-analysis published in the journal Molecular Ecology in 2003 (Slate & Phua 2003). The goal of this article is to formalize the definition of meta-analysis for the authors, editors, reviewers and readers of Molecular Ecology by completing a review of the meta-analyses previously published in this journal. We also provide a brief overview of the many components required for meta-analysis with a more specific discussion of the issues related to the field of molecular ecology, including the use and statistical considerations of Wright's FST and its related analogues as effect sizes in meta-analysis. We performed a literature review to identify articles published as 'meta-analyses' in Molecular Ecology, which were then evaluated by at least two reviewers. We specifically targeted Molecular Ecology publications because as a flagship journal in this field, meta-analyses published in Molecular Ecology have the potential to set the standard for meta-analyses in other journals. We found that while many of these reviewed articles were strong meta-analyses, others failed to follow standard meta-analytical techniques. One of these unsatisfactory meta-analyses was in fact a secondary analysis. Other studies attempted meta-analyses but lacked the fundamental statistics that are considered necessary for an effective and powerful meta-analysis. By drawing attention to the inconsistency of studies labelled as meta-analyses, we emphasize the importance of understanding the components of traditional meta-analyses to fully embrace the strengths of quantitative data synthesis in the field of molecular ecology. © 2015 John Wiley & Sons Ltd.

  14. Methodology Series Module 6: Systematic Reviews and Meta-analysis.

    Science.gov (United States)

    Setia, Maninder Singh

    2016-01-01

    Systematic reviews and meta-analysis have become an important of biomedical literature, and they provide the "highest level of evidence" for various clinical questions. There are a lot of studies - sometimes with contradictory conclusions - on a particular topic in literature. Hence, as a clinician, which results will you believe? What will you tell your patient? Which drug is better? A systematic review or a meta-analysis may help us answer these questions. In addition, it may also help us understand the quality of the articles in literature or the type of studies that have been conducted and published (example, randomized trials or observational studies). The first step it to identify a research question for systematic review or meta-analysis. The next step is to identify the articles that will be included in the study. This will be done by searching various databases; it is important that the researcher should search for articles in more than one database. It will also be useful to form a group of researchers and statisticians that have expertise in conducting systematic reviews and meta-analysis before initiating them. We strongly encourage the readers to register their proposed review/meta-analysis with PROSPERO. Finally, these studies should be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis checklist.

  15. Genome-wide meta-analysis identifies novel determinants of circulating serum progranulin.

    Science.gov (United States)

    Tönjes, Anke; Scholz, Markus; Krüger, Jacqueline; Krause, Kerstin; Schleinitz, Dorit; Kirsten, Holger; Gebhardt, Claudia; Marzi, Carola; Grallert, Harald; Ladenvall, Claes; Heyne, Henrike; Laurila, Esa; Kriebel, Jennifer; Meisinger, Christa; Rathmann, Wolfgang; Gieger, Christian; Groop, Leif; Prokopenko, Inga; Isomaa, Bo; Beutner, Frank; Kratzsch, Jürgen; Fischer-Rosinsky, Antje; Pfeiffer, Andreas; Krohn, Knut; Spranger, Joachim; Thiery, Joachim; Blüher, Matthias; Stumvoll, Michael; Kovacs, Peter

    2018-02-01

    Progranulin is a secreted protein with important functions in processes including immune and inflammatory response, metabolism and embryonic development. The present study aimed at identification of genetic factors determining progranulin concentrations. We conducted a genome-wide association meta-analysis for serum progranulin in three independent cohorts from Europe: Sorbs (N = 848) and KORA (N = 1628) from Germany and PPP-Botnia (N = 335) from Finland (total N = 2811). Single nucleotide polymorphisms (SNPs) associated with progranulin levels were replicated in two additional German cohorts: LIFE-Heart Study (Leipzig; N = 967) and Metabolic Syndrome Berlin Potsdam (Berlin cohort; N = 833). We measured mRNA expression of genes in peripheral blood mononuclear cells (PBMC) by micro-arrays and performed mRNA expression quantitative trait and expression-progranulin association studies to functionally substantiate identified loci. Finally, we conducted siRNA silencing experiments in vitro to validate potential candidate genes within the associated loci. Heritability of circulating progranulin levels was estimated at 31.8% and 26.1% in the Sorbs and LIFE-Heart cohort, respectively. SNPs at three loci reached study-wide significance (rs660240 in CELSR2-PSRC1-MYBPHL-SORT1, rs4747197 in CDH23-PSAP and rs5848 in GRN) explaining 19.4%/15.0% of the variance and 61%/57% of total heritability in the Sorbs/LIFE-Heart Study. The strongest evidence for association was at rs660240 (P = 5.75 × 10-50), which was also associated with mRNA expression of PSRC1 in PBMC (P = 1.51 × 10-21). Psrc1 knockdown in murine preadipocytes led to a consecutive 30% reduction in progranulin secretion. In conclusion, the present meta-GWAS combined with mRNA expression identified three loci associated with progranulin and supports the role of PSRC1 in the regulation of progranulin secretion. © The Author(s) 2017. Published by Oxford University Press. All rights

  16. Rethinking Meta-Analysis: Applications for Air Pollution Data and Beyond

    Science.gov (United States)

    Goodman, Julie E; Petito Boyce, Catherine; Sax, Sonja N; Beyer, Leslie A; Prueitt, Robyn L

    2015-01-01

    Meta-analyses offer a rigorous and transparent systematic framework for synthesizing data that can be used for a wide range of research areas, study designs, and data types. Both the outcome of meta-analyses and the meta-analysis process itself can yield useful insights for answering scientific questions and making policy decisions. Development of the National Ambient Air Quality Standards illustrates many potential applications of meta-analysis. These applications demonstrate the strengths and limitations of meta-analysis, issues that arise in various data realms, how meta-analysis design choices can influence interpretation of results, and how meta-analysis can be used to address bias and heterogeneity. Reviewing available data from a meta-analysis perspective can provide a useful framework and impetus for identifying and refining strategies for future research. Moreover, increased pervasiveness of a meta-analysis mindset—focusing on how the pieces of the research puzzle fit together—would benefit scientific research and data syntheses regardless of whether or not a quantitative meta-analysis is undertaken. While an individual meta-analysis can only synthesize studies addressing the same research question, the results of separate meta-analyses can be combined to address a question encompassing multiple data types. This observation applies to any scientific or policy area where information from a variety of disciplines must be considered to address a broader research question. PMID:25969128

  17. Meta-analysis of genome-wide association studies identifies eight new loci for type 2 diabetes in east Asians

    DEFF Research Database (Denmark)

    Cho, Yoon Shin; Chen, Chien-Hsiun; Hu, Cheng

    2012-01-01

    We conducted a three-stage genetic study to identify susceptibility loci for type 2 diabetes (T2D) in east Asian populations. We followed our stage 1 meta-analysis of eight T2D genome-wide association studies (6,952 cases with T2D and 11,865 controls) with a stage 2 in silico replication analysis...... (5,843 cases and 4,574 controls) and a stage 3 de novo replication analysis (12,284 cases and 13,172 controls). The combined analysis identified eight new T2D loci reaching genome-wide significance, which mapped in or near GLIS3, PEPD, FITM2-R3HDML-HNF4A, KCNK16, MAEA, GCC1-PAX4, PSMD6 and ZFAND3...

  18. GWAMA: software for genome-wide association meta-analysis

    Directory of Open Access Journals (Sweden)

    Mägi Reedik

    2010-05-01

    Full Text Available Abstract Background Despite the recent success of genome-wide association studies in identifying novel loci contributing effects to complex human traits, such as type 2 diabetes and obesity, much of the genetic component of variation in these phenotypes remains unexplained. One way to improving power to detect further novel loci is through meta-analysis of studies from the same population, increasing the sample size over any individual study. Although statistical software analysis packages incorporate routines for meta-analysis, they are ill equipped to meet the challenges of the scale and complexity of data generated in genome-wide association studies. Results We have developed flexible, open-source software for the meta-analysis of genome-wide association studies. The software incorporates a variety of error trapping facilities, and provides a range of meta-analysis summary statistics. The software is distributed with scripts that allow simple formatting of files containing the results of each association study and generate graphical summaries of genome-wide meta-analysis results. Conclusions The GWAMA (Genome-Wide Association Meta-Analysis software has been developed to perform meta-analysis of summary statistics generated from genome-wide association studies of dichotomous phenotypes or quantitative traits. Software with source files, documentation and example data files are freely available online at http://www.well.ox.ac.uk/GWAMA.

  19. Metastatic canine mammary carcinomas can be identified by a gene expression profile that partly overlaps with human breast cancer profiles

    International Nuclear Information System (INIS)

    Klopfleisch, Robert; Lenze, Dido; Hummel, Michael; Gruber, Achim D

    2010-01-01

    Similar to human breast cancer mammary tumors of the female dog are commonly associated with a fatal outcome due to the development of distant metastases. However, the molecular defects leading to metastasis are largely unknown and the value of canine mammary carcinoma as a model for human breast cancer is unclear. In this study, we analyzed the gene expression signatures associated with mammary tumor metastasis and asked for parallels with the human equivalent. Messenger RNA expression profiles of twenty-seven lymph node metastasis positive or negative canine mammary carcinomas were established by microarray analysis. Differentially expressed genes were functionally characterized and associated with molecular pathways. The findings were also correlated with published data on human breast cancer. Metastatic canine mammary carcinomas had 1,011 significantly differentially expressed genes when compared to non-metastatic carcinomas. Metastatic carcinomas had a significant up-regulation of genes associated with cell cycle regulation, matrix modulation, protein folding and proteasomal degradation whereas cell differentiation genes, growth factor pathway genes and regulators of actin organization were significantly down-regulated. Interestingly, 265 of the 1,011 differentially expressed canine genes are also related to human breast cancer and, vice versa, parts of a human prognostic gene signature were identified in the expression profiles of the metastatic canine tumors. Metastatic canine mammary carcinomas can be discriminated from non-metastatic carcinomas by their gene expression profiles. More than one third of the differentially expressed genes are also described of relevance for human breast cancer. Many of the differentially expressed genes are linked to functions and pathways which appear to be relevant for the induction and maintenance of metastatic progression and may represent new therapeutic targets. Furthermore, dogs are in some aspects suitable as a

  20. Identifying null meta-analyses that are ripe for updating

    Directory of Open Access Journals (Sweden)

    Fang Manchun

    2003-07-01

    Full Text Available Abstract Background As an increasingly large number of meta-analyses are published, quantitative methods are needed to help clinicians and systematic review teams determine when meta-analyses are not up to date. Methods We propose new methods for determining when non-significant meta-analytic results might be overturned, based on a prediction of the number of participants required in new studies. To guide decision making, we introduce the "new participant ratio", the ratio of the actual number of participants in new studies to the predicted number required to obtain statistical significance. A simulation study was conducted to study the performance of our methods and a real meta-analysis provides further evidence. Results In our three simulation configurations, our diagnostic test for determining whether a meta-analysis is out of date had sensitivity of 55%, 62%, and 49% with corresponding specificity of 85%, 80%, and 90% respectively. Conclusions Simulations suggest that our methods are able to detect out-of-date meta-analyses. These quick and approximate methods show promise for use by systematic review teams to help decide whether to commit the considerable resources required to update a meta-analysis. Further investigation and evaluation of the methods is required before they can be recommended for general use.

  1. Analysis of methylation profiling data of hyperplasia and primary and metastatic endometrial cancers.

    Science.gov (United States)

    Wu, Xihai; Miao, Jilan; Jiang, Jingyan; Liu, Fangmei

    2017-10-01

    Endometrial cancer is a prevalent cancer, and its metastasis causes low survival rate. This study aims to utilize DNA methylation data to investigate the mechanism of the development and metastasis of endometrial cancer. Methylation profiling data were down-loaded from Gene Expression Omnibus, including 8 hyperplasias, 33 primary and 53 metastatic endometrial cancers. COHCAP package and annotation files were utilized to identify differentially methylated genes (DMGs) and CpG islands between the three different endometrial diseases. STRING database and Cytoscape were used to analyze and visualize protein-protein interactions (PPIs) between DMGs. CytoNCA plugin was utilized to identify key nodes in PPI network. A total of 610, 1076, and 501 DMGs were identified between primary endometrial cancer and hyperplasia, metastatic endometrial cancer and hyperplasia, as well as metastatic and primary endometrial cancers, respectively. For the three DMG sets, 53 common hypermethylated DMGs (e.g. PAX6 and INSR) and 6 common hypomethylated DMGs (e.g. PRDM8, KLHL14, and DUSP6) were found. For primary-hyperplasia DMG set and metastasis-hyperplasia DMG set, 527 common DMGs were found. For these common DMGs, a PPI network involving 692 PPIs was constructed. For DMGs between metastatic and primary endometrial cancers, a PPI network involving 673 PPIs was established, with PAX6 and INSR in the top 20 DMGs in both networks. PRDM8, KLHL14, and DUSP6 had hypomethylated CpG islands. DMGs comparison, PPI network analysis, and analysis of differentially methylated CpG islands indicated that PAX6, INSR, PRDM8, KLHL14, and DUSP6 might participate in the development and metastasis of endometrial cancer. Copyright © 2017. Published by Elsevier B.V.

  2. A genome-wide association meta-analysis identifies new childhood obesity loci

    Science.gov (United States)

    Bradfield, Jonathan P.; Taal, H. Rob; Timpson, Nicholas J.; Scherag, André; Lecoeur, Cecile; Warrington, Nicole M.; Hypponen, Elina; Holst, Claus; Valcarcel, Beatriz; Thiering, Elisabeth; Salem, Rany M.; Schumacher, Fredrick R.; Cousminer, Diana L.; Sleiman, Patrick M.A.; Zhao, Jianhua; Berkowitz, Robert I.; Vimaleswaran, Karani S.; Jarick, Ivonne; Pennell, Craig E.; Evans, David M.; St. Pourcain, Beate; Berry, Diane J.; Mook-Kanamori, Dennis O; Hofman, Albert; Rivadeinera, Fernando; Uitterlinden, André G.; van Duijn, Cornelia M.; van der Valk, Ralf J.P.; de Jongste, Johan C.; Postma, Dirkje S.; Boomsma, Dorret I.; Gauderman, William J.; Hassanein, Mohamed T.; Lindgren, Cecilia M.; Mägi, Reedik; Boreham, Colin A.G.; Neville, Charlotte E.; Moreno, Luis A.; Elliott, Paul; Pouta, Anneli; Hartikainen, Anna-Liisa; Li, Mingyao; Raitakari, Olli; Lehtimäki, Terho; Eriksson, Johan G.; Palotie, Aarno; Dallongeville, Jean; Das, Shikta; Deloukas, Panos; McMahon, George; Ring, Susan M.; Kemp, John P.; Buxton, Jessica L.; Blakemore, Alexandra I.F.; Bustamante, Mariona; Guxens, Mònica; Hirschhorn, Joel N.; Gillman, Matthew W.; Kreiner-Møller, Eskil; Bisgaard, Hans; Gilliland, Frank D.; Heinrich, Joachim; Wheeler, Eleanor; Barroso, Inês; O'Rahilly, Stephen; Meirhaeghe, Aline; Sørensen, Thorkild I.A.; Power, Chris; Palmer, Lyle J.; Hinney, Anke; Widen, Elisabeth; Farooqi, I. Sadaf; McCarthy, Mark I.; Froguel, Philippe; Meyre, David; Hebebrand, Johannes; Jarvelin, Marjo-Riitta; Jaddoe, Vincent W.V.; Smith, George Davey; Hakonarson, Hakon; Grant, Struan F.A.

    2012-01-01

    Multiple genetic variants have been associated with adult obesity and a few with severe obesity in childhood; however, less progress has been made to establish genetic influences on common early-onset obesity. We performed a North American-Australian-European collaborative meta-analysis of fourteen studies consisting of 5,530 cases (≥95th percentile of body mass index (BMI)) and 8,318 controls (<50th percentile of BMI) of European ancestry. Taking forward the eight novel signals yielding association with P < 5×10−6 in to nine independent datasets (n = 2,818 cases and 4,083 controls) we observed two loci that yielded a genome wide significant combined P-value, namely near OLFM4 on 13q14 (rs9568856; P=1.82×10−9; OR=1.22) and within HOXB5 on 17q21 (rs9299; P=3.54×10−9; OR=1.14). Both loci continued to show association when including two extreme childhood obesity cohorts (n = 2,214 cases and 2,674 controls). Finally, these two loci yielded directionally consistent associations in the GIANT meta-analysis of adult BMI1. PMID:22484627

  3. A meta-analysis of gemcitabine containing chemotherapy for locally advanced and metastatic pancreatic adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Ma Yue

    2011-03-01

    Full Text Available Abstract Background The objectives of the present study are to investigate the efficacy and safety profile of gemcitabine-based combinations in the treatment of locally advanced and metastatic pancreatic adenocarcinoma (LA/MPC. Methods We performed a computerized search using combinations of the following keywords: "chemotherapy", "gemcitabine", "trial", and "pancreatic cancer". Results Thirty-five trials were included in the present analysis, with a total of 9,979 patients accrued. The analysis showed that the gemcitabine-based combination therapy was associated with significantly better overall survival (OS (ORs, 1.15; p = 0.011, progression-free survival (PFS (ORs, 1.27; p Conclusions Gemcitabine in combination with capecitabine or oxaliplatin was associated with enhanced OS and ORR as compared with gemcitabine in monotherapy, which are likely to become the preferred standard first-line treatment of LA/MPC.

  4. Efficacy and safety of endocrine monotherapy as first-line treatment for hormone-sensitive advanced breast cancer: A network meta-analysis.

    Science.gov (United States)

    Zhang, Jingwen; Huang, Yanhong; Wang, Changyi; He, Yuanfang; Zheng, Shukai; Wu, Kusheng

    2017-08-01

    Endocrine therapy was recommended as the preferred first-line treatment for hormone receptor-positive (HR+, i.e., ER+ and/or PgR+), human epidermal growth factor receptor-2-negative (HER2-) postmenopausal advanced breast cancer (ABC), but which endocrine monotherapy is optimal lacks consensus. We aimed to identify the optimal endocrine monotherapy with a network meta-analysis. We performed a network meta-analysis for a comprehensive analysis of 6 first-line endocrine monotherapies (letrozole, anastrozole, exemestane, tamoxifen, fulvestrant 250 mg and 500 mg) for HR+ HER2- metastatic or locally advanced breast cancer in postmenopausal patients. The main outcomes were objective response rate (ORR), time to progression (TTP), and progression-free survival (PFS). Secondary outcomes were adverse events. We identified 27 articles of 8 randomized controlled trials including 3492 patients in the network meta-analysis. For ORR, the treatments ranked in descending order of effectiveness were letrozole > exemestane > anastrozole > fulvestrant 500 mg > tamoxifen > fulvestrant 250 mg. For TTP/PFS, the order was fulvestrant 500 mg > letrozole > anastrozole > exemestane > tamoxifen > fulvestrant 250 mg. We directly compared adverse events and found that tamoxifen produced more hot flash events than fulvestrant 250 mg. Fulvestrant 500 mg and letrozole might be optimal first-line endocrine monotherapy choices for HR+ HER2- ABC because of efficacious ORR and TTP/PFS, with a favorable tolerability profile. However, direct comparisons among endocrine monotherapies in the first-line therapy setting are still required to robustly demonstrate any differences among these endocrine agents. Clinical choices should also depend on the specific disease situation and duration of endocrine therapy.

  5. Meta-analysis identifies novel risk loci and yields systematic insights into the biology of male-pattern baldness.

    Science.gov (United States)

    Heilmann-Heimbach, Stefanie; Herold, Christine; Hochfeld, Lara M; Hillmer, Axel M; Nyholt, Dale R; Hecker, Julian; Javed, Asif; Chew, Elaine G Y; Pechlivanis, Sonali; Drichel, Dmitriy; Heng, Xiu Ting; Del Rosario, Ricardo C-H; Fier, Heide L; Paus, Ralf; Rueedi, Rico; Galesloot, Tessel E; Moebus, Susanne; Anhalt, Thomas; Prabhakar, Shyam; Li, Rui; Kanoni, Stavroula; Papanikolaou, George; Kutalik, Zoltán; Deloukas, Panos; Philpott, Michael P; Waeber, Gérard; Spector, Tim D; Vollenweider, Peter; Kiemeney, Lambertus A L M; Dedoussis, George; Richards, J Brent; Nothnagel, Michael; Martin, Nicholas G; Becker, Tim; Hinds, David A; Nöthen, Markus M

    2017-03-08

    Male-pattern baldness (MPB) is a common and highly heritable trait characterized by androgen-dependent, progressive hair loss from the scalp. Here, we carry out the largest GWAS meta-analysis of MPB to date, comprising 10,846 early-onset cases and 11,672 controls from eight independent cohorts. We identify 63 MPB-associated loci (Pbiological basis with numerous other human phenotypes and may deserve evaluation as an early prognostic marker, for example, for prostate cancer, sudden cardiac arrest and neurodegenerative disorders.

  6. Identifying Effective Components of Child Maltreatment Interventions: A Meta-analysis.

    Science.gov (United States)

    van der Put, Claudia E; Assink, Mark; Gubbels, Jeanne; Boekhout van Solinge, Noëlle F

    2018-06-01

    There is a lack of knowledge about specific components that make interventions effective in preventing or reducing child maltreatment. The aim of the present meta-analysis was to increase this knowledge by summarizing findings on effects of interventions for child maltreatment and by examining potential moderators of this effect, such as intervention components and study characteristics. Identifying effective components is essential for developing or improving child maltreatment interventions. A literature search yielded 121 independent studies (N = 39,044) examining the effects of interventions for preventing or reducing child maltreatment. From these studies, 352 effect sizes were extracted. The overall effect size was significant and small in magnitude for both preventive interventions (d = 0.26, p child maltreatment. For preventive interventions, larger effect sizes were found for short-term interventions (0-6 months), interventions focusing on increasing self-confidence of parents, and interventions delivered by professionals only. Further, effect sizes of preventive interventions increased as follow-up duration increased, which may indicate a sleeper effect of preventive interventions. For curative interventions, larger effect sizes were found for interventions focusing on improving parenting skills and interventions providing social and/or emotional support. Interventions can be effective in preventing or reducing child maltreatment. Theoretical and practical implications are discussed.

  7. Meta-Analyst: software for meta-analysis of binary, continuous and diagnostic data

    Directory of Open Access Journals (Sweden)

    Schmid Christopher H

    2009-12-01

    Full Text Available Abstract Background Meta-analysis is increasingly used as a key source of evidence synthesis to inform clinical practice. The theory and statistical foundations of meta-analysis continually evolve, providing solutions to many new and challenging problems. In practice, most meta-analyses are performed in general statistical packages or dedicated meta-analysis programs. Results Herein, we introduce Meta-Analyst, a novel, powerful, intuitive, and free meta-analysis program for the meta-analysis of a variety of problems. Meta-Analyst is implemented in C# atop of the Microsoft .NET framework, and features a graphical user interface. The software performs several meta-analysis and meta-regression models for binary and continuous outcomes, as well as analyses for diagnostic and prognostic test studies in the frequentist and Bayesian frameworks. Moreover, Meta-Analyst includes a flexible tool to edit and customize generated meta-analysis graphs (e.g., forest plots and provides output in many formats (images, Adobe PDF, Microsoft Word-ready RTF. The software architecture employed allows for rapid changes to be made to either the Graphical User Interface (GUI or to the analytic modules. We verified the numerical precision of Meta-Analyst by comparing its output with that from standard meta-analysis routines in Stata over a large database of 11,803 meta-analyses of binary outcome data, and 6,881 meta-analyses of continuous outcome data from the Cochrane Library of Systematic Reviews. Results from analyses of diagnostic and prognostic test studies have been verified in a limited number of meta-analyses versus MetaDisc and MetaTest. Bayesian statistical analyses use the OpenBUGS calculation engine (and are thus as accurate as the standalone OpenBUGS software. Conclusion We have developed and validated a new program for conducting meta-analyses that combines the advantages of existing software for this task.

  8. Gene expression meta-analysis identifies metastatic pathways and transcription factors in breast cancer

    DEFF Research Database (Denmark)

    Thomassen, Mads; Tan, Qihua; Kruse, Torben

    2008-01-01

    ABSTRACT: BACKGROUND: Metastasis is believed to progress in several steps including different pathways but the determination and understanding of these mechanisms is still fragmentary. Microarray analysis of gene expression patterns in breast tumors has been used to predict outcome in recent stud...

  9. Genome-wide association meta-analysis of 78,308 individuals identifies new loci and genes influencing human intelligence.

    Science.gov (United States)

    Sniekers, Suzanne; Stringer, Sven; Watanabe, Kyoko; Jansen, Philip R; Coleman, Jonathan R I; Krapohl, Eva; Taskesen, Erdogan; Hammerschlag, Anke R; Okbay, Aysu; Zabaneh, Delilah; Amin, Najaf; Breen, Gerome; Cesarini, David; Chabris, Christopher F; Iacono, William G; Ikram, M Arfan; Johannesson, Magnus; Koellinger, Philipp; Lee, James J; Magnusson, Patrik K E; McGue, Matt; Miller, Mike B; Ollier, William E R; Payton, Antony; Pendleton, Neil; Plomin, Robert; Rietveld, Cornelius A; Tiemeier, Henning; van Duijn, Cornelia M; Posthuma, Danielle

    2017-07-01

    Intelligence is associated with important economic and health-related life outcomes. Despite intelligence having substantial heritability (0.54) and a confirmed polygenic nature, initial genetic studies were mostly underpowered. Here we report a meta-analysis for intelligence of 78,308 individuals. We identify 336 associated SNPs (METAL P intelligence in childhood (0.45) and adulthood (0.80), we show substantial genetic correlation (r g = 0.89, LD score regression P = 5.4 × 10 -29 ). These findings provide new insight into the genetic architecture of intelligence.

  10. Addition of bevacizumab to first-line chemotherapy in advanced colorectal cancer: a systematic review and meta-analysis, with emphasis on chemotherapy subgroups

    Directory of Open Access Journals (Sweden)

    Macedo Ligia

    2012-03-01

    Full Text Available Abstract Background Bevacizumab has an important role in first-line treatment of metastatic colorectal cancer. However, clinical trials studying its effect have involved distinct chemotherapy regimens with divergent results. The aim of this meta-analysis is to gather current data and evaluate not only the efficacy of bevacizumab, but also the impact of divergent backbone regimens. Methods A wide search of randomized clinical trials using bevacizumab in first-line metastatic colorectal cancer was performed in Embase, MEDLINE, LILACS and Cochrane databases. Meeting presentations and abstracts were also investigated. The resulting data were examined and included in the meta-analysis according to the type of regimen. Results Six trials, totaling 3060 patients, were analyzed. There was an advantage to using bevacizumab for overall survival (OS and progression-free survival (PFS (HR = 0.84; CI: 0.77-0.91; P Conclusions Bevacizumab has efficacy in first-line treatment of advanced colorectal cancer, but the current data are insufficient to support efficacy in all regimens, especially infusional fluorouracil regimens, like FOLFIRI and FOLFOX.

  11. Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution

    NARCIS (Netherlands)

    I.M. Heid (Iris); A.U. Jackson (Anne); J.C. Randall (Joshua); T.W. Winkler (Thomas); L. Qi (Lu); V. Ssteinthorsdottir (Valgerdur); G. Tthorleifsson (Ggudmar); M.C. Zillikens (Carola); E.K. Sspeliotes (Eelizabeth); R. Mägi (Reedik); T. Workalemahu (Tsegaselassie); C.C. White (Charles); N. Bouatia-Naji (Nabila); T.B. Harris (Tamara); S.I. Berndt (Sonja); E. Ingelsson (Erik); C.J. Willer (Cristen); J. Luan; S. Vedantam (Sailaja); T. Eesko (Tõnu); T.O. Kilpeläinen (Tuomas); Z. Kutalik (Zoltán); S. Li (Shengxu); K.L. Monda (Keri); A.L. Dixon (Anna); C. Holmes (Christopher); R.C. Kaplan (Robert); L. Liang (Liming); J. Min (Josine); M.F. Moffatt (Miriam); C. Molony (Cliona); G. Nicholson (Ggeorge); E.E. Sschadt (Eeric); K.T. Zondervan (Krina); M.F. Feitosa (Mary Furlan); T. Ferreira (Teresa); H.L. Allen; R.J. Weyant (Robert); E. Wheeler (Eleanor); A.R. Wood (Andrew); K. Eestrada (Karol); M.E. Goddard (Michael); G. Lettre (Guillaume); M. Mangino (Massimo); D.R. Nyholt (Dale); S. Purcell (Shaun); A.V. Ssmith; P.M. Visscher (Peter); J. Yang (Joanna); S.A. McCcarroll (Ssteven); J. Nemesh (James); B.F. Voight (Benjamin); D. Absher (Devin); N. Amin (Najaf); T. Aspelund (Thor); L. Coin (Lachlan); N.L. Glazer (Nicole); C. Hayward (Caroline); N. Heard-Ccosta (Nancy); J.J. Hottenga (Jouke Jan); A. Johansson (Åsa); T. Johnson (Toby); M. Kaakinen (Marika); K. Kapur (Karen); S. Ketkar (Shamika); J.W. Knowles (Joshua); P. Kraft (Peter); A. Kraja (Aldi); C. Lamina (Claudia); M.F. Leitzmann (Michael); B. McKknight (Barbara); A.D. Morris (Andrew); K. Oong (Ken); J.R.B. Perry (John); M.J. Peters (Marjolein); O. Polasek (Ozren); I. Prokopenko (Inga); N.W. Rayner (Nigel William); S. Ripatti (Samuli); F. Rivadeneira Ramirez (Fernando); N.R. Robertson (Neil); S. Sanna (Serena); U. Sovio (Ulla); I. Surakka (Ida); A. Teumer (Alexander); S. van Wingerden (Sophie); V. Vitart (Veronique); J.H. Zhao (Jing Hua); C. Cavalcanti-Proença (Christine); P.S. Chines (Peter); E. Fisher (Eeva); J.R. Kulzer (Jennifer); C. Lecoeur (Cécile); N. Narisu (Narisu); C. Sandholt (Camilla); L.J. Scott (Laura); K. Silander (Kaisa); K. Stark (Klaus); M.L. Tammesoo; T.M. Teslovich (Tanya); N.J. Timpson (Nicholas); R.P. Welch (Ryan); D.I. Chasman (Daniel); M.N. Cooper (Matthew); J.O. Jansson; J. Kettunen (Johannes); R. Wlawrence (Robert); N. Pellikka (Niina); M. Perola (Markus); L. Vandenput (Liesbeth); H. Alavere (Helene); P. Almgren (Peter); L.D. Atwood (Larry); A.J. Bennett (Amanda); R. Biffar (Reiner); L.L. Bonnycastle (Lori); S.R. Bornstein (Stefan); T.A. Buchanan (Thomas); H. Campbell (Harry); I.N.M. Day (Ian); M. Dei (Mariano); M. Dörr (Marcus); P. Eelliott (Paul); M.R. Eerdos (Micheal); J.G. Eeriksson (Johan); N.B. Freimer (Nelson); M. Fu (Mao); S. Gaget (Stefan); E.J.C. de Geus (Eco); A.P. Gjesing (Anette); H. Grallert (Harald); J. Gräßler (Jürgen); C.J. Groves (Christopher); C. Guiducci (Candace); A.L. Hartikainen; N. Hassanali (Neelam); A.S. Havulinna (Aki); K.H. Herzig; A.A. Hicks (Andrew); J. Hui (Jennie); W. Igl (Wilmar); P. Jousilahti (Pekka); A. Jula (Antti); E. Kajantie (Eero); L. Kinnunen (Leena); I. Kolcic (Ivana); S. Koskinen (Seppo); P. Kovacs (Peter); H.K. Kroemer (Heyo); V. Krzelj (Vjekoslav); J. Kuusisto (Johanna); K. Kvaløy (Kirsti); J. Laitinen (Jaana); O. Lantieri (Olivier); G.M. Lathrop (Mark); M.L. Lokki; R.N. Luben (Robert); B. Ludwig (Barbara); W.L. McArdle (Wendy); A. McCcarthy (Anne); M.A. Morken (Mario); M. Nelis (Mari); M.J. Neville (Matthew); G. Paré (Guillaume); A.N. Parker (Alex); J. Peden (John); I. Pichler (Irene); K.H. Pietilainen (Kirsi Hannele); C.P. Platou (Carl); A. Pouta (Anneli); M. Ridderstråle (Martin); N.J. Samani (Nilesh); J. Saramies (Jouko); J. Sinisalo (Juha); J.H. Smit (Jan); R.J. Strawbridge (Rona); H.M. Stringham (Heather); A.J. Swift (Amy); M. Teder-Llaving (Maris); B. Thomson (Brian); G. Usala; J.B.J. van Meurs (Joyce); G.J. van Ommen (Gert); V. Vatin (Vincent); C.B. Volpato; H. Wallaschofski (Henri); G.B. Walters (Bragi); E. Widen (Elisabeth); S.H. Wild (Sarah); G.A.H.M. Willemsen (Gonneke); D.R. Witte (Deniel); L. Zgaga (Lina); P. Zitting (Paavo); J.P. Beilby (John); A. James (Alan); M. Kähönen (Mika); T. Lehtimäki (Terho); M.S. Nieminen (Markku); C. Ohlsson (Claes); C. Palmer (Cameron); O. Raitakari (Olli); P.M. Ridker (Paul); M. Stumvoll (Michael); A. Tönjes (Anke); J. Viikari (Jorma); B. Balkau (Beverley); Y. Ben-Shlomo; R.N. Bergman (Richard); H. Boeing (Heiner); A.V. Smith (Albert Vernon); S. Eebrahim (Shah); P. Froguel (Philippe); T. Hansen (Torben); C. Hengstenberg (Christian); K. Hveem (Kristian); B. Isomaa (Bo); T. Jørgensen (Torben); F. Karpe (Fredrik); K-T. Khaw (Kay-Tee); M. Laakso (Markku); D.A. Lawlor (Debbie); M. Marre (Michel); T. Meitinger (Thomas); A. Metspalu (Andres); K. Midthjell (Kristian); O. Pedersen (Oluf); V. Salomaa (Veikko); P.E.H. Schwarz (Peter); T. Tuomi (Tiinamaija); J. Tuomilehto (Jaakko); T.T. Valle (Timo); N.J. Wareham (Nick); A.M. Arnold (Alice); J.S. Beckmann (Jacques); S.M. Bergmann (Sven); E.A. Boerwinkle (Eric); D.I. Boomsma (Dorret); M. Caulfield (Mark); F.S. Collins (Francis); G. Eeiriksdottir (Gudny); V. Gudnason (Vilmundur); U. Gyllensten (Ulf); A. Hamsten (Anders); A.T. Hattersley (Andrew); A. Hofman (Albert); F.B. Hu (Frank); T. Illig (Thomas); C. Iribarren (Carlos); M.R. Järvelin; W.H.L. Kao (Wen); J. Kaprio (Jaakko); L.J. Launer (Lenore); P. Munroe (Patricia); B.A. Oostra (Ben); B.W.J.H. Penninx (Brenda); P.P. Pramstaller (Peter Paul); B.M. Psaty (Bruce); T. Quertermous (Thomas); A. Rissanen (Aila); I. Rudan (Igor); A.R. Shuldiner (Alan); N. Soranzo (Nicole); T.D. Spector (Timothy); A.C. Syvanen; M. Uda (Manuela); A.G. Uitterlinden (André); H. Völzke (Henry); P. Vollenweider (Peter); J.F. Wilson (James); J.C.M. Witteman (Jacqueline); A.F. Wright (Alan); G.R. Abecasis (Gonçalo); M. Boehnke (Michael); I.B. Borecki (Ingrid); P. Deloukas (Panagiotis); T.M. Frayling (Timothy); L. Groop (Leif); T. Haritunians (Talin); D.J. Hunter (David); K.E. North (Kari); J.R. O'Cconnell (Jeffrey); L. Peltonen (Leena Johanna); D. Schlessinger; D.P. Strachan (David); J.N. Hirschhorn (Joel); T.L. Assimes (Themistocles); H.E. Wichmann (Heinz Erich); U. Thorsteinsdottir (Unnur); C.M. van Duijn (Cornelia); K. Stefansson (Kari); L.A. Cupples (Adrienne); R.J.F. Loos (Ruth); I.E. Barroso (Inês); C.S. Fox (Caroline); K.L. Mohlke (Karen); C.M. Lindgren (Cecilia); R.M. Watanabe (Richard); M.N. Weedon (Michael)

    2010-01-01

    textabstractWaist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association

  12. Systematic review with meta-analysis

    DEFF Research Database (Denmark)

    Roda, G; Narula, N; Pinotti, R

    2017-01-01

    and meta-analysis of epidemiological studies reporting on extension of ulcerative colitis to determine frequency of disease extension in patients with limited ulcerative colitis at diagnosis. METHODS: We performed a systematic literature search to identify studies on disease extension of ulcerative colitis...... (UC) and predictors of disease progression. RESULTS: Overall, 41 studies were eligible for systematic review but only 30 for meta-analysis. The overall pooled frequency of UC extension was 22.8% with colonic extension being 17.8% at 5 years and 31% at 10 years. Extension was 17.8% (95% CI 11...... in patients from North America (37.8%) than from Europe (19.6%) (Pmeta-analysis, approximately one quarter of patients with limited UC extend over time with most extension occurring during the first 10 years. Rate of extension depends on age at diagnosis and geographic origin...

  13. Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes

    DEFF Research Database (Denmark)

    Zeggini, Eleftheria; Scott, Laura J; Saxena, Richa

    2008-01-01

    analyses had limited power to identify variants with modest effects, we carried out meta-analysis of three T2D GWA scans comprising 10,128 individuals of European descent and approximately 2.2 million SNPs (directly genotyped and imputed), followed by replication testing in an independent sample......Genome-wide association (GWA) studies have identified multiple loci at which common variants modestly but reproducibly influence risk of type 2 diabetes (T2D). Established associations to common and rare variants explain only a small proportion of the heritability of T2D. As previously published...

  14. MetaPhinder-Identifying Bacteriophage Sequences in Metagenomic Data Sets

    DEFF Research Database (Denmark)

    Jurtz, Vanessa Isabell; Villarroel, Julia; Lund, Ole

    2016-01-01

    genome structure of many bacteriophages. The method is demonstrated to outperform both BLAST methods based on single hits and methods based on k-mer comparisons. MetaPhinder is available as a web service at the Center for Genomic Epidemiology https://cge.cbs.dtu.dk/services/MetaPhinder/, while the source...... and understand them. Here we present MetaPhinder, a method to identify assembled genomic fragments (i.e. contigs) of phage origin in metage-nomic data sets. The method is based on a comparison to a database of whole genome bacteriophage sequences, integrating hits to multiple genomes to accomodate for the mosaic...... code can be downloaded from https://bitbucket.org/genomicepidemiology/metaphinder or https://github.com/vanessajurtz/MetaPhinder....

  15. Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption

    NARCIS (Netherlands)

    M. Cornelis (Marilyn); E.M. Byrne; T. Esko (Tõnu); M.A. Nalls (Michael); A. Ganna (Andrea); N.P. Paynter (Nina); K.L. Monda (Keri); N. Amin (Najaf); K. Fischer (Krista); F. Renström (Frida); J.S. Ngwa; V. Huikari (Ville); A. Cavadino (Alana); I.M. Nolte (Ilja M.); A. Teumer (Alexander); K. Yu; P. Marques-Vidal; R. Rawal; A. Manichaikul (Ani); M.K. Wojczynski (Mary ); J.M. Vink; J.H. Zhao (Jing Hua); G. Burlutsky (George); J. Lahti (Jari); V. Mikkilä (Vera); R.N. Lemaitre (Rozenn ); J. Eriksson; S. Musani (Solomon); T. Tanaka; F. Geller (Frank); J. Luan; J. Hui; R. Mägi (Reedik); M. Dimitriou (Maria); M. Garcia (Melissa); W.-K. Ho; M.J. Wright (Margaret); L.M. Rose (Lynda M.); P.K.E. Magnusson (Patrik K. E.); N.L. Pedersen (Nancy L.); D.J. Couper (David); B.A. Oostra (Ben); A. Hofman (Albert); M.A. Ikram (Arfan); H.W. Tiemeier (Henning); A.G. Uitterlinden (André); F.J.A. van Rooij (Frank); I. Barroso; I. Johansson (Ingegerd); L. Xue (Luting); M. Kaakinen (Marika); L. Milani (Lili); C. Power (Christine); H. Snieder (Harold); R.P. Stolk; S.E. Baumeister (Sebastian); R. Biffar; F. Gu; F. Bastardot (Francois); Z. Kutalik; D.R. Jacobs (David); N.G. Forouhi (Nita G.); E. Mihailov (Evelin); L. Lind (Lars); C. Lindgren; K. Michaëlsson; A.P. Morris (Andrew); M.K. Jensen (Majken K.); K.T. Khaw; R.N. Luben (Robert); J.J. Wang; S. Männistö (Satu); M.-M. Perälä; M. Kähönen (Mika); T. Lehtimäki (Terho); J. Viikari (Jorma); D. Mozaffarian; K. Mukamal (Kenneth); B.M. Psaty (Bruce); A. Döring; A.C. Heath (Andrew C.); G.W. Montgomery (Grant W.); N. Dahmen (N.); T. Carithers; K.L. Tucker; L. Ferrucci (Luigi); H.A. Boyd; M. Melbye (Mads); J.L. Treur; D. Mellström (Dan); J.J. Hottenga (Jouke Jan); I. Prokopenko (Inga); A. Tönjes (Anke); P. Deloukas (Panagiotis); S. Kanoni (Stavroula); M. Lorentzon (Mattias); D.K. Houston; Y. Liu; J. Danesh (John); A. Rasheed; M.A. Mason; A.B. Zonderman; L. Franke (Lude); B.S. Kristal; J. Karjalainen (Juha); D.R. Reed; H.-J. Westra; M.K. Evans; D. Saleheen; T.B. Harris (Tamara); G.V. Dedoussis (George V.); G.C. Curhan (Gary); M. Stumvoll (Michael); J. Beilby (John); L.R. Pasquale; B. Feenstra; S. Bandinelli; J.M. Ordovas; A.T. Chan; U. Peters (Ulrike); C. Ohlsson (Claes); C. Gieger (Christian); N.G. Martin (Nicholas); M. Waldenberger (Melanie); D.S. Siscovick (David); O. Raitakari (Olli); J.G. Eriksson (Johan G.); P. Mitchell (Paul); D. Hunter (David); P. Kraft (Peter); E.B. Rimm (Eric B.); D.I. Boomsma (Dorret); I.B. Borecki (Ingrid); R.J.F. Loos (Ruth); N.J. Wareham (Nick); P.K. Vollenweider (Peter K.); N. Caporaso; H.J. Grabe (Hans Jörgen); M.L. Neuhouser (Marian L.); B.H.R. Wolffenbuttel (Bruce H. R.); F.B. Hu (Frank); E. Hypponen (Elina); M.-R. Jarvelin (Marjo-Riitta); L.A. Cupples (Adrienne); P.W. Franks; P.M. Ridker (Paul); C.M. van Duijn (Cornelia); G. Heiss (Gerardo); A. Metspalu (Andres); K.E. North (Kari); E. Ingelsson (Erik); J.A. Nettleton; R.M. van Dam (Rob); D.I. Chasman (Daniel)

    2015-01-01

    textabstractCoffee, a major dietary source of caffeine, is among the most widely consumed beverages in the world and has received considerable attention regarding health risks and benefits. We conducted a genome-wide (GW) meta-analysis of predominately regular-type coffee consumption (cups per day)

  16. Longitudinal Meta-analysis

    NARCIS (Netherlands)

    Hox, J.J.; Maas, C.J.M.; Lensvelt-Mulders, G.J.L.M.

    2004-01-01

    The goal of meta-analysis is to integrate the research results of a number of studies on a specific topic. Characteristic for meta-analysis is that in general only the summary statistics of the studies are used and not the original data. When the published research results to be integrated

  17. Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption

    NARCIS (Netherlands)

    Cornelis, M. C.; Byrne, E. M.; Esko, T.; Nalls, M. A.; Ganna, A.; Paynter, N.; Monda, K. L.; Amin, N.; Fischer, K.; Renstrom, F.; Ngwa, J. S.; Huikari, V.; Cavadino, A.; Nolte, I. M.; Teumer, A.; Yu, K.; Marques-Vidal, P.; Rawal, R.; Manichaikul, A.; Wojczynski, M. K.; Vink, J. M.; Zhao, J. H.; Burlutsky, G.; Lahti, J.; Mikkila, V.; Lemaitre, R. N.; Eriksson, J.; Musani, S. K.; Tanaka, T.; Geller, F.; Luan, J.; Hui, J.; Maegi, R.; Dimitriou, M.; Garcia, M. E.; Ho, W-K; Wright, M. J.; Rose, L. M.; Magnusson, P. K. E.; Pedersen, N. L.; Couper, D.; Oostra, B. A.; Hofman, A.; Ikram, M. A.; Tiemeier, H. W.; Uitterlinden, A. G.; van Rooij, F. J. A.; Barroso, I.; Johansson, I.; Xue, L.; Kaakinen, M.; Milani, L.; Power, C.; Snieder, H.; Stolk, R. P.; Baumeister, S. E.; Biffar, R.; Gu, F.; Bastardot, F.; Kutalik, Z.; Jacobs, D. R.; Forouhi, N. G.; Mihailov, E.; Lind, L.; Lindgren, C.; Michaelsson, K.; Morris, A.; Jensen, M.; Khaw, K-T; Luben, R. N.; Wang, J. J.; Mannisto, S.; Perala, M-M; Kahonen, M.; Lehtimaki, T.; Viikari, J.; Mozaffarian, D.; Mukamal, K.; Psaty, B. M.; Doering, A.; Heath, A. C.; Montgomery, G. W.; Dahmen, N.; Carithers, T.; Tucker, K. L.; Ferrucci, L.; Boyd, H. A.; Melbye, M.; Treur, J. L.; Mellstrom, D.; Hottenga, J. J.; Prokopenko, I.; Toenjes, A.; Deloukas, P.; Kanoni, S.; Lorentzon, M.; Houston, D. K.; Liu, Y.; Danesh, J.; Rasheed, A.; Mason, M. A.; Zonderman, A. B.; Franke, L.; Kristal, B. S.; Karjalainen, J.; Reed, D. R.; Westra, H-J; Evans, M. K.; Saleheen, D.; Harris, T. B.; Dedoussis, G.; Curhan, G.; Stumvoll, M.; Beilby, J.; Pasquale, L. R.; Feenstra, B.; Bandinelli, S.; Ordovas, J. M.; Chan, A. T.; Peters, U.; Ohlsson, C.; Gieger, C.; Martin, N. G.; Waldenberger, M.; Siscovick, D. S.; Raitakari, O.; Eriksson, J. G.; Mitchell, P.; Hunter, D. J.; Kraft, P.; Rimm, E. B.; Boomsma, D. I.; Borecki, I. B.; Loos, R. J. F.; Wareham, N. J.; Vollenweider, P.; Caporaso, N.; Grabe, H. J.; Neuhouser, M. L.; Wolffenbuttel, B. H. R.; Hu, F. B.; Hyppoenen, E.; Jarvelin, M-R; Cupples, L. A.; Franks, P. W.; Ridker, P. M.; van Duijn, C. M.; Heiss, G.; Metspalu, A.; North, K. E.; Ingelsson, E.; Nettleton, J. A.; van Dam, R. M.; Chasman, D. I.

    Coffee, a major dietary source of caffeine, is among the most widely consumed beverages in the world and has received considerable attention regarding health risks and benefits. We conducted a genome-wide (GW) meta-analysis of predominately regular-type coffee consumption (cups per day) among up to

  18. Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption

    NARCIS (Netherlands)

    Cornelis, M. C.; Byrne, E. M.; Esko, T.; Nalls, M. A.; Ganna, A.; Paynter, N.; Monda, K. L.; Amin, N.; Fischer, K.; Renstrom, F.; Ngwa, J. S.; Huikari, V.; Cavadino, A.; Nolte, I. M.; Teumer, A.; Yu, K.; Marques-Vidal, P.; Rawal, R.; Manichaikul, A.; Wojczynski, M. K.; Vink, J. M.; Zhao, J. H.; Burlutsky, G.; Lahti, J.; Mikkilä, V.; Lemaitre, R. N.; Eriksson, J.; Musani, S. K.; Tanaka, T.; Geller, F.; Luan, J.; Hui, J.; Mägi, R.; Dimitriou, M.; Garcia, M. E.; Ho, W.-K.; Wright, M. J.; Rose, L. M.; Magnusson, P. K. E.; Pedersen, N. L.; Couper, D.; Oostra, B. A.; Hofman, A.; Ikram, M. A.; Tiemeier, H. W.; Uitterlinden, A. G.; van Rooij, F. J. A.; Barroso, I.; Johansson, I.; Xue, L.; Kaakinen, M.; Milani, L.; Power, C.; Snieder, H.; Stolk, R. P.; Baumeister, S. E.; Biffar, R.; Gu, F.; Bastardot, F.; Kutalik, Z.; Jacobs, D. R.; Forouhi, N. G.; Mihailov, E.; Lind, L.; Lindgren, C.; Michaëlsson, K.; Morris, A.; Jensen, M.; Khaw, K.-T.; Luben, R. N.; Wang, J. J.; Männistö, S.; Perälä, M.-M.; Kähönen, M.; Lehtimäki, T.; Viikari, J.; Mozaffarian, D.; Mukamal, K.; Psaty, B. M.; Döring, A.; Heath, A. C.; Montgomery, G. W.; Dahmen, N.; Carithers, T.; Tucker, K. L.; Ferrucci, L.; Boyd, H. A.; Melbye, M.; Treur, J. L.; Mellström, D.; Hottenga, J. J.; Prokopenko, I.; Tönjes, A.; Deloukas, P.; Kanoni, S.; Lorentzon, M.; Houston, D. K.; Liu, Y.; Danesh, J.; Rasheed, A.; Mason, M. A.; Zonderman, A. B.; Franke, L.; Kristal, B. S.; Karjalainen, J.; Reed, D. R.; Westra, H.-J.; Evans, M. K.; Saleheen, D.; Harris, T. B.; Dedoussis, G.; Curhan, G.; Stumvoll, M.; Beilby, J.; Pasquale, L. R.; Feenstra, B.; Bandinelli, S.; Ordovas, J. M.; Chan, A. T.; Peters, U.; Ohlsson, C.; Gieger, C.; Martin, N. G.; Waldenberger, M.; Siscovick, D. S.; Raitakari, O.; Eriksson, J. G.; Mitchell, P.; Hunter, D. J.; Kraft, P.; Rimm, E. B.; Boomsma, D. I.; Borecki, I. B.; Loos, R. J. F.; Wareham, N. J.; Vollenweider, P.; Caporaso, N.; Grabe, H. J.; Neuhouser, M. L.; Wolffenbuttel, B. H. R.; Hu, F. B.; Hyppönen, E.; Järvelin, M.-R.; Cupples, L. A.; Franks, P. W.; Ridker, P. M.; van Duijn, C. M.; Heiss, G.; Metspalu, A.; North, K. E.; Ingelsson, E.; Nettleton, J. A.; van Dam, R. M.; Chasman, D. I.; Nalls, Michael A.; Plagnol, Vincent; Hernandez, Dena G.; Sharma, Manu; Sheerin, Una-Marie; Saad, Mohamad; Simón-Sánchez, Javier; Schulte, Claudia; Lesage, Suzanne; Sveinbjörnsdóttir, Sigurlaug; Arepalli, Sampath; Barker, Roger; Ben-Shlomo, Yoav; Berendse, Henk W.; Berg, Daniela; Bhatia, Kailash; de Bie, Rob M. A.; Biffi, Alessandro; Bloem, Bas; Bochdanovits, Zoltan; Bonin, Michael; Bras, M.; Brockmann, Kathrin; Brooks, Janet; Burn, David J.; Charlesworth, Gavin; Chen, Honglei; Chinnery, Patrick F.; Chong, Sean; Clarke, Carl E.; Cookson, Mark R.; Cooper, J. Mark; Corvol, Jean Christophe; Counsell, Carl; Damier, Philippe; Dartigues, Jean-François; Deloukas, Panos; Deuschl, Günther; Dexter, David T.; van Dijk, Karin D.; Dillman, Allissa; Durif, Frank; Dürr, Alexandra; Edkins, Sarah; Evans, Jonathan R.; Foltynie, Thomas; Dong, Jing; Gardner, Michelle; Gibbs, J. Raphael; Goate, Alison; Gray, Emma; Guerreiro, Rita; Harris, Clare; van Hilten, Jacobus J.; Hofman, Albert; Hollenbeck, Albert; Holton, Janice; Hu, Michele; Huang, Xuemei; Hershey, Milton S.; Wurster, Isabel; Mätzler, Walter; Hudson, Gavin; Hunt, Sarah E.; Huttenlocher, Johanna; Illig, Thomas; München, Helmholtz Zentrum; Jónsson, Pálmi V.; Lambert, Jean-Charles; Langford, Cordelia; Lees, Andrew; Lichtner, Peter; Limousin, Patricia; Lopez, Grisel; Lorenz, Delia; McNeill, Alisdair; Moorby, Catriona; Moore, Matthew; Morris, Huw R.; Morrison, Karen E.; O' Sullivan, Sean S.; Pearson, Justin; Perlmutter, Joel S.; Pétursson, Hjörvar; Pollak, Pierre; Potter, Simon; Ravina, Bernard; Revesz, Tamas; Riess, Olaf; Rivadeneira, Fernando; Rizzu, Patrizia; Ryten, Mina; Sawcer, Stephen; Schapira, Anthony; Scheffer, Hans; Shaw, Karen; Sidransky, Ellen; Smith, Colin; Spencer, Chris C. A.; Stefánsson, Hreinn; Bettella, Francesco; Stockton, Joanna D.; Strange, Amy; Talbot, Kevin; Tanner, M.; Tashakkori-Ghanbaria, Avazeh; Tison, François; Trabzuni, Daniah; Traynor, Bryan J.; Uitterlinden, André G.; Velseboer, Daan; Vidailhet, Marie; Walker, Robert; van de Warrenburg, Bart; Wickremaratchi, Mirdhu; Williams, Nigel; Williams-Gray, Caroline H.; Winder-Rhodes, Sophie; Stefánsson, Kári; Martinez, Maria; Sabatier, Paul; Wood, Nicholas W.; Hardy, John; Heutink, Peter; Brice, Alexis; Gasser, Thomas; Singleton, Andrew B.; Singleton, Andrew; Cookson, Mark; Hernandez, Dena; Nalls, Michael; Zonderman, Alan; Ferrucci, Luigi; Johnson, Robert; Longo, Dan; O'Brien, Richard; Traynor, Bryan; Troncoso, Juan; van der Brug, Marcel; Zielke, Ronald; Weale, Michael; Ramasamy, Adaikalavan; Box, P. O.

    2015-01-01

    Coffee, a major dietary source of caffeine, is among the most widely consumed beverages in the world and has received considerable attention regarding health risks and benefits. We conducted a genome-wide (GW) meta-analysis of predominately regular-type coffee consumption (cups per day) among up to

  19. MetaGenyo: a web tool for meta-analysis of genetic association studies.

    Science.gov (United States)

    Martorell-Marugan, Jordi; Toro-Dominguez, Daniel; Alarcon-Riquelme, Marta E; Carmona-Saez, Pedro

    2017-12-16

    Genetic association studies (GAS) aims to evaluate the association between genetic variants and phenotypes. In the last few years, the number of this type of study has increased exponentially, but the results are not always reproducible due to experimental designs, low sample sizes and other methodological errors. In this field, meta-analysis techniques are becoming very popular tools to combine results across studies to increase statistical power and to resolve discrepancies in genetic association studies. A meta-analysis summarizes research findings, increases statistical power and enables the identification of genuine associations between genotypes and phenotypes. Meta-analysis techniques are increasingly used in GAS, but it is also increasing the amount of published meta-analysis containing different errors. Although there are several software packages that implement meta-analysis, none of them are specifically designed for genetic association studies and in most cases their use requires advanced programming or scripting expertise. We have developed MetaGenyo, a web tool for meta-analysis in GAS. MetaGenyo implements a complete and comprehensive workflow that can be executed in an easy-to-use environment without programming knowledge. MetaGenyo has been developed to guide users through the main steps of a GAS meta-analysis, covering Hardy-Weinberg test, statistical association for different genetic models, analysis of heterogeneity, testing for publication bias, subgroup analysis and robustness testing of the results. MetaGenyo is a useful tool to conduct comprehensive genetic association meta-analysis. The application is freely available at http://bioinfo.genyo.es/metagenyo/ .

  20. Large-Scale Gene-Centric Meta-Analysis across 39 Studies Identifies Type 2 Diabetes Loci

    NARCIS (Netherlands)

    Saxena, Richa; Elbers, Clara C.; Guo, Yiran; Peter, Inga; Gaunt, Tom R.; Mega, Jessica L.; Lanktree, Matthew B.; Tare, Archana; Almoguera Castillo, Berta; Li, Yun R.; Johnson, Toby; Bruinenberg, Marcel; Gilbert-Diamond, Diane; Rajagopalan, Ramakrishnan; Voight, Benjamin F.; Balasubramanyam, Ashok; Barnard, John; Bauer, Florianne; Baumert, Jens; Bhangale, Tushar; Boehm, Bernhard O.; Braund, Peter S.; Burton, Paul R.; Chandrupatla, Hareesh R.; Clarke, Robert; Cooper-DeHoff, Rhonda M.; Crook, Errol D.; Davey-Smith, George; Day, Ian N.; de Boer, Anthonius; de Groot, Mark C. H.; Drenos, Fotios; Ferguson, Jane; Fox, Caroline S.; Furlong, Clement E.; Gibson, Quince; Gieger, Christian; Gilhuijs-Pederson, Lisa A.; Glessner, Joseph T.; Goel, Anuj; Gong, Yan; Grant, Struan F. A.; Kumari, Meena; van der Harst, Pim; van Vliet-Ostaptchouk, Jana V.; Verweij, Niek; Wolffenbuttel, Bruce H. R.; Hofker, Marten H.; Asselbergs, Folkert W.; Wijmenga, Cisca

    2012-01-01

    To identify genetic factors contributing to type 2 diabetes (T2D), we performed large-scale meta-analyses by using a custom similar to 50,000 SNP genotyping array (the ITMAT-Broad-CARe array) with similar to 2000 candidate genes in 39 multiethnic population-based studies, case-control studies, and

  1. Genome-wide association scan meta-analysis identifies three Loci influencing adiposity and fat distribution.

    Directory of Open Access Journals (Sweden)

    Cecilia M Lindgren

    2009-06-01

    Full Text Available To identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580 informative for adult waist circumference (WC and waist-hip ratio (WHR. We selected 26 SNPs for follow-up, for which the evidence of association with measures of central adiposity (WC and/or WHR was strong and disproportionate to that for overall adiposity or height. Follow-up studies in a maximum of 70,689 individuals identified two loci strongly associated with measures of central adiposity; these map near TFAP2B (WC, P = 1.9x10(-11 and MSRA (WC, P = 8.9x10(-9. A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6x10(-8. The variants near TFAP2B appear to influence central adiposity through an effect on overall obesity/fat-mass, whereas LYPLAL1 displays a strong female-only association with fat distribution. By focusing on anthropometric measures of central obesity and fat distribution, we have identified three loci implicated in the regulation of human adiposity.

  2. Association Between Chromosome 9p21 Variants and the Ankle-Brachial Index Identified by a Meta-Analysis of 21 Genome-Wide Association Studies

    DEFF Research Database (Denmark)

    Murabito, Joanne M; White, Charles C; Kavousi, Maryam

    2012-01-01

    BACKGROUND: -Genetic determinants of peripheral arterial disease (PAD) remain largely unknown. To identify genetic variants associated with the ankle-brachial index (ABI), a noninvasive measure of PAD, we conducted a meta-analysis of genome-wide association study data from 21 population-based coh...

  3. Association Between Chromosome 9p21 Variants and the Ankle-Brachial Index Identified by a Meta-Analysis of 21 Genome-Wide Association Studies

    NARCIS (Netherlands)

    Murabito, Joanne M.; White, Charles C.; Kavousi, Maryam; Sun, Yan V.; Feitosa, Mary F.; Nambi, Vijay; Lamina, Claudia; Schillert, Arne; Coassin, Stefan; Bis, Joshua C.; Broer, Linda; Crawford, Dana C.; Franceschini, Nora; Frikke-Schmidt, Ruth; Haun, Margot; Holewijn, Suzanne; Huffman, Jennifer E.; Hwang, Shih-Jen; Kiechl, Stefan; Kollerits, Barbara; Montasser, May E.; Nolte, Ilja M.; Rudock, Megan E.; Senft, Andrea; Teumer, Alexander; van der Harst, Pim; Vitart, Veronique; Waite, Lindsay L.; Wood, Andrew R.; Wassel, Christina L.; Absher, Devin M.; Allison, Matthew A.; Amin, Najaf; Arnold, Alice; Asselbergs, Folkert W.; Aulchenko, Yurii; Bandinelli, Stefania; Barbalic, Maja; Boban, Mladen; Brown-Gentry, Kristin; Couper, David J.; Criqui, Michael H.; Dehghan, Abbas; den Heijer, Martin; Dieplinger, Benjamin; Ding, Jingzhong; Doerr, Marcus; Espinola-Klein, Christine; Felix, Stephan B.; Ferrucci, Luigi; Folsom, Aaron R.; Fraedrich, Gustav; Gibson, Quince; Goodloe, Robert; Gunjaca, Grgo; Haltmayer, Meinhard; Heiss, Gerardo; Hofman, Albert; Kieback, Arne; Kiemeney, Lambertus A.; Kolcic, Ivana; Kullo, Iftikhar J.; Kritchevsky, Stephen B.; Lackner, Karl J.; Li, Xiaohui; Lieb, Wolfgang; Lohman, Kurt; Meisinger, Christa; Melzer, David; Mohler, Emile R.; Mudnic, Ivana; Mueller, Thomas; Navis, Gerjan; Oberhollenzer, Friedrich; Olin, Jeffrey W.; O'Connell, Jeff; O'Donnell, Christopher J.; Palmas, Walter; Penninx, Brenda W.; Petersmann, Astrid; Polasek, Ozren; Psaty, Bruce M.; Rantner, Barbara; Rice, Ken; Rivadeneira, Fernando; Rotter, Jerome I.; Seldenrijk, Adrie; Stadler, Marietta; Summerer, Monika; Tanaka, Toshiko; Tybjaerg-Hansen, Anne; Uitterlinden, Andre G.; van Gilst, Wiek H.; Vermeulen, Sita H.; Wild, Sarah H.; Wild, Philipp S.; Willeit, Johann; Zeller, Tanja; Zemunik, Tatijana; Zgaga, Lina; Assimes, Themistocles L.; Blankenberg, Stefan; Campbell, Harry; Boerwinkle, Eric; Cooke, John P.; de Graaf, Jacqueline; Herrington, David; Kardia, Sharon L. R.; Mitchell, Braxton D.; Murray, Anna; Muenzel, Thomas; Newman, Anne B.; Oostra, Ben A.; Rudan, Igor; Shuldiner, Alan R.; Snieder, Harold; van Duijn, Cornelia M.; Voelker, Uwe; Wright, Alan F.; Wichmann, H. -Erich; Wilson, James F.; Witteman, Jacqueline C. M.; Liu, Yongmei; Hayward, Caroline; Borecki, Ingrid B.; Ziegler, Andreas; North, Kari E.; Cupples, L. Adrienne; Kronenberg, Florian; Dorr, M.; Munzel, T.; Volker, U.

    Background-Genetic determinants of peripheral arterial disease (PAD) remain largely unknown. To identify genetic variants associated with the ankle-brachial index (ABI), a noninvasive measure of PAD, we conducted a meta-analysis of genome-wide association study data from 21 population-based cohorts.

  4. Trial Sequential Analysis in systematic reviews with meta-analysis

    Directory of Open Access Journals (Sweden)

    Jørn Wetterslev

    2017-03-01

    Full Text Available Abstract Background Most meta-analyses in systematic reviews, including Cochrane ones, do not have sufficient statistical power to detect or refute even large intervention effects. This is why a meta-analysis ought to be regarded as an interim analysis on its way towards a required information size. The results of the meta-analyses should relate the total number of randomised participants to the estimated required meta-analytic information size accounting for statistical diversity. When the number of participants and the corresponding number of trials in a meta-analysis are insufficient, the use of the traditional 95% confidence interval or the 5% statistical significance threshold will lead to too many false positive conclusions (type I errors and too many false negative conclusions (type II errors. Methods We developed a methodology for interpreting meta-analysis results, using generally accepted, valid evidence on how to adjust thresholds for significance in randomised clinical trials when the required sample size has not been reached. Results The Lan-DeMets trial sequential monitoring boundaries in Trial Sequential Analysis offer adjusted confidence intervals and restricted thresholds for statistical significance when the diversity-adjusted required information size and the corresponding number of required trials for the meta-analysis have not been reached. Trial Sequential Analysis provides a frequentistic approach to control both type I and type II errors. We define the required information size and the corresponding number of required trials in a meta-analysis and the diversity (D2 measure of heterogeneity. We explain the reasons for using Trial Sequential Analysis of meta-analysis when the actual information size fails to reach the required information size. We present examples drawn from traditional meta-analyses using unadjusted naïve 95% confidence intervals and 5% thresholds for statistical significance. Spurious conclusions in

  5. Comparative proteomic investigation of metastatic and non-metastatic osteosarcoma cells of human and canine origin.

    Directory of Open Access Journals (Sweden)

    Jahnabi Roy

    Full Text Available Osteosarcoma is the most common bone cancer in dogs and people. In order to improve clinical outcomes, it is necessary to identify proteins that are differentially expressed by metastatic cells. Membrane bound proteins are responsible for multiple pro-metastatic functions. Therefore characterizing the differential expression of membranous proteins between metastatic and non-metastatic clonal variants will allow the discovery of druggable targets and consequently improve treatment methodology. The objective of this investigation was to systemically identify the membrane-associated proteomics of metastatic and non-metastatic variants of human and canine origin. Two clonal variants of divergent in vivo metastatic potential from human and canine origins were used. The plasma membranes were isolated and peptide fingerprinting was used to identify differentially expressed proteins. Selected proteins were further validated using western blotting, flow cytometry, confocal microscopy and immunohistochemistry. Over 500 proteins were identified for each cell line with nearly 40% of the proteins differentially regulated. Conserved between both species, metastatic variants demonstrated significant differences in expression of membrane proteins that are responsible for pro-metastatic functions. Additionally, CD147, CD44 and vimentin were validated using various biochemical techniques. Taken together, through a comparative proteomic approach we have identified several differentially expressed cell membrane proteins that will help in the development of future therapeutics.

  6. Comparative proteomic investigation of metastatic and non-metastatic osteosarcoma cells of human and canine origin.

    Science.gov (United States)

    Roy, Jahnabi; Wycislo, Kathryn L; Pondenis, Holly; Fan, Timothy M; Das, Aditi

    2017-01-01

    Osteosarcoma is the most common bone cancer in dogs and people. In order to improve clinical outcomes, it is necessary to identify proteins that are differentially expressed by metastatic cells. Membrane bound proteins are responsible for multiple pro-metastatic functions. Therefore characterizing the differential expression of membranous proteins between metastatic and non-metastatic clonal variants will allow the discovery of druggable targets and consequently improve treatment methodology. The objective of this investigation was to systemically identify the membrane-associated proteomics of metastatic and non-metastatic variants of human and canine origin. Two clonal variants of divergent in vivo metastatic potential from human and canine origins were used. The plasma membranes were isolated and peptide fingerprinting was used to identify differentially expressed proteins. Selected proteins were further validated using western blotting, flow cytometry, confocal microscopy and immunohistochemistry. Over 500 proteins were identified for each cell line with nearly 40% of the proteins differentially regulated. Conserved between both species, metastatic variants demonstrated significant differences in expression of membrane proteins that are responsible for pro-metastatic functions. Additionally, CD147, CD44 and vimentin were validated using various biochemical techniques. Taken together, through a comparative proteomic approach we have identified several differentially expressed cell membrane proteins that will help in the development of future therapeutics.

  7. Four Susceptibility Loci for Gallstone Disease Identified in a Meta-analysis of Genome-Wide Association Studies

    DEFF Research Database (Denmark)

    Joshi, Amit D; Andersson, Charlotte; Buch, Stephan

    2016-01-01

    discovery studies (8720 cases and 55,152 controls). We performed an inverse variance weighted, fixed-effects meta-analysis of study-specific estimates to identify single-nucleotide polymorphisms that were associated independently with gallstone disease. Associations were replicated in 6489 cases and 62...... in TM4SF4 (OR, 1.12; 95% CI, 1.08-1.16; P = 6.09 × 10(-11)), rs2547231 in SULT2A1 (encodes a sulfoconjugation enzyme that acts on hydroxysteroids and cholesterol-derived sterol bile acids) (OR, 1.17; 95% CI, 1.12-1.21; P = 2.24 × 10(-10)), rs1260326 in glucokinase regulatory protein (OR, 1.12; 95% CI, 1...

  8. Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47

    DEFF Research Database (Denmark)

    Anderson, Carl A; Boucher, Gabrielle; Lees, Charlie W

    2011-01-01

    Genome-wide association studies and candidate gene studies in ulcerative colitis have identified 18 susceptibility loci. We conducted a meta-analysis of six ulcerative colitis genome-wide association study datasets, comprising 6,687 cases and 19,718 controls, and followed up the top association...... signals in 9,628 cases and 12,917 controls. We identified 29 additional risk loci (P associated loci to 47. After annotating associated regions using GRAIL, expression quantitative trait loci data and correlations with non-synonymous SNPs, we...... identified many candidate genes that provide potentially important insights into disease pathogenesis, including IL1R2, IL8RA-IL8RB, IL7R, IL12B, DAP, PRDM1, JAK2, IRF5, GNA12 and LSP1. The total number of confirmed inflammatory bowel disease risk loci is now 99, including a minimum of 28 shared association...

  9. No survival benefit from adding cetuximab or panitumumab to oxaliplatin-based chemotherapy in the first-line treatment of metastatic colorectal cancer in KRAS wild type patients: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Si-wei Zhou

    Full Text Available The efficacy of combined therapies of oxaliplatin-based chemotherapy and anti-epidermal growth factor receptor (anti-EGFR monoclonal antibodies (MAbs remains controversial in colorectal cancer (CRC. The aim of this study is to estimate the efficacy and safety of adding cetuximab or panitumumab to oxaliplatin-based chemotherapy in the first line treatment in KRAS wild type patients with metastatic colorectal cancer (mCRC through meta-analysis.Medline, EMBASE, and Cochrane library, American Society of Clinical Oncology (ASCO and European Society for Medical Oncology (ESMO were searched. Eligible studies were randomized controlled trials (RCTs which evaluated oxaliplatin-based chemotherapy with or without anti-EGFR drugs (cetuximab or panitumumab in untreated KRAS wild type patients with mCRC. The outcomes included overall survival (OS, progression-free survival (PFS, overall response rate (ORR and toxicities. Hazard ratios (HR and risk ratio (RR were used for the meta-analysis and were expressed with 95% confidence intervals.This meta-analysis included four RCTs with 1270 patients, and all of the patients were administered oxaliplatin-based chemotherapy regimens with or without anti-EGFR MAbs. The result of heterogeneity of OS was not significant. Compared with chemotherapy alone, the addition of cetuximab or panitumumab didn't result in significant improvement in OS (HR = 1.00, 95%CI [0.88, 1.13], P = 0.95 or PFS (HR = 0.86, 95%CI [0.71, 1.04], P = 0.13. The subgroup analysis of cetuximab also revealed no significant benefit in OS (HR = 1.02, 95%CI [0.89, 1.18], P = 0.75 or in PFS (HR = 0.87, 95%CI [0.65, 1.17], P = 0.36. Patients who received combined therapy didn't have a higher ORR (Risk Ratio = 1.08, 95%CI [0.86, 1.36]. Toxicities slightly increased in anti-EGFR drugs group.The addition of cetuximab or panitumumab to oxaliplatin-based chemotherapy in first-line treatment of mCRC in wild type KRAS population did not improve efficacy in

  10. A meta-analysis of cerebrovascular disease and hyperhomocysteinaemia

    DEFF Research Database (Denmark)

    Nielsen, G M; Tvedegaard, K C; Andersen, Niels Trolle

    2000-01-01

    Hyperhomocysteinaemia has been identified as a risk factor for stroke and cerebrovascular disease in several studies. To evaluate the evidence we performed a meta-analysis. We found 21 studies searching Medline from 1966-July 1999 using the key words homocysteine, homocystine and cerebrovascular...... was used. The reports on 8 cross-sectional and 4 longitudinal studies gave data on the mean and standard deviations of plasma or serum homocysteine for both cases and controls, and these studies were included in the meta-analysis. The results of the 5 excluded studies all pointed to a positive relationship...

  11. The prevalence of food allergy: A meta-analysis

    DEFF Research Database (Denmark)

    Rona, Roberto J.; Keil, Thomas; Summers, Colin

    2007-01-01

    Background: There is uncertainty about the prevalence of food allergy in communities. Objective: To assess the prevalence of food allergy by performing a meta-analysis according to the method of assessment used. Methods: The foods assessed were cow's milk, hen's egg, peanut, fish, shellfish....... The meta-analysis included only original studies. They were stratified by age groups: infant/preschool, school children, and adults. Results: A total of 934 articles were identified, but only 51 were considered appropriate for inclusion. The prevalence of self-reported food allergy was very high compared...

  12. Conducting Meta-Analysis Using SAS

    CERN Document Server

    Arthur, Winfried; Huffcutt, Allen I; Arthur, Winfred

    2001-01-01

    Conducting Meta-Analysis Using SAS reviews the meta-analysis statistical procedure and shows the reader how to conduct one using SAS. It presents and illustrates the use of the PROC MEANS procedure in SAS to perform the data computations called for by the two most commonly used meta-analytic procedures, the Hunter & Schmidt and Glassian approaches. This book serves as both an operational guide and user's manual by describing and explaining the meta-analysis procedures and then presenting the appropriate SAS program code for computing the pertinent statistics. The practical, step-by-step instru

  13. Surrogacy of progression free survival for overall survival in metastatic breast cancer studies: Meta-analyses of published studies.

    Science.gov (United States)

    Kundu, Madan G; Acharyya, Suddhasatta

    2017-02-01

    PFS is often used as a surrogate endpoint for OS in metastatic breast cancer studies. We have evaluated the association of treatment effect on PFS with significant HR OS (and how this association is affected by other factors) in published prospective metastatic breast cancer studies. A systematic literature search in PubMed identified prospective metastatic breast cancer studies. Treatment effects on PFS were determined using hazard ratio (HR PFS ), increase in median PFS (ΔMED PFS ) and % increase in median PFS (%ΔMED PFS ). Diagnostic accuracy of PFS measures (HR PFS , ΔMED PFS and %ΔMED PFS ) in predicting significant HR OS was assessed using receiver operating characteristic (ROC) curves and classification tree approach (CART). Seventy-four cases (i.e., treatment to control comparisons) from 65 individual publications were identified for the analyses. Of these, 16 cases reported significant treatment effect on HR OS at 5% level of significance. Median number of deaths reported in these cases were 153. Area under the ROC curve (AUC) for diagnostic measures as HR PFS , ΔMED PFS and %ΔMED PFS were 0.69, 0.70 and 0.75, respectively. Classification tree results identified %ΔMED PFS and number of deaths as diagnostic measure for significant HR OS . Only 7.9% (3/39) cases with ΔMED PFS shorter than 48.27% reported significant HR OS . There were 7 cases with ΔMED PFS of 48.27% or more and number of deaths reported as 227 or more - of these 5 cases reported significant HR OS . %ΔMED PFS was found to be a better diagnostic measure for predicting significant HR OS . Our analysis results also suggest that consideration of total number of deaths may further improve its diagnostic performance. Based on our study results, the studies with 50% improvement in median PFS are more likely to produce significant HR OS if the total number of OS events at the time of analysis is 227 or more. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Optimal duration of androgen deprivation therapy following radiation therapy in intermediate- or high-risk non-metastatic prostate cancer: a systematic review and meta-analysis

    Energy Technology Data Exchange (ETDEWEB)

    Leal, Frederico; Figueiredo, Maximiliano Augusto Novis de; Sasse, Andre Deeke, E-mail: sasse@cevon.com.br [Universidade Estadual de Campinas (UNICAMP), SP (Brazil)

    2015-05-15

    Objectives: to investigate current evidence on the optimal duration of adjuvant hormone deprivation for prostate cancer treated with radiation therapy with curative intent. Materials and Methods: A systematic search was performed in electronic databases. Data from randomized trials comparing different durations of hormone blockade was collected for pooled analysis. Overall survival, disease-free survival, disease-specific survival and toxicity were the outcomes of interest. Meta-analyses were performed using random-effects model. Results: Six studies met the eligibility criteria. For overall survival, the pooled data from the studies demonstrated a statistically significant benefit for longer hormone deprivation (Hazard Ratio 0.84; 95% CI 0.74 - 0.96). A statistically significant benefit was also found for disease-free survival (Hazard Ratio 0.74; 95% CI 0.62 - 0.89), and disease-specific survival (Hazard Ratio 0.73; 95% CI 0.62 - 0.85). Studies with longer blockade duration arm demonstrated greater benefit. Toxicity was low, with no increase in cardiovascular events. Conclusions: Longer duration of androgen deprivation combined to radiotherapy prolongs OS, DFS and DSS in patients with intermediate and high-risk non-metastatic prostate cancer. However, this evidence is based on trials using older radiation techniques, and further research of combination of androgen deprivation and new RT technologies may be warranted. (author)

  15. A meta-analysis of genome-wide association studies of breast cancer identifies two novel susceptibility loci at 6q14 and 20q11

    NARCIS (Netherlands)

    Siddiq, Afshan; Couch, Fergus J.; Chen, Gary K.; Lindström, Sara; Eccles, Diana; Millikan, Robert C.; Michailidou, Kyriaki; Stram, Daniel O.; Beckmann, Lars; Rhie, Suhn Kyong; Ambrosone, Christine B.; Aittomäki, Kristiina; Amiano, Pilar; Apicella, Carmel; Baglietto, Laura; Bandera, Elisa V.; Beckmann, Matthias W.; Berg, Christine D.; Bernstein, Leslie; Blomqvist, Carl; Brauch, Hiltrud; Brinton, Louise; Bui, Quang M.; Buring, Julie E.; Buys, Saundra S.; Campa, Daniele; Carpenter, Jane E.; Chasman, Daniel I.; Chang-Claude, Jenny; Chen, Constance; Clavel-Chapelon, Françoise; Cox, Angela; Cross, Simon S.; Czene, Kamila; Deming, Sandra L.; Diasio, Robert B.; Diver, W. Ryan; Dunning, Alison M.; Durcan, Lorraine; Ekici, Arif B.; Fasching, Peter A.; Feigelson, Heather Spencer; Fejerman, Laura; Figueroa, Jonine D.; Fletcher, Olivia; Flesch-Janys, Dieter; Gaudet, Mia M.; Gerty, Susan M.; Rodriguez-Gil, Jorge L.; Giles, Graham G.; van Gils, Carla H.; Godwin, Andrew K.; Graham, Nikki; Greco, Dario; Hall, Per; Hankinson, Susan E.; Hartmann, Arndt; Hein, Rebecca; Heinz, Judith; Hoover, Robert N.; Hopper, John L.; Hu, Jennifer J.; Huntsman, Scott; Ingles, Sue A.; Irwanto, Astrid; Isaacs, Claudine; Jacobs, Kevin B.; John, Esther M.; Justenhoven, Christina; Kaaks, Rudolf; Kolonel, Laurence N.; Coetzee, Gerhard A.; Lathrop, Mark; Le Marchand, Loic; Lee, Adam M.; Lee, I.-Min; Lesnick, Timothy; Lichtner, Peter; Liu, Jianjun; Lund, Eiliv; Makalic, Enes; Martin, Nicholas G.; McLean, Catriona A.; Meijers-Heijboer, Hanne; Meindl, Alfons; Miron, Penelope; Monroe, Kristine R.; Montgomery, Grant W.; Müller-Myhsok, Bertram; Nickels, Stefan; Nyante, Sarah J.; Olswold, Curtis; Overvad, Kim; Palli, Domenico; Park, Daniel J.; Palmer, Julie R.; Pathak, Harsh; Peto, Julian; Pharoah, Paul; Rahman, Nazneen; Rivadeneira, Fernando; Schmidt, Daniel F.; Schmutzler, Rita K.; Slager, Susan; Southey, Melissa C.; Stevens, Kristen N.; Sinn, Hans-Peter; Press, Michael F.; Ross, Eric; Riboli, Elio; Ridker, Paul M.; Schumacher, Fredrick R.; Severi, Gianluca; dos Santos Silva, Isabel; Stone, Jennifer; Sund, Malin; Tapper, William J.; Thun, Michael J.; Travis, Ruth C.; Turnbull, Clare; Uitterlinden, Andre G.; Waisfisz, Quinten; Wang, Xianshu; Wang, Zhaoming; Weaver, Joellen; Schulz-Wendtland, Rüdiger; Wilkens, Lynne R.; van den Berg, David; Zheng, Wei; Ziegler, Regina G.; Ziv, Elad; Nevanlinna, Heli; Easton, Douglas F.; Hunter, David J.; Henderson, Brian E.; Chanock, Stephen J.; Garcia-Closas, Montserrat; Kraft, Peter; Haiman, Christopher A.; Vachon, Celine M.

    2012-01-01

    Genome-wide association studies (GWAS) of breast cancer defined by hormone receptor status have revealed loci contributing to susceptibility of estrogen receptor (ER)-negative subtypes. To identify additional genetic variants for ER-negative breast cancer, we conducted the largest meta-analysis of

  16. Causal Meta-Analysis : Methodology and Applications

    NARCIS (Netherlands)

    Bax, L.J.

    2009-01-01

    Meta-analysis is a statistical method to summarize research data from multiple studies in a quantitative manner. This dissertation addresses a number of methodological topics in causal meta-analysis and reports the development and validation of meta-analysis software. In the first (methodological)

  17. Retrospective Analysis of Outcome of Patients with Metastatic Leiomyosarcoma in a Tertiary Referral Center.

    Science.gov (United States)

    van Cann, Tom; Cornillie, Jasmien; Wozniak, Agnieszka; Debiec-Rychter, Maria; Sciot, Raf; Hompes, Daphne; Vergote, Ignace; Schöffski, Patrick

    2018-01-01

    Leiomyosarcoma is a common subtype of soft tissue sarcoma originating from smooth muscle. We evaluated the clinical course and treatment outcome of patients with metastatic leiomyosarcoma. We retrospectively reviewed the records of patients at the University Hospitals Leuven. We identified 122 patients with metastatic leiomyosarcoma, 77 female, median age 59.5 years. Most patients developed leiomyosarcoma in the extremities (35%), the uterus (20%) or the abdomen (19%); 69% developed metachronous metastasis, 31% had synchronous metastatic disease. Most patients (74%) received palliative systemic therapy. The most common first-line treatments were doxorubicin (n = 47) and an anthracycline combined with an alkylator (n = 28). The objective response rate to first-line palliative systemic therapy was 20% and the median progression-free survival was 4.9 months (range 0.1-17.1). The median survival from diagnosis of metastasis was 20.5 months (range 0.4-126.9). On multivariate analysis, metachronous disease, no progressive disease as best response to first-line treatment, the possibility of metastasectomy with curative intent and use of palliative radiotherapy were indicators for better survival. The prognosis of patients with metastatic leiomyosarcoma is limited and objective responses to first-line systemic therapy are rare. The treatment of metastatic leiomyosarcoma remains an unmet medical need. © 2018 S. Karger GmbH, Freiburg.

  18. Selenium Exposure and Cancer Risk: an Updated Meta-analysis and Meta-regression

    Science.gov (United States)

    Cai, Xianlei; Wang, Chen; Yu, Wanqi; Fan, Wenjie; Wang, Shan; Shen, Ning; Wu, Pengcheng; Li, Xiuyang; Wang, Fudi

    2016-01-01

    The objective of this study was to investigate the associations between selenium exposure and cancer risk. We identified 69 studies and applied meta-analysis, meta-regression and dose-response analysis to obtain available evidence. The results indicated that high selenium exposure had a protective effect on cancer risk (pooled OR = 0.78; 95%CI: 0.73–0.83). The results of linear and nonlinear dose-response analysis indicated that high serum/plasma selenium and toenail selenium had the efficacy on cancer prevention. However, we did not find a protective efficacy of selenium supplement. High selenium exposure may have different effects on specific types of cancer. It decreased the risk of breast cancer, lung cancer, esophageal cancer, gastric cancer, and prostate cancer, but it was not associated with colorectal cancer, bladder cancer, and skin cancer. PMID:26786590

  19. Meta-analysis a structural equation modeling approach

    CERN Document Server

    Cheung, Mike W-L

    2015-01-01

    Presents a novel approach to conducting meta-analysis using structural equation modeling. Structural equation modeling (SEM) and meta-analysis are two powerful statistical methods in the educational, social, behavioral, and medical sciences. They are often treated as two unrelated topics in the literature. This book presents a unified framework on analyzing meta-analytic data within the SEM framework, and illustrates how to conduct meta-analysis using the metaSEM package in the R statistical environment. Meta-Analysis: A Structural Equation Modeling Approach begins by introducing the impo

  20. A novel bi-level meta-analysis approach: applied to biological pathway analysis.

    Science.gov (United States)

    Nguyen, Tin; Tagett, Rebecca; Donato, Michele; Mitrea, Cristina; Draghici, Sorin

    2016-02-01

    The accumulation of high-throughput data in public repositories creates a pressing need for integrative analysis of multiple datasets from independent experiments. However, study heterogeneity, study bias, outliers and the lack of power of available methods present real challenge in integrating genomic data. One practical drawback of many P-value-based meta-analysis methods, including Fisher's, Stouffer's, minP and maxP, is that they are sensitive to outliers. Another drawback is that, because they perform just one statistical test for each individual experiment, they may not fully exploit the potentially large number of samples within each study. We propose a novel bi-level meta-analysis approach that employs the additive method and the Central Limit Theorem within each individual experiment and also across multiple experiments. We prove that the bi-level framework is robust against bias, less sensitive to outliers than other methods, and more sensitive to small changes in signal. For comparative analysis, we demonstrate that the intra-experiment analysis has more power than the equivalent statistical test performed on a single large experiment. For pathway analysis, we compare the proposed framework versus classical meta-analysis approaches (Fisher's, Stouffer's and the additive method) as well as against a dedicated pathway meta-analysis package (MetaPath), using 1252 samples from 21 datasets related to three human diseases, acute myeloid leukemia (9 datasets), type II diabetes (5 datasets) and Alzheimer's disease (7 datasets). Our framework outperforms its competitors to correctly identify pathways relevant to the phenotypes. The framework is sufficiently general to be applied to any type of statistical meta-analysis. The R scripts are available on demand from the authors. sorin@wayne.edu Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e

  1. MetaMeta: integrating metagenome analysis tools to improve taxonomic profiling.

    Science.gov (United States)

    Piro, Vitor C; Matschkowski, Marcel; Renard, Bernhard Y

    2017-08-14

    Many metagenome analysis tools are presently available to classify sequences and profile environmental samples. In particular, taxonomic profiling and binning methods are commonly used for such tasks. Tools available among these two categories make use of several techniques, e.g., read mapping, k-mer alignment, and composition analysis. Variations on the construction of the corresponding reference sequence databases are also common. In addition, different tools provide good results in different datasets and configurations. All this variation creates a complicated scenario to researchers to decide which methods to use. Installation, configuration and execution can also be difficult especially when dealing with multiple datasets and tools. We propose MetaMeta: a pipeline to execute and integrate results from metagenome analysis tools. MetaMeta provides an easy workflow to run multiple tools with multiple samples, producing a single enhanced output profile for each sample. MetaMeta includes a database generation, pre-processing, execution, and integration steps, allowing easy execution and parallelization. The integration relies on the co-occurrence of organisms from different methods as the main feature to improve community profiling while accounting for differences in their databases. In a controlled case with simulated and real data, we show that the integrated profiles of MetaMeta overcome the best single profile. Using the same input data, it provides more sensitive and reliable results with the presence of each organism being supported by several methods. MetaMeta uses Snakemake and has six pre-configured tools, all available at BioConda channel for easy installation (conda install -c bioconda metameta). The MetaMeta pipeline is open-source and can be downloaded at: https://gitlab.com/rki_bioinformatics .

  2. An Evaluation of Algorithms for Identifying Metastatic Breast, Lung, or Colorectal Cancer in Administrative Claims Data.

    Science.gov (United States)

    Whyte, Joanna L; Engel-Nitz, Nicole M; Teitelbaum, April; Gomez Rey, Gabriel; Kallich, Joel D

    2015-07-01

    Administrative health care claims data are used for epidemiologic, health services, and outcomes cancer research and thus play a significant role in policy. Cancer stage, which is often a major driver of cost and clinical outcomes, is not typically included in claims data. Evaluate algorithms used in a dataset of cancer patients to identify patients with metastatic breast (BC), lung (LC), or colorectal (CRC) cancer using claims data. Clinical data on BC, LC, or CRC patients (between January 1, 2007 and March 31, 2010) were linked to a health care claims database. Inclusion required health plan enrollment ≥3 months before initial cancer diagnosis date. Algorithms were used in the claims database to identify patients' disease status, which was compared with physician-reported metastases. Generic and tumor-specific algorithms were evaluated using ICD-9 codes, varying diagnosis time frames, and including/excluding other tumors. Positive and negative predictive values, sensitivity, and specificity were assessed. The linked databases included 14,480 patients; of whom, 32%, 17%, and 14.2% had metastatic BC, LC, and CRC, respectively, at diagnosis and met inclusion criteria. Nontumor-specific algorithms had lower specificity than tumor-specific algorithms. Tumor-specific algorithms' sensitivity and specificity were 53% and 99% for BC, 55% and 85% for LC, and 59% and 98% for CRC, respectively. Algorithms to distinguish metastatic BC, LC, and CRC from locally advanced disease should use tumor-specific primary cancer codes with 2 claims for the specific primary cancer >30-42 days apart to reduce misclassification. These performed best overall in specificity, positive predictive values, and overall accuracy to identify metastatic cancer in a health care claims database.

  3. Energy efficiency in Germany - a meta-analysis. Analysis and recommendations

    International Nuclear Information System (INIS)

    Bauernhansl, Thomas

    2014-01-01

    The Stuttgart Institute of energy efficiency in production compiled the first meta-analysis ''Energy Efficiency in Germany''.It provides facts and figures on the development atatus and knowledge level of energy efficiency in Germany. The study shows the contribution have been made by individual measures and the potentials which are known, but have not yet been lifted. For this meta-analysis more than 250 items available from research institutions, government departments, professional and industry associations have been identified with the main topic of energy efficiency and evaluated. It provides an overview of the status of development and is an important reference work for industry, associations and politics. [de

  4. Genome-wide meta-analysis identifies multiple novel associations and ethnic heterogeneity of psoriasis susceptibility

    NARCIS (Netherlands)

    Yin, Xianyong; Low, Hui Qi; Wang, Ling; Li, Yonghong; Ellinghaus, Eva; Han, Jiali; Estivill, Xavier; Sun, Liangdan; Zuo, Xianbo; Shen, Changbing; Zhu, Caihong; Zhang, Anping; Sanchez, Fabio; Padyukov, Leonid; Catanese, Joseph J; Krueger, Gerald G; Duffin, Kristina Callis; Mucha, Sören; Weichenthal, Michael; Weidinger, Stephan; Lieb, Wolfgang; Foo, Jia Nee; Li, Yi; Sim, Karseng; Liany, Herty; Irwan, Ishak; Teo, Yikying; Theng, Colin T S; Gupta, Rashmi; Bowcock, Anne; De Jager, Philip L; Qureshi, Abrar A; de Bakker, Paul I W; Seielstad, Mark; Liao, Wilson; Ståhle, Mona; Franke, Andre; Zhang, Xuejun; Liu, Jianjun

    2015-01-01

    Psoriasis is a common inflammatory skin disease with complex genetics and different degrees of prevalence across ethnic populations. Here we present the largest trans-ethnic genome-wide meta-analysis (GWMA) of psoriasis in 15,369 cases and 19,517 controls of Caucasian and Chinese ancestries. We

  5. Meta-analysis of Genome Wide Association Studies Identifies Genetic Markers of Late Toxicity Following Radiotherapy for Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Sarah L. Kerns

    2016-08-01

    Full Text Available Nearly 50% of cancer patients undergo radiotherapy. Late radiotherapy toxicity affects quality-of-life in long-term cancer survivors and risk of side-effects in a minority limits doses prescribed to the majority of patients. Development of a test predicting risk of toxicity could benefit many cancer patients. We aimed to meta-analyze individual level data from four genome-wide association studies from prostate cancer radiotherapy cohorts including 1564 men to identify genetic markers of toxicity. Prospectively assessed two-year toxicity endpoints (urinary frequency, decreased urine stream, rectal bleeding, overall toxicity and single nucleotide polymorphism (SNP associations were tested using multivariable regression, adjusting for clinical and patient-related risk factors. A fixed-effects meta-analysis identified two SNPs: rs17599026 on 5q31.2 with urinary frequency (odds ratio [OR] 3.12, 95% confidence interval [CI] 2.08–4.69, p-value 4.16 × 10−8 and rs7720298 on 5p15.2 with decreased urine stream (OR 2.71, 95% CI 1.90–3.86, p-value = 3.21 × 10−8. These SNPs lie within genes that are expressed in tissues adversely affected by pelvic radiotherapy including bladder, kidney, rectum and small intestine. The results show that heterogeneous radiotherapy cohorts can be combined to identify new moderate-penetrance genetic variants associated with radiotherapy toxicity. The work provides a basis for larger collaborative efforts to identify enough variants for a future test involving polygenic risk profiling.

  6. Citation analysis of meta-analysis articles on posttraumatic stress disorder.

    Science.gov (United States)

    Liao, Xi-Ming; Chen, Ping-Yan

    2011-04-01

    In the past two decades enormously scientific researches on posttraumatic stress disorder (PTSD) have been undertaken and many related meta-analyses have been published. Citation analysis was used to get comprehensive perspectives of meta-analysis articles (MA articles) on PTSD for the purpose of facilitating the researchers, physicians and policy-makers to understand the PTSD. MA articles on PTSD in any languages from January 1980 to March 2009 were included if they presented meta-analytical methods and received at least one citation recorded in the Web of Science (WoS). Whereas studies, in which any effect sizes of PTSD were not distinguished from other psychological disorders, were excluded. Citations to and by identified MA articles were documented basing on records in WoS. Citation analysis was used to examine distribution patterns of characteristics and citation impact of MA articles on PTSD. Canonical analysis was used to explore the relationship between the characteristics of MA articles and citation impact. Thirty-four MA articles published during 1998 and 2008 were identified and revealed multiple study topics on PTSD: 10 (29.4%) were about epidemiology, 13 (38.2%) about treatment or intervention, 6 (17.6%) about pathophysiology or neurophysiology or neuroendocrine, 3 (8.8%) about childhood and 2 (5.9%) about psychosocial adversity. Two articles cited most frequently with 456 and 145 counts were published in Journal of Consulting and Clinical Psychology by Brewin (2000) and Psychological Bulletin by Ozer (2003), respectively. Mean cited count was 7.48 ± 10.56 and mean age (year 2009 minus article publication year) was (4.24 ± 2.91) years. They had been cited approximately by 67 disciplines and by authors from 42 countries or territories. Characteristics of meta-analysis highly correlated with citation impact and reflected by canonical correlation of 0.899 (P < 0.000 01). The age of MA articles predicted their citation impact. Citation analysis would

  7. MetaComp: comprehensive analysis software for comparative meta-omics including comparative metagenomics.

    Science.gov (United States)

    Zhai, Peng; Yang, Longshu; Guo, Xiao; Wang, Zhe; Guo, Jiangtao; Wang, Xiaoqi; Zhu, Huaiqiu

    2017-10-02

    During the past decade, the development of high throughput nucleic sequencing and mass spectrometry analysis techniques have enabled the characterization of microbial communities through metagenomics, metatranscriptomics, metaproteomics and metabolomics data. To reveal the diversity of microbial communities and interactions between living conditions and microbes, it is necessary to introduce comparative analysis based upon integration of all four types of data mentioned above. Comparative meta-omics, especially comparative metageomics, has been established as a routine process to highlight the significant differences in taxon composition and functional gene abundance among microbiota samples. Meanwhile, biologists are increasingly concerning about the correlations between meta-omics features and environmental factors, which may further decipher the adaptation strategy of a microbial community. We developed a graphical comprehensive analysis software named MetaComp comprising a series of statistical analysis approaches with visualized results for metagenomics and other meta-omics data comparison. This software is capable to read files generated by a variety of upstream programs. After data loading, analyses such as multivariate statistics, hypothesis testing of two-sample, multi-sample as well as two-group sample and a novel function-regression analysis of environmental factors are offered. Here, regression analysis regards meta-omic features as independent variable and environmental factors as dependent variables. Moreover, MetaComp is capable to automatically choose an appropriate two-group sample test based upon the traits of input abundance profiles. We further evaluate the performance of its choice, and exhibit applications for metagenomics, metaproteomics and metabolomics samples. MetaComp, an integrative software capable for applying to all meta-omics data, originally distills the influence of living environment on microbial community by regression analysis

  8. Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci

    DEFF Research Database (Denmark)

    Jones, Gregory T; Tromp, Gerard; Kuivaniemi, Helena

    2017-01-01

    studies (GWAS). Through a meta-analysis of 6 GWAS datasets and a validation study totalling 10,204 cases and 107,766 controls we identified 4 new AAA risk loci: 1q32.3 (SMYD2), 13q12.11 (LINC00540), 20q13.12 (near PCIF1/MMP9/ZNF335), and 21q22.2 (ERG). In various database searches we observed no new...... associations between the lead AAA SNPs and coronary artery disease, blood pressure, lipids or diabetes. Network analyses identified ERG, IL6R and LDLR as modifiers of MMP9, with a direct interaction between ERG and MMP9. The 4 new risk loci for AAA appear to be specific for AAA compared with other...

  9. A Meta-Analysis on Unconscious Thought Effects

    NARCIS (Netherlands)

    Strick, M.A.; Dijksterhuis, A.J.; Bos, M.W.; Sjoerdsma, A.; Baaren, R.B. van; Nordgren, L.F.

    2011-01-01

    A meta-analysis was performed on the unconscious thought effect (UTE). All available published and unpublished data on unconscious thought were included. Our aims were to provide a statistically robust estimate of the effect size of the UTE, to identify significant moderators, and to

  10. Meta-analysis of SNPs involved in variance heterogeneity using Levene's test for equal variances

    Science.gov (United States)

    Deng, Wei Q; Asma, Senay; Paré, Guillaume

    2014-01-01

    Meta-analysis is a commonly used approach to increase the sample size for genome-wide association searches when individual studies are otherwise underpowered. Here, we present a meta-analysis procedure to estimate the heterogeneity of the quantitative trait variance attributable to genetic variants using Levene's test without needing to exchange individual-level data. The meta-analysis of Levene's test offers the opportunity to combine the considerable sample size of a genome-wide meta-analysis to identify the genetic basis of phenotypic variability and to prioritize single-nucleotide polymorphisms (SNPs) for gene–gene and gene–environment interactions. The use of Levene's test has several advantages, including robustness to departure from the normality assumption, freedom from the influence of the main effects of SNPs, and no assumption of an additive genetic model. We conducted a meta-analysis of the log-transformed body mass index of 5892 individuals and identified a variant with a highly suggestive Levene's test P-value of 4.28E-06 near the NEGR1 locus known to be associated with extreme obesity. PMID:23921533

  11. WITHDRAWN: Chemoimmunotherapy versus chemotherapy for metastatic malignant melanoma.

    Science.gov (United States)

    Sasse, Andre D; Sasse, Emma C; Clark, Luciana Go; Clark, Otavio Augusto Camara

    2018-02-06

    Malignant melanoma, one of the most aggressive of all skin cancers, is increasing in incidence throughout the world. Surgery remains the cornerstone of curative treatment in earlier stages. Metastatic disease is incurable in most affected people, because melanoma does not respond to most systemic treatments. A number of novel approaches are under evaluation and have shown promising results, but they are usually associated with increased toxicity and cost. The combination of chemotherapy and immunotherapy has been reported to improve treatment results, but it is still unclear whether evidence exists to support this choice, compared with chemotherapy alone. No language restrictions were imposed. To compare the effects of therapy with chemotherapy and immunotherapy (chemoimmunotherapy) versus chemotherapy alone in people with metastatic malignant melanoma. We searched the Cochrane Skin Group Specialised Register (14 February 2006), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 3, 2005), MEDLINE (2003 to 30 January 2006 ), EMBASE (2003 to 20 July 2005) and LILACS (1982 to 20 February 2006). References, conference proceedings, and databases of ongoing trials were also used to locate trials. All randomised controlled trials that compared the use of chemotherapy versus chemoimmunotherapy on people of any age, diagnosed with metastatic melanoma. Two authors independently assessed each study to determine whether it met the pre-defined selection criteria, with differences being resolved through discussion with the review team. Two authors independently extracted the data from the articles using data extraction forms. Quality assessment included an evaluation of various components associated with biased estimates of treatment effect. Whenever possible, a meta-analysis was performed on the extracted data, in order to calculate a weighed treatment effect across trials. Eighteen studies met our criteria and were included in the meta-analysis

  12. Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies

    Science.gov (United States)

    Elks, Cathy E.; Perry, John R.B.; Sulem, Patrick; Chasman, Daniel I.; Franceschini, Nora; He, Chunyan; Lunetta, Kathryn L.; Visser, Jenny A.; Byrne, Enda M.; Cousminer, Diana L.; Gudbjartsson, Daniel F.; Esko, Tõnu; Feenstra, Bjarke; Hottenga, Jouke-Jan; Koller, Daniel L.; Kutalik, Zoltán; Lin, Peng; Mangino, Massimo; Marongiu, Mara; McArdle, Patrick F.; Smith, Albert V.; Stolk, Lisette; van Wingerden, Sophie W.; Zhao, Jing Hua; Albrecht, Eva; Corre, Tanguy; Ingelsson, Erik; Hayward, Caroline; Magnusson, Patrik K.E.; Smith, Erin N.; Ulivi, Shelia; Warrington, Nicole M.; Zgaga, Lina; Alavere, Helen; Amin, Najaf; Aspelund, Thor; Bandinelli, Stefania; Barroso, Ines; Berenson, Gerald S.; Bergmann, Sven; Blackburn, Hannah; Boerwinkle, Eric; Buring, Julie E.; Busonero, Fabio; Campbell, Harry; Chanock, Stephen J.; Chen, Wei; Cornelis, Marilyn C.; Couper, David; Coviello, Andrea D.; d’Adamo, Pio; de Faire, Ulf; de Geus, Eco J.C.; Deloukas, Panos; Döring, Angela; Smith, George Davey; Easton, Douglas F.; Eiriksdottir, Gudny; Emilsson, Valur; Eriksson, Johan; Ferrucci, Luigi; Folsom, Aaron R.; Foroud, Tatiana; Garcia, Melissa; Gasparini, Paolo; Geller, Frank; Gieger, Christian; Gudnason, Vilmundur; Hall, Per; Hankinson, Susan E.; Ferreli, Liana; Heath, Andrew C.; Hernandez, Dena G.; Hofman, Albert; Hu, Frank B.; Illig, Thomas; Järvelin, Marjo-Riitta; Johnson, Andrew D.; Karasik, David; Khaw, Kay-Tee; Kiel, Douglas P.; Kilpeläinen, Tuomas O.; Kolcic, Ivana; Kraft, Peter; Launer, Lenore J.; Laven, Joop S.E.; Li, Shengxu; Liu, Jianjun; Levy, Daniel; Martin, Nicholas G.; McArdle, Wendy L.; Melbye, Mads; Mooser, Vincent; Murray, Jeffrey C.; Murray, Sarah S.; Nalls, Michael A.; Navarro, Pau; Nelis, Mari; Ness, Andrew R.; Northstone, Kate; Oostra, Ben A.; Peacock, Munro; Palmer, Lyle J.; Palotie, Aarno; Paré, Guillaume; Parker, Alex N.; Pedersen, Nancy L.; Peltonen, Leena; Pennell, Craig E.; Pharoah, Paul; Polasek, Ozren; Plump, Andrew S.; Pouta, Anneli; Porcu, Eleonora; Rafnar, Thorunn; Rice, John P.; Ring, Susan M.; Rivadeneira, Fernando; Rudan, Igor; Sala, Cinzia; Salomaa, Veikko; Sanna, Serena; Schlessinger, David; Schork, Nicholas J.; Scuteri, Angelo; Segrè, Ayellet V.; Shuldiner, Alan R.; Soranzo, Nicole; Sovio, Ulla; Srinivasan, Sathanur R.; Strachan, David P.; Tammesoo, Mar-Liis; Tikkanen, Emmi; Toniolo, Daniela; Tsui, Kim; Tryggvadottir, Laufey; Tyrer, Jonathon; Uda, Manuela; van Dam, Rob M.; van Meurs, Joyve B.J.; Vollenweider, Peter; Waeber, Gerard; Wareham, Nicholas J.; Waterworth, Dawn M.; Weedon, Michael N.; Wichmann, H. Erich; Willemsen, Gonneke; Wilson, James F.; Wright, Alan F.; Young, Lauren; Zhai, Guangju; Zhuang, Wei Vivian; Bierut, Laura J.; Boomsma, Dorret I.; Boyd, Heather A.; Crisponi, Laura; Demerath, Ellen W.; van Duijn, Cornelia M.; Econs, Michael J.; Harris, Tamara B.; Hunter, David J.; Loos, Ruth J.F.; Metspalu, Andres; Montgomery, Grant W.; Ridker, Paul M.; Spector, Tim D.; Streeten, Elizabeth A.; Stefansson, Kari; Thorsteinsdottir, Unnur; Uitterlinden, André G.; Widen, Elisabeth; Murabito, Joanne M.; Ong, Ken K.; Murray, Anna

    2011-01-01

    To identify loci for age at menarche, we performed a meta-analysis of 32 genome-wide association studies in 87,802 women of European descent, with replication in up to 14,731 women. In addition to the known loci at LIN28B (P=5.4×10−60) and 9q31.2 (P=2.2×10−33), we identified 30 novel menarche loci (all P<5×10−8) and found suggestive evidence for a further 10 loci (P<1.9×10−6). New loci included four previously associated with BMI (in/near FTO, SEC16B, TRA2B and TMEM18), three in/near other genes implicated in energy homeostasis (BSX, CRTC1, and MCHR2), and three in/near genes implicated in hormonal regulation (INHBA, PCSK2 and RXRG). Ingenuity and MAGENTA pathway analyses identified coenzyme A and fatty acid biosynthesis as biological processes related to menarche timing. PMID:21102462

  13. OHBM 2017: Practical intensity based meta-analysis

    OpenAIRE

    Maumet, Camille

    2017-01-01

    "Practical intensity-based meta-analysis" slides from my talk in the OHBM 2017 educational talk on Neuroimaging meta-analysis.http://www.humanbrainmapping.org/files/2017/ED Courses/Neuroimaging Meta-Analysis.pdf

  14. Systematic review, meta-analysis, and meta-regression: Successful second-line treatment for Helicobacter pylori.

    Science.gov (United States)

    Muñoz, Neus; Sánchez-Delgado, Jordi; Baylina, Mireia; Puig, Ignasi; López-Góngora, Sheila; Suarez, David; Calvet, Xavier

    2018-06-01

    Multiple Helicobacter pylori second-line schedules have been described as potentially useful. It remains unclear, however, which are the best combinations, and which features of second-line treatments are related to better cure rates. The aim of this study was to determine that second-line treatments achieved excellent (>90%) cure rates by performing a systematic review and when possible a meta-analysis. A meta-regression was planned to determine the characteristics of treatments achieving excellent cure rates. A systematic review for studies evaluating second-line Helicobacter pylori treatment was carried out in multiple databases. A formal meta-analysis was performed when an adequate number of comparative studies was found, using RevMan5.3. A meta-regression for evaluating factors predicting cure rates >90% was performed using Stata Statistical Software. The systematic review identified 115 eligible studies, including 203 evaluable treatment arms. The results were extremely heterogeneous, with 61 treatment arms (30%) achieving optimal (>90%) cure rates. The meta-analysis favored quadruple therapies over triple (83.2% vs 76.1%, OR: 0.59:0.38-0.93; P = .02) and 14-day quadruple treatments over 7-day treatments (91.2% vs 81.5%, OR; 95% CI: 0.42:0.24-0.73; P = .002), although the differences were significant only in the per-protocol analysis. The meta-regression did not find any particular characteristics of the studies to be associated with excellent cure rates. Second-line Helicobacter pylori treatments achieving>90% cure rates are extremely heterogeneous. Quadruple therapy and 14-day treatments seem better than triple therapies and 7-day ones. No single characteristic of the treatments was related to excellent cure rates. Future approaches suitable for infectious diseases-thus considering antibiotic resistances-are needed to design rescue treatments that consistently achieve excellent cure rates. © 2018 John Wiley & Sons Ltd.

  15. MetaEasy: A Meta-Analysis Add-In for Microsoft Excel

    Directory of Open Access Journals (Sweden)

    Evangelos Kontopantelis

    2009-04-01

    Full Text Available Meta-analysis is a statistical methodology that combines or integrates the results ofseveral independent clinical trials considered by the analyst to be `combinable' (Huque1988. However, completeness and user-friendliness are uncommon both in specialisedmeta-analysis software packages and in mainstream statistical packages that have to relyon user-written commands. We implemented the meta-analysis methodology in an Mi-crosoft Excel add-in which is freely available and incorporates more meta-analysis models(including the iterative maximum likelihood and prole likelihood than are usually avail-able, while paying particular attention to the user-friendliness of the package.

  16. Molecular Subgroup of Primary Prostate Cancer Presenting with Metastatic Biology.

    Science.gov (United States)

    Walker, Steven M; Knight, Laura A; McCavigan, Andrena M; Logan, Gemma E; Berge, Viktor; Sherif, Amir; Pandha, Hardev; Warren, Anne Y; Davidson, Catherine; Uprichard, Adam; Blayney, Jaine K; Price, Bethanie; Jellema, Gera L; Steele, Christopher J; Svindland, Aud; McDade, Simon S; Eden, Christopher G; Foster, Chris; Mills, Ian G; Neal, David E; Mason, Malcolm D; Kay, Elaine W; Waugh, David J; Harkin, D Paul; Watson, R William; Clarke, Noel W; Kennedy, Richard D

    2017-10-01

    Approximately 4-25% of patients with early prostate cancer develop disease recurrence following radical prostatectomy. To identify a molecular subgroup of prostate cancers with metastatic potential at presentation resulting in a high risk of recurrence following radical prostatectomy. Unsupervised hierarchical clustering was performed using gene expression data from 70 primary resections, 31 metastatic lymph nodes, and 25 normal prostate samples. Independent assay validation was performed using 322 radical prostatectomy samples from four sites with a mean follow-up of 50.3 months. Molecular subgroups were identified using unsupervised hierarchical clustering. A partial least squares approach was used to generate a gene expression assay. Relationships with outcome (time to biochemical and metastatic recurrence) were analysed using multivariable Cox regression and log-rank analysis. A molecular subgroup of primary prostate cancer with biology similar to metastatic disease was identified. A 70-transcript signature (metastatic assay) was developed and independently validated in the radical prostatectomy samples. Metastatic assay positive patients had increased risk of biochemical recurrence (multivariable hazard ratio [HR] 1.62 [1.13-2.33]; p=0.0092) and metastatic recurrence (multivariable HR=3.20 [1.76-5.80]; p=0.0001). A combined model with Cancer of the Prostate Risk Assessment post surgical (CAPRA-S) identified patients at an increased risk of biochemical and metastatic recurrence superior to either model alone (HR=2.67 [1.90-3.75]; pmolecular subgroup of primary prostate cancers with metastatic potential. The metastatic assay may improve the ability to detect patients at risk of metastatic recurrence following radical prostatectomy. The impact of adjuvant therapies should be assessed in this higher-risk population. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  17. Introduction, comparison, and validation of Meta-Essentials: A free and simple tool for meta-analysis.

    Science.gov (United States)

    Suurmond, Robert; van Rhee, Henk; Hak, Tony

    2017-12-01

    We present a new tool for meta-analysis, Meta-Essentials, which is free of charge and easy to use. In this paper, we introduce the tool and compare its features to other tools for meta-analysis. We also provide detailed information on the validation of the tool. Although free of charge and simple, Meta-Essentials automatically calculates effect sizes from a wide range of statistics and can be used for a wide range of meta-analysis applications, including subgroup analysis, moderator analysis, and publication bias analyses. The confidence interval of the overall effect is automatically based on the Knapp-Hartung adjustment of the DerSimonian-Laird estimator. However, more advanced meta-analysis methods such as meta-analytical structural equation modelling and meta-regression with multiple covariates are not available. In summary, Meta-Essentials may prove a valuable resource for meta-analysts, including researchers, teachers, and students. © 2017 The Authors. Research Synthesis Methods published by John Wiley & Sons Ltd.

  18. Global Prevalence of Elder Abuse: A Meta-analysis and Meta-regression.

    Science.gov (United States)

    Ho, C Sh; Wong, S Y; Chiu, M M; Ho, R Cm

    2017-06-01

    Elder abuse is increasingly recognised as a global public health and social problem. There has been limited inter-study comparison of the prevalence and risk factors for elder abuse. This study aimed to estimate the pooled and subtype prevalence of elder abuse worldwide and identify significant associated risk factors. We conducted a meta-analysis and meta-regression of 34 population-based and 17 non-population-based studies. The pooled prevalences of elder abuse were 10.0% (95% confidence interval, 5.2%-18.6%) and 34.3% (95% confidence interval, 22.9%-47.8%) in population-based studies and third party- or caregiver-reported studies, respectively. Being in a marital relationship was found to be a significant moderator using random-effects model. This meta-analysis revealed that third parties or caregivers were more likely to report abuse than older abused adults. Subgroup analyses showed that females and those resident in non-western countries were more likely to be abused. Emotional abuse was the most prevalent elder abuse subtype and financial abuse was less commonly reported by third parties or caregivers. Heterogeneity in the prevalence was due to the high proportion of married older adults in the sample. Subgroup analysis showed that cultural factors, subtypes of abuse, and gender also contributed to heterogeneity in the pooled prevalence of elder abuse.

  19. Revisiting a Meta-Analysis of Helpful Aspects of Therapy in a Community Counselling Service

    Science.gov (United States)

    Quick, Emma L; Dowd, Claire; Spong, Sheila

    2018-01-01

    This small scale mixed methods study examines helpful events in a community counselling setting, categorising impacts of events according to Timulak's [(2007). Identifying core categories of client-identified impact of helpful events in psychotherapy: A qualitative meta-analysis. "Psychotherapy Research," 17, 305-314] meta-synthesis of…

  20. Chemotherapy increases long-term survival in patients with adult medulloblastoma--a literature-based meta-analysis.

    Science.gov (United States)

    Kocakaya, Selin; Beier, Christoph Patrick; Beier, Dagmar

    2016-03-01

    Adult medulloblastoma is a potentially curable malignant entity with an incidence of 0.5-1 per million. Valid data on prognosis, treatment, and demographics are lacking, as most current knowledge stems from retrospective studies. Surgical resection followed by radiotherapy are accepted parts of treatment regimes; however, established prognostic factors and data clarifying the role of chemotherapy are missing. We investigated 227 publications from 1969-2013, with 907 identifiable, individual patients being available for meta-analysis. Demographic data, risk stratification, and treatment of these patients were similar to previous cohorts. The median overall survival (mOS) was 65 months (95% CI: 54.6-75.3) , the 5-year overall survival was 50.9% with 16% of the patients dying more than 5 years after diagnosis. Incomplete resection, clinical and radiological signs for brainstem infiltration, and abstinence from radiotherapy were predictive of worse outcome. Metastatic disease at tumor recurrence was identified as a new prognostic factor, while neither metastasis at initial diagnosis nor desmoplastic/classic histology was correlated with survival. Patients receiving chemotherapy first-line survived significantly longer (mOS: 108 mo, 95% CI: 68.6-148.4) than patients treated with radiation alone (mOS: 57 mo, 95% CI: 39.6-74.4) or patients who received chemotherapy at tumor recurrence. This effect was not biased by tumor stage or decade of treatment. Importantly, (neo)adjuvant chemotherapy also significantly increased the chance for long-term survival (>5 y) compared with radiotherapy alone or chemotherapy at tumor recurrence. This meta-analysis clarifies relevant prognostic factors and suggests that chemotherapy as part of first-line therapy improves overall survival and increases the proportion of patients with long-term survival. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions

  1. Trial Sequential Analysis in systematic reviews with meta-analysis

    DEFF Research Database (Denmark)

    Wetterslev, Jørn; Jakobsen, Janus Christian; Gluud, Christian

    2017-01-01

    BACKGROUND: Most meta-analyses in systematic reviews, including Cochrane ones, do not have sufficient statistical power to detect or refute even large intervention effects. This is why a meta-analysis ought to be regarded as an interim analysis on its way towards a required information size...... from traditional meta-analyses using unadjusted naïve 95% confidence intervals and 5% thresholds for statistical significance. Spurious conclusions in systematic reviews with traditional meta-analyses can be reduced using Trial Sequential Analysis. Several empirical studies have demonstrated...

  2. Online open neuroimaging mass meta-analysis

    DEFF Research Database (Denmark)

    Nielsen, Finn Årup; Kempton, Matthew J.; Williams, Steven C. R.

    We describe a system for meta-analysis where a wiki stores numerical data in a simple format and a web service performs the numerical computation. We initially apply the system on multiple meta-analyses of structural neuroimaging data results. The described system allows for mass meta-analysis, e...

  3. Neutrophil-to-lymphocyte Ratio, Platelet-to-lymphocyte Ratio, and C-reactive Protein as New and Simple Prognostic Factors in Patients With Metastatic Renal Cell Cancer Treated With Tyrosine Kinase Inhibitors: A Systemic Review and Meta-analysis.

    Science.gov (United States)

    Semeniuk-Wojtaś, Aleksandra; Lubas, Arkadiusz; Stec, Rafał; Syryło, Tomasz; Niemczyk, Stanisław; Szczylik, Cezary

    2018-02-02

    Inflammation plays a crucial role in cancer development. In this study, we evaluate the prognostic values of systemic inflammation markers such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and C-reactive protein (CRP) for the progression-free survival and overall survival in patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitors. PubMed and the Cochrane Library databases were searched for published studies on the effect of NLR, PLR, and CRP in patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitors. In the meta-analysis, NLR (hazard ratio [HR], 2.01; 95% confidence interval [CI], 1.27-3.18; P = .003) and PLR (HR, 6.96; 95% CI, 5.04-9.62; P < .001) had a significant influence on progression-free survival, whereas all considered proinflammatory markers had a significant impact on overall survival: NLR (HR, 2.14; 95% CI, 1.67-2.73; P < .001), PLR (HR, 14.67; 95% CI, 11.10-19.57; P < .001), and CRP (HR, 1.96; 95% CI, 1.26-3.05; P = .003). Inflammation markers such as NLR, PLR, and CRP are predictors of clinical outcome and could provide additional information to individualize treatment. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  4. Meta-DiSc: a software for meta-analysis of test accuracy data.

    Science.gov (United States)

    Zamora, Javier; Abraira, Victor; Muriel, Alfonso; Khan, Khalid; Coomarasamy, Arri

    2006-07-12

    Systematic reviews and meta-analyses of test accuracy studies are increasingly being recognised as central in guiding clinical practice. However, there is currently no dedicated and comprehensive software for meta-analysis of diagnostic data. In this article, we present Meta-DiSc, a Windows-based, user-friendly, freely available (for academic use) software that we have developed, piloted, and validated to perform diagnostic meta-analysis. Meta-DiSc a) allows exploration of heterogeneity, with a variety of statistics including chi-square, I-squared and Spearman correlation tests, b) implements meta-regression techniques to explore the relationships between study characteristics and accuracy estimates, c) performs statistical pooling of sensitivities, specificities, likelihood ratios and diagnostic odds ratios using fixed and random effects models, both overall and in subgroups and d) produces high quality figures, including forest plots and summary receiver operating characteristic curves that can be exported for use in manuscripts for publication. All computational algorithms have been validated through comparison with different statistical tools and published meta-analyses. Meta-DiSc has a Graphical User Interface with roll-down menus, dialog boxes, and online help facilities. Meta-DiSc is a comprehensive and dedicated test accuracy meta-analysis software. It has already been used and cited in several meta-analyses published in high-ranking journals. The software is publicly available at http://www.hrc.es/investigacion/metadisc_en.htm.

  5. Bayesian meta-analysis models for microarray data: a comparative study

    Directory of Open Access Journals (Sweden)

    Song Joon J

    2007-03-01

    Full Text Available Abstract Background With the growing abundance of microarray data, statistical methods are increasingly needed to integrate results across studies. Two common approaches for meta-analysis of microarrays include either combining gene expression measures across studies or combining summaries such as p-values, probabilities or ranks. Here, we compare two Bayesian meta-analysis models that are analogous to these methods. Results Two Bayesian meta-analysis models for microarray data have recently been introduced. The first model combines standardized gene expression measures across studies into an overall mean, accounting for inter-study variability, while the second combines probabilities of differential expression without combining expression values. Both models produce the gene-specific posterior probability of differential expression, which is the basis for inference. Since the standardized expression integration model includes inter-study variability, it may improve accuracy of results versus the probability integration model. However, due to the small number of studies typical in microarray meta-analyses, the variability between studies is challenging to estimate. The probability integration model eliminates the need to model variability between studies, and thus its implementation is more straightforward. We found in simulations of two and five studies that combining probabilities outperformed combining standardized gene expression measures for three comparison values: the percent of true discovered genes in meta-analysis versus individual studies; the percent of true genes omitted in meta-analysis versus separate studies, and the number of true discovered genes for fixed levels of Bayesian false discovery. We identified similar results when pooling two independent studies of Bacillus subtilis. We assumed that each study was produced from the same microarray platform with only two conditions: a treatment and control, and that the data sets

  6. Meta-analysis: Nitroglycerin for prevention of post-ERCP pancreatitis

    DEFF Research Database (Denmark)

    Nøjgaard, C; Matzen, P; Andersen, Per Kragh

    2009-01-01

    BACKGROUND: Acute pancreatitis after ERCP is a severe side effect. AIM: To evaluate the preventive effect of nitroglycerin on post-ERCP pancreatitis by a meta-analysis of randomized clinical studies. METHODS: We searched on Pubmed, Embase, Cochrane Library and all abstracts presented at Digestive......-ERCP pancreatitis after administration of nitroglycerin were identified. Meta-analysis including all five studies showed a relative risk (RR) of 0.61 (95% CI; 0.44, 0.86) with the number needed to treat (NNT) of 26 (95% CI: 16, 82). Three studies evaluated nitroglycerin administered by a dermal patch reaching...... together an RR of 0.66 (95% CI; 0.43, 1.01). The use of nitroglycerin is associated with a significantly increased risk of hypotension (RR 2.25) and headache (RR 3.64). No difference in mortality was observed. CONCLUSIONS: Overall, our meta-analysis supports the use of nitroglycerin in the prevention...

  7. Genome-wide joint meta-analysis of SNP and SNP-by-smoking interaction identifies novel loci for pulmonary function.

    Directory of Open Access Journals (Sweden)

    Dana B Hancock

    Full Text Available Genome-wide association studies have identified numerous genetic loci for spirometic measures of pulmonary function, forced expiratory volume in one second (FEV(1, and its ratio to forced vital capacity (FEV(1/FVC. Given that cigarette smoking adversely affects pulmonary function, we conducted genome-wide joint meta-analyses (JMA of single nucleotide polymorphism (SNP and SNP-by-smoking (ever-smoking or pack-years associations on FEV(1 and FEV(1/FVC across 19 studies (total N = 50,047. We identified three novel loci not previously associated with pulmonary function. SNPs in or near DNER (smallest P(JMA = 5.00×10(-11, HLA-DQB1 and HLA-DQA2 (smallest P(JMA = 4.35×10(-9, and KCNJ2 and SOX9 (smallest P(JMA = 1.28×10(-8 were associated with FEV(1/FVC or FEV(1 in meta-analysis models including SNP main effects, smoking main effects, and SNP-by-smoking (ever-smoking or pack-years interaction. The HLA region has been widely implicated for autoimmune and lung phenotypes, unlike the other novel loci, which have not been widely implicated. We evaluated DNER, KCNJ2, and SOX9 and found them to be expressed in human lung tissue. DNER and SOX9 further showed evidence of differential expression in human airway epithelium in smokers compared to non-smokers. Our findings demonstrated that joint testing of SNP and SNP-by-environment interaction identified novel loci associated with complex traits that are missed when considering only the genetic main effects.

  8. An overview of meta-analysis for clinicians

    Science.gov (United States)

    Lee, Young Ho

    2018-01-01

    The number of medical studies being published is increasing exponentially, and clinicians must routinely process large amounts of new information. Moreover, the results of individual studies are often insufficient to provide confident answers, as their results are not consistently reproducible. A meta-analysis is a statistical method for combining the results of different studies on the same topic and it may resolve conflicts among studies. Meta-analysis is being used increasingly and plays an important role in medical research. This review introduces the basic concepts, steps, advantages, and caveats of meta-analysis, to help clinicians understand it in clinical practice and research. A major advantage of a meta-analysis is that it produces a precise estimate of the effect size, with considerably increased statistical power, which is important when the power of the primary study is limited because of a small sample size. A meta-analysis may yield conclusive results when individual studies are inconclusive. Furthermore, meta-analyses investigate the source of variation and different effects among subgroups. In summary, a meta-analysis is an objective, quantitative method that provides less biased estimates on a specific topic. Understanding how to conduct a meta-analysis aids clinicians in the process of making clinical decisions. PMID:29277096

  9. An overview of meta-analysis for clinicians.

    Science.gov (United States)

    Lee, Young Ho

    2018-03-01

    The number of medical studies being published is increasing exponentially, and clinicians must routinely process large amounts of new information. Moreover, the results of individual studies are often insufficient to provide confident answers, as their results are not consistently reproducible. A meta-analysis is a statistical method for combining the results of different studies on the same topic and it may resolve conflicts among studies. Meta-analysis is being used increasingly and plays an important role in medical research. This review introduces the basic concepts, steps, advantages, and caveats of meta-analysis, to help clinicians understand it in clinical practice and research. A major advantage of a meta-analysis is that it produces a precise estimate of the effect size, with considerably increased statistical power, which is important when the power of the primary study is limited because of a small sample size. A meta-analysis may yield conclusive results when individual studies are inconclusive. Furthermore, meta-analyses investigate the source of variation and different effects among subgroups. In summary, a meta-analysis is an objective, quantitative method that provides less biased estimates on a specific topic. Understanding how to conduct a meta-analysis aids clinicians in the process of making clinical decisions.

  10. Meta-analysis of genome-wide association studies identifies three new risk loci for atopic dermatitis

    DEFF Research Database (Denmark)

    Paternoster, Lavinia; Standl, Marie; Chen, Chih-Mei

    2011-01-01

    Atopic dermatitis (AD) is a commonly occurring chronic skin disease with high heritability. Apart from filaggrin (FLG), the genes influencing atopic dermatitis are largely unknown. We conducted a genome-wide association meta-analysis of 5,606 affected individuals and 20,565 controls from 16...

  11. Meta-Analysis of Genome-Wide Association Studies Identifies Six New Loci for Serum Calcium Concentrations

    NARCIS (Netherlands)

    C.M. O'Seaghdha (Conall); H. Wu (Hongsheng); Q. Yang (Qiong); K. Kapur (Karen); I. Guessous (Idris); P. Zuber (Patrick); A. Köttgen (Anna); C. Stoudmann (Candice); A. Teumer (Alexander); Z. Kutalik (Zoltán); M. Mangino (Massimo); A. Dehghan (Abbas); W. Zhang (Weihua); G. Eiriksdottir (Gudny); G. Li (Guo); T. Tanaka (Toshiko); L. Portas (Laura); L.M. Lopez (Lorna); C. Hayward (Caroline); K. Lohman (Kurt); K. Matsuda (Koichi); S. Padmanabhan (Sandosh); D. Firsov (Dmitri); R. Sorice; S. Ulivi (Shelia); A.C. Brockhaus (A. Catharina); M.E. Kleber (Marcus); A. Mahajan (Anubha); F.D.J. Ernst (Florian); V. Gudnason (Vilmundur); L.J. Launer (Lenore); A. Mace (Aurelien); E.A. Boerwinkle (Eric); D.E. Arking (Dan); C. Tanikawa (Chizu); Y. Nakamura (Yusuke); M.J. Brown (Morris); J.-M. Gaspoz (Jean-Michel); J.-M. Theler (Jean-Marc); D.S. Siscovick (David); B.M. Psaty (Bruce); S.M. Bergmann (Sven); P. Vollenweider (Peter); V. Vitart (Veronique); A.F. Wright (Alan); T. Zemunik (Tatijana); M. Boban (Mladen); I. Kolcic (Ivana); P. Navarro (Pau); E.M. Brown (Edward); K. Estrada Gil (Karol); J. Ding (Jingzhong); T.B. Harris (Tamara); S. Bandinelli (Stefania); D.G. Hernandez (Dena); A. Singleton (Andrew); S. Girotto; D. Ruggiero; P. d' Adamo (Pio); A. Robino (Antonietta); T. Meitinger (Thomas); C. Meisinger (Christa); G. Davies (Gail); J.M. Starr (John); J.C. Chambers (John); B.O. Boehm (Bernhard); B. Winkelmann; J. Huang (Jian); D. Murgia (Daniela); S.H. Wild (Sarah); H. Campbell (Harry); A.D. Morris (Andrew); O.H. Franco (Oscar); A. Hofman (Albert); A.G. Uitterlinden (André); F. Rivadeneira Ramirez (Fernando); U. Vol̈ker (Uwe); M. Hannemann (Mario); R. Biffar (Reiner); W. Hoffmann (Wolfgang); S.-Y. Shin; P. Lescuyer (Pierre); H. Henry (Hughes); C. Schurmann (Claudia); P. Munroe (Patricia); P. Gasparini (Paolo); N. Pirastu (Nicola); M. Ciullo; C. Gieger (Christian); W. März (Winfried); L. Lind (Lars); T.D. Spector (Timothy); G.D. Smith; I. Rudan (Igor); J.F. Wilson (James); O. Polasek (Ozren); I.J. Deary (Ian); M. Pirastu (Mario); L. Ferrucci (Luigi); Y. Liu (YongMei); B. Kestenbaum (Bryan); J.S. Kooner (Jaspal); J.C.M. Witteman (Jacqueline); M. Nauck (Matthias); W.H.L. Kao (Wen); H. Wallaschofski (Henri); O. Bonny (Olivier); C. Fox (Craig); M. Bochud (Murielle)

    2013-01-01

    textabstractCalcium is vital to the normal functioning of multiple organ systems and its serum concentration is tightly regulated. Apart from CASR, the genes associated with serum calcium are largely unknown. We conducted a genome-wide association meta-analysis of 39,400 individuals from 17

  12. How to conduct a qualitative meta-analysis: Tailoring methods to enhance methodological integrity.

    Science.gov (United States)

    Levitt, Heidi M

    2018-05-01

    Although qualitative research has long been of interest in the field of psychology, meta-analyses of qualitative literatures (sometimes called meta-syntheses) are still quite rare. Like quantitative meta-analyses, these methods function to aggregate findings and identify patterns across primary studies, but their aims, procedures, and methodological considerations may vary. This paper explains the function of qualitative meta-analyses and their methodological development. Recommendations have broad relevance but are framed with an eye toward their use in psychotherapy research. Rather than arguing for the adoption of any single meta-method, this paper advocates for considering how procedures can best be selected and adapted to enhance a meta-study's methodological integrity. Through the paper, recommendations are provided to help researchers identify procedures that can best serve their studies' specific goals. Meta-analysts are encouraged to consider the methodological integrity of their studies in relation to central research processes, including identifying a set of primary research studies, transforming primary findings into initial units of data for a meta-analysis, developing categories or themes, and communicating findings. The paper provides guidance for researchers who desire to tailor meta-analytic methods to meet their particular goals while enhancing the rigor of their research.

  13. Radiosurgery of Glomus Jugulare Tumors: A Meta-Analysis

    International Nuclear Information System (INIS)

    Guss, Zachary D.; Batra, Sachin; Limb, Charles J.; Li, Gordon; Sughrue, Michael E.; Redmond, Kristin; Rigamonti, Daniele; Parsa, Andrew T.; Chang, Steven; Kleinberg, Lawrence; Lim, Michael

    2011-01-01

    Purpose: During the past two decades, radiosurgery has arisen as a promising approach to the management of glomus jugulare. In the present study, we report on a systematic review and meta-analysis of the available published data on the radiosurgical management of glomus jugulare tumors. Methods and Materials: To identify eligible studies, systematic searches of all glomus jugulare tumors treated with radiosurgery were conducted in major scientific publication databases. The data search yielded 19 studies, which were included in the meta-analysis. The data from 335 glomus jugulare patients were extracted. The fixed effects pooled proportions were calculated from the data when Cochrane's statistic was statistically insignificant and the inconsistency among studies was 36 months. In these studies, 95% of patients achieved clinical control and 96% achieved tumor control. The gamma knife, linear accelerator, and CyberKnife technologies all exhibited high rates of tumor and clinical control. Conclusions: The present study reports the results of a meta-analysis for the radiosurgical management of glomus jugulare. Because of its high effectiveness, we suggest considering radiosurgery for the primary management of glomus jugulare tumors.

  14. Prognostic implication of the metastatic lesion-to-ovarian cancer standardised uptake value ratio in advanced serous epithelial ovarian cancer

    International Nuclear Information System (INIS)

    Chung, Hyun Hoon; Lee, Maria; Kim, Hee-Seung; Kim, Jae-Weon; Park, Noh-Hyun; Song, Yong Sang; Cheon, Gi Jeong

    2017-01-01

    To evaluate the prognostic value of metabolic activity of metastatic lesions measured by 18 F-flurodeoxyglucose ( 18 F-FDG) uptake on preoperative positron emission tomography/computed tomography (PET/CT) in patients with advanced serous epithelial ovarian cancer (EOC). Clinico-pathological variables and PET/CT parameters such as the maximum standardised uptake value of the ovarian cancer (SUV ovary ), metastatic lesions (SUV meta ), and the metastatic lesion-to-ovarian cancer standardised uptake value ratio (SUV meta /SUV ovary ) were assessed in International Federation of Gynaecology and Obstetrics (FIGO) stage III, IV patients. Clinico-pathological data were retrospectively reviewed for 94 eligible patients. The median progression-free survival (PFS) was 18.5 months (range, 6-90 months), and 57 (60.6%) patients experienced recurrence. Older age [P = 0.017, hazard ratio (HR) 1.036, 95% CI 1.006-1.066], residual disease after surgery (P = 0.024, HR 1.907, 95% CI 1.087-3.346), and high SUV meta /SUV ovary (P = 0.019, HR 2.321, 95% CI 1.148-4.692) were independent risk factors of recurrence. Patients with high SUV meta /SUV ovary showed a significantly worse PFS than those with low SUV meta /SUV ovary (P = 0.007, log-rank test). Preoperative SUV meta /SUV ovary was significantly associated with recurrence and has an incremental prognostic value for PFS in patients with advanced serous EOC. (orig.)

  15. Network meta-analysis: an introduction for pharmacists.

    Science.gov (United States)

    Xu, Yina; Amiche, Mohamed Amine; Tadrous, Mina

    2018-05-21

    Network meta-analysis is a new tool used to summarize and compare studies for multiple interventions, irrespective of whether these interventions have been directly evaluated against each other. Network meta-analysis is quickly becoming the standard in conducting therapeutic reviews and clinical guideline development. However, little guidance is available to help pharmacists review network meta-analysis studies in their practice. Major institutions such as the Cochrane Collaboration, Agency for Healthcare Research and Quality, Canadian Agency for Drugs and Technologies in Health, and National Institute for Health and Care Excellence Decision Support Unit have endorsed utilizing network meta-analysis to establish therapeutic evidence and inform decision making. Our objective is to introduce this novel technique to pharmacy practitioners, and highlight key assumptions behind network meta-analysis studies.

  16. Meta-analysis of randomized clinical trials in the era of individual patient data sharing.

    Science.gov (United States)

    Kawahara, Takuya; Fukuda, Musashi; Oba, Koji; Sakamoto, Junichi; Buyse, Marc

    2018-06-01

    Individual patient data (IPD) meta-analysis is considered to be a gold standard when the results of several randomized trials are combined. Recent initiatives on sharing IPD from clinical trials offer unprecedented opportunities for using such data in IPD meta-analyses. First, we discuss the evidence generated and the benefits obtained by a long-established prospective IPD meta-analysis in early breast cancer. Next, we discuss a data-sharing system that has been adopted by several pharmaceutical sponsors. We review a number of retrospective IPD meta-analyses that have already been proposed using this data-sharing system. Finally, we discuss the role of data sharing in IPD meta-analysis in the future. Treatment effects can be more reliably estimated in both types of IPD meta-analyses than with summary statistics extracted from published papers. Specifically, with rich covariate information available on each patient, prognostic and predictive factors can be identified or confirmed. Also, when several endpoints are available, surrogate endpoints can be assessed statistically. Although there are difficulties in conducting, analyzing, and interpreting retrospective IPD meta-analysis utilizing the currently available data-sharing systems, data sharing will play an important role in IPD meta-analysis in the future.

  17. Spatial Bayesian latent factor regression modeling of coordinate-based meta-analysis data.

    Science.gov (United States)

    Montagna, Silvia; Wager, Tor; Barrett, Lisa Feldman; Johnson, Timothy D; Nichols, Thomas E

    2018-03-01

    Now over 20 years old, functional MRI (fMRI) has a large and growing literature that is best synthesised with meta-analytic tools. As most authors do not share image data, only the peak activation coordinates (foci) reported in the article are available for Coordinate-Based Meta-Analysis (CBMA). Neuroimaging meta-analysis is used to (i) identify areas of consistent activation; and (ii) build a predictive model of task type or cognitive process for new studies (reverse inference). To simultaneously address these aims, we propose a Bayesian point process hierarchical model for CBMA. We model the foci from each study as a doubly stochastic Poisson process, where the study-specific log intensity function is characterized as a linear combination of a high-dimensional basis set. A sparse representation of the intensities is guaranteed through latent factor modeling of the basis coefficients. Within our framework, it is also possible to account for the effect of study-level covariates (meta-regression), significantly expanding the capabilities of the current neuroimaging meta-analysis methods available. We apply our methodology to synthetic data and neuroimaging meta-analysis datasets. © 2017, The International Biometric Society.

  18. Spatial Bayesian Latent Factor Regression Modeling of Coordinate-based Meta-analysis Data

    Science.gov (United States)

    Montagna, Silvia; Wager, Tor; Barrett, Lisa Feldman; Johnson, Timothy D.; Nichols, Thomas E.

    2017-01-01

    Summary Now over 20 years old, functional MRI (fMRI) has a large and growing literature that is best synthesised with meta-analytic tools. As most authors do not share image data, only the peak activation coordinates (foci) reported in the paper are available for Coordinate-Based Meta-Analysis (CBMA). Neuroimaging meta-analysis is used to 1) identify areas of consistent activation; and 2) build a predictive model of task type or cognitive process for new studies (reverse inference). To simultaneously address these aims, we propose a Bayesian point process hierarchical model for CBMA. We model the foci from each study as a doubly stochastic Poisson process, where the study-specific log intensity function is characterised as a linear combination of a high-dimensional basis set. A sparse representation of the intensities is guaranteed through latent factor modeling of the basis coefficients. Within our framework, it is also possible to account for the effect of study-level covariates (meta-regression), significantly expanding the capabilities of the current neuroimaging meta-analysis methods available. We apply our methodology to synthetic data and neuroimaging meta-analysis datasets. PMID:28498564

  19. Risk factors for radiation-induced hypothyroidism: A Literature-Based Meta-Analysis

    DEFF Research Database (Denmark)

    Vogelius, Ivan R; Bentzen, Søren; Maraldo, Maja V

    2011-01-01

    BACKGROUND: A systematic overview and meta-analysis of studies reporting data on hypothyroidism (HT) after radiation therapy was conducted to identify risk factors for development of HT. METHODS: Published studies were identified from the PubMed and Embase databases and by hand-searching published...... reviews. Studies allowing the extraction of odds ratios (OR) for HT in 1 or more of several candidate clinical risk groups were included. A meta-analysis of the OR for development of HT with or without each of the candidate risk factors was performed. Furthermore, studies allowing the extraction......% risk of HT at a dose of 45 Gy but with considerable variation in the dose response between studies. Chemotherapy and age were not associated with risk of HT in this analysis. CONCLUSIONS: Several clinical risk factors for HT were identified. The risk of HT increases with increasing radiation dose...

  20. Tutoring Adolescents in Literacy: A Meta-Analysis

    Science.gov (United States)

    Jun, Seung Won; Ramirez, Gloria; Cumming, Alister

    2010-01-01

    What does research reveal about tutoring adolescents in literacy? We conducted a meta-analysis, identifying 152 published studies, of which 12 met rigorous inclusion criteria. We analyzed the 12 studies for the effects of tutoring according to the type, focus, and amount of tutoring; the number, age, and language background of students; and the…

  1. Reproducibility analysis of the stability and treatment of vertebral metastatic lesions

    Directory of Open Access Journals (Sweden)

    Raphael de Rezende Pratali

    2014-09-01

    Full Text Available OBJECTIVES: To investigate the reproducibility among spine surgeons in defining the treatment of vertebral metastatic lesions, taking into account the mechanical stability of injuries. METHODS: Twenty cases of isolated vertebral metastatic lesions were presented to ten experts. Their opinion was then asked about the stability of the lesion, as well as their treatment option. RESULTS: The interobserver Kappa coefficient obtained both for stability analysis as to the decision of the treatment was poor (0.334 and 0.248, respectively. CONCLUSIONS: Poor interobserver reproducibility was observed in deciding the treatment of vertebral metastatic lesions when considering the stability of the lesions.

  2. Statistical Power in Meta-Analysis

    Science.gov (United States)

    Liu, Jin

    2015-01-01

    Statistical power is important in a meta-analysis study, although few studies have examined the performance of simulated power in meta-analysis. The purpose of this study is to inform researchers about statistical power estimation on two sample mean difference test under different situations: (1) the discrepancy between the analytical power and…

  3. Cholelithiasis, cholecystectomy and risk of hepatocellular carcinoma: A meta-analysis

    Directory of Open Access Journals (Sweden)

    Lingyun Guo

    2014-01-01

    Full Text Available Available evidence of the relationship between cholelithiasis, cholecystectomy, and risk of liver cancer and hence we conducted a meta-analysis to investigate the relationships. PubMed, EMBASE, and ISI Web of Knowledge were searched to identify all published cohort studies and case-control studies that evaluated the relationships of cholelithiasis, cholecystectomy and risk of liver cancer and single-cohort studies which evaluated the incidence of liver cancer among patients who understood cholecystectomy (up to February 2013. Comprehensive meta-analysis software was used for meta-analysis. A total of 11 observational studies (six cohort studies and five case-control studies were included in this meta-analysis. The result from meta-analysis showed that cholecystectomy (risk ratio [RR]: 1.59, 95% confidence interval [CI]: 1.01-2.51, I2 = 72% and cholecystolithiasis (RR: 5.40, 95% CI: 3.69-7.89, I2 = 93% was associated with more liver cancer, especially for intrahepatic cholangiocarcinoma (ICC (cholecystectomy: RR: 3.51, 95% CI: 1.84-6.71, I2 = 26%; cholecystolithiasis: RR: 11.06, 95% CI: 6.99-17.52, I2 = 0%. The pooled standardized incidence rates (SIR of liver cancer in patients who understood cholecystectomy showed cholecystectomy might increase the incidence of liver cancer (SIR: 1.57, 95% CI: 1.13-2.20, I2 = 15%. Based on the results of the meta-analysis, cholecystectomy and cholecystolithiasis seemed to be involved in the development of liver cancer, especially for ICC. However, most available studies were case-control studies and short-term cohort studies, so the future studies should more long-term cohort studies should be well-conducted to evaluate the long-term relationship.

  4. Periodontal disease and risk of preeclampsia: a meta-analysis of observational studies.

    Directory of Open Access Journals (Sweden)

    Ben-Juan Wei

    Full Text Available BACKGROUND: Many epidemiological studies have found a positive association between periodontal disease (PD and the risk of preeclampsia, but the magnitude of this association varies and independent studies have reported conflicting findings. We performed a meta-analysis to ascertain the relationship between PD and preeclampsia. METHODS: The PubMed database was searched up to January 12, 2013, for relevant observational studies on an association between PD and the risk of preeclampsia. Data were extracted and analyzed independently by two authors. The meta-analysis was performed using comprehensive meta-analysis software. RESULTS: Thirteen observational case-control studies and two cohort studies, involving 1089 preeclampsia patients, were identified. Based on a random-effects meta-analysis, a significant association between PD and preeclampsia was identified (odds ratio = 2.79, 95% confidence interval CI, 2.01-3.01, P<0.0001. CONCLUSIONS: Although the causality remains unclear, the association between PD and preeclampsia may reflect the induction of PD by the preeclamptic state, or it may be part of an overall exaggerated inflammatory response to pregnancy. Larger randomized controlled trials with preeclampsia as the primary outcome and pathophysiological studies are required to explore causality and to dissect the biological mechanisms involved.

  5. The impact of pneumatic tube system on routine laboratory parameters: a systematic review and meta-analysis.

    Science.gov (United States)

    Kapoula, Georgia V; Kontou, Panagiota I; Bagos, Pantelis G

    2017-10-26

    Pneumatic tube system (PTS) is a widely used method of transporting blood samples in hospitals. The aim of this study was to evaluate the effects of the PTS transport in certain routine laboratory parameters as it has been implicated with hemolysis. A systematic review and a meta-analysis were conducted. PubMed and Scopus databases were searched (up until November 2016) to identify prospective studies evaluating the impact of PTS transport in hematological, biochemical and coagulation measurements. The random-effects model was used in the meta-analysis utilizing the mean difference (MD). Heterogeneity was quantitatively assessed using the Cohran's Q and the I2 index. Subgroup analysis, meta-regression analysis, sensitivity analysis, cumulative meta-analysis and assessment of publication bias were performed for all outcomes. From a total of 282 studies identified by the searching procedure, 24 were finally included in the meta-analysis. The meta-analysis yielded statistically significant results for potassium (K) [MD=0.04 mmol/L; 95% confidence interval (CI)=0.015-0.065; p=0.002], lactate dehydrogenase (LDH) (MD=10.343 U/L; 95% CI=6.132-14.554; panalysis and random-effects meta-regression analysis according to the speed and distance of the samples traveled via the PTS revealed that there is relation between the rate and the distance of PTS with the measurements of K, LDH, white blood cells and red blood cells. This meta-analysis suggests that PTS may be associated with alterations in K, LDH and AST measurements. Although these findings may not have any significant clinical effect on laboratory results, it is wise that each hospital validates their PTS.

  6. Food and drug cues activate similar brain regions: a meta-analysis of functional MRI studies.

    Science.gov (United States)

    Tang, D W; Fellows, L K; Small, D M; Dagher, A

    2012-06-06

    In healthy individuals, food cues can trigger hunger and feeding behavior. Likewise, smoking cues can trigger craving and relapse in smokers. Brain imaging studies report that structures involved in appetitive behaviors and reward, notably the insula, striatum, amygdala and orbital frontal cortex, tend to be activated by both visual food and smoking cues. Here, by carrying out a meta-analysis of human neuro-imaging studies, we investigate the neural network activated by: 1) food versus neutral cues (14 studies, 142 foci) 2) smoking versus neutral cues (15 studies, 176 foci) 3) smoking versus neutral cues when correlated with craving scores (7 studies, 108 foci). PubMed was used to identify cue-reactivity imaging studies that compared brain response to visual food or smoking cues to neutral cues. Fourteen articles were identified for the food meta-analysis and fifteen articles were identified for the smoking meta-analysis. Six articles were identified for the smoking cue correlated with craving analysis. Meta-analyses were carried out using activation likelihood estimation. Food cues were associated with increased blood oxygen level dependent (BOLD) response in the left amygdala, bilateral insula, bilateral orbital frontal cortex, and striatum. Smoking cues were associated with increased BOLD signal in the same areas, with the exception of the insula. However, the smoking meta-analysis of brain maps correlating cue-reactivity with subjective craving did identify the insula, suggesting that insula activation is only found when craving levels are high. The brain areas identified here are involved in learning, memory and motivation, and their cue-induced activity is an index of the incentive salience of the cues. Using meta-analytic techniques to combine a series of studies, we found that food and smoking cues activate comparable brain networks. There is significant overlap in brain regions responding to conditioned cues associated with natural and drug rewards

  7. A meta-analysis of electroconvulsive therapy efficacy in depression

    NARCIS (Netherlands)

    Kho, King Han; van Vreeswijk, Michiel Floris; Simpson, Steve; Zwinderman, Aeilko H.

    2003-01-01

    Recently published controlled studies comparing electroconvulsive therapy (ECT) with other treatments for depression offer the opportunity to perform a meta-analysis of ECT in depression. Fifteen studies were identified which fulfilled the inclusion criteria. From these controlled trials, 20 effect

  8. Meta-analysis identifies five novel loci associated with endometriosis highlighting key genes involved in hormone metabolism

    DEFF Research Database (Denmark)

    Sapkota, Yadav; Steinthorsdottir, Valgerdur; Morris, Andrew P.

    2017-01-01

    Endometriosis is a heritable hormone-dependent gynecological disorder, associated with severe pelvic pain and reduced fertility; however, its molecular mechanisms remain largely unknown. Here we perform a meta-analysis of 11 genome-wide association case-control data sets, totalling 17,045 endomet...

  9. Prognostic implication of the metastatic lesion-to-ovarian cancer standardised uptake value ratio in advanced serous epithelial ovarian cancer

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Hyun Hoon; Lee, Maria; Kim, Hee-Seung; Kim, Jae-Weon; Park, Noh-Hyun; Song, Yong Sang [Seoul National University College of Medicine, Department of Obstetrics and Gynaecology, Cancer Research Institute, Seoul (Korea, Republic of); Cheon, Gi Jeong [Seoul National University College of Medicine, Department of Nuclear Medicine, Cancer Research Institute, Seoul (Korea, Republic of)

    2017-11-15

    To evaluate the prognostic value of metabolic activity of metastatic lesions measured by {sup 18}F-flurodeoxyglucose ({sup 18}F-FDG) uptake on preoperative positron emission tomography/computed tomography (PET/CT) in patients with advanced serous epithelial ovarian cancer (EOC). Clinico-pathological variables and PET/CT parameters such as the maximum standardised uptake value of the ovarian cancer (SUV{sub ovary}), metastatic lesions (SUV{sub meta}), and the metastatic lesion-to-ovarian cancer standardised uptake value ratio (SUV{sub meta}/SUV{sub ovary}) were assessed in International Federation of Gynaecology and Obstetrics (FIGO) stage III, IV patients. Clinico-pathological data were retrospectively reviewed for 94 eligible patients. The median progression-free survival (PFS) was 18.5 months (range, 6-90 months), and 57 (60.6%) patients experienced recurrence. Older age [P = 0.017, hazard ratio (HR) 1.036, 95% CI 1.006-1.066], residual disease after surgery (P = 0.024, HR 1.907, 95% CI 1.087-3.346), and high SUV{sub meta}/SUV{sub ovary} (P = 0.019, HR 2.321, 95% CI 1.148-4.692) were independent risk factors of recurrence. Patients with high SUV{sub meta}/SUV{sub ovary} showed a significantly worse PFS than those with low SUV{sub meta}/SUV{sub ovary} (P = 0.007, log-rank test). Preoperative SUV{sub meta}/SUV{sub ovary} was significantly associated with recurrence and has an incremental prognostic value for PFS in patients with advanced serous EOC. (orig.)

  10. Meta-analysis of Drosophila circadian microarray studies identifies a novel set of rhythmically expressed genes.

    Directory of Open Access Journals (Sweden)

    Kevin P Keegan

    2007-11-01

    Full Text Available Five independent groups have reported microarray studies that identify dozens of rhythmically expressed genes in the fruit fly Drosophila melanogaster. Limited overlap among the lists of discovered genes makes it difficult to determine which, if any, exhibit truly rhythmic patterns of expression. We reanalyzed data from all five reports and found two sources for the observed discrepancies, the use of different expression pattern detection algorithms and underlying variation among the datasets. To improve upon the methods originally employed, we developed a new analysis that involves compilation of all existing data, application of identical transformation and standardization procedures followed by ANOVA-based statistical prescreening, and three separate classes of post hoc analysis: cross-correlation to various cycling waveforms, autocorrelation, and a previously described fast Fourier transform-based technique. Permutation-based statistical tests were used to derive significance measures for all post hoc tests. We find application of our method, most significantly the ANOVA prescreening procedure, significantly reduces the false discovery rate relative to that observed among the results of the original five reports while maintaining desirable statistical power. We identify a set of 81 cycling transcripts previously found in one or more of the original reports as well as a novel set of 133 transcripts not found in any of the original studies. We introduce a novel analysis method that compensates for variability observed among the original five Drosophila circadian array reports. Based on the statistical fidelity of our meta-analysis results, and the results of our initial validation experiments (quantitative RT-PCR, we predict many of our newly found genes to be bona fide cyclers, and suggest that they may lead to new insights into the pathways through which clock mechanisms regulate behavioral rhythms.

  11. When Is Hub Gene Selection Better than Standard Meta-Analysis?

    Science.gov (United States)

    Langfelder, Peter; Mischel, Paul S.; Horvath, Steve

    2013-01-01

    Since hub nodes have been found to play important roles in many networks, highly connected hub genes are expected to play an important role in biology as well. However, the empirical evidence remains ambiguous. An open question is whether (or when) hub gene selection leads to more meaningful gene lists than a standard statistical analysis based on significance testing when analyzing genomic data sets (e.g., gene expression or DNA methylation data). Here we address this question for the special case when multiple genomic data sets are available. This is of great practical importance since for many research questions multiple data sets are publicly available. In this case, the data analyst can decide between a standard statistical approach (e.g., based on meta-analysis) and a co-expression network analysis approach that selects intramodular hubs in consensus modules. We assess the performance of these two types of approaches according to two criteria. The first criterion evaluates the biological insights gained and is relevant in basic research. The second criterion evaluates the validation success (reproducibility) in independent data sets and often applies in clinical diagnostic or prognostic applications. We compare meta-analysis with consensus network analysis based on weighted correlation network analysis (WGCNA) in three comprehensive and unbiased empirical studies: (1) Finding genes predictive of lung cancer survival, (2) finding methylation markers related to age, and (3) finding mouse genes related to total cholesterol. The results demonstrate that intramodular hub gene status with respect to consensus modules is more useful than a meta-analysis p-value when identifying biologically meaningful gene lists (reflecting criterion 1). However, standard meta-analysis methods perform as good as (if not better than) a consensus network approach in terms of validation success (criterion 2). The article also reports a comparison of meta-analysis techniques applied to

  12. When is hub gene selection better than standard meta-analysis?

    Directory of Open Access Journals (Sweden)

    Peter Langfelder

    Full Text Available Since hub nodes have been found to play important roles in many networks, highly connected hub genes are expected to play an important role in biology as well. However, the empirical evidence remains ambiguous. An open question is whether (or when hub gene selection leads to more meaningful gene lists than a standard statistical analysis based on significance testing when analyzing genomic data sets (e.g., gene expression or DNA methylation data. Here we address this question for the special case when multiple genomic data sets are available. This is of great practical importance since for many research questions multiple data sets are publicly available. In this case, the data analyst can decide between a standard statistical approach (e.g., based on meta-analysis and a co-expression network analysis approach that selects intramodular hubs in consensus modules. We assess the performance of these two types of approaches according to two criteria. The first criterion evaluates the biological insights gained and is relevant in basic research. The second criterion evaluates the validation success (reproducibility in independent data sets and often applies in clinical diagnostic or prognostic applications. We compare meta-analysis with consensus network analysis based on weighted correlation network analysis (WGCNA in three comprehensive and unbiased empirical studies: (1 Finding genes predictive of lung cancer survival, (2 finding methylation markers related to age, and (3 finding mouse genes related to total cholesterol. The results demonstrate that intramodular hub gene status with respect to consensus modules is more useful than a meta-analysis p-value when identifying biologically meaningful gene lists (reflecting criterion 1. However, standard meta-analysis methods perform as good as (if not better than a consensus network approach in terms of validation success (criterion 2. The article also reports a comparison of meta-analysis techniques

  13. When is hub gene selection better than standard meta-analysis?

    Science.gov (United States)

    Langfelder, Peter; Mischel, Paul S; Horvath, Steve

    2013-01-01

    Since hub nodes have been found to play important roles in many networks, highly connected hub genes are expected to play an important role in biology as well. However, the empirical evidence remains ambiguous. An open question is whether (or when) hub gene selection leads to more meaningful gene lists than a standard statistical analysis based on significance testing when analyzing genomic data sets (e.g., gene expression or DNA methylation data). Here we address this question for the special case when multiple genomic data sets are available. This is of great practical importance since for many research questions multiple data sets are publicly available. In this case, the data analyst can decide between a standard statistical approach (e.g., based on meta-analysis) and a co-expression network analysis approach that selects intramodular hubs in consensus modules. We assess the performance of these two types of approaches according to two criteria. The first criterion evaluates the biological insights gained and is relevant in basic research. The second criterion evaluates the validation success (reproducibility) in independent data sets and often applies in clinical diagnostic or prognostic applications. We compare meta-analysis with consensus network analysis based on weighted correlation network analysis (WGCNA) in three comprehensive and unbiased empirical studies: (1) Finding genes predictive of lung cancer survival, (2) finding methylation markers related to age, and (3) finding mouse genes related to total cholesterol. The results demonstrate that intramodular hub gene status with respect to consensus modules is more useful than a meta-analysis p-value when identifying biologically meaningful gene lists (reflecting criterion 1). However, standard meta-analysis methods perform as good as (if not better than) a consensus network approach in terms of validation success (criterion 2). The article also reports a comparison of meta-analysis techniques applied to

  14. Acute toxicity tests and meta-analysis identify gaps in tropical ecotoxicology for amphibians.

    Science.gov (United States)

    Ghose, Sonia L; Donnelly, Maureen A; Kerby, Jacob; Whitfield, Steven M

    2014-09-01

    Amphibian populations are declining worldwide, particularly in tropical regions where amphibian diversity is highest. Pollutants, including agricultural pesticides, have been identified as a potential contributor to decline, yet toxicological studies of tropical amphibians are very rare. The present study assesses toxic effects on amphibians of 10 commonly used commercial pesticides in tropical agriculture using 2 approaches. First, the authors conducted 8-d toxicity assays with formulations of each pesticide using individually reared red-eyed tree frog (Agalychnis callidryas) tadpoles. Second, they conducted a review of available data for the lethal concentration to kill 50% of test animals from the US Environmental Protection Agency's ECOTOX database to allow comparison with their findings. Lethal concentration estimates from the assays ranged over several orders of magnitude. The nematicides terbufos and ethoprophos and the fungicide chlorothalonil were very highly toxic, with evident effects within an order of magnitude of environmental concentrations. Acute toxicity assays and meta-analysis show that nematicides and fungicides are generally more toxic than herbicides yet receive far less research attention than less toxic herbicides. Given that the tropics have a high diversity of amphibians, the findings emphasize the need for research into the effects of commonly used pesticides in tropical countries and should help guide future ecotoxicological research in tropical regions. © 2014 SETAC.

  15. Mucin Expression in Colorectal Cancer (CRC): Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Niv, Yaron; Rokkas, Theodore

    2018-05-18

    A body of evidence has suggested that mucins play an important role in adhesion, invasion, and cancer metastasis. However, this evidence is scarce and sometimes confusing. We performed a systematic review and meta-analysis of available studies to better define the role of mucins in the behavior of colorectal cancer (CRC). Medical literature was searched through November 30, 2017, using suitable keywords. Pooled estimates, that is, odd ratios (ORs), were obtained using fixed or random-effects models, as appropriate. Heterogeneity between studies was evaluated with the Cochran Q test and I values, whereas the likelihood of publication bias was assessed by constructing funnel plots. Their symmetry was estimated by the Begg and Mazumdar adjusted rank correlation test and by the Egger regression test. A total of 2234 CRC patients were included in 12 studies, eligible for meta-analysis. There was a significant difference concerning total mucin expression between CRC patients and controls [pooled ORs (95% confidence interval)=8.156 (2.624-25.354), test for overall effect Z=3.627, PCRC, that is advanced stage versus localized disease [ORs (95% confidence interval)=2.724 (1.211-6.127), Z= 2.423, P=0.015], as opposed to MUC2 and MUC4. MUC1 is overexpressed in CRC tissue comparing with healthy mucosa, and may have a role in the neoplastic transformation and metastatic process. MUC2 has probably no role in carcinogenesis.

  16. Meta-STEPP: subpopulation treatment effect pattern plot for individual patient data meta-analysis.

    Science.gov (United States)

    Wang, Xin Victoria; Cole, Bernard; Bonetti, Marco; Gelber, Richard D

    2016-09-20

    We have developed a method, called Meta-STEPP (subpopulation treatment effect pattern plot for meta-analysis), to explore treatment effect heterogeneity across covariate values in the meta-analysis setting for time-to-event data when the covariate of interest is continuous. Meta-STEPP forms overlapping subpopulations from individual patient data containing similar numbers of events with increasing covariate values, estimates subpopulation treatment effects using standard fixed-effects meta-analysis methodology, displays the estimated subpopulation treatment effect as a function of the covariate values, and provides a statistical test to detect possibly complex treatment-covariate interactions. Simulation studies show that this test has adequate type-I error rate recovery as well as power when reasonable window sizes are chosen. When applied to eight breast cancer trials, Meta-STEPP suggests that chemotherapy is less effective for tumors with high estrogen receptor expression compared with those with low expression. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  17. A Systematic Review and Meta-Analysis of Baseline Ohip-Edent Scores.

    Science.gov (United States)

    Duale, J M J; Patel, Y A; Wu, J; Hyde, T P

    2018-03-01

    OHIP-EDENT is widely used in the literature to assess Oral-Health-Related-Quality-of-Life (OHRQoL) for edentulous patients. However the normal variance and mean of the baseline OHIP scores has not been reported. It would facilitate critical appraisal of studies if we had knowledge of the normal variation and mean of baseline OHIP-EDENT scores. An established figure for baseline OHIP-EDENT, obtained from a meta-analysis, would simplify comparisons of studies and quantify variations in initial OHRQoL of the trial participants. The aim of this study is to quantify a normal baseline value for pre-operative OHIP-EDENT scores by a systematic review and meta-analysis of the available literature. A systematic literature review was carried. 83 papers were identified that included OHIP-EDENT values. After screening and eligibility assessment, 7 papers were selected and included in the meta-analysis. A meta-analysis for the 7 papers by a random-effect model yielded a mean baseline OHIP-EDENT score of 28.63 with a 95% Confidence intervals from 21.93 to 35.34. A pre-operative baseline OHIP-EDENT has been established by meta-analysis of published papers. This will facilitate the comparison of the initial OHRQoL of one study population to that found elsewhere in the published literature. Copyright© 2018 Dennis Barber Ltd.

  18. The Psychological Effects of Meditation: A Meta-Analysis

    Science.gov (United States)

    Sedlmeier, Peter; Eberth, Juliane; Schwarz, Marcus; Zimmermann, Doreen; Haarig, Frederik; Jaeger, Sonia; Kunze, Sonja

    2012-01-01

    In this meta-analysis, we give a comprehensive overview of the effects of meditation on psychological variables that can be extracted from empirical studies, concentrating on the effects of meditation on nonclinical groups of adult meditators. Mostly because of methodological problems, almost 3/4 of an initially identified 595 studies had to be…

  19. Dealing with missing standard deviation and mean values in meta-analysis of continuous outcomes: a systematic review.

    Science.gov (United States)

    Weir, Christopher J; Butcher, Isabella; Assi, Valentina; Lewis, Stephanie C; Murray, Gordon D; Langhorne, Peter; Brady, Marian C

    2018-03-07

    Rigorous, informative meta-analyses rely on availability of appropriate summary statistics or individual participant data. For continuous outcomes, especially those with naturally skewed distributions, summary information on the mean or variability often goes unreported. While full reporting of original trial data is the ideal, we sought to identify methods for handling unreported mean or variability summary statistics in meta-analysis. We undertook two systematic literature reviews to identify methodological approaches used to deal with missing mean or variability summary statistics. Five electronic databases were searched, in addition to the Cochrane Colloquium abstract books and the Cochrane Statistics Methods Group mailing list archive. We also conducted cited reference searching and emailed topic experts to identify recent methodological developments. Details recorded included the description of the method, the information required to implement the method, any underlying assumptions and whether the method could be readily applied in standard statistical software. We provided a summary description of the methods identified, illustrating selected methods in example meta-analysis scenarios. For missing standard deviations (SDs), following screening of 503 articles, fifteen methods were identified in addition to those reported in a previous review. These included Bayesian hierarchical modelling at the meta-analysis level; summary statistic level imputation based on observed SD values from other trials in the meta-analysis; a practical approximation based on the range; and algebraic estimation of the SD based on other summary statistics. Following screening of 1124 articles for methods estimating the mean, one approximate Bayesian computation approach and three papers based on alternative summary statistics were identified. Illustrative meta-analyses showed that when replacing a missing SD the approximation using the range minimised loss of precision and generally

  20. Dietary patterns and colorectal cancer risk: a meta-analysis.

    Science.gov (United States)

    Feng, Yu-Liang; Shu, Long; Zheng, Pei-Fen; Zhang, Xiao-Yan; Si, Cai-Juan; Yu, Xiao-Long; Gao, Wei; Zhang, Lun

    2017-05-01

    The analysis of dietary patterns has recently drawn considerable attention as a method of investigating the association between the overall whole diet and the risk of colorectal cancer. However, the results have yielded conflicting findings. Here, we carried out a meta-analysis to identify the association between dietary patterns and the risk of colorectal cancer. A total of 40 studies fulfilled the inclusion criteria and were included in this meta-analysis. The highest category of 'healthy' dietary pattern compared with the lowest category was apparently associated with a decreased risk for colorectal cancer [odds ratio (OR)=0.75; confidence interval (CI): 0.68-0.83; Pcolorectal cancer was shown for the highest compared with the lowest category of a 'western-style' dietary pattern (OR=1.40; CI: 1.26-1.56; Pcolorectal cancer in the highest compared with the lowest category of 'alcohol-consumption' pattern (OR=1.44; CI: 1.13-1.82; P=0.003). The results of this meta-analysis indicate that a 'healthy' dietary pattern may decrease the risk of colorectal cancer, whereas 'western-style' and 'alcohol-consumption' patterns may increase the risk of colorectal cancer.

  1. Neutrophil/lymphocyte ratio and platelet/lymphocyte ratio in mood disorders: A meta-analysis.

    Science.gov (United States)

    Mazza, Mario Gennaro; Lucchi, Sara; Tringali, Agnese Grazia Maria; Rossetti, Aurora; Botti, Eugenia Rossana; Clerici, Massimo

    2018-06-08

    The immune and inflammatory system is involved in the etiology of mood disorders. Neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR) and monocyte/lymphocyte ratio (MLR) are inexpensive and reproducible biomarkers of inflammation. This is the first meta-analysis exploring the role of NLR and PLR in mood disorder. We identified 11 studies according to our inclusion criteria from the main Electronic Databases. Meta-analyses were carried out generating pooled standardized mean differences (SMDs) between index and healthy controls (HC). Heterogeneity was estimated. Relevant sensitivity and meta-regression analyses were conducted. Subjects with bipolar disorder (BD) had higher NLR and PLR as compared with HC (respectively SMD = 0.672; p analysis evidenced an influence of bipolar phase on the overall estimate whit studies including subjects in manic and any bipolar phase showing a significantly higher NLR and PLR as compared with HC whereas the effect was not significant among studies including only euthymic bipolar subjects. Meta-regression showed that age and sex influenced the relationship between BD and NLR but not the relationship between BD and PLR. Meta-analysis was not carried out for MLR because our search identified only one study when comparing BD to HC, and only one study when comparing MDD to HC. Subjects with major depressive disorder (MDD) had higher NLR as compared with HC (SMD = 0.670; p = 0.028; I 2  = 89.931%). Heterogeneity-based sensitivity analyses and meta-regression confirmed these findings. Our meta-analysis supports the hypothesis that an inflammatory activation occurs in mood disorders and NLR and PLR may be useful to detect this activation. More researches including comparison of NLR, PLR and MLR between different bipolar phases and between BD and MDD are needed. Copyright © 2018 Elsevier Inc. All rights reserved.

  2. Macroeconomics of natural disasters : Meta-analysis and policy options

    NARCIS (Netherlands)

    P.A.G. van Bergeijk (Peter); S. Lazzaroni (Sara)

    2013-01-01

    textabstractWe use the case of the impact of natural disasters to analyse strengths and weaknesses of meta-analysis in an emerging research field. Macroeconomists have published on this issue since 2002 (we identified 22 studies to date). The results of the studies are contradictory and

  3. Association between developmental defects of enamel and dental caries: A systematic review and meta-analysis.

    Science.gov (United States)

    Vargas-Ferreira, F; Salas, M M S; Nascimento, G G; Tarquinio, S B C; Faggion, C M; Peres, M A; Thomson, W M; Demarco, F F

    2015-06-01

    Dental caries is the main problem oral health and it is not well established in the literature if the enamel defects are a risk factor for its development. Studies have reported a potential association between developmental defects enamel (DDE) and dental caries occurrence. We investigated the association between DDE and caries in permanent dentition of children and teenagers. A systematic review was carried out using four databases (Pubmed, Web of Science, Embase, and Science Direct), which were searched from their earliest records until December 31, 2014. Population-based studies assessing differences in dental caries experience according to the presence of enamel defects (and their types) were included. PRISMA guidelines for reporting systematic reviews were followed. Meta-analysis was performed to assess the pooled effect, and meta-regression was carried out to identify heterogeneity sources. From the 2558 initially identified papers, nine studies fulfilled all inclusion criteria after checking the titles, abstracts, references, and complete reading. Seven of them were included in the meta-analysis with random model. A positive association between enamel defects and dental caries was identified; meta-analysis showed that individuals with DDE had higher pooled odds of having dental caries experience [OR 2.21 (95% CI 1.3; 3.54)]. Meta-regression analysis demonstrated that adjustment for sociodemographic factors, countries' socioeconomic status, and bias (quality of studies) explained the high heterogeneity observed. A higher chance of dental caries should be expected among individuals with enamel defects. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Bayesian Meta-Analysis of Coefficient Alpha

    Science.gov (United States)

    Brannick, Michael T.; Zhang, Nanhua

    2013-01-01

    The current paper describes and illustrates a Bayesian approach to the meta-analysis of coefficient alpha. Alpha is the most commonly used estimate of the reliability or consistency (freedom from measurement error) for educational and psychological measures. The conventional approach to meta-analysis uses inverse variance weights to combine…

  5. Meta-analysis of genome-wide association studies identifies novel loci that influence cupping and the glaucomatous process

    NARCIS (Netherlands)

    Springelkamp, Henriët; Höhn, René; Mishra, Aniket; Hysi, Pirro G; Khor, Chiea-Chuen; Loomis, Stephanie J; Bailey, Jessica N Cooke; Gibson, Jane; Thorleifsson, Gudmar; Janssen, Sarah F; Luo, Xiaoyan; Ramdas, Wishal D; Vithana, Eranga; Nongpiur, Monisha E; Montgomery, Grant W; Xu, Liang; Mountain, Jenny E; Gharahkhani, Puya; Lu, Yi; Amin, Najaf; Karssen, Lennart C; Sim, Kar-Seng; van Leeuwen, Elisabeth M; Iglesias, Adriana I; Verhoeven, Virginie J M; Hauser, Michael A; Loon, Seng-Chee; Despriet, Dominiek D G; Nag, Abhishek; Venturini, Cristina; Sanfilippo, Paul G; Schillert, Arne; Kang, Jae H; Landers, John; Jonasson, Fridbert; Cree, Angela J; van Koolwijk, Leonieke M E; Rivadeneira, Fernando; Souzeau, Emmanuelle; Jonsson, Vesteinn; Menon, Geeta; Weinreb, Robert N; de Jong, Paulus T V M; Oostra, Ben A; Uitterlinden, André G; Hofman, Albert; Ennis, Sarah; Thorsteinsdottir, Unnur; Burdon, Kathryn P; Spector, Timothy D; Mirshahi, Alireza; Saw, Seang-Mei; Vingerling, Johannes R; Teo, Yik-Ying; Haines, Jonathan L; Wolfs, Roger C W; Lemij, Hans G; Tai, E-Shyong; Jansonius, Nomdo M; Jonas, Jost B; Cheng, Ching-Yu; Aung, Tin; Viswanathan, Ananth C; Klaver, Caroline C W; Craig, Jamie E; Macgregor, Stuart; Mackey, David A; Lotery, Andrew J; Stefansson, Kari; Bergen, Arthur A B; Young, Terri L; Wiggs, Janey L; Pfeiffer, Norbert; Wong, Tien-Yin; Pasquale, Louis R; Hewitt, Alex W; van Duijn, Cornelia M; Hammond, Christopher J

    2014-01-01

    Glaucoma is characterized by irreversible optic nerve degeneration and is the most frequent cause of irreversible blindness worldwide. Here, the International Glaucoma Genetics Consortium conducts a meta-analysis of genome-wide association studies of vertical cup-disc ratio (VCDR), an important

  6. Trial Sequential Methods for Meta-Analysis

    Science.gov (United States)

    Kulinskaya, Elena; Wood, John

    2014-01-01

    Statistical methods for sequential meta-analysis have applications also for the design of new trials. Existing methods are based on group sequential methods developed for single trials and start with the calculation of a required information size. This works satisfactorily within the framework of fixed effects meta-analysis, but conceptual…

  7. Risk factor screening to identify women requiring oral glucose tolerance testing to diagnose gestational diabetes: A systematic review and meta-analysis and analysis of two pregnancy cohorts.

    Directory of Open Access Journals (Sweden)

    Diane Farrar

    Full Text Available Easily identifiable risk factors including: obesity and ethnicity at high risk of diabetes are commonly used to indicate which women should be offered the oral glucose tolerance test (OGTT to diagnose gestational diabetes (GDM. Evidence regarding these risk factors is limited however. We conducted a systematic review (SR and meta-analysis and individual participant data (IPD analysis to evaluate the performance of risk factors in identifying women with GDM.We searched MEDLINE, Medline in Process, Embase, Maternity and Infant Care and the Cochrane Central Register of Controlled Trials (CENTRAL up to August 2016 and conducted additional reference checking. We included observational, cohort, case-control and cross-sectional studies reporting the performance characteristics of risk factors used to identify women at high risk of GDM. We had access to IPD from the Born in Bradford and Atlantic Diabetes in Pregnancy cohorts, all pregnant women in the two cohorts with data on risk factors and OGTT results were included.Twenty nine published studies with 211,698 women for the SR and a further 14,103 women from two birth cohorts (Born in Bradford and the Atlantic Diabetes in Pregnancy study for the IPD analysis were included. Six studies assessed the screening performance of guidelines; six examined combinations of risk factors; eight evaluated the number of risk factors and nine examined prediction models or scores. Meta-analysis using data from published studies suggests that irrespective of the method used, risk factors do not identify women with GDM well. Using IPD and combining risk factors to produce the highest sensitivities, results in low specificities (and so higher false positives. Strategies that use the risk factors of age (>25 or >30 and BMI (>25 or 30 perform as well as other strategies with additional risk factors included.Risk factor screening methods are poor predictors of which pregnant women will be diagnosed with GDM. A simple

  8. Osteosarcoma: A Meta-Analysis and Review of the Literature.

    Science.gov (United States)

    Friebele, Jill C; Peck, Jeffrey; Pan, Xueliang; Abdel-Rasoul, Mahmoud; Mayerson, Joel L

    2015-12-01

    Over the past 30 years, treatment advances and the addition of neoadjuvant chemotherapy have led to improved 5-year survival in patients with osteosarcoma. More recent literature suggests the overall prognosis remains highly variable, with little improvement since the introduction of neoadjuvant chemotherapy. Tumor necrosis is an important predictor of patient prognosis. Necrosis of more than 90% correlates with overall survival (OS) approaching 75%. We reviewed the history of osteosarcoma treatment and survival and performed a meta-analysis of the 2000-2011 literature. Forty articles were included in the study. Five-year OS was 63% (95% confidence interval, 60%-66%) in studies that included patients with metastatic and nonmetastatic disease and 71% (95% confidence interval, 67%-76%) in studies that included only patients with nonmetastatic disease. Fifty percent of the patients in the studies of those with nonmetastatic osteosarcoma achieved 90% necrosis on histology. Five-year OS and number of patients achieving 90% necrosis are consistent with previous reports. Research is needed to improve treatment regimens and patient outcomes.

  9. Smoking and olfactory dysfunction: A systematic literature review and meta-analysis.

    Science.gov (United States)

    Ajmani, Gaurav S; Suh, Helen H; Wroblewski, Kristen E; Pinto, Jayant M

    2017-08-01

    A systematic review and meta-analysis of the literature was undertaken, examining the association between tobacco smoking and olfactory function in humans, utilizing PubMed and Web of Science (1970-2015) as data sources. Systematic literature review and meta-analysis. This database review of studies of smoking and olfaction, with a focus on identifying high-quality studies (based on modified versions of the Newcastle-Ottawa Scale), used validated olfactory tests among the generally healthy population. We identified 11 studies meeting inclusion criteria. Of 10 cross-sectional studies, two were excluded from meta-analysis because the cohorts they studied were included in another article in the review. In meta-analysis, current smokers had substantially higher odds of olfactory dysfunction compared to never smokers (odds ratio [OR] = 1.59, 95% confidence interval [CI] = 1.37-1.85). In contrast, former smokers were found to have no difference in risk of impaired olfaction compared to never smokers (OR = 1.05, 95% CI = 0.91-1.21). The single longitudinal study reviewed found a trend toward increased risk of olfactory decline over time in ever smokers; this trend was stronger in current as compared to former smokers. Current smoking, but not former smoking, is associated with significantly increased risk of olfactory dysfunction, suggesting that the effects of smoking on olfaction may be reversible. Future studies that prospectively evaluate the impact of smoking cessation on improvement in olfactory function are warranted. N/A. Laryngoscope, 127:1753-1761, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

  10. Gene expression profiles help identify the Tissue of Origin for metastatic brain cancers

    Directory of Open Access Journals (Sweden)

    VandenBerg Scott R

    2010-04-01

    Full Text Available Abstract Background Metastatic brain cancers are the most common intracranial tumor and occur in about 15% of all cancer patients. In up to 10% of these patients, the primary tumor tissue remains unknown, even after a time consuming and costly workup. The Pathwork® Tissue of Origin Test (Pathwork Diagnostics, Redwood City, CA, USA is a gene expression test to aid in the diagnosis of metastatic, poorly differentiated and undifferentiated tumors. It measures the expression pattern of 1,550 genes in these tumors and compares it to the expression pattern of a panel of 15 known tumor types. The purpose of this study was to evaluate the performance of the Tissue of Origin Test in the diagnosis of primary sites for metastatic brain cancer patients. Methods Fifteen fresh-frozen metastatic brain tumor specimens of known origins met specimen requirements. These specimens were entered into the study and processed using the Tissue of Origin Test. Results were compared to the known primary site and the agreement between the two results was assessed. Results Fourteen of the fifteen specimens produced microarray data files that passed all quality metrics. One originated from a tissue type that was off-panel. Among the remaining 13 cases, the Tissue of Origin Test accurately predicted the available diagnosis in 12/13 (92.3% cases. Discussion This study demonstrates the accuracy of the Tissue of Origin Test when applied to predict the tissue of origin of metastatic brain tumors. This test could be a very useful tool for pathologists as they classify metastatic brain cancers.

  11. Garlic intake lowers fasting blood glucose: meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Hou, Li-qiong; Liu, Yun-hui; Zhang, Yi-yi

    2015-01-01

    Garlic is a common spicy flavouring agent also used for certain therapeutic purposes. Garlic's effects on blood glucose have been the subject of many clinical and animal studies, however, studies reporting hypoglycemic effects of garlic in humans are conflicting. A comprehensive literature search was conducted to identify relevant trials of garlic or garlic extracts on markers of glycemic control [fasting blood glucose (FBG), postprandial glucose (PPG), glycosylated haemoglobin (HbA1c)]. A meta-analysis of the effect of garlic intake on human was done to assess garlic's effectiveness in lowering glucose levels. Two reviewers extracted data from each of the identified studies. Seven eligible randomized controlled trials with 513 subjects were identified. Pooled analyses showed that garlic intake results in a statistically significant lowering in FBG [SMD=-1.67; 95% CI (-2.80, -0.55), p=0.004]. Our pooled analyses did not include PPG control and HbA1c outcomes. Because only 1 study included in the meta-analysis reported PPG variables and only 2 studies reported HbA1c variables. In conclusion, the current meta-analysis showed that the administration of garlic resulted in a significant reduction in FBG concentrations. More trials are needed to investigate the effectiveness of garlic on HbA1c and PPG.

  12. META-ANALYSIS: THE WAY FORWARD IN MEDICAL DISCOVERY

    African Journals Online (AJOL)

    data, and (6) report the results. Define the Research Question. A meta-analysis begins with a question. Common questions addressed in meta-analyses are whether one. META-ANALYSIS: THE WAY FORWARD IN MEDICAL DISCOVERY. Akinyemi J.O. MSc (Medical Statistics), B Tech (Comp. Sc.) Correspondence:.

  13. Efficacy of escitalopram compared to citalopram: a meta-analysis.

    Science.gov (United States)

    Montgomery, Stuart; Hansen, Thomas; Kasper, Siegfried

    2011-03-01

    The aim of this review was to assess the clinical relevance of the relative antidepressant efficacy of escitalopram and citalopram by meta-analysis. Studies in major depressive disorder (MDD) with both escitalopram and citalopram treatment arms were identified. Adult patients had to meet DSM-IV criteria for MDD. The primary outcome measure was the treatment difference in Montgomery-Asberg Depression Rating Scale (MADRS) total score at week 8 (or last assessment if escitalopram, n=995; citalopram, n=1014). Escitalopram was significantly more effective than citalopram in overall treatment effect, with an estimated mean treatment difference of 1.7 points at week 8 (or last assessment if escitalopram. In this meta-analysis, the statistically significant superior efficacy of escitalopram compared to citalopram was shown to be clinically relevant.

  14. Meta-Analysis in Stata Using Gllamm

    Science.gov (United States)

    Bagos, Pantelis G.

    2015-01-01

    There are several user-written programs for performing meta-analysis in Stata (Stata Statistical Software: College Station, TX: Stata Corp LP). These include metan, metareg, mvmeta, and glst. However, there are several cases for which these programs do not suffice. For instance, there is no software for performing univariate meta-analysis with…

  15. Using structural equation modeling for network meta-analysis.

    Science.gov (United States)

    Tu, Yu-Kang; Wu, Yun-Chun

    2017-07-14

    Network meta-analysis overcomes the limitations of traditional pair-wise meta-analysis by incorporating all available evidence into a general statistical framework for simultaneous comparisons of several treatments. Currently, network meta-analyses are undertaken either within the Bayesian hierarchical linear models or frequentist generalized linear mixed models. Structural equation modeling (SEM) is a statistical method originally developed for modeling causal relations among observed and latent variables. As random effect is explicitly modeled as a latent variable in SEM, it is very flexible for analysts to specify complex random effect structure and to make linear and nonlinear constraints on parameters. The aim of this article is to show how to undertake a network meta-analysis within the statistical framework of SEM. We used an example dataset to demonstrate the standard fixed and random effect network meta-analysis models can be easily implemented in SEM. It contains results of 26 studies that directly compared three treatment groups A, B and C for prevention of first bleeding in patients with liver cirrhosis. We also showed that a new approach to network meta-analysis based on the technique of unrestricted weighted least squares (UWLS) method can also be undertaken using SEM. For both the fixed and random effect network meta-analysis, SEM yielded similar coefficients and confidence intervals to those reported in the previous literature. The point estimates of two UWLS models were identical to those in the fixed effect model but the confidence intervals were greater. This is consistent with results from the traditional pairwise meta-analyses. Comparing to UWLS model with common variance adjusted factor, UWLS model with unique variance adjusted factor has greater confidence intervals when the heterogeneity was larger in the pairwise comparison. The UWLS model with unique variance adjusted factor reflects the difference in heterogeneity within each comparison

  16. Meta-Analysis of Coefficient Alpha

    Science.gov (United States)

    Rodriguez, Michael C.; Maeda, Yukiko

    2006-01-01

    The meta-analysis of coefficient alpha across many studies is becoming more common in psychology by a methodology labeled reliability generalization. Existing reliability generalization studies have not used the sampling distribution of coefficient alpha for precision weighting and other common meta-analytic procedures. A framework is provided for…

  17. Data analysis with the DIANA meta-scheduling approach

    International Nuclear Information System (INIS)

    Anjum, A; McClatchey, R; Willers, I

    2008-01-01

    The concepts, design and evaluation of the Data Intensive and Network Aware (DIANA) meta-scheduling approach for solving the challenges of data analysis being faced by CERN experiments are discussed in this paper. Our results suggest that data analysis can be made robust by employing fault tolerant and decentralized meta-scheduling algorithms supported in our DIANA meta-scheduler. The DIANA meta-scheduler supports data intensive bulk scheduling, is network aware and follows a policy centric meta-scheduling. In this paper, we demonstrate that a decentralized and dynamic meta-scheduling approach is an effective strategy to cope with increasing numbers of users, jobs and datasets. We present 'quality of service' related statistics for physics analysis through the application of a policy centric fair-share scheduling model. The DIANA meta-schedulers create a peer-to-peer hierarchy of schedulers to accomplish resource management that changes with evolving loads and is dynamic and adapts to the volatile nature of the resources

  18. Macroeconomics of Natural Disasters: Strengths and Weaknesses of Meta-Analysis Versus Review of Literature.

    Science.gov (United States)

    A G van Bergeijk, Peter; Lazzaroni, Sara

    2015-06-01

    We use the case of the macroeconomic impact of natural disasters to analyze strengths and weaknesses of meta-analysis in an emerging research field. Macroeconomists have published on this issue since 2002 (we identified 60 studies to date). The results of the studies are contradictory and therefore the need to synthesize the available research is evident. Meta-analysis is a useful method in this field. An important aim of our article is to show how one can use the identified methodological characteristics to better understand the robustness and importance of new findings. To provide a comparative perspective, we contrast our meta-analysis and its findings with the major influential research synthesis in the field: the IPCC's 2012 special report Managing the Risks of Extreme Events and Disasters to Advance Climate Change Adaptation. We show that the IPCC could have been more confident about the negative economic impact of disasters and more transparent on inclusion and qualification of studies, if it had been complemented by a meta-analysis. Our meta-analysis shows that, controlling for modeling strategies and data set, the impact of disasters is significantly negative. The evidence is strongest for direct costs studies where we see no difference between our larger sample and the studies included in the IPCC report. Direct cost studies and indirect cost studies differ significantly, both in terms of the confidence that can be attached to a negative impact of natural disasters and in terms of the sources of heterogeneity of the findings reported in the primary studies. © 2015 Society for Risk Analysis.

  19. Swimming attendance during childhood and development of asthma: Meta-analysis.

    Science.gov (United States)

    Valeriani, Federica; Protano, Carmela; Vitali, Matteo; Romano Spica, Vincenzo

    2017-05-01

    The association between asthma and swimming pool attendance has not been demonstrated and currently there are conflicting results. In order to clarify the association between asthma diagnosis in children and swimming pool attendance, and to assess the consistency of the available epidemiological studies, we completed a literature analysis on the relationship between the exposure to disinfection by-products in indoor swimming pools during childhood and asthma diagnosis. Following the Meta-analysis of Observational Studies in Epidemiology (MOOSE) and Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) criteria, a systematic review and meta-analysis was performed by searching MEDLINE via PubMed, TOXNET, and Scopus databases (from inception to 20 April 2015) using the key word "Asthma" together with "swimming pool", "disinfection by-products", "indoor air pollution" and "children". Inclusion criteria were: English language, a complete analytic study design involving a cohort of children (0-16 years), a well-defined definition of exposure, and the presence of data on effect and variance. Studies on in vivo, in vitro or professional and accidental exposure were excluded. After a screening process, seven reports (n = 5851 subjects) were included out of a total of 2928 references. The reported OR of the association between swimming pool attendance and asthma prevalence ranged from 0.58 to 2.30. The present meta-analysis failed to identify a significant difference in asthma development between children attending swimming pools and controls (OR, 1.084; 95% CI: 0.89-1.31). Swimming in childhood does not increase the likelihood of doctor-diagnosed asthma. Based on this meta-analysis review, the association of the disease with indoor pool attendance is still unclear. © 2016 Japan Pediatric Society.

  20. Nutritional support in chronic obstructive pulmonary disease: a systematic review and meta-analysis.

    Science.gov (United States)

    Collins, Peter F; Stratton, Rebecca J; Elia, Marinos

    2012-06-01

    The efficacy of nutritional support in the management of malnutrition in chronic obstructive pulmonary disease (COPD) is controversial. Previous meta-analyses, based on only cross-sectional analysis at the end of intervention trials, found no evidence of improved outcomes. The objective was to conduct a meta-analysis of randomized controlled trials (RCTs) to clarify the efficacy of nutritional support in improving intake, anthropometric measures, and grip strength in stable COPD. Literature databases were searched to identify RCTs comparing nutritional support with controls in stable COPD. Thirteen RCTs (n = 439) of nutritional support [dietary advice (1 RCT), oral nutritional supplements (ONS; 11 RCTs), and enteral tube feeding (1 RCT)] with a control comparison were identified. An analysis of the changes induced by nutritional support and those obtained only at the end of the intervention showed significantly greater increases in mean total protein and energy intakes with nutritional support of 14.8 g and 236 kcal daily. Meta-analyses also showed greater mean (±SE) improvements in favor of nutritional support for body weight (1.94 ± 0.26 kg, P groups. This systematic review and meta-analysis showed that nutritional support, mainly in the form of ONS, improves total intake, anthropometric measures, and grip strength in COPD. These results contrast with the results of previous analyses that were based on only cross-sectional measures at the end of intervention trials.

  1. Genome-wide association meta-analysis of human longevity identifies a novel locus conferring survival beyond 90 years of age

    DEFF Research Database (Denmark)

    Deelen, Joris; Beekman, Marian; Uh, Hae-Won

    2014-01-01

    descent (≥ 85 years) and 16 121 younger controls (controls. In addition, we performed a subset analysis in cases aged ≥ 90 years. We observed genome-wide significant association with longevity, as reflected...... by survival to ages beyond 90 years, at a novel locus, rs2149954, on chromosome 5q33.3 (OR = 1.10, P = 1.74 × 10(-8)). We also confirmed association of rs4420638 on chromosome 19q13.32 (OR = 0.72, P = 3.40 × 10(-36)), representing the TOMM40/APOE/APOC1 locus. In a prospective meta-analysis (n = 34 103......, independent of blood pressure. We report on the first GWAS-identified longevity locus on chromosome 5q33.3 influencing survival in the general European population. The minor allele of this locus associates with low blood pressure in middle age, although the contribution of this allele to survival may be less...

  2. Diagnostic performance of neck circumference to identify overweight and obesity as defined by body mass index in children and adolescents: systematic review and meta-analysis.

    Science.gov (United States)

    Ma, Chunming; Wang, Rui; Liu, Yue; Lu, Qiang; Liu, Xiaoli; Yin, Fuzai

    2017-05-01

    The neck circumference (NC) has been shown to be an accurate index for screening overweight and obesity in children and adolescents. To perform a meta-analysis to assess the performance of NC for the assessment of overweight and obesity. Data sources were PubMed and EMBASE up to March 2016. Studies providing measures of diagnostic performance of NC and using body mass index as reference standard were included. Six eligible studies that evaluated 11 214 children and adolescents aged 6-18 years were included in the meta-analysis. NC showed pooled sensitivity to detect high body mass index of 0.780 (95% confidence interval [CI] = 0.765-0.794), specificity of 0.746 (95% CI =  0.736-0.756) and a diagnostic odds ratio of 17.343 (95% CI =  8.743-34.405). The NC had moderate diagnostic accuracy for identifying overweight and obesity in children and adolescents.

  3. A Meta-Analysis Identifies New Loci Associated with Body Mass index in Individuals of African Ancestry

    Science.gov (United States)

    Monda, Keri L.; Chen, Gary K.; Taylor, Kira C.; Palmer, Cameron; Edwards, Todd L.; Lange, Leslie A.; Ng, Maggie C.Y.; Adeyemo, Adebowale A.; Allison, Matthew A.; Bielak, Lawrence F.; Chen, Guanji; Graff, Mariaelisa; Irvin, Marguerite R.; Rhie, Suhn K.; Li, Guo; Liu, Yongmei; Liu, Youfang; Lu, Yingchang; Nalls, Michael A.; Sun, Yan V.; Wojczynski, Mary K.; Yanek, Lisa R.; Aldrich, Melinda C.; Ademola, Adeyinka; Amos, Christopher I.; Bandera, Elisa V.; Bock, Cathryn H.; Britton, Angela; Broeckel, Ulrich; Cai, Quiyin; Caporaso, Neil E.; Carlson, Chris; Carpten, John; Casey, Graham; Chen, Wei-Min; Chen, Fang; Chen, Yii-Der I.; Chiang, Charleston W.K.; Coetzee, Gerhard A.; Demerath, Ellen; Deming-Halverson, Sandra L.; Driver, Ryan W.; Dubbert, Patricia; Feitosa, Mary F.; Freedman, Barry I.; Gillanders, Elizabeth M.; Gottesman, Omri; Guo, Xiuqing; Haritunians, Talin; Harris, Tamara; Harris, Curtis C.; Hennis, Anselm JM; Hernandez, Dena G.; McNeill, Lorna H.; Howard, Timothy D.; Howard, Barbara V.; Howard, Virginia J.; Johnson, Karen C.; Kang, Sun J.; Keating, Brendan J.; Kolb, Suzanne; Kuller, Lewis H.; Kutlar, Abdullah; Langefeld, Carl D.; Lettre, Guillaume; Lohman, Kurt; Lotay, Vaneet; Lyon, Helen; Manson, JoAnn E.; Maixner, William; Meng, Yan A.; Monroe, Kristine R.; Morhason-Bello, Imran; Murphy, Adam B.; Mychaleckyj, Josyf C.; Nadukuru, Rajiv; Nathanson, Katherine L.; Nayak, Uma; N’Diaye, Amidou; Nemesure, Barbara; Wu, Suh-Yuh; Leske, M. Cristina; Neslund-Dudas, Christine; Neuhouser, Marian; Nyante, Sarah; Ochs-Balcom, Heather; Ogunniyi, Adesola; Ogundiran, Temidayo O.; Ojengbede, Oladosu; Olopade, Olufunmilayo I.; Palmer, Julie R.; Ruiz-Narvaez, Edward A.; Palmer, Nicholette D.; Press, Michael F.; Rampersaud, Evandine; Rasmussen-Torvik, Laura J.; Rodriguez-Gil, Jorge L.; Salako, Babatunde; Schadt, Eric E.; Schwartz, Ann G.; Shriner, Daniel A.; Siscovick, David; Smith, Shad B.; Wassertheil-Smoller, Sylvia; Speliotes, Elizabeth K.; Spitz, Margaret R.; Sucheston, Lara; Taylor, Herman; Tayo, Bamidele O.; Tucker, Margaret A.; Van Den Berg, David J.; Velez Edwards, Digna R.; Wang, Zhaoming; Wiencke, John K.; Winkler, Thomas W.; Witte, John S.; Wrensch, Margaret; Wu, Xifeng; Yang, James J.; Levin, Albert M.; Young, Taylor R.; Zakai, Neil A.; Cushman, Mary; Zanetti, Krista A.; Zhao, Jing Hua; Zhao, Wei; Zheng, Yonglan; Zhou, Jie; Ziegler, Regina G.; Zmuda, Joseph M.; Fernandes, Jyotika K.; Gilkeson, Gary S.; Kamen, Diane L.; Hunt, Kelly J.; Spruill, Ida J.; Ambrosone, Christine B.; Ambs, Stefan; Arnett, Donna K.; Atwood, Larry; Becker, Diane M.; Berndt, Sonja I.; Bernstein, Leslie; Blot, William J.; Borecki, Ingrid B.; Bottinger, Erwin P.; Bowden, Donald W.; Burke, Gregory; Chanock, Stephen J.; Cooper, Richard S.; Ding, Jingzhong; Duggan, David; Evans, Michele K.; Fox, Caroline; Garvey, W. Timothy; Bradfield, Jonathan P.; Hakonarson, Hakon; Grant, Struan F.A.; Hsing, Ann; Chu, Lisa; Hu, Jennifer J.; Huo, Dezheng; Ingles, Sue A.; John, Esther M.; Jordan, Joanne M.; Kabagambe, Edmond K.; Kardia, Sharon L.R.; Kittles, Rick A.; Goodman, Phyllis J.; Klein, Eric A.; Kolonel, Laurence N.; Le Marchand, Loic; Liu, Simin; McKnight, Barbara; Millikan, Robert C.; Mosley, Thomas H.; Padhukasahasram, Badri; Williams, L. Keoki; Patel, Sanjay R.; Peters, Ulrike; Pettaway, Curtis A.; Peyser, Patricia A.; Psaty, Bruce M.; Redline, Susan; Rotimi, Charles N.; Rybicki, Benjamin A.; Sale, Michèle M.; Schreiner, Pamela J.; Signorello, Lisa B.; Singleton, Andrew B.; Stanford, Janet L.; Strom, Sara S.; Thun, Michael J.; Vitolins, Mara; Zheng, Wei; Moore, Jason H.; Williams, Scott M.; Zhu, Xiaofeng; Zonderman, Alan B.; Kooperberg, Charles; Papanicolaou, George; Henderson, Brian E.; Reiner, Alex P.; Hirschhorn, Joel N.; Loos, Ruth JF; North, Kari E.; Haiman, Christopher A.

    2013-01-01

    Genome-wide association studies (GWAS) have identified 36 loci associated with body mass index (BMI), predominantly in populations of European ancestry. We conducted a meta-analysis to examine the association of >3.2 million SNPs with BMI in 39,144 men and women of African ancestry, and followed up the most significant associations in an additional 32,268 individuals of African ancestry. We identified one novel locus at 5q33 (GALNT10, rs7708584, p=3.4×10−11) and another at 7p15 when combined with data from the Giant consortium (MIR148A/NFE2L3, rs10261878, p=1.2×10−10). We also found suggestive evidence of an association at a third locus at 6q16 in the African ancestry sample (KLHL32, rs974417, p=6.9×10−8). Thirty-two of the 36 previously established BMI variants displayed directionally consistent effect estimates in our GWAS (binomial p=9.7×10−7), of which five reached genome-wide significance. These findings provide strong support for shared BMI loci across populations as well as for the utility of studying ancestrally diverse populations. PMID:23583978

  4. Forecasting urban water demand: A meta-regression analysis.

    Science.gov (United States)

    Sebri, Maamar

    2016-12-01

    Water managers and planners require accurate water demand forecasts over the short-, medium- and long-term for many purposes. These range from assessing water supply needs over spatial and temporal patterns to optimizing future investments and planning future allocations across competing sectors. This study surveys the empirical literature on the urban water demand forecasting using the meta-analytical approach. Specifically, using more than 600 estimates, a meta-regression analysis is conducted to identify explanations of cross-studies variation in accuracy of urban water demand forecasting. Our study finds that accuracy depends significantly on study characteristics, including demand periodicity, modeling method, forecasting horizon, model specification and sample size. The meta-regression results remain robust to different estimators employed as well as to a series of sensitivity checks performed. The importance of these findings lies in the conclusions and implications drawn out for regulators and policymakers and for academics alike. Copyright © 2016. Published by Elsevier Ltd.

  5. Elevated osteopontin and thrombospondin expression identifies malignant human breast carcinoma but is not indicative of metastatic status

    International Nuclear Information System (INIS)

    Wang-Rodriguez, Jessica; Urquidi, Virginia; Rivard, Amber; Goodison, Steve

    2003-01-01

    Our previous characterization of a human breast tumor metastasis model identified several candidate metastasis genes. The expression of osteopontin (OPN) correlated with the metastatic phenotype, whereas thrombospondin-1 (TSP-1) and tyrosinase-related protein-1 (TYRP-1) correlated with the nonmetastatic phenotype of independent MDA-MB-435 cell lines implanted orthotopically into athymic mice. The aim of the present study was to examine the cellular distribution of these molecules in human breast tissue and to determine whether the relative expression level of these three genes is associated with human breast tumor metastasis. Sixty-eight fresh, frozen specimens including 31 primary infiltrating ductal carcinomas, 22 nodal metastases, 10 fibroadenomas, and five normal breast tissues were evaluated for OPN expression, TSP-1 expression and TYRP-1 expression. Immunohistochemistry was performed to monitor the cellular distribution and to qualitatively assess expression. Quantitative analysis was achieved by enrichment of breast epithelial cells using laser-capture microdissection and subsequent real-time, quantitative PCR. The epithelial components of the breast tissue were the source of OPN and TSP-1 expression, whereas TYRP-1 was present in both the epithelial and stromal components. Both OPN and TSP-1 expression were significantly higher in malignant epithelial sources over normal and benign epithelial sources, but no difference in expression levels was evident between primary tumors with or without metastases, nor between primary and metastatic carcinomas. Elevated expression of OPN and TSP-1 may play a role in the pathogenesis of breast cancer. The multiplex analysis of these molecules may enhance our ability to diagnose and/or prognosticate human breast malignancy

  6. Relaxation training for anxiety: a ten-years systematic review with meta-analysis.

    Science.gov (United States)

    Manzoni, Gian Mauro; Pagnini, Francesco; Castelnuovo, Gianluca; Molinari, Enrico

    2008-06-02

    Relaxation training is a common treatment for anxiety problems. Lacking is a recent quantitative meta-analysis that enhances understanding of the variability and clinical significance of anxiety reduction outcomes after relaxation treatment. All studies (1997-2007), both RCT, observational and without control group, evaluating the efficacy of relaxation training (Jacobson's progressive relaxation, autogenic training, applied relaxation and meditation) for anxiety problems and disorders were identified by comprehensive electronic searches with Pubmed, Psychinfo and Cochrane Registers, by checking references of relevant studies and of other reviews. Our primary outcome was anxiety measured with psychometric questionnaires. Meta-analysis was undertaken synthesizing the data from all trials, distinguishing within and between effect sizes. 27 studies qualified for the inclusion in the meta-analysis. As hypothesized, relaxation training showed a medium-large effect size in the treatment of anxiety. Cohen's d was .57 (95% CI: .52 to .68) in the within analysis and .51 (95% CI: .46 to .634) in the between group analysis. Efficacy was higher for meditation, among volunteers and for longer treatments. Implications and limitations are discussed. The results show consistent and significant efficacy of relaxation training in reducing anxiety. This meta-analysis extends the existing literature through facilitation of a better understanding of the variability and clinical significance of anxiety improvement subsequent to relaxation training.

  7. MetaSeq: privacy preserving meta-analysis of sequencing-based association studies.

    Science.gov (United States)

    Singh, Angad Pal; Zafer, Samreen; Pe'er, Itsik

    2013-01-01

    Human genetics recently transitioned from GWAS to studies based on NGS data. For GWAS, small effects dictated large sample sizes, typically made possible through meta-analysis by exchanging summary statistics across consortia. NGS studies groupwise-test for association of multiple potentially-causal alleles along each gene. They are subject to similar power constraints and therefore likely to resort to meta-analysis as well. The problem arises when considering privacy of the genetic information during the data-exchange process. Many scoring schemes for NGS association rely on the frequency of each variant thus requiring the exchange of identity of the sequenced variant. As such variants are often rare, potentially revealing the identity of their carriers and jeopardizing privacy. We have thus developed MetaSeq, a protocol for meta-analysis of genome-wide sequencing data by multiple collaborating parties, scoring association for rare variants pooled per gene across all parties. We tackle the challenge of tallying frequency counts of rare, sequenced alleles, for metaanalysis of sequencing data without disclosing the allele identity and counts, thereby protecting sample identity. This apparent paradoxical exchange of information is achieved through cryptographic means. The key idea is that parties encrypt identity of genes and variants. When they transfer information about frequency counts in cases and controls, the exchanged data does not convey the identity of a mutation and therefore does not expose carrier identity. The exchange relies on a 3rd party, trusted to follow the protocol although not trusted to learn about the raw data. We show applicability of this method to publicly available exome-sequencing data from multiple studies, simulating phenotypic information for powerful meta-analysis. The MetaSeq software is publicly available as open source.

  8. Systematic review and meta-analysis: tools for the information age.

    Science.gov (United States)

    Weatherall, Mark

    2017-11-01

    The amount of available biomedical information is vast and growing. Natural limitations of the way clinicians and researchers approach this treasure trove of information comprise difficulties locating the information, and once located, cognitive biases may lead to inappropriate use of the information. Systematic reviews and meta-analyses represent important tools in the information age to improve knowledge and action. Systematic reviews represent a census approach to identifying literature to avoid non-response bias. They are a necessary prelude to producing combined quantitative summaries of associations or treatment effects. Meta-analysis comprises the arithmetical techniques for producing combined summaries from individual study reports. Careful, thoughtful and rigorous use of these tools is likely to enhance knowledge and action. Use of standard guidelines, such as the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, or embedding these activities within collaborative groups such as the Cochrane Collaboration, are likely to lead to more useful systematic review and meta-analysis reporting. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  9. Novel non-HLA-susceptible regions determined by meta-analysis of ...

    Indian Academy of Sciences (India)

    We identified novel non-HLA-susceptible regions for ankylosing spondylitis (AS) by applying the genome-search-meta-analysis (GSMA) method to combine the previous four AS genomewide scan studies including 479 families with 1175 affected individuals. Three original genomescans were mainly analysed for Caucasian ...

  10. Multivariate Methods for Meta-Analysis of Genetic Association Studies.

    Science.gov (United States)

    Dimou, Niki L; Pantavou, Katerina G; Braliou, Georgia G; Bagos, Pantelis G

    2018-01-01

    Multivariate meta-analysis of genetic association studies and genome-wide association studies has received a remarkable attention as it improves the precision of the analysis. Here, we review, summarize and present in a unified framework methods for multivariate meta-analysis of genetic association studies and genome-wide association studies. Starting with the statistical methods used for robust analysis and genetic model selection, we present in brief univariate methods for meta-analysis and we then scrutinize multivariate methodologies. Multivariate models of meta-analysis for a single gene-disease association studies, including models for haplotype association studies, multiple linked polymorphisms and multiple outcomes are discussed. The popular Mendelian randomization approach and special cases of meta-analysis addressing issues such as the assumption of the mode of inheritance, deviation from Hardy-Weinberg Equilibrium and gene-environment interactions are also presented. All available methods are enriched with practical applications and methodologies that could be developed in the future are discussed. Links for all available software implementing multivariate meta-analysis methods are also provided.

  11. Primary tumor resection in metastatic breast cancer: A propensity-matched analysis, 1988-2011 SEER data base.

    Science.gov (United States)

    Vohra, Nasreen A; Brinkley, Jason; Kachare, Swapnil; Muzaffar, Mahvish

    2018-03-02

    Primary tumor resection (PTR) in metastatic breast cancer is not a standard treatment modality, and its impact on survival is conflicting. The primary objective of this study was to analyze impact of PTR on survival in metastatic patients with breast cancer. A retrospective study of metastatic patients with breast cancer was conducted using the 1988-2011 Surveillance, Epidemiology, and End Results (SEER) data base. Cox proportional hazards regression models were used to evaluate the relationship between PTR and survival and to adjust for the heterogeneity between the groups, and a propensity score-matched analysis was also performed. A total of 29 916 patients with metastatic breast cancer were included in the study, and 15 129 (51%) of patients underwent primary tumor resection, and 14 787 (49%) patients did not undergo surgery. Overall, decreasing trend in PTR for metastatic breast cancer in last decades was noted. Primary tumor resection was associated with a longer median OS (34 vs 18 months). In a propensity score-matched analysis, prognosis was also more favorable in the resected group (P = .0017). Primary tumor resection in metastatic breast cancer was associated with survival improvement, and the improvement persisted in propensity-matched analysis. © 2018 Wiley Periodicals, Inc.

  12. a meta-analysis

    Indian Academy of Sciences (India)

    Chrissa G. Tsiara

    2018-03-13

    Mar 13, 2018 ... a meta-analysis of case–control studies was conducted. Univariate and ...... recent hepatitis C virus: potential benefit for ribavirin use in. HCV/HIV ... C/G polymorphism in breast pathologies and in HIV-infected patients.

  13. A genome-wide association meta-analysis identifies new childhood obesity loci

    DEFF Research Database (Denmark)

    Bradfield, Jonathan P; Taal, H Rob; Timpson, Nicholas J

    2012-01-01

    Multiple genetic variants have been associated with adult obesity and a few with severe obesity in childhood; however, less progress has been made in establishing genetic influences on common early-onset obesity. We performed a North American, Australian and European collaborative meta...

  14. Game-based digital interventions for depression therapy: a systematic review and meta-analysis.

    Science.gov (United States)

    Li, Jinhui; Theng, Yin-Leng; Foo, Schubert

    2014-08-01

    The aim of this study was to review the existing literature on game-based digital interventions for depression systematically and examine their effectiveness through a meta-analysis of randomized controlled trials (RCTs). Database searching was conducted using specific search terms and inclusion criteria. A standard meta-analysis was also conducted of available RCT studies with a random effects model. The standard mean difference (Cohen's d) was used to calculate the effect size of each study. Nineteen studies were included in the review, and 10 RCTs (eight studies) were included in the meta-analysis. Four types of game interventions-psycho-education and training, virtual reality exposure therapy, exercising, and entertainment-were identified, with various types of support delivered and populations targeted. The meta-analysis revealed a moderate effect size of the game interventions for depression therapy at posttreatment (d=-0.47 [95% CI -0.69 to -0.24]). A subgroup analysis showed that interventions based on psycho-education and training had a smaller effect than those based on the other forms, and that self-help interventions yielded better outcomes than supported interventions. A higher effect was achieved when a waiting list was used as the control. The review and meta-analysis support the effectiveness of game-based digital interventions for depression. More large-scale, high-quality RCT studies with sufficient long-term data for treatment evaluation are needed.

  15. Meta-analysis identifies novel risk loci and yields systematic insights into the biology of male-pattern baldness

    NARCIS (Netherlands)

    Heilmann-Heimbach, S.; Herold, C.; Hochfeld, L.M.; Hillmer, A.M.; Nyholt, D.R.; Hecker, J.; Javed, A.; Chew, E.G.; Pechlivanis, S.; Drichel, D.; Heng, X.T.; Rosario, R.C. Del; Fier, H.L.; Paus, R.; Rueedi, R.; Galesloot, T.E.; Moebus, S.; Anhalt, T.; Prabhakar, S.; Li, R.; Kanoni, S.; Papanikolaou, G.; Kutalik, Z.; Deloukas, P.; Philpott, M.P.; Waeber, G.; Spector, T.D.; Vollenweider, P.; Kiemeney, L.A.L.M.; Dedoussis, G.; Richards, J.B.; Nothnagel, M.; Martin, N.G.; Becker, T.; Hinds, D.A.; Nothen, M.M.

    2017-01-01

    Male-pattern baldness (MPB) is a common and highly heritable trait characterized by androgen-dependent, progressive hair loss from the scalp. Here, we carry out the largest GWAS meta-analysis of MPB to date, comprising 10,846 early-onset cases and 11,672 controls from eight independent cohorts. We

  16. Simulation-based power calculations for planning a two-stage individual participant data meta-analysis.

    Science.gov (United States)

    Ensor, Joie; Burke, Danielle L; Snell, Kym I E; Hemming, Karla; Riley, Richard D

    2018-05-18

    Researchers and funders should consider the statistical power of planned Individual Participant Data (IPD) meta-analysis projects, as they are often time-consuming and costly. We propose simulation-based power calculations utilising a two-stage framework, and illustrate the approach for a planned IPD meta-analysis of randomised trials with continuous outcomes where the aim is to identify treatment-covariate interactions. The simulation approach has four steps: (i) specify an underlying (data generating) statistical model for trials in the IPD meta-analysis; (ii) use readily available information (e.g. from publications) and prior knowledge (e.g. number of studies promising IPD) to specify model parameter values (e.g. control group mean, intervention effect, treatment-covariate interaction); (iii) simulate an IPD meta-analysis dataset of a particular size from the model, and apply a two-stage IPD meta-analysis to obtain the summary estimate of interest (e.g. interaction effect) and its associated p-value; (iv) repeat the previous step (e.g. thousands of times), then estimate the power to detect a genuine effect by the proportion of summary estimates with a significant p-value. In a planned IPD meta-analysis of lifestyle interventions to reduce weight gain in pregnancy, 14 trials (1183 patients) promised their IPD to examine a treatment-BMI interaction (i.e. whether baseline BMI modifies intervention effect on weight gain). Using our simulation-based approach, a two-stage IPD meta-analysis has meta-analysis was appropriate. Pre-specified adjustment for prognostic factors would increase power further. Incorrect dichotomisation of BMI would reduce power by over 20%, similar to immediately throwing away IPD from ten trials. Simulation-based power calculations could inform the planning and funding of IPD projects, and should be used routinely.

  17. Meta-analysis of Arabidopsis KANADI1 direct target genes identifies basic growth-promoting module acting upstream of hormonal signaling pathways

    DEFF Research Database (Denmark)

    Xie, Yakun; Straub, Daniel; Eguen, Teinai Ebimienere

    2015-01-01

    An intricate network of antagonistically acting transcription factors mediates formation of a flat leaf lamina of Arabidopsis thaliana plants. In this context, members of the class III homeodomain leucine zipper (HD-ZIPIII) transcription factor family specify the adaxial domain (future upper side......) of the leaf, while antagonistically acting KANADI transcription factors determine the abaxial domain (future lower side). Here we used an mRNA-seq approach to identify genes regulated by KANADI1 (KAN1) and subsequently performed a meta-analysis approach combining our datasets with published genome......-wide datasets. Our analysis revealed that KAN1 acts upstream of several genes encoding auxin biosynthetic enzymes. When exposed to shade, we find three YUCCA genes, YUC2, YUC5 and YUC8 to be transcriptionally upregulated, which correlates with an increase in the levels of free auxin. When ectopically expressed...

  18. Online Open Neuroimaging Mass Meta-Analysis with a Wiki

    DEFF Research Database (Denmark)

    Nielsen, Finn Arup; Kempton, Matthew J.; Williams, Steven C. R.

    2015-01-01

    We describe a system for meta-analysis where a wiki stores numerical data in a simple comma-separated values format and a web service performs the numerical statistical computation. We initially apply the system on multiple meta-analyses of structural neuroimaging data results. The described system...... allows for mass meta-analysis, e.g., meta-analysis across multiple brain regions and multiple mental disorders providing an overview of important relationships and their uncertainties in a collaborative environment....

  19. The countermovement jump to monitor neuromuscular status: A meta-analysis.

    Science.gov (United States)

    Claudino, João Gustavo; Cronin, John; Mezêncio, Bruno; McMaster, Daniel Travis; McGuigan, Michael; Tricoli, Valmor; Amadio, Alberto Carlos; Serrão, Julio Cerca

    2017-04-01

    The primary objective of this meta-analysis was to compare countermovement jump (CMJ) performance in studies that reported the highest value as opposed to average value for the purposes of monitoring neuromuscular status (i.e., fatigue and supercompensation). The secondary aim was to determine the sensitivity of the dependent variables. Systematic review with meta-analysis. The meta-analysis was conducted on the highest or average of a number of CMJ variables. Multiple literature searches were undertaken in Pubmed, Scopus, and Web of Science to identify articles utilizing CMJ to monitor training status. Effect sizes (ES) with 95% confidence interval (95% CI) were calculated using the mean and standard deviation of the pre- and post-testing data. The coefficient of variation (CV) with 95% CI was also calculated to assess the level of instability of each variable. Heterogeneity was assessed using a random-effects model. 151 articles were included providing a total of 531 ESs for the meta-analyses; 85.4% of articles used highest CMJ height, 13.2% used average and 1.3% used both when reporting changes in CMJ performance. Based on the meta-analysis, average CMJ height was more sensitive than highest CMJ height in detecting CMJ fatigue and supercompensation. Furthermore, other CMJ variables such as peak power, mean power, peak velocity, peak force, mean impulse, and power were sensitive in tracking the supercompensation effects of training. The average CMJ height was more sensitive than highest CMJ height in monitoring neuromuscular status; however, further investigation is needed to determine the sensitivity of other CMJ performance variables. Copyright © 2016 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

  20. A meta-analysis of genome-wide association scans identifies IL18RAP, PTPN2, TAGAP, and PUS10 as shared risk loci for Crohn's disease and celiac disease.

    Directory of Open Access Journals (Sweden)

    Eleonora A M Festen

    2011-01-01

    Full Text Available Crohn's disease (CD and celiac disease (CelD are chronic intestinal inflammatory diseases, involving genetic and environmental factors in their pathogenesis. The two diseases can co-occur within families, and studies suggest that CelD patients have a higher risk to develop CD than the general population. These observations suggest that CD and CelD may share common genetic risk loci. Two such shared loci, IL18RAP and PTPN2, have already been identified independently in these two diseases. The aim of our study was to explicitly identify shared risk loci for these diseases by combining results from genome-wide association study (GWAS datasets of CD and CelD. Specifically, GWAS results from CelD (768 cases, 1,422 controls and CD (3,230 cases, 4,829 controls were combined in a meta-analysis. Nine independent regions had nominal association p-value <1.0 x 10⁻⁵ in this meta-analysis and showed evidence of association to the individual diseases in the original scans (p-value < 1 x 10⁻² in CelD and < 1 x 10⁻³ in CD. These include the two previously reported shared loci, IL18RAP and PTPN2, with p-values of 3.37 x 10⁻⁸ and 6.39 x 10⁻⁹, respectively, in the meta-analysis. The other seven had not been reported as shared loci and thus were tested in additional CelD (3,149 cases and 4,714 controls and CD (1,835 cases and 1,669 controls cohorts. Two of these loci, TAGAP and PUS10, showed significant evidence of replication (Bonferroni corrected p-values <0.0071 in the combined CelD and CD replication cohorts and were firmly established as shared risk loci of genome-wide significance, with overall combined p-values of 1.55 x 10⁻¹⁰ and 1.38 x 10⁻¹¹ respectively. Through a meta-analysis of GWAS data from CD and CelD, we have identified four shared risk loci: PTPN2, IL18RAP, TAGAP, and PUS10. The combined analysis of the two datasets provided the power, lacking in the individual GWAS for single diseases, to detect shared loci with a

  1. Meta-analysis in clinical trials revisited.

    Science.gov (United States)

    DerSimonian, Rebecca; Laird, Nan

    2015-11-01

    In this paper, we revisit a 1986 article we published in this Journal, Meta-Analysis in Clinical Trials, where we introduced a random-effects model to summarize the evidence about treatment efficacy from a number of related clinical trials. Because of its simplicity and ease of implementation, our approach has been widely used (with more than 12,000 citations to date) and the "DerSimonian and Laird method" is now often referred to as the 'standard approach' or a 'popular' method for meta-analysis in medical and clinical research. The method is especially useful for providing an overall effect estimate and for characterizing the heterogeneity of effects across a series of studies. Here, we review the background that led to the original 1986 article, briefly describe the random-effects approach for meta-analysis, explore its use in various settings and trends over time and recommend a refinement to the method using a robust variance estimator for testing overall effect. We conclude with a discussion of repurposing the method for Big Data meta-analysis and Genome Wide Association Studies for studying the importance of genetic variants in complex diseases. Published by Elsevier Inc.

  2. Evaluating the Quality of Evidence from a Network Meta-Analysis

    Science.gov (United States)

    Salanti, Georgia; Del Giovane, Cinzia; Chaimani, Anna; Caldwell, Deborah M.; Higgins, Julian P. T.

    2014-01-01

    Systematic reviews that collate data about the relative effects of multiple interventions via network meta-analysis are highly informative for decision-making purposes. A network meta-analysis provides two types of findings for a specific outcome: the relative treatment effect for all pairwise comparisons, and a ranking of the treatments. It is important to consider the confidence with which these two types of results can enable clinicians, policy makers and patients to make informed decisions. We propose an approach to determining confidence in the output of a network meta-analysis. Our proposed approach is based on methodology developed by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group for pairwise meta-analyses. The suggested framework for evaluating a network meta-analysis acknowledges (i) the key role of indirect comparisons (ii) the contributions of each piece of direct evidence to the network meta-analysis estimates of effect size; (iii) the importance of the transitivity assumption to the validity of network meta-analysis; and (iv) the possibility of disagreement between direct evidence and indirect evidence. We apply our proposed strategy to a systematic review comparing topical antibiotics without steroids for chronically discharging ears with underlying eardrum perforations. The proposed framework can be used to determine confidence in the results from a network meta-analysis. Judgements about evidence from a network meta-analysis can be different from those made about evidence from pairwise meta-analyses. PMID:24992266

  3. Meta-analysis of genome-wide association studies identifies six new Loci for serum calcium concentrations.

    Directory of Open Access Journals (Sweden)

    Conall M O'Seaghdha

    Full Text Available Calcium is vital to the normal functioning of multiple organ systems and its serum concentration is tightly regulated. Apart from CASR, the genes associated with serum calcium are largely unknown. We conducted a genome-wide association meta-analysis of 39,400 individuals from 17 population-based cohorts and investigated the 14 most strongly associated loci in ≤ 21,679 additional individuals. Seven loci (six new regions in association with serum calcium were identified and replicated. Rs1570669 near CYP24A1 (P = 9.1E-12, rs10491003 upstream of GATA3 (P = 4.8E-09 and rs7481584 in CARS (P = 1.2E-10 implicate regions involved in Mendelian calcemic disorders: Rs1550532 in DGKD (P = 8.2E-11, also associated with bone density, and rs7336933 near DGKH/KIAA0564 (P = 9.1E-10 are near genes that encode distinct isoforms of diacylglycerol kinase. Rs780094 is in GCKR. We characterized the expression of these genes in gut, kidney, and bone, and demonstrate modulation of gene expression in bone in response to dietary calcium in mice. Our results shed new light on the genetics of calcium homeostasis.

  4. Meta-analysis: Risk of dry mouth with second generation antidepressants.

    Science.gov (United States)

    Cappetta, Kiley; Beyer, Chad; Johnson, Jessica A; Bloch, Michael H

    2018-06-08

    The goal of this meta-analysis was to quantify the risk of dry mouth associated with commonly prescribed antidepressant agents and examine the potential implications of medication class, dose, and pharmacodynamics and dose on risk of treatment-induced dry mouth. A PubMed search was conducted to identify double-blind, randomized, placebo-controlled trials examining the efficacy and tolerability of second generation antidepressant medications for adults with depressive disorders, anxiety disorders, and OCD. A random-effects meta-analysis was used to quantify the pooled risk ratio of treatment-emergent dry mouth with second generation antidepressants compared to placebo. Stratified subgroup analysis and meta-regression was utilized to further examine the effects antidepressant agent, class, dosage, indication, and receptor affinity profile on the measured risk of dry mouth. 99 trials involving 20,868 adults. SNRIs (Relative Risk (RR)=2.24, 95% Confidence Interval (CI): 1.95-2.58, z=11.2, pz=5.8, pz=10.32, pz=5.85, pz=3.26, p=0.001) and Alpha-2 (PE=0.49, 95% CI: 0.22-0.75, z=3.64, pz=2.10, p<0.05) was significantly associated with increased risk of dry mouth. The current meta-analysis suggests that SSRIs, SNRIs, and atypical antidepressants are all associated with varying degrees of increased risk of dry mouth. SNRIs were associated with a significantly greater risk of dry mouth compared to SSRIs. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Meta-analysis of Genome-Wide Association Studies Identifies Novel Loci Associated With Optic Disc Morphology

    OpenAIRE

    Springelkamp, Henriët; Mishra, Aniket; Hysi, Pirro G.; Gharahkhani, Puya; Höhn, René; Khor, Chiea-Chuen; Cooke Bailey, Jessica N.; Luo, Xiaoyan; Ramdas, Wishal D.; Vithana, Eranga; Koh, Victor; Yazar, Seyhan; Xu, Liang; Forward, Hannah; Kearns, Lisa S.

    2015-01-01

    Primary open-angle glaucoma is the most common optic neuropathy and an important cause of irreversible blindness worldwide. The optic nerve head or optic disc is divided in two parts: a central cup (without nerve fibers) surrounded by the neuroretinal rim (containing axons of the retinal ganglion cells). The International Glaucoma Genetics Consortium conducted a meta-analysis of genome-wide association studies consisting of 17,248 individuals of European ancestry and 6,841 individuals of Asia...

  6. Meta-analysis of Gaussian individual patient data: Two-stage or not two-stage?

    Science.gov (United States)

    Morris, Tim P; Fisher, David J; Kenward, Michael G; Carpenter, James R

    2018-04-30

    Quantitative evidence synthesis through meta-analysis is central to evidence-based medicine. For well-documented reasons, the meta-analysis of individual patient data is held in higher regard than aggregate data. With access to individual patient data, the analysis is not restricted to a "two-stage" approach (combining estimates and standard errors) but can estimate parameters of interest by fitting a single model to all of the data, a so-called "one-stage" analysis. There has been debate about the merits of one- and two-stage analysis. Arguments for one-stage analysis have typically noted that a wider range of models can be fitted and overall estimates may be more precise. The two-stage side has emphasised that the models that can be fitted in two stages are sufficient to answer the relevant questions, with less scope for mistakes because there are fewer modelling choices to be made in the two-stage approach. For Gaussian data, we consider the statistical arguments for flexibility and precision in small-sample settings. Regarding flexibility, several of the models that can be fitted only in one stage may not be of serious interest to most meta-analysis practitioners. Regarding precision, we consider fixed- and random-effects meta-analysis and see that, for a model making certain assumptions, the number of stages used to fit this model is irrelevant; the precision will be approximately equal. Meta-analysts should choose modelling assumptions carefully. Sometimes relevant models can only be fitted in one stage. Otherwise, meta-analysts are free to use whichever procedure is most convenient to fit the identified model. © 2018 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.

  7. Large meta-analysis of genome-wide association studies identifies five loci for lean body mass

    DEFF Research Database (Denmark)

    Zillikens, M Carola; Demissie, Serkalem; Hsu, Yi-Hsiang

    2017-01-01

    Lean body mass, consisting mostly of skeletal muscle, is important for healthy aging. We performed a genome-wide association study for whole body (20 cohorts of European ancestry with n = 38,292) and appendicular (arms and legs) lean body mass (n = 28,330) measured using dual energy X-ray absorpt...... a meta-analysis of genome-wide association studies for whole body lean body mass and find five novel genetic loci to be significantly associated.......-ray absorptiometry or bioelectrical impedance analysis, adjusted for sex, age, height, and fat mass. Twenty-one single-nucleotide polymorphisms were significantly associated with lean body mass either genome wide (p 

  8. Advances in meta-analysis: examples from internal medicine to neurology.

    Science.gov (United States)

    Copetti, Massimiliano; Fontana, Andrea; Graziano, Giusi; Veneziani, Federica; Siena, Federica; Scardapane, Marco; Lucisano, Giuseppe; Pellegrini, Fabio

    2014-01-01

    We review the state of the art in meta-analysis and data pooling following the evolution of the statistical models employed. Starting from a classic definition of meta-analysis of published data, a set of apparent antinomies which characterized the development of the meta-analytic tools are reconciled in dichotomies where the second term represents a possible generalization of the first one. Particular attention is given to the generalized linear mixed models as an overall framework for meta-analysis. Bayesian meta-analysis is discussed as a further possibility of generalization for sensitivity analysis and the use of priors as a data augmentation approach. We provide relevant examples to underline how the need for adequate methods to solve practical issues in specific areas of research have guided the development of advanced methods in meta-analysis. We show how all the advances in meta-analysis naturally merge into the unified framework of generalized linear mixed models and reconcile apparently conflicting approaches. All these complex models can be easily implemented with the standard commercial software available. © 2013 S. Karger AG, Basel.

  9. Meta-analysis: Problems with Russian Publications.

    Science.gov (United States)

    Verbitskaya, E V

    2015-01-01

    Meta-analysis is a powerful tool to identify Evidence Based medical technologies (interventions) for use in every day practice. Meta-analysis uses statistical approaches to combine results from multiple studies in an effort to increase power (over individual studies), improve estimates of the size of the effect and/or to resolve uncertainty when reports disagree. Meta-analysis is a quantitative, formal study design used to systematically assess previous research studies to derive conclusions from this research. Meta-analysis may provide more precise estimate of the effect of treatment or risk factor for a disease, or other outcomes, than any individual study contributing to the pooled analysis.We have quite a substantial number of Russian medical publications, but not so many Meta-Analyses published in Russian. Russian publications are cited in English language papers not so often. A total of 90% of clinical studies included in published Meta-Analyses incorporate only English language papers. International studies or papers with Russian co-authors are published in English language. The main question is: what is the problem with inclusion of Russian medical publications in Meta-Analysis? The main reasons for this are the following: 1) It is difficult to find Russian papers, difficult to work with them and to work with Russian journals:a. There are single Russian Biomedical Journals, which are translated into English and are included in databases (PubMed, Scopus and other), despite the fact that all of them have English language abstracts.b. The majority the meta-analyses authors use in their work different citation management software such as the Mendeley, Reference Manager, ProCite, EndNote, and others. These citation management systems allow scientists to organize their own literature databases with internet searches and have adds-on for the Office programs what makes process of literature citation very convenient. The Internet sites of the majority of

  10. Identification of cytokinin-responsive genes using microarray meta-analysis and RNA-Seq in Arabidopsis.

    Science.gov (United States)

    Bhargava, Apurva; Clabaugh, Ivory; To, Jenn P; Maxwell, Bridey B; Chiang, Yi-Hsuan; Schaller, G Eric; Loraine, Ann; Kieber, Joseph J

    2013-05-01

    Cytokinins are N(6)-substituted adenine derivatives that play diverse roles in plant growth and development. We sought to define a robust set of genes regulated by cytokinin as well as to query the response of genes not represented on microarrays. To this end, we performed a meta-analysis of microarray data from a variety of cytokinin-treated samples and used RNA-seq to examine cytokinin-regulated gene expression in Arabidopsis (Arabidopsis thaliana). Microarray meta-analysis using 13 microarray experiments combined with empirically defined filtering criteria identified a set of 226 genes differentially regulated by cytokinin, a subset of which has previously been validated by other methods. RNA-seq validated about 73% of the up-regulated genes identified by this meta-analysis. In silico promoter analysis indicated an overrepresentation of type-B Arabidopsis response regulator binding elements, consistent with the role of type-B Arabidopsis response regulators as primary mediators of cytokinin-responsive gene expression. RNA-seq analysis identified 73 cytokinin-regulated genes that were not represented on the ATH1 microarray. Representative genes were verified using quantitative reverse transcription-polymerase chain reaction and NanoString analysis. Analysis of the genes identified reveals a substantial effect of cytokinin on genes encoding proteins involved in secondary metabolism, particularly those acting in flavonoid and phenylpropanoid biosynthesis, as well as in the regulation of redox state of the cell, particularly a set of glutaredoxin genes. Novel splicing events were found in members of some gene families that are known to play a role in cytokinin signaling or metabolism. The genes identified in this analysis represent a robust set of cytokinin-responsive genes that are useful in the analysis of cytokinin function in plants.

  11. Relaxation training for anxiety: a ten-years systematic review with meta-analysis

    Science.gov (United States)

    Manzoni, Gian Mauro; Pagnini, Francesco; Castelnuovo, Gianluca; Molinari, Enrico

    2008-01-01

    Background Relaxation training is a common treatment for anxiety problems. Lacking is a recent quantitative meta-analysis that enhances understanding of the variability and clinical significance of anxiety reduction outcomes after relaxation treatment. Methods All studies (1997–2007), both RCT, observational and without control group, evaluating the efficacy of relaxation training (Jacobson's progressive relaxation, autogenic training, applied relaxation and meditation) for anxiety problems and disorders were identified by comprehensive electronic searches with Pubmed, Psychinfo and Cochrane Registers, by checking references of relevant studies and of other reviews. Our primary outcome was anxiety measured with psychometric questionnaires. Meta-analysis was undertaken synthesizing the data from all trials, distinguishing within and between effect sizes. Results 27 studies qualified for the inclusion in the meta-analysis. As hypothesized, relaxation training showed a medium-large effect size in the treatment of anxiety. Cohen's d was .57 (95% CI: .52 to .68) in the within analysis and .51 (95% CI: .46 to .634) in the between group analysis. Efficacy was higher for meditation, among volunteers and for longer treatments. Implications and limitations are discussed. Conclusion The results show consistent and significant efficacy of relaxation training in reducing anxiety. This meta-analysis extends the existing literature through facilitation of a better understanding of the variability and clinical significance of anxiety improvement subsequent to relaxation training. PMID:18518981

  12. Relaxation training for anxiety: a ten-years systematic review with meta-analysis

    Directory of Open Access Journals (Sweden)

    Castelnuovo Gianluca

    2008-06-01

    Full Text Available Abstract Background Relaxation training is a common treatment for anxiety problems. Lacking is a recent quantitative meta-analysis that enhances understanding of the variability and clinical significance of anxiety reduction outcomes after relaxation treatment. Methods All studies (1997–2007, both RCT, observational and without control group, evaluating the efficacy of relaxation training (Jacobson's progressive relaxation, autogenic training, applied relaxation and meditation for anxiety problems and disorders were identified by comprehensive electronic searches with Pubmed, Psychinfo and Cochrane Registers, by checking references of relevant studies and of other reviews. Our primary outcome was anxiety measured with psychometric questionnaires. Meta-analysis was undertaken synthesizing the data from all trials, distinguishing within and between effect sizes. Results 27 studies qualified for the inclusion in the meta-analysis. As hypothesized, relaxation training showed a medium-large effect size in the treatment of anxiety. Cohen's d was .57 (95% CI: .52 to .68 in the within analysis and .51 (95% CI: .46 to .634 in the between group analysis. Efficacy was higher for meditation, among volunteers and for longer treatments. Implications and limitations are discussed. Conclusion The results show consistent and significant efficacy of relaxation training in reducing anxiety. This meta-analysis extends the existing literature through facilitation of a better understanding of the variability and clinical significance of anxiety improvement subsequent to relaxation training.

  13. The potential for meta-analysis to support decision analysis in ecology.

    Science.gov (United States)

    Mengersen, Kerrie; MacNeil, M Aaron; Caley, M Julian

    2015-06-01

    Meta-analysis and decision analysis are underpinned by well-developed methods that are commonly applied to a variety of problems and disciplines. While these two fields have been closely linked in some disciplines such as medicine, comparatively little attention has been paid to the potential benefits of linking them in ecology, despite reasonable expectations that benefits would be derived from doing so. Meta-analysis combines information from multiple studies to provide more accurate parameter estimates and to reduce the uncertainty surrounding them. Decision analysis involves selecting among alternative choices using statistical information that helps to shed light on the uncertainties involved. By linking meta-analysis to decision analysis, improved decisions can be made, with quantification of the costs and benefits of alternate decisions supported by a greater density of information. Here, we briefly review concepts of both meta-analysis and decision analysis, illustrating the natural linkage between them and the benefits from explicitly linking one to the other. We discuss some examples in which this linkage has been exploited in the medical arena and how improvements in precision and reduction of structural uncertainty inherent in a meta-analysis can provide substantive improvements to decision analysis outcomes by reducing uncertainty in expected loss and maximising information from across studies. We then argue that these significant benefits could be translated to ecology, in particular to the problem of making optimal ecological decisions in the face of uncertainty. Copyright © 2013 John Wiley & Sons, Ltd.

  14. Steep Delay Discounting and Addictive Behavior: A Meta-Analysis of Continuous Associations

    Science.gov (United States)

    Amlung, Michael; Vedelago, Lana; Acker, John; Balodis, Iris; MacKillop, James

    2016-01-01

    Aims To synthesize continuous associations between delayed reward discounting (DRD) and both addiction severity and quantity-frequency (QF); to examine moderators of these relationships; and to investigate publication bias. Methods Meta-analysis of published studies examining continuous associations between DRD and addictive behaviors. Published, peer-reviewed studies on addictive behaviors (alcohol, tobacco, cannabis, stimulants, opiates, and gambling) were identified via PubMed, MEDLINE, and PsycInfo. Studies were restricted to DRD measures of monetary gains. Random effects meta-analysis was conducted using Pearson’s r as the effect size. Publication bias was evaluated using fail-safe N, Begg-Mazumdar and Egger’s tests, meta-regression of publication year and effect size, and imputation of missing studies. Results The primary meta-analysis revealed a small magnitude effect size that was highly significant (r = 0.14, p addictive behavior (p = 0.30) or DRD assessment (p = 0.90). Indices of publication bias suggested a modest impact of unpublished findings. Conclusions Delayed reward discounting is robustly associated with continuous measures of addiction severity and quantity-frequency. This relation is generally robust across type of addictive behavior and delayed reward discounting assessment modality. PMID:27450931

  15. Longitudinal analysis of meta-analysis literatures in the database of ISI Web of Science.

    Science.gov (United States)

    Zhu, Changtai; Jiang, Ting; Cao, Hao; Sun, Wenguang; Chen, Zhong; Liu, Jinming

    2015-01-01

    The meta-analysis is regarded as an important evidence for making scientific decision. The database of ISI Web of Science collected a great number of high quality literatures including meta-analysis literatures. However, it is significant to understand the general characteristics of meta-analysis literatures to outline the perspective of meta-analysis. In this present study, we summarized and clarified some features on these literatures in the database of ISI Web of Science. We retrieved the meta-analysis literatures in the database of ISI Web of Science including SCI-E, SSCI, A&HCI, CPCI-S, CPCI-SSH, CCR-E, and IC. The annual growth rate, literature category, language, funding, index citation, agencies and countries/territories of the meta-analysis literatures were analyzed, respectively. A total of 95,719 records, which account for 0.38% (99% CI: 0.38%-0.39%) of all literatures, were found in the database. From 1997 to 2012, the annual growth rate of meta-analysis literatures was 18.18%. The literatures involved in many categories, languages, fundings, citations, publication agencies, and countries/territories. Interestingly, the index citation frequencies of the meta-analysis were significantly higher than that of other type literatures such as multi-centre study, randomize controlled trial, cohort study, case control study, and cases report (Panalysis has been becoming more and more prominent in recent years. In future, in order to promote the validity of meta-analysis, the CONSORT and PRISMA standard should be continuously popularized in the field of evidence-based medicine.

  16. Comparative efficacy, tolerability, and survival outcomes of various radiopharmaceuticals in castration-resistant prostate cancer with bone metastasis: a meta-analysis of randomized controlled trials

    Directory of Open Access Journals (Sweden)

    Tunio M

    2015-09-01

    Full Text Available Mutahir Tunio,1 Mushabbab Al Asiri,1 Abdulrehman Al Hadab,1 Yasser Bayoumi2 1Radiation Oncology, Comprehensive Cancer Center, King Fahad Medical City, Riyadh, Saudi Arabia; 2Radiation Oncology, National Cancer Institute, Cairo University, Cairo, Egypt Background: A meta-analysis was conducted to assess the impact of radiopharmaceuticals (RPs in castration-resistant prostate cancer (CRPC on pain control, symptomatic skeletal events (SSEs, toxicity profile, quality of life (QoL, and overall survival (OS.Materials and methods: The PubMed/MEDLINE, CANCERLIT, EMBASE, Cochrane Library database, and other search engines were searched to identify randomized controlled trials (RCTs comparing RPs with control (placebo or radiation therapy in metastatic CRPC. Data were extracted and assessed for the risk of bias (Cochrane’s risk of bias tool. Pooled data were expressed as odds ratio (OR, with 95% confidence intervals (CIs; Mantel–Haenszel fixed-effects model.Results: Eight RCTs with a total patient population of 1,877 patients were identified. The use of RP was associated with significant reduction in pain intensity and SSE (OR: 0.63, 95% CI: 0.51–0.78, I2=27%, P<0.0001, improved QoL (OR: 0.71, 95% CI: 0.55–0.91, I2=65%, three trials, 1,178 patients, P=0.006, and a minimal improved OS (OR: 0.84, 95% CI: 0.64–1.04, I2=47%, seven trials, 1,845 patients, P=0.11. A subgroup analysis suggested an improved OS with radium-223 (OR: 0.68, 95% CI: 0.51–0.90, one trial, 921 patients and strontium-89 (OR: 0.21, 95% CI: 0.05–0.91, one trial, 49 patients. Strontium-89 (five trials was associated with increased rates of grade 3 and 4 thrombocytopenia (OR: 4.26, 95% CI: 2.22–8.18, P=0.01, leucopenia (OR: 7.98, 95% CI: 1.82–34.95, P=0.02, pain flare (OR: 6.82, 95% CI: 3.42–13.55, P=0.04, and emesis (OR: 3.61, 95% CI: 1.76–7.40, P=0.02.Conclusion: The use of RPs was associated with significant reduction in SSEs and improved QoL, while the radium-223

  17. Outcomes of colon resection in patients with metastatic colon cancer.

    Science.gov (United States)

    Moghadamyeghaneh, Zhobin; Hanna, Mark H; Hwang, Grace; Mills, Steven; Pigazzi, Alessio; Stamos, Michael J; Carmichael, Joseph C

    2016-08-01

    Patients with advanced colorectal cancer have a high incidence of postoperative complications. We sought to identify outcomes of patients who underwent resection for colon cancer by cancer stage. The National Surgical Quality Improvement Program database was used to evaluate all patients who underwent colon resection with a diagnosis of colon cancer from 2012 to 2014. Multivariate logistic regression analysis was performed to investigate patient outcomes by cancer stage. A total of 7,786 colon cancer patients who underwent colon resection were identified. Of these, 10.8% had metastasis at the time of operation. Patients with metastatic disease had significantly increased risks of perioperative morbidity (adjusted odds ratio [AOR]: 1.44, P = .01) and mortality (AOR: 3.72, P = .01). Patients with metastatic disease were significantly younger (AOR: .99, P colon cancer have metastatic disease. Postoperative morbidity and mortality are significantly higher than in patients with localized disease. Published by Elsevier Inc.

  18. Genome-wide association study meta-analysis of European and Asian-ancestry samples identifies three novel loci associated with bipolar disorder.

    Science.gov (United States)

    Chen, D T; Jiang, X; Akula, N; Shugart, Y Y; Wendland, J R; Steele, C J M; Kassem, L; Park, J-H; Chatterjee, N; Jamain, S; Cheng, A; Leboyer, M; Muglia, P; Schulze, T G; Cichon, S; Nöthen, M M; Rietschel, M; McMahon, F J; Farmer, A; McGuffin, P; Craig, I; Lewis, C; Hosang, G; Cohen-Woods, S; Vincent, J B; Kennedy, J L; Strauss, J

    2013-02-01

    Meta-analyses of bipolar disorder (BD) genome-wide association studies (GWAS) have identified several genome-wide significant signals in European-ancestry samples, but so far account for little of the inherited risk. We performed a meta-analysis of ∼750,000 high-quality genetic markers on a combined sample of ∼14,000 subjects of European and Asian-ancestry (phase I). The most significant findings were further tested in an extended sample of ∼17,700 cases and controls (phase II). The results suggest novel association findings near the genes TRANK1 (LBA1), LMAN2L and PTGFR. In phase I, the most significant single nucleotide polymorphism (SNP), rs9834970 near TRANK1, was significant at the P=2.4 × 10(-11) level, with no heterogeneity. Supportive evidence for prior association findings near ANK3 and a locus on chromosome 3p21.1 was also observed. The phase II results were similar, although the heterogeneity test became significant for several SNPs. On the basis of these results and other established risk loci, we used the method developed by Park et al. to estimate the number, and the effect size distribution, of BD risk loci that could still be found by GWAS methods. We estimate that >63,000 case-control samples would be needed to identify the ∼105 BD risk loci discoverable by GWAS, and that these will together explain <6% of the inherited risk. These results support previous GWAS findings and identify three new candidate genes for BD. Further studies are needed to replicate these findings and may potentially lead to identification of functional variants. Sample size will remain a limiting factor in the discovery of common alleles associated with BD.

  19. Integrative Genome Comparison of Primary and Metastatic Melanomas

    Science.gov (United States)

    Feng, Bin; Nazarian, Rosalynn M.; Bosenberg, Marcus; Wu, Min; Scott, Kenneth L.; Kwong, Lawrence N.; Xiao, Yonghong; Cordon-Cardo, Carlos; Granter, Scott R.; Ramaswamy, Sridhar; Golub, Todd; Duncan, Lyn M.; Wagner, Stephan N.; Brennan, Cameron; Chin, Lynda

    2010-01-01

    A cardinal feature of malignant melanoma is its metastatic propensity. An incomplete view of the genetic events driving metastatic progression has been a major barrier to rational development of effective therapeutics and prognostic diagnostics for melanoma patients. In this study, we conducted global genomic characterization of primary and metastatic melanomas to examine the genomic landscape associated with metastatic progression. In addition to uncovering three genomic subclasses of metastastic melanomas, we delineated 39 focal and recurrent regions of amplification and deletions, many of which encompassed resident genes that have not been implicated in cancer or metastasis. To identify progression-associated metastasis gene candidates, we applied a statistical approach, Integrative Genome Comparison (IGC), to define 32 genomic regions of interest that were significantly altered in metastatic relative to primary melanomas, encompassing 30 resident genes with statistically significant expression deregulation. Functional assays on a subset of these candidates, including MET, ASPM, AKAP9, IMP3, PRKCA, RPA3, and SCAP2, validated their pro-invasion activities in human melanoma cells. Validity of the IGC approach was further reinforced by tissue microarray analysis of Survivin showing significant increased protein expression in thick versus thin primary cutaneous melanomas, and a progression correlation with lymph node metastases. Together, these functional validation results and correlative analysis of human tissues support the thesis that integrated genomic and pathological analyses of staged melanomas provide a productive entry point for discovery of melanoma metastases genes. PMID:20520718

  20. Metastatic and non-metastatic lymph nodes. Quantification and different distribution of iodine uptake assessed by dual-energy CT

    Energy Technology Data Exchange (ETDEWEB)

    Rizzo, Stefania [European Institute of Oncology, Department of Radiology, Milan (Italy); Radice, Davide [Department of Epidemiology and Biostatistics, Milan (Italy); Femia, Marco; Vigorito, Raffaella [Universita di Milano, Department of Health Sciences, Milan (Italy); De Marco, Paolo; Origgi, Daniela [Medical Physics, European Institute of Oncology, Milan (Italy); Preda, Lorenzo [Division of Radiology, National Centre of Oncological Hadrontherapy (CNAO Foundation), Pavia (Italy); University of Pavia, Department of Clinical, Surgical, Diagnostic and Paediatric Sciences, Pavia (Italy); Barberis, Massimo [European Institute of Oncology, Department of Pathology, Milan (Italy); Mauri, Giovanni [European Institute of Oncology, Division of Interventional Radiology, Milan (Italy); Mauro, Alberto [GE Medical Systems Italia SpA, Milan (Italy); Bellomi, Massimo [European Institute of Oncology, Department of Radiology, Milan (Italy); Universita di Milano, Department of Oncology, Milan (Italy)

    2018-02-15

    To evaluate quantification of iodine uptake in metastatic and non-metastatic lymph nodes (LNs) by dual-energy CT (DECT) and to assess if the distribution of iodine within LNs at DECT correlates with the pathological structure. Ninety LNs from 37 patients (23 with lung and 14 with gynaecological malignancies) were retrospectively selected. Information of LNs sent for statistical analysis included Hounsfield units (HU) at different energy levels; decomposition material densities fat-iodine, iodine-fat, iodine-water, water-iodine. Statistical analysis included evaluation of interobserver variability, material decomposition densities and spatial HU distribution within LNs. Interobserver agreement was excellent. There was a significant difference in iodine-fat and iodine-water decompositions comparing metastatic and non-metastatic LNs (p < 0.001); fat-iodine and water-iodine did not show significant differences. HU distribution showed a significant gradient from centre to periphery within non-metastatic LNs that was significant up to 20-30% from the centre, whereas metastatic LNs showed a more homogeneous distribution of HU, with no significant gradient. DECT demonstrated a lower iodine uptake in metastatic compared to non-metastatic LNs. Moreover, the internal iodine distribution showed an evident gradient of iodine distribution from centre to periphery in non-metastatic LNs, and a more homogeneous distribution within metastatic LNs, which corresponded to the pathological structure. (orig.)

  1. Meta-analysis of gene-environment-wide association scans accounting for education level identifies additional loci for refractive error

    NARCIS (Netherlands)

    Fan, Q.; Verhoeven, V.J.; Wojciechowski, R.; Barathi, V.A.; Hysi, P.G.; Guggenheim, J.A.; Hohn, R.; Vitart, V.; Khawaja, A.P.; Yamashiro, K.; Hosseini, S.M.; Lehtimaki, T.; Lu, Y.; Haller, T.; Xie, J.; Delcourt, C; Pirastu, M.; Wedenoja, J.; Gharahkhani, P.; Venturini, C.; Miyake, M.; Hewitt, A.W.; Guo, X.; Mazur, J.; Huffman, J.E.; Williams, K.M.; Polasek, O.; Campbell, H.; Rudan, I.; Vatavuk, Z.; Wilson, J.F.; Joshi, P.K.; McMahon, G.; St Pourcain, B.; Evans, D.M.; Simpson, C.L.; Schwantes-An, T.H.; Igo, R.P., Jr.; Mirshahi, A.; Cougnard-Gregoire, A.; Bellenguez, C.; Blettner, M.; Raitakari, O.; Kahonen, M.; Seppala, I.; Zeller, T.; Meitinger, T.; Ried, J.S.; Gieger, C.; Portas, L.; Leeuwen, E.M. van; Amin, N.; Uitterlinden, A.G.; Rivadeneira, F.; Hofman, A.; Vingerling, J.R.; Wang, Y.X.; Wang, X.; Boh, E.T.H.; Ikram, M.K.; Sabanayagam, C.; Gupta, P.; Tan, V.; Zhou, L; Ho, C.E.; Lim, W.; Beuerman, R.W.; Siantar, R.; Tai, E.S.; Vithana, E.; Mihailov, E.; Khor, C.C.; Hayward, C.; Luben, R.N.; Foster, P.J.; Klein, B.E.; Klein, R.; Wong, H.S.; Mitchell, P.; Metspalu, A.; Aung, T.; Young, T.L.; He, M.; Parssinen, O.; Duijn, C.M. van; Wang, J.J.; Williams, C.; Jonas, J.B.; Teo, Y.Y.; Mackey, D.A.; Oexle, K.; Yoshimura, N.; Paterson, A.D.; Pfeiffer, N.; Wong, T.Y.; Baird, P.N.; Stambolian, D.; Wilson, J.E.; Cheng, C.Y.; Hammond, C.J.; Klaver, C.C.W.; et al.,

    2016-01-01

    Myopia is the most common human eye disorder and it results from complex genetic and environmental causes. The rapidly increasing prevalence of myopia poses a major public health challenge. Here, the CREAM consortium performs a joint meta-analysis to test single-nucleotide polymorphism (SNP) main

  2. Meta-analysis of gene-environment-wide association scans accounting for education level identifies additional loci for refractive error

    NARCIS (Netherlands)

    Q. Fan (Qiao); V.J.M. Verhoeven (Virginie); R. Wojciechowski (Robert); V.A. Barathi (Veluchamy); P.G. Hysi (Pirro); J. Guggenheim (Jean); R. Höhn (René); V. Vitart (Veronique); A.P. Khawaja (Anthony P.); K. Yamashiro (Kenji); S.M. Hosseini (S Mohsen); T. Lehtimäki (Terho); Y. Lu (Yi); T. Haller (Toomas); J. Xie (Jing); C. Delcourt (Cécile); M. Pirastu (Mario); J. Wedenoja (Juho); P. Gharahkhani (Puya); C. Venturini (Cristina); M. Miyake (Masahiro); A.W. Hewit (Alex); X. Guo (Xiaobo); J. Mazur (Johanna); J.E. Huffman (Jenifer E.); K.M. Williams (Katie M.); O. Polasek (Ozren); H. Campbell (Harry); I. Rudan (Igor); Z. Vatavuk (Zoran); J.F. Wilson (James F); P.K. Joshi (Peter); G. Mcmahon (George); B. St Pourcain (Beate); D.M. Evans (David); C.L. Simpson (Claire); T.-H. Schwantes-An (Tae-Hwi); R.P. Igo Jr. (Robert); A. Mirshahi (Alireza); A. Cougnard-Grégoire (Audrey); C. Bellenguez (Céline); M. Blettner (Maria); O. Raitakari (Olli); M. Kähönen (Mika); I. Seppälä (Ilkka); T. Zeller (Tanja); T. Meitinger (Thomas); J.S. Ried (Janina); C. Gieger (Christian); L. Portas (Laura); E.M. van Leeuwen (Elisa); N. Amin (Najaf); A.G. Uitterlinden (André); F. Rivadeneira Ramirez (Fernando); A. Hofman (Albert); J.R. Vingerling (Hans); Y. Wang (Ying); X. Wang (Xu); E. Tai-Hui Boh (Eileen); M.K. Ikram (Kamran); C. Sabanayagam (Charumathi); P. Gupta (Preeti); V. Tan (Vincent); L. Zhou (Lei); C.E.H. Ho (Candice E. H.); W. Lim (Wan'E); R.W. Beuerman (Roger W.); R. Siantar (Rosalynn); E.-S. Tai (E-Shyong); E.N. Vithana (Eranga); E. Mihailov (Evelin); C.C. Khor; C. Hayward (Caroline); R.N. Luben (Robert); P.J. Foster (Paul); B.E.K. Klein (Barbara); R. Klein (Ronald); H.-S. Wong (Hoi-Suen); P. Mitchell (Paul); A. Metspalu (Andres); T. Aung (Tin); T.L. Young (Terri L.); M. He (Mingguang); O. Pärssinen (Olavi); C.M. van Duijn (Cornelia); J. Jin Wang (Jie); C. Williams (Cathy); J.B. Jonas (Jost B.); Y.Y. Teo (Yik Ying); D.A. Mackey (David); K. Oexle (Konrad); N. Yoshimura; A.D. Paterson (Andrew D.); N. Pfeiffer (Norbert); T.Y. Wong (Tien Yin); P.N. Baird (Paul); D. Stambolian (Dwight); J.E.B. Wilson (Joan E. Bailey); C-Y. Cheng (Ching-Yu); C.J. Hammond (Christopher J.); C.C.W. Klaver (Caroline); S-M. Saw (Seang-Mei); J.S. Rahi (Jugnoo); J.-F. Korobelnik (Jean-François); J.P. Kemp (John); N.J. Timpson (Nicholas); G.D. Smith; J.E. Craig (Jamie E.); K.P. Burdon (Kathryn P.); R. Fogarty (Rhys); S.K. Iyengar (Sudha); E.Y. Chew (Emily); S. Janmahasatian (Sarayut); N.G. Martin (Nicholas); S. MacGregor (Stuart); L. Xu (Liang); M. Schache (Maria); M. Nangia (Monika); S. Panda-Jonas (Songhomitra); A.F. Wright (Alan); J.R. Fondran (Jeremy R.); J.H. Lass (Jonathan H.); S. Feng (Sheng); J.H. Zhao (Jing Hua); K.T. Khaw; N.J. Wareham (Nick); T. Rantanen (Taina); J. Kaprio (Jaakko); C.P. Pang (Chi Pui); L.J. Chen (Li Jia); P.O. Tam (Pancy O.); V. Jhanji (Vishal); A.L. Young (Alvin L.); A. Döring (Angela); L.J. Raffel (Leslie); M.-F. Cotch (Mary-Frances); X. Li (Xiaohui); S.P. Yip (Shea Ping); M.K.H. Yap (Maurice K.H.); G. Biino (Ginevra); S. Vaccargiu (Simona); M. Fossarello (Maurizio); B. Fleck (Brian); S. Yazar (Seyhan); J.W.L. Tideman (J. Willem L.); M. Tedja (Milly); T. Léveillard (Thierry); M.A. Morrison (Margaux A.); L.A. Farrer (Lindsay); X. Zhou (Xiangtian); W. Chen (Wei); N. Mizuki (Nobuhisa); A. Meguro (Akira); K.M. Makela (Kari Matti)

    2016-01-01

    textabstractMyopia is the most common human eye disorder and it results from complex genetic and environmental causes. The rapidly increasing prevalence of myopia poses a major public health challenge. Here, the CREAM consortium performs a joint meta-analysis to test single-nucleotide polymorphism

  3. Genome wide single cell analysis of chemotherapy resistant metastatic cells in a case of gastroesophageal adenocarcinoma

    International Nuclear Information System (INIS)

    Hjortland, Geir Olav; Fodstad, Oystein; Smeland, Sigbjorn; Hovig, Eivind; Meza-Zepeda, Leonardo A; Beiske, Klaus; Ree, Anne H; Tveito, Siri; Hoifodt, Hanne; Bohler, Per J; Hole, Knut H; Myklebost, Ola

    2011-01-01

    Metastatic progression due to development or enrichment of therapy-resistant tumor cells is eventually lethal. Molecular characterization of such chemotherapy resistant tumor cell clones may identify markers responsible for malignant progression and potential targets for new treatment. Here, in a case of stage IV adenocarcinoma of the gastroesophageal junction, we report the successful genome wide analysis using array comparative genomic hybridization (CGH) of DNA from only fourteen tumor cells using a bead-based single cell selection method from a bone metastasis progressing during chemotherapy. In a case of metastatic adenocarcinoma of the gastroesophageal junction, the progression of bone metastasis was observed during a chemotherapy regimen of epirubicin, oxaliplatin and capecitabine, whereas lung-, liver and lymph node metastases as well as the primary tumor were regressing. A bone marrow aspirate sampled at the site of progressing metastasis in the right iliac bone was performed, and single cell molecular analysis using array-CGH of Epithelial Specific Antigen (ESA)-positive metastatic cells, and revealed two distinct regions of amplification, 12p12.1 and 17q12-q21.2 amplicons, containing the KRAS (12p) and ERBB2 (HER2/NEU) (17q) oncogenes. Further intrapatient tumor heterogeneity of these highlighted gene copy number changes was analyzed by fluorescence in situ hybridization (FISH) in all available primary and metastatic tumor biopsies, and ErbB2 protein expression was investigated by immunohistochemistry. ERBB2 was heterogeneously amplified by FISH analysis in the primary tumor, as well as liver and bone metastasis, but homogenously amplified in biopsy specimens from a progressing bone metastasis after three initial cycles of chemotherapy, indicating a possible enrichment of erbB2 positive tumor cells in the progressing bone marrow metastasis during chemotherapy. A similar amplification profile was detected for wild-type KRAS, although more heterogeneously

  4. Multiple Sclerosis Increases Fracture Risk: A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Guixian Dong

    2015-01-01

    Full Text Available Purpose. The association between multiple sclerosis (MS and fracture risk has been reported, but results of previous studies remain controversial and ambiguous. To assess the association between MS and fracture risk, a meta-analysis was performed. Method. Based on comprehensive searches of the PubMed, Embase, and Web of Science, we identified outcome data from all articles estimating the association between MS and fracture risk. The pooled risk ratios (RRs with 95% confidence intervals (CIs were calculated. Results. A significant association between MS and fracture risk was found. This result remained statistically significant when the adjusted RRs were combined. Subgroup analysis stratified by the site of fracture suggested significant associations between MS and tibia fracture risk, femur fracture risk, hip fracture risk, pelvis fracture risk, vertebrae fracture risk, and humerus fracture risk. In the subgroup analysis by gender, female MS patients had increased fracture risk. When stratified by history of drug use, use of antidepressants, hypnotics/anxiolytics, anticonvulsants, and glucocorticoids increased the risk of fracture risk in MS patients. Conclusions. This meta-analysis demonstrated that MS was significantly associated with fracture risk.

  5. Multivariate meta-analysis: Potential and promise

    Science.gov (United States)

    Jackson, Dan; Riley, Richard; White, Ian R

    2011-01-01

    The multivariate random effects model is a generalization of the standard univariate model. Multivariate meta-analysis is becoming more commonly used and the techniques and related computer software, although continually under development, are now in place. In order to raise awareness of the multivariate methods, and discuss their advantages and disadvantages, we organized a one day ‘Multivariate meta-analysis’ event at the Royal Statistical Society. In addition to disseminating the most recent developments, we also received an abundance of comments, concerns, insights, critiques and encouragement. This article provides a balanced account of the day's discourse. By giving others the opportunity to respond to our assessment, we hope to ensure that the various view points and opinions are aired before multivariate meta-analysis simply becomes another widely used de facto method without any proper consideration of it by the medical statistics community. We describe the areas of application that multivariate meta-analysis has found, the methods available, the difficulties typically encountered and the arguments for and against the multivariate methods, using four representative but contrasting examples. We conclude that the multivariate methods can be useful, and in particular can provide estimates with better statistical properties, but also that these benefits come at the price of making more assumptions which do not result in better inference in every case. Although there is evidence that multivariate meta-analysis has considerable potential, it must be even more carefully applied than its univariate counterpart in practice. Copyright © 2011 John Wiley & Sons, Ltd. PMID:21268052

  6. Transcriptomic responses to biotic stresses in Malus x domestica: a meta-analysis study.

    Science.gov (United States)

    Balan, Bipin; Marra, Francesco Paolo; Caruso, Tiziano; Martinelli, Federico

    2018-01-31

    RNA-Seq analysis is a strong tool to gain insight into the molecular responses to biotic stresses in plants. The objective of this work is to identify specific and common molecular responses between different transcriptomic data related to fungi, virus and bacteria attacks in Malus x domestica. We analyzed seven transcriptomic datasets in Malus x domestica divided in responses to fungal pathogens, virus (Apple Stem Grooving Virus) and bacteria (Erwinia amylovora). Data were dissected using an integrated approach of pathway- and gene- set enrichment analysis, Mapman visualization tool, gene ontology analysis and inferred protein-protein interaction network. Our meta-analysis revealed that the bacterial infection enhanced specifically genes involved in sugar alcohol metabolism. Brassinosteroids were upregulated by fungal pathogens while ethylene was highly affected by Erwinia amylovora. Gibberellins and jasmonates were strongly repressed by fungal and viral infections. The protein-protein interaction network highlighted the role of WRKYs in responses to the studied pathogens. In summary, our meta-analysis provides a better understanding of the Malus X domestica transcriptome responses to different biotic stress conditions; we anticipate that these insights will assist in the development of genetic resistance and acute therapeutic strategies. This work would be an example for next meta-analysis works aiming at identifying specific common molecular features linked with biotic stress responses in other specialty crops.

  7. A meta-analysis of combination therapy versus single-agent therapy in anthracycline- and taxane-pretreated metastatic breast cancer: results from nine randomized Phase III trials

    Directory of Open Access Journals (Sweden)

    Xu L

    2016-07-01

    Full Text Available Liang Xu,1,2,* Xiaobo Wu,3,* Chun Hu,1,2 Zhiying Zhang,4 Le Zhang,1,2 Shujing Liang,1,2 Yingchun Xu,5 Fengchun Zhang1,2 1Department of Oncology, Suzhou Kowloon Hospital, Shanghai Jiaotong University School of Medicine, Suzhou, 2Department of Oncology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 3Prevention and Cure Center of Breast Disease, Third Hospital of Nanchang, Nanchang, 4Graduate School, Xuzhou Medical College, Xuzhou, 5Department of Oncology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: Nowadays, the philosophy of treating metastatic breast cancer (MBC is slowly evolving. Especially for the anthracycline- and taxane-pretreated MBC patients, no standard therapy exists in this setting. Whether to choose doublet agents or single agent as salvage treatment remains fiercely debated. Thus, we conducted a meta-analysis to resolve this problem. Databases including PubMed, EMBASE, and Cochrane library were searched for Phase III randomized clinical trials (published before August 2015 comparing the efficacy and adverse effects between the combination therapy and single-agent therapy in anthracycline- and taxane-pretreated MBC patients. The primary end point was the overall survival (OS, and the secondary end points were the progression-free survival (PFS, overall response rate (ORR, and grade 3 or 4 toxicities. The pooled hazard ratio (HR and pooled risk ratio (RR were used to evaluate the efficacy. Analyses were also performed to estimate the side effects and safety of both groups. In all, nine eligible randomized clinical trials were included in this meta-analysis. Improvements were proven in the doublet agents group on OS (HR 0.90, 95% confidence interval [CI] 0.84–0.96, P=0.002, PFS (HR 0.81, 95% CI 0.76–0.88, P<0.001, and ORR (RR 1.72, 95% CI 1.34–2.21, P<0.001. Notably, subgroup analysis

  8. Robotic thyroidectomy versus endoscopic thyroidectomy: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Lin Shuang

    2012-11-01

    Full Text Available Abstract Background To conduct a meta-analysis to determine the relative merits of robotic thyroidectomy (RT and endoscopic thyroidectomy (ET. Methods A literature search was performed to identify comparative studies reporting peri-operative outcomes for RT and ET. Pooled odds ratios (ORs and weighted mean differences (WMDs with 95% confidence interval (95% CI were calculated using either a fixed-effects or a random-effects model. Results Six studies matched the selection criteria, which reported on 2048 subjects, of whom 978 underwent RT and 1070 underwent ET. Comparing the outcomes of RT with ET, this meta-analysis indicated that RT was associated with more complications (WMD = 1.51, 95% CI 1.18 to 1.94 and greater amount of drainage fluid (WMD = 17.10, 95% CI 5.69 to 28.51. Meanwhile, operating time (WMD = 1.50, 95% CI −39.59 to 42.58, conversion (WMD = 0.63, 95% CI 0.07 to 6.17, post-operative hospital stay (WMD = −0.05; 95% CI −0.18 to 0.08, and the number of lymph nodes harvested (WMD = 0.62, 95% CI −0.29 to 1.53 were similar for both procedures. Conclusion The results of this meta-analysis indicated that RT is associated with an increased risk of complications and a greater amount of drainage fluid. Therefore, RT does not appear to have any advantage over ET. Further studies are required to confirm these results.

  9. Meta-analysis in microbiology

    Directory of Open Access Journals (Sweden)

    N Pabalan

    2014-01-01

    Full Text Available The use of meta-analysis in microbiology may facilitate decision-making that impacts public health policy. Directed at clinicians and researchers in microbiology, this review outlines the steps in performing this statistical technique, addresses its biases and describes its value in this discipline. The survey to estimate extent of the use of meta-analyses in microbiology shows the remarkable growth in the use of this research methodology, from a minimal Asian output to a level comparable with those of Europe and North America in the last 7 years.

  10. Meta-analysis of 28,141 individuals identifies common variants within five new loci that influence uric acid concentrations

    NARCIS (Netherlands)

    M. Kolz (Melanie); T. Johnson (Toby); S. Sanna (Serena); A. Teumer (Alexander); V. Vitart (Veronique); M. Perola (Markus); M. Mangino (Massimo); E. Albrecht (Eva); C. Wallace (Chris); M. Farrall (Martin); A. Johansson (Åsa); A.S. Dimas (Antigone); Y.S. Aulchenko (Yurii); J.S. Beckmann (Jacques); S.M. Bergmann (Sven); M. Bochud (Murielle); M.J. Brown (Morris); H. Campbell (Harry); J. Connell (John); A. Dominiczak (Anna); G. Homuth (Georg); C. Lamina (Claudia); M.I. McCarthy (Mark); T. Meitinger (Thomas); V. Mooser (Vincent); P. Munroe (Patricia); M. Nauck (Matthias); J. Peden (John); H. Prokisch (Holger); P. Salo (Perttu); V. Salomaa (Veikko); N.J. Samani (Nilesh); D. Schlessinger (David); M. Uda (Manuela); G. Waeber (Gérard); D. Waterworth (Dawn); R. Wang-Sattler (Rui); A.F. Wright (Alan); J. Adamski (Jerzy); J.B. Whitfield (John); U. Gyllensten (Ulf); J.F. Wilson (James); I. Rudan (Igor); P.P. Pramstaller (Peter Paul); H. Watkins (Hugh); A. Doering (Angela); H.E. Wichmann (Erich); T.D. Spector (Tim); L. Peltonen (Leena Johanna); H. Völzke (Henry); R. Nagaraja (Ramaiah); P. Vollenweider (Peter); M. Caulfield (Mark); T. Illig (Thomas); C. Gieger (Christian); U. Völker (Uwe)

    2009-01-01

    textabstractElevated serum uric acid levels cause gout and are a risk factor for cardiovascular disease and diabetes. To investigate the polygenetic basis of serum uric acid levels, we conducted a meta-analysis of genome-wide association scans from 14 studies totalling 28,141 participants of

  11. New Blood Pressure-Associated Loci Identified in Meta-Analyses of 475 000 Individuals

    DEFF Research Database (Denmark)

    Kraja, Aldi T.; Cook, James P.; Warren, Helen R.

    2017-01-01

    Background - Genome-wide association studies have recently identified >400 loci that harbor DNA sequence variants that influence blood pressure (BP). Our earlier studies identified and validated 56 single nucleotide variants (SNVs) associated with BP from meta-analyses of exome chip genotype data...

  12. Contemporary meta-analysis of short-term probiotic consumption on gastrointestinal transit.

    Science.gov (United States)

    Miller, Larry E; Zimmermann, Angela K; Ouwehand, Arthur C

    2016-06-07

    To determine the efficacy of probiotic supplementation on intestinal transit time (ITT) in adults and to identify factors that influence these outcomes. We conducted a systematic review of randomized controlled trials of probiotic supplementation that measured ITT in adults. Study quality was assessed using the Jadad scale. A random effects meta-analysis was performed with standardized mean difference (SMD) of ITT between probiotic and control groups as the primary outcome. Meta-regression and subgroup analyses examined the impact of moderator variables on SMD of ITT. A total of 15 clinical trials with 17 treatment effects representing 675 subjects were included in this analysis. Probiotic supplementation was moderately efficacious in decreasing ITT compared to control, with an SMD of 0.38 (95%CI: 0.23-0.53, P probiotics in subjects with vs without constipation (SMD: 0.57 vs 0.22, P probiotic strains (R (2) = 20%, P probiotics in meta-regression. Medium to large treatment effects were identified with B. lactis HN019 (SMD: 0.67, P probiotic strains yielded negligible reductions in ITT relative to control. Probiotic supplementation is moderately efficacious for reducing ITT in adults. Probiotics were most efficacious in constipated subjects, when evaluated in high-quality studies, and with certain probiotic strains.

  13. Determinants of investment behaviour. Methods and applications of meta-analysis

    International Nuclear Information System (INIS)

    Koetse, M.J.

    2006-01-01

    Meta-analysis is gradually gaining ground in economics as a research method to objectively and quantitatively summarise a body of existing empirical evidence. This dissertation studies the performance of well-known meta-analytic models and presents two meta-analysis applications. Despite its many attractive features, meta-analysis faces several methodical difficulties, especially when applied in economic research. We investigate two specific methodical problems that any meta-analysis in economics will have to deal with, viz., systematic effect-size variation due to primary-study misspecifications, and random effect-size heterogeneity. Using Monte-Carlo analysis we investigate the effects of these methodical problems on the results of a meta-analysis, and study the small-sample properties of several well-known and often applied meta-estimators. The focus of the meta-analysis applications is on two topics that are relevant for understanding investment behaviour, viz., the impact of uncertainty on investment spending, and the potential for substitution of capital for energy in production processes. In the first application we aim to shed light on the direction of the relationship between investment and uncertainty, and to uncover which factors are empirically relevant for explaining the wide variety in study outcomes. In the second application our goal is to analyse the direction and magnitude of capital-energy substitution potential, and to analyse the empirical relevance of suggested sources of variation in elasticity estimates

  14. Determinants of investment behaviour. Methods and applications of meta-analysis

    Energy Technology Data Exchange (ETDEWEB)

    Koetse, M.J.

    2006-03-14

    Meta-analysis is gradually gaining ground in economics as a research method to objectively and quantitatively summarise a body of existing empirical evidence. This dissertation studies the performance of well-known meta-analytic models and presents two meta-analysis applications. Despite its many attractive features, meta-analysis faces several methodical difficulties, especially when applied in economic research. We investigate two specific methodical problems that any meta-analysis in economics will have to deal with, viz., systematic effect-size variation due to primary-study misspecifications, and random effect-size heterogeneity. Using Monte-Carlo analysis we investigate the effects of these methodical problems on the results of a meta-analysis, and study the small-sample properties of several well-known and often applied meta-estimators. The focus of the meta-analysis applications is on two topics that are relevant for understanding investment behaviour, viz., the impact of uncertainty on investment spending, and the potential for substitution of capital for energy in production processes. In the first application we aim to shed light on the direction of the relationship between investment and uncertainty, and to uncover which factors are empirically relevant for explaining the wide variety in study outcomes. In the second application our goal is to analyse the direction and magnitude of capital-energy substitution potential, and to analyse the empirical relevance of suggested sources of variation in elasticity estimates.

  15. Mass shootings: a meta-analysis of the dose-response relationship.

    Science.gov (United States)

    Wilson, Laura C

    2014-12-01

    A meta-analysis was conducted to examine the dose-response theory as it relates to posttraumatic stress symptoms (PTSSs) following mass shootings. It was hypothesized that greater exposure to a mass shooting would be associated with greater PTSSs. Trauma exposure in the current study was broadly defined as the extent to which a person experienced or learned about a mass shooting. The meta-analysis identified 11 qualifying studies that included 13 independent effect sizes from a total of 8,047 participants. The overall weighted mean effect size, based on a random effects model, was r = .19, p shooting on the relationship between exposure and PTSSs. Because so few studies satisfied the inclusion criteria, the present study also documents that this area of the literature is underresearched. Copyright © 2014 International Society for Traumatic Stress Studies.

  16. Breed differences in dogs sensitivity to human points: a meta-analysis.

    Science.gov (United States)

    Dorey, Nicole R; Udell, Monique A R; Wynne, Clive D L

    2009-07-01

    The last decade has seen a substantial increase in research on the behavioral and cognitive abilities of pet dogs, Canis familiaris. The most commonly used experimental paradigm is the object-choice task in which a dog is given a choice of two containers and guided to the reinforced object by human pointing gestures. We review here studies of this type and attempt a meta-analysis of the available data. In the meta-analysis breeds of dogs were grouped into the eight categories of the American Kennel Club, and into four clusters identified by Parker and Ostrander [Parker, H.G., Ostrander, E.A., 2005. Canine genomics and genetics: running with the pack. PLoS Genet. 1, 507-513] on the basis of a genetic analysis. No differences in performance between breeds categorized in either fashion were identified. Rather, all dog breeds appear to be similarly and highly successful in following human points to locate desired food. We suggest this result could be due to the paucity of data available in published studies, and the restricted range of breeds tested.

  17. Meta-analysis of genome-wide linkage studies in BMI and obesity

    NARCIS (Netherlands)

    Saunders, Catherine L.; Chiodini, Benedetta D.; Sham, Pak; Lewis, Cathryn M.; Abkevich, Victor; Adeyemo, Adebowale A.; de Andrade, Mariza; Arya, Rector; Berenson, Gerald S.; Blangero, John; Boehnke, Michael; Borecki, Ingrid B.; Chagnon, Yvon C.; Chen, Wei; Comuzzie, Anthony G.; Deng, Hong-Wen; Duggirala, Ravindranath; Feitosa, Mary F.; Froguel, Philippe; Hanson, Robert L.; Hebebrand, Johannes; Huezo-Dias, Patricia; Kissebah, Ahmed H.; Li, Weidong; Luke, Amy; Martin, Lisa J.; Nash, Matthew; Ohman, Muena; Palmer, Lyle J.; Peltonen, Leena; Perola, Markus; Price, R. Arlen; Redline, Susan; Srinivasan, Sathanur R.; Stern, Michael P.; Stone, Steven; Stringham, Heather; Turner, Stephen; Wijmenga, Cisca; Collier, David A.

    Objective: The objective was to provide an overall assessment of genetic linkage data of BMI and BMI-defined obesity using a nonparametric genome scan meta-analysis. Research Methods and Procedures: We identified 37 published studies containing data on over 31,000 individuals from more than >10,000

  18. A meta-analysis of the effects of β-adrenergic blockers in chronic heart failure.

    Science.gov (United States)

    Zhang, Xiaojian; Shen, Chengwu; Zhai, Shujun; Liu, Yukun; Yue, Wen-Wei; Han, Li

    2016-10-01

    Adrenergic β-blockers are drugs that bind to, but do not activate β-adrenergic receptors. Instead they block the actions of β-adrenergic agonists and are used for the treatment of various diseases such as cardiac arrhythmias, angina pectoris, myocardial infarction, hypertension, headache, migraines, stress, anxiety, prostate cancer, and heart failure. Several meta-analysis studies have shown that β-blockers improve the heart function and reduce the risks of cardiovascular events, rate of mortality, and sudden death through chronic heart failure (CHF) of patients. The present study identified results from recent meta-analyses of β-adrenergic blockers and their usefulness in CHF. Databases including Medline/Embase/Cochrane Central Register of Controlled Trials (CENTRAL), and PubMed were searched for the periods May, 1985 to March, 2011 and June, 2013 to August, 2015, and a number of studies identified. Results of those studies showed that use of β-blockers was associated with decreased sudden cardiac death in patients with heart failure. However, contradictory results have also been reported. The present meta-analysis aimed to determine the efficacy of β-blockers on mortality and morbidity in patients with heart failure. The results showed that mortality was significantly reduced by β-blocker treatment prior to the surgery of heart failure patients. The results from the meta-analysis studies showed that β-blocker treatment in heart failure patients correlated with a significant decrease in long-term mortality, even in patients that meet one or more exclusion criteria of the MERIT-HF study. In summary, the findings of the current meta-analysis revealed beneficial effects different β-blockers have on patients with heart failure or related heart disease.

  19. Meta-analysis of individual registry results enhances international registry collaboration.

    Science.gov (United States)

    Paxton, Elizabeth W; Mohaddes, Maziar; Laaksonen, Inari; Lorimer, Michelle; Graves, Stephen E; Malchau, Henrik; Namba, Robert S; Kärrholm, John; Rolfson, Ola; Cafri, Guy

    2018-03-28

    Background and purpose - Although common in medical research, meta-analysis has not been widely adopted in registry collaborations. A meta-analytic approach in which each registry conducts a standardized analysis on its own data followed by a meta-analysis to calculate a weighted average of the estimates allows collaboration without sharing patient-level data. The value of meta-analysis as an alternative to individual patient data analysis is illustrated in this study by comparing the risk of revision of porous tantalum cups versus other uncemented cups in primary total hip arthroplasties from Sweden, Australia, and a US registry (2003-2015). Patients and methods - For both individual patient data analysis and meta-analysis approaches a Cox proportional hazard model was fit for time to revision, comparing porous tantalum (n = 23,201) with other uncemented cups (n = 128,321). Covariates included age, sex, diagnosis, head size, and stem fixation. In the meta-analysis approach, treatment effect size (i.e., Cox model hazard ratio) was calculated within each registry and a weighted average for the individual registries' estimates was calculated. Results - Patient-level data analysis and meta-analytic approaches yielded the same results with the porous tantalum cups having a higher risk of revision than other uncemented cups (HR (95% CI) 1.6 (1.4-1.7) and HR (95% CI) 1.5 (1.4-1.7), respectively). Adding the US cohort to the meta-analysis led to greater generalizability, increased precision of the treatment effect, and similar findings (HR (95% CI) 1.6 (1.4-1.7)) with increased risk of porous tantalum cups. Interpretation - The meta-analytic technique is a viable option to address privacy, security, and data ownership concerns allowing more expansive registry collaboration, greater generalizability, and increased precision of treatment effects.

  20. Drivers of Wetland Conversion: a Global Meta-Analysis

    NARCIS (Netherlands)

    van Asselen, S.; Verburg, P.H.; Vermaat, J.E.; Janse, J.

    2013-01-01

    Meta-analysis of case studies has become an important tool for synthesizing case study findings in land change. Meta-analyses of deforestation, urbanization, desertification and change in shifting cultivation systems have been published. This present study adds to this literature, with an analysis

  1. DNA adducts and cancer risk in prospective studies: a pooled analysis and a meta-analysis

    DEFF Research Database (Denmark)

    Veglia, Fabrizio; Loft, Steffen; Matullo, Giuseppe

    2008-01-01

    in which bulky DNA adducts have been measured in blood samples collected from healthy subjects (N = 1947; average follow-up 51-137 months). In addition, we have performed a meta-analysis by identifying all articles on the same subject published up to the end of 2006, including case-control studies......). The association was evident only in current smokers and was absent in former smokers. Also the meta-analysis, which included both lung and bladder cancers, showed a statistically significant association in current smokers, whereas the results in never smokers were equivocal; in former smokers, no association......Bulky DNA adducts are biomarkers of exposure to aromatic compounds and of the ability of the individual to metabolically activate carcinogens and to repair DNA damage. Their ability to predict cancer onset is uncertain. We have performed a pooled analysis of three prospective studies on cancer risk...

  2. A Western Dietary Pattern Increases Prostate Cancer Risk: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Fabiani, Roberto; Minelli, Liliana; Bertarelli, Gaia; Bacci, Silvia

    2016-10-12

    Dietary patterns were recently applied to examine the relationship between eating habits and prostate cancer (PC) risk. While the associations between PC risk with the glycemic index and Mediterranean score have been reviewed, no meta-analysis is currently available on dietary patterns defined by "a posteriori" methods. A literature search was carried out (PubMed, Web of Science) to identify studies reporting the relationship between dietary patterns and PC risk. Relevant dietary patterns were selected and the risks estimated were calculated by a random-effect model. Multivariable-adjusted odds ratios (ORs), for a first-percentile increase in dietary pattern score, were combined by a dose-response meta-analysis. Twelve observational studies were included in the meta-analysis which identified a "Healthy pattern" and a "Western pattern". The Healthy pattern was not related to PC risk (OR = 0.96; 95% confidence interval (CI): 0.88-1.04) while the Western pattern significantly increased it (OR = 1.34; 95% CI: 1.08-1.65). In addition, the "Carbohydrate pattern", which was analyzed in four articles, was positively associated with a higher PC risk (OR = 1.64; 95% CI: 1.35-2.00). A significant linear trend between the Western ( p = 0.011) pattern, the Carbohydrate ( p = 0.005) pattern, and the increment of PC risk was observed. The small number of studies included in the meta-analysis suggests that further investigation is necessary to support these findings.

  3. Plasma Exchange for Renal Vasculitis and Idiopathic Rapidly Progressive Glomerulonephritis: A Meta-analysis

    DEFF Research Database (Denmark)

    Walsh, Michael; Catapano, Fausta; Szpirt, Wladimir

    2010-01-01

    exchange did not differ significantly across the range of baseline serum creatinine values (P = 0.7) or number of plasma exchange treatments (P = 0.8). The RR for end-stage renal disease was 0.64 (95% CI, 0.47-0.88; P = 0.006), whereas the RR for death alone was 1.01 (95% CI, 0.71-1.4; P = 0......BACKGROUND:: Plasma exchange may be effective adjunctive treatment for renal vasculitis. We performed a systematic review and meta-analysis of randomized controlled trials of plasma exchange for renal vasculitis. STUDY DESIGN:: Systematic review and meta-analysis of articles identified from...

  4. Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease

    NARCIS (Netherlands)

    Schunkert, Heribert; König, Inke R.; Kathiresan, Sekar; Reilly, Muredach P.; Assimes, Themistocles L.; Holm, Hilma; Preuss, Michael; Stewart, Alexandre F. R.; Barbalic, Maja; Gieger, Christian; Absher, Devin; Aherrahrou, Zouhair; Allayee, Hooman; Altshuler, David; Anand, Sonia S.; Andersen, Karl; Anderson, Jeffrey L.; Ardissino, Diego; Ball, Stephen G.; Balmforth, Anthony J.; Barnes, Timothy A.; Becker, Diane M.; Becker, Lewis C.; Berger, Klaus; Bis, Joshua C.; Boekholdt, S. Matthijs; Boerwinkle, Eric; Braund, Peter S.; Brown, Morris J.; Burnett, Mary Susan; Buysschaert, Ian; Carlquist, John F.; Chen, Li; Cichon, Sven; Codd, Veryan; Davies, Robert W.; Dedoussis, George; Dehghan, Abbas; Demissie, Serkalem; Devaney, Joseph M.; Diemert, Patrick; Do, Ron; Doering, Angela; Eifert, Sandra; Mokhtari, Nour Eddine El; Ellis, Stephen G.; Elosua, Roberto; Engert, James C.; Epstein, Stephen E.; de Faire, Ulf; Fischer, Marcus; Folsom, Aaron R.; Freyer, Jennifer; Gigante, Bruna; Girelli, Domenico; Gretarsdottir, Solveig; Gudnason, Vilmundur; Gulcher, Jeffrey R.; Halperin, Eran; Hammond, Naomi; Hazen, Stanley L.; Hofman, Albert; Horne, Benjamin D.; Illig, Thomas; Iribarren, Carlos; Jones, Gregory T.; Jukema, J. Wouter; Kaiser, Michael A.; Kaplan, Lee M.; Kastelein, John J. P.; Khaw, Kay-Tee; Knowles, Joshua W.; Kolovou, Genovefa; Kong, Augustine; Laaksonen, Reijo; Lambrechts, Diether; Leander, Karin; Lettre, Guillaume; Li, Mingyao; Lieb, Wolfgang; Loley, Christina; Lotery, Andrew J.; Mannucci, Pier M.; Maouche, Seraya; Martinelli, Nicola; McKeown, Pascal P.; Meisinger, Christa; Meitinger, Thomas; Melander, Olle; Merlini, Pier Angelica; Mooser, Vincent; Morgan, Thomas; Mühleisen, Thomas W.; Muhlestein, Joseph B.; Münzel, Thomas; Musunuru, Kiran; Nahrstaedt, Janja; Nelson, Christopher P.; Nöthen, Markus M.; Olivieri, Oliviero; Patel, Riyaz S.; Patterson, Chris C.; Peters, Annette; Peyvandi, Flora; Qu, Liming; Quyyumi, Arshed A.; Rader, Daniel J.; Rallidis, Loukianos S.; Rice, Catherine; Rosendaal, Frits R.; Rubin, Diana; Salomaa, Veikko; Sampietro, M. Lourdes; Sandhu, Manj S.; Schadt, Eric; Schäfer, Arne; Schillert, Arne; Schreiber, Stefan; Schrezenmeir, Jürgen; Schwartz, Stephen M.; Siscovick, David S.; Sivananthan, Mohan; Sivapalaratnam, Suthesh; Smith, Albert; Smith, Tamara B.; Snoep, Jaapjan D.; Soranzo, Nicole; Spertus, John A.; Stark, Klaus; Stirrups, Kathy; Stoll, Monika; Tang, W. H. Wilson; Tennstedt, Stephanie; Thorgeirsson, Gudmundur; Thorleifsson, Gudmar; Tomaszewski, Maciej; Uitterlinden, Andre G.; van Rij, Andre M.; Voight, Benjamin F.; Wareham, Nick J.; Wells, George A.; Wichmann, H.-Erich; Wild, Philipp S.; Willenborg, Christina; Witteman, Jaqueline C. M.; Wright, Benjamin J.; Ye, Shu; Zeller, Tanja; Ziegler, Andreas; Cambien, Francois; Goodall, Alison H.; Cupples, L. Adrienne; Quertermous, Thomas; März, Winfried; Hengstenberg, Christian; Blankenberg, Stefan; Ouwehand, Willem H.; Hall, Alistair S.; Deloukas, Panos; Thompson, John R.; Stefansson, Kari; Roberts, Robert; Thorsteinsdottir, Unnur; O'Donnell, Christopher J.; McPherson, Ruth; Erdmann, Jeanette; Samani, Nilesh J.

    2011-01-01

    We performed a meta-analysis of 14 genome-wide association studies of coronary artery disease (CAD) comprising 22,233 individuals with CAD (cases) and 64,762 controls of European descent followed by genotyping of top association signals in 56,682 additional individuals. This analysis identified 13

  5. The performance of blood pressure-to-height ratio as a screening measure for identifying children and adolescents with hypertension: a meta-analysis.

    Science.gov (United States)

    Ma, Chunming; Liu, Yue; Lu, Qiang; Lu, Na; Liu, Xiaoli; Tian, Yiming; Wang, Rui; Yin, Fuzai

    2016-02-01

    The blood pressure-to-height ratio (BPHR) has been shown to be an accurate index for screening hypertension in children and adolescents. The aim of the present study was to perform a meta-analysis to assess the performance of BPHR for the assessment of hypertension. Electronic and manual searches were performed to identify studies of the BPHR. After methodological quality assessment and data extraction, pooled estimates of the sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, area under the receiver operating characteristic curve and summary receiver operating characteristics were assessed systematically. The extent of heterogeneity for it was assessed. Six studies were identified for analysis. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio values of BPHR, for assessment of hypertension, were 96% [95% confidence interval (CI)=0.95-0.97], 90% (95% CI=0.90-0.91), 10.68 (95% CI=8.03-14.21), 0.04 (95% CI=0.03-0.07) and 247.82 (95% CI=114.50-536.34), respectively. The area under the receiver operating characteristic curve was 0.9472. The BPHR had higher diagnostic accuracies for identifying hypertension in children and adolescents.

  6. Indirect health costs in ulcerative colitis and Crohn's disease: a systematic review and meta-analysis.

    Science.gov (United States)

    Kawalec, Paweł; Malinowski, Krzysztof Piotr

    2015-04-01

    The aim of this systematic review was to collect all current data on indirect costs related to inflammatory bowel disease as well as assessing homogeneity and comparability, and conducting a meta-analysis. Costs were collected using databases from Medline, Embase and Centre for Reviews and Dissemination databases, then average annual cost per patient was calculated and expressed in 2013-rate USD using the consumer price index and purchasing power parity (scenario 1) and then adjusted to specific gross domestic product (scenario 2) to make them comparable. The studies were then included in quantitative synthesis using the meta-analysis and bootstrap methods. This systematic review was carried out and reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. From 18 publications, overall annual indirect costs per patient as a result of the quantitative synthesis among all studies eligible for meta-analysis ranged from US$2425.01-US$9622.15 depending on the scenario and model used for analysis. The cost of presenteeism was assessed in only two studies. Considering heterogeneity among all identified studies random-effect model presented the most accurate results of meta-analysis equal to US$7189.27 and US$9622.15 per patient per year for scenario 1 and scenario 2, respectively. This systematic review revealed the existence of a relatively small number of studies that reported on the great economic burden of the disease upon society. A great variety of methodologies and cost components resulted in a very large discrepancy in indirect costs and made meta-analysis difficult to perform, so two scenarios were considered and meta-analysis conducted in subgroups to make data more comparable.

  7. Increased Expression and Aberrant Localization of Mucin 13 in Metastatic Colon Cancer

    Science.gov (United States)

    Gupta, Brij K.; Maher, Diane M.; Ebeling, Mara C.; Sundram, Vasudha; Koch, Michael D.; Lynch, Douglas W.; Bohlmeyer, Teresa; Watanabe, Akira; Aburatani, Hiroyuki; Puumala, Susan E.; Jaggi, Meena

    2012-01-01

    MUC13 is a newly identified transmembrane mucin. Although MUC13 is known to be overexpressed in ovarian and gastric cancers, limited information is available regarding the expression of MUC13 in metastatic colon cancer. Herein, we investigated the expression profile of MUC13 in colon cancer using a novel anti-MUC13 monoclonal antibody (MAb, clone ppz0020) by immunohistochemical (IHC) analysis. A cohort of colon cancer samples and tissue microarrays containing adjacent normal, non-metastatic colon cancer, metastatic colon cancer, and liver metastasis tissues was used in this study to investigate the expression pattern of MUC13. IHC analysis revealed significantly higher (pcolon cancer samples compared with faint or very low expression in adjacent normal tissues. Interestingly, metastatic colon cancer and liver metastasis tissue samples demonstrated significantly (pcolon cancer and adjacent normal colon samples. Moreover, cytoplasmic and nuclear MUC13 expression correlated with larger and poorly differentiated tumors. Four of six tested colon cancer cell lines also expressed MUC13 at RNA and protein levels. These studies demonstrate a significant increase in MUC13 expression in metastatic colon cancer and suggest a correlation between aberrant MUC13 localization (cytoplasmic and nuclear expression) and metastatic colon cancer. PMID:22914648

  8. Prognostic factors of early metastasis and mortality in dogs with appendicular osteosarcoma after receiving surgery : an individual patient data meta-analysis

    NARCIS (Netherlands)

    Schmidt, A.F.; Nielen, M.; Klungel, O.H.; Hoes, A.W.; de Boer, A.; Groenwold, R.H.H.; Kirpensteijn, J.

    2013-01-01

    Recently an aggregated data meta-analysis showed that serum alkaline phosphatase (SALP) and proximal humerus location are predictors for shorter survival in canine osteosarcoma. To identify additional prognostic factors of mortality and metastasis an individual patient data meta-analysis (IPDMA) was

  9. Meta-analysis indicates that the European GWAS-identified risk SNP rs1344706 within ZNF804A is not associated with schizophrenia in Han Chinese population.

    Directory of Open Access Journals (Sweden)

    Ming Li

    Full Text Available Recent genetic association studies have implicated several candidate susceptibility variants for schizophrenia among general populations. Rs1344706, an intronic SNP within ZNF804A, was identified as one of the most compelling candidate risk SNPs for schizophrenia in Europeans through genome-wide association studies (GWASs and replications as well as large-scale meta-analyses. However, in Han Chinese, the results for rs1344706 are inconsistent, and whether rs1344706 is an authentic risk SNP for schizophrenia in Han Chinese is inconclusive. Here, we conducted a systematic meta-analysis of rs1344706 with schizophrenia in Chinese population by combining all available case-control samples (N = 12, including a total of 8,982 cases and 12,342 controls. The results of our meta-analysis were not able to confirm an association of rs1344706 A-allele with schizophrenia (p = 0.10, odds ratio = 1.06, 95% confidence interval = 0.99-1.13. Such absence of association was further confirmed by the non-superiority test (p = 0.0003, suggesting that rs1344706 is not a risk SNP for schizophrenia in Han Chinese. Detailed examinations of individual samples revealed potential sampling bias in previous replication studies in Han Chinese. The absence of rs1344706 association in Han Chinese suggest a potential genetic heterogeneity in the susceptibility of schizophrenia on this locus and also demonstrate the difficulties in replicating genome-wide association findings of schizophrenia across different ethnic populations.

  10. Meta-Analysis for Primary and Secondary Data Analysis: The Super-Experiment Metaphor.

    Science.gov (United States)

    Jackson, Sally

    1991-01-01

    Considers the relation between meta-analysis statistics and analysis of variance statistics. Discusses advantages and disadvantages as a primary data analysis tool. Argues that the two approaches are partial paraphrases of one another. Advocates an integrative approach that introduces the best of meta-analytic thinking into primary analysis…

  11. Identifying Generalizable Image Segmentation Parameters for Urban Land Cover Mapping through Meta-Analysis and Regression Tree Modeling

    Directory of Open Access Journals (Sweden)

    Brian A. Johnson

    2018-01-01

    Full Text Available The advent of very high resolution (VHR satellite imagery and the development of Geographic Object-Based Image Analysis (GEOBIA have led to many new opportunities for fine-scale land cover mapping, especially in urban areas. Image segmentation is an important step in the GEOBIA framework, so great time/effort is often spent to ensure that computer-generated image segments closely match real-world objects of interest. In the remote sensing community, segmentation is frequently performed using the multiresolution segmentation (MRS algorithm, which is tuned through three user-defined parameters (the scale, shape/color, and compactness/smoothness parameters. The scale parameter (SP is the most important parameter and governs the average size of generated image segments. Existing automatic methods to determine suitable SPs for segmentation are scene-specific and often computationally intensive, so an approach to estimating appropriate SPs that is generalizable (i.e., not scene-specific could speed up the GEOBIA workflow considerably. In this study, we attempted to identify generalizable SPs for five common urban land cover types (buildings, vegetation, roads, bare soil, and water through meta-analysis and nonlinear regression tree (RT modeling. First, we performed a literature search of recent studies that employed GEOBIA for urban land cover mapping and extracted the MRS parameters used, the image properties (i.e., spatial and radiometric resolutions, and the land cover classes mapped. Using this data extracted from the literature, we constructed RT models for each land cover class to predict suitable SP values based on the: image spatial resolution, image radiometric resolution, shape/color parameter, and compactness/smoothness parameter. Based on a visual and quantitative analysis of results, we found that for all land cover classes except water, relatively accurate SPs could be identified using our RT modeling results. The main advantage of our

  12. Predictors of Shunt-dependent Hydrocephalus After Aneurysmal Subarachnoid Hemorrhage? A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Xie, Zhiyi; Hu, Xin; Zan, Xin; Lin, Sen; Li, Hao; You, Chao

    2017-10-01

    Hydrocephalus is a well-recognized complication after aneurysmal subarachnoid hemorrhage (aSAH). This study aimed to identify predictors for shunt-dependent hydrocephalus (SDHC) after aSAH via a systematic review and meta-analysis. A systematic search was conducted using the Embase, MEDLINE, and Web of Science databases for studies pertaining to aSAH and SDHC. Risk factors were assessed by meta-analysis when they were reported by at least 2 studies. The results were presented as odd ratios or risk ratios according to the study design with the corresponding 95% confidence intervals (CI). Twenty-five studies were included. In primary analysis of 14 potential risk factors, 12 were identified as predictors of SDHC after aSAH including age ≥50 years, female gender, high Hunt-Hess grade, Glasgow Coma Scale ≤8, Fisher grade ≥3, acute hydrocephalus, external ventricular drainage insertion, intraventricular hemorrhage, postcirculation aneurysm, anterior communicating artery aneurysm, meningitis, and rebleeding. The meta-analysis based on cohort studies found a significantly increased risk for SDHC in patients with aSAH treated by coiling (risk ratio, 1.16; 95% CI, 1.05-1.29), while the meta-analysis based on case-controlled studies failed to replicate this finding (odds ratio, 1.27; 95% CI, 0.95-1.71). Several new predictors of SDHC after aSAH were identified that may assist with the early recognition and prevention of SDHC. The controversial evidence found in this study was insufficient to support the potential of neurosurgical clipping for reducing the risk of shunt dependency. Further well-designed studies are warranted to explore the effect of treatment modality on SDHC risk. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Ischiofemoral impingement syndrome: a meta-analysis

    Energy Technology Data Exchange (ETDEWEB)

    Singer, Adam D.; Subhawong, Ty K.; Jose, Jean; Tresley, Jonathan; Clifford, Paul D. [Jackson Memorial Hospital, Department of Diagnostic Radiology, Section of Musculoskeletal Imaging, Miami, FL (United States)

    2015-06-01

    The aims of this article are to review the imaging characteristics of ischiofemoral impingement (IFI), summarize measurement thresholds for radiologic diagnosis based on a meta-analysis of the literature and raise awareness among radiologists and clinicians of this entity. A PubMed search restricted to the English language containing the keywords ''ischiofemoral impingement'' and ''quadratus femoris MRI'' was performed, and citations in these articles were also used to identify a total of 27 studies discussing ischiofemoral impingement. After excluding case reports and non-representative studies, there were five remaining articles including 193 hip MRIs of IFI in 154 subjects (133 female, 21 male) and 135 asymptomatic control hip MRIs from 74 subjects (55 female, 19 male). Additionally, we performed a retrospective database search of pelvic and hip MRI reports from our institution including the terms ''quadratus femoris'' or ''ischiofemoral impingement'' from a 9-year period and 24 hip MRIs from 21 patients (18 female, 3 male) with IFI with 5 asymptomatic contralateral control hip MRIs identified. In all, 217 hip MRIs of IFI and 140 control cases were included. A meta-analysis of these hip MRIs was conducted to determine optimal thresholds of the ischiofemoral space (IFS) and quadratus femoris space (QFS) for identifying IFI. Cases of IFI showed significantly smaller IFS and QFS compared to controls (14.91 ± 4.8 versus 26.01 ± 7.98 and 9.57 ± 3.7 versus 15.97 ± 6.07, measured in mm, respectively, p < 0.0001 for both). Pooled analysis revealed that for IFS, using a cutoff of ≤15 mm yielded a sensitivity of 76.9 %, specificity of 81.0 % and overall accuracy of 78.3 %. For QFS, a cutoff of ≤ 10.0 mm resulted in 78.7 % sensitivity, 74.1 % specificity and 77.1 % overall accuracy. IFI is a potential cause of hip pain that can be accurately diagnosed with MRI in conjunction with

  14. metaCCA: summary statistics-based multivariate meta-analysis of genome-wide association studies using canonical correlation analysis.

    Science.gov (United States)

    Cichonska, Anna; Rousu, Juho; Marttinen, Pekka; Kangas, Antti J; Soininen, Pasi; Lehtimäki, Terho; Raitakari, Olli T; Järvelin, Marjo-Riitta; Salomaa, Veikko; Ala-Korpela, Mika; Ripatti, Samuli; Pirinen, Matti

    2016-07-01

    A dominant approach to genetic association studies is to perform univariate tests between genotype-phenotype pairs. However, analyzing related traits together increases statistical power, and certain complex associations become detectable only when several variants are tested jointly. Currently, modest sample sizes of individual cohorts, and restricted availability of individual-level genotype-phenotype data across the cohorts limit conducting multivariate tests. We introduce metaCCA, a computational framework for summary statistics-based analysis of a single or multiple studies that allows multivariate representation of both genotype and phenotype. It extends the statistical technique of canonical correlation analysis to the setting where original individual-level records are not available, and employs a covariance shrinkage algorithm to achieve robustness.Multivariate meta-analysis of two Finnish studies of nuclear magnetic resonance metabolomics by metaCCA, using standard univariate output from the program SNPTEST, shows an excellent agreement with the pooled individual-level analysis of original data. Motivated by strong multivariate signals in the lipid genes tested, we envision that multivariate association testing using metaCCA has a great potential to provide novel insights from already published summary statistics from high-throughput phenotyping technologies. Code is available at https://github.com/aalto-ics-kepaco anna.cichonska@helsinki.fi or matti.pirinen@helsinki.fi Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press.

  15. The Economic Value of Mangroves: A Meta-Analysis

    Science.gov (United States)

    Marwa Salem; D. Evan Mercer

    2012-01-01

    This paper presents a synthesis of the mangrove ecosystem valuation literature through a meta-regression analysis. The main contribution of this study is that it is the first meta-analysis focusing solely on mangrove forests, whereas previous studies have included different types of wetlands. The number of studies included in the regression analysis is 44 for a total...

  16. Processes that Inform Multicultural Supervision: A Qualitative Meta-Analysis.

    Science.gov (United States)

    Tohidian, Nilou B; Quek, Karen Mui-Teng

    2017-10-01

    As the fields of counseling and psychotherapy have become more cognizant that individuals, couples, and families bring with them a myriad of diversity factors into therapy, multicultural competency has also become a crucial component in the development of clinicians during clinical supervision and training. We employed a qualitative meta-analysis to provide a detailed and comprehensive description of similar themes identified in primary qualitative studies that have investigated supervisory practices with an emphasis on diversity. Findings revealed six meta-categories, namely: (a) Supervisor's Multicultural Stances; (b) Supervisee's Multicultural Encounters; (c) Competency-Based Content in Supervision; (d) Processes Surrounding Multicultural Supervision; (e) Culturally Attuned Interventions; and (f) Multicultural Supervisory Alliance. Implications for practice are discussed. © 2017 American Association for Marriage and Family Therapy.

  17. Occurrence of Phlebitis: A Systematic Review and Meta-analysis.

    Science.gov (United States)

    Chang, Wen P; Peng, Yu X

    Peripheral venous catheters (PVCs) are commonly used in clinical practice. However, varying degrees of phlebitis often occur in patients receiving intravenous injections. The relevant literature suggests that phlebitis occurrence is highly associated with the catheter gauge, insertion site, and catheterization duration. Nevertheless, no meta-analysis has been performed on the influence of these three factors on the occurrence of phlebitis. The objective of this study was to determine whether any significant differences exist in the occurrence of phlebitis between catheters of 20 gauge or smaller and those larger than 20 gauge, between catheters inserted in the antecubital fossa and those inserted in other locations on the upper limbs, or between catheters inserted for more than 96 hours and those inserted for 96 hours or less. Using a systematic approach, we searched for literature published between 2006 and 2017 in the Cumulative Index to Nursing and Allied Health Literature (CINAHL), PubMed, ProQuest, and Cochrane Library databases. We used Comprehensive Meta-analysis Version 2 to perform our meta-analysis. After the screening and review processes, we identified 17 studies that met our selection conditions. Among these studies, 14 contained complete data for meta-analysis. These studies involved 4,343 patients and 5,846 PVCs. Regarding the overall effect size in the meta-analysis, the results of the forest plot comparing catheters of 20 gauge or smaller and those larger than 20 gauge presented a risk ratio (RR) of 0.88 (95% confidence interval [0.67, 1.17], p = .380), indicating no statistically significant difference in the occurrence of phlebitis between catheters of the aforementioned gauges. The results of the forest plot comparing catheters inserted in the antecubital fossa and those inserted in other locations on the upper limbs presented an RR of 1.05 (95% confidence interval [0.82, 1.34], p = .696), indicating no statistically significant difference in

  18. A meta-analysis of peripheral blood nerve growth factor levels in patients with schizophrenia.

    Science.gov (United States)

    Qin, X-Y; Wu, H-T; Cao, C; Loh, Y P; Cheng, Y

    2017-09-01

    Neurotrophins particularly brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are crucial modulators in the neurodevelopment and maintenance of central and peripheral nervous systems. Neurotrophin hypothesis of schizophrenia (SCZ) postulated that the changes in the brains of SCZ patients are the result of disturbances of developing processes involving neurotrophic factors. This hypothesis was mainly supported by the abnormal regulation of BDNF in SCZ, especially the decreased peripheral blood BDNF levels in SCZ patients validated by several meta-analyses. However, the regulation of NGF in SCZ remains unclear because of the inconsistent findings from the clinical studies. Therefore, we undertook, to the best of our knowledge, the first systematic review with a meta-analysis to quantitatively summarize the peripheral blood NGF data in SCZ patients compared with healthy control (HC) subjects. A systematic search of Pubmed, PsycINFO and Web of Science identified 13 articles encompassing a sample of 1693 individuals for the meta-analysis. Random-effects meta-analysis showed that patients with SCZ had significantly decreased peripheral blood levels of NGF when compared with the HC subjects (Hedges's g=-0.633, 95% confidence interval (CI)=-0.948 to -0.318, Pmeta-regression analyses showed that age, gender and sample size had no moderating effects on the outcome of the meta-analysis, whereas disease severity might be a confounding factor for the meta-analysis. These results demonstrated that patients with SCZ are accompanied by the decreased peripheral blood NGF levels, strengthening the clinical evidence of an abnormal neurotrophin profile in the patients with SCZ.

  19. Efficacy and safety of regorafenib in the treatment of metastatic colorectal cancer: A systematic review.

    Science.gov (United States)

    Røed Skårderud, Maria; Polk, Anne; Kjeldgaard Vistisen, Kirsten; Larsen, Finn Ole; Nielsen, Dorte Lisbet

    2018-01-01

    Despite advances in the treatment of colorectal cancer, third-line treatment options are still limited. Regorafenib was approved in 2012 for the treatment of patients with metastatic colorectal cancer previously treated with approved standard therapy. The purpose of this review is to present existing clinical data on regorafenib. We systematically searched the PubMed and Embase databases, as well as ASCO and ESMO conference abstracts, for studies in English including ≥30 patients, evaluating the efficacy and safety of regorafenib in patients with metastatic colorectal cancer. A meta-analysis was conducted on the published, randomized phase III trials. 24 eligible studies were included. In two phase III trials, regorafenib significantly increased overall survival (OS), progression free survival (PFS), and disease control rate when compared to placebo. Survival benefits of 1.4 and 2.5 months were presented. The meta-analysis indicated a significant greater treatment effect on OS (hazard ratio 0.67) and PFS (hazard ratio 0.40), compared to placebo. The non-randomized studies mostly supported these results. The most frequently reported adverse events were hand-foot-skin reaction (25%-86%), hypertension (11%-47%) and fatigue (2%-73%). Large phase III randomized trials indicate that regorafenib provides a benefit in OS and PFS when compared to placebo. Adverse events were common, but manageable and typical of multi-target tyrosine kinase inhibitors. Further research is needed to investigate alternative approaches to the dosing of regorafenib and to explore clinical and molecular biomarkers that can guide patient selection. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. How Acute Total Sleep Loss Affects the Attending Brain: A Meta-Analysis of Neuroimaging Studies

    Science.gov (United States)

    Ma, Ning; Dinges, David F.; Basner, Mathias; Rao, Hengyi

    2015-01-01

    Study Objectives: Attention is a cognitive domain that can be severely affected by sleep deprivation. Previous neuroimaging studies have used different attention paradigms and reported both increased and reduced brain activation after sleep deprivation. However, due to large variability in sleep deprivation protocols, task paradigms, experimental designs, characteristics of subject populations, and imaging techniques, there is no consensus regarding the effects of sleep loss on the attending brain. The aim of this meta-analysis was to identify brain activations that are commonly altered by acute total sleep deprivation across different attention tasks. Design: Coordinate-based meta-analysis of neuroimaging studies of performance on attention tasks during experimental sleep deprivation. Methods: The current version of the activation likelihood estimation (ALE) approach was used for meta-analysis. The authors searched published articles and identified 11 sleep deprivation neuroimaging studies using different attention tasks with a total of 185 participants, equaling 81 foci for ALE analysis. Results: The meta-analysis revealed significantly reduced brain activation in multiple regions following sleep deprivation compared to rested wakefulness, including bilateral intraparietal sulcus, bilateral insula, right prefrontal cortex, medial frontal cortex, and right parahippocampal gyrus. Increased activation was found only in bilateral thalamus after sleep deprivation compared to rested wakefulness. Conclusion: Acute total sleep deprivation decreases brain activation in the fronto-parietal attention network (prefrontal cortex and intraparietal sulcus) and in the salience network (insula and medial frontal cortex). Increased thalamic activation after sleep deprivation may reflect a complex interaction between the de-arousing effects of sleep loss and the arousing effects of task performance on thalamic activity. Citation: Ma N, Dinges DF, Basner M, Rao H. How acute total

  1. The TEACCH program for children and adults with autism: a meta-analysis of intervention studies.

    Science.gov (United States)

    Virues-Ortega, Javier; Julio, Flávia M; Pastor-Barriuso, Roberto

    2013-12-01

    The intervention program for autism known as Treatment and Education of Autistic and Related Communication Handicapped Children (TEACCH) is considered an emerging practice for autism. In the present study we used state-of-the-art meta-analytical procedures to examine the pooled clinical effects of TEACCH in a variety of outcomes. A total of 13 studies were selected for meta-analysis totaling 172 individuals with autism exposed to TEACCH. Standardized measures of perceptual, motor, adaptive, verbal and cognitive skills were identified as treatment outcomes. We used inverse-variance weighted random effects meta-analysis supplemented with quality assessment, sensitivity analysis, meta-regression, and heterogeneity and publication bias tests. The results suggested that TEACCH effects on perceptual, motor, verbal and cognitive skills were of small magnitude in the meta-analyzed studies. Effects over adaptive behavioral repertoires including communication, activities of daily living, and motor functioning were within the negligible to small range. There were moderate to large gains in social behavior and maladaptive behavior. The effects of the TEACCH program were not moderated by aspects of the intervention such as duration (total weeks), intensity (hours per week), and setting (home-based vs. center-based). While the present meta-analysis provided limited support for the TEACCH program as a comprehensive intervention, our results should be considered exploratory owing to the limited pool of studies available. © 2013.

  2. Alcohol consumption and the neoplastic progression in Barrett's esophagus: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Zhifeng Lou

    Full Text Available PURPOSE: In the developed countries, the incidence of esophageal adenocarcinoma (EAC is increasing over recent decades. The purpose of this meta-analysis was to arrive at quantitative conclusions about the contribution of alcohol intakes and the progression of Barrett's esophagus. METHODS: A comprehensive, systematic bibliographic search of medical literature published up to Oct 2013 was conducted to identify relevant studies. A meta-analysis was conducted for alcohol consumption on the Barrett's esophagus progression. RESULTS: A total of 882 cases in 6,867 individuals from 14 observational studies were indemnified in this meta-analysis. The result of this current meta-analysis, including 10 case-control and 4 cohort studies, indicated that alcohol consumption was not associated with the neoplastic progression in Barrett's esophagus (RR, 1.17; 95% CI, 0.93-1.48. When stratified by the study designs, no significant association was detected in either high vs low group or ever vs never group. CONCLUSIONS: Alcohol drinking is not associated with risk of neoplastic progression in Barrett's esophagus. Further well designed studies are needed in this area.

  3. Methadone Poisoning in Children: A Systematic Review and Meta-Analysis in Iran

    Directory of Open Access Journals (Sweden)

    Yasaman Allameh

    2017-05-01

    Full Text Available Context Symptoms of methadone poisoning, as one of the most dangerous types of poisoning, are very serious in children. Objectives The aim of this study was to describe causes and clinical symptoms of methadone poisoning in children admitted to hospitals in Iran. Data Sources Relevant studies published in national and international journals before January 29, 2016 were identified by studying the available databases, including PubMed, Web of Sciences, Google Scholar, Scopus, SID, Iranmedex, MagIran, and Irandoc. Study Selection After excluding duplicate, irrelevant, and low-quality articles, relevant papers were entered into the meta-analysis. The prevalence, mean, and standard deviation of methadone poisoning symptoms in children were statistically analyzed, using Stata version 11, and causes of methadone poisoning were presented in tables. Data Extraction Studies with unknown sample sizes, abstracts without access to full text, articles with quality assessment scores below 15.5, and studies carried out on non-Iranian populations were excluded from the meta-analysis. Results During the initial advanced search, 1594 articles were identified. After quality assessment, 12 papers were found eligible for the final systematic review and meta-analysis, based on the inclusion and exclusion criteria. The reported symptoms included drowsiness, vomiting, apnea, cyanosis, seizure, ataxia, and delirium. In the meta-analysis, prevalence of symptoms in referred patients was estimated at 44% (0.95% confidence interval, 0.288 to 0.609. The causes of poisoning in children included accidental feeding by parents, storage of drugs in inappropriate containers, parental addiction, and low educational level of parents. Conclusions It is important to keep methadone in a suitable container away from children. Also, it is essential to focus on educating parents on health issues of their children.

  4. Faith-adapted psychological therapies for depression and anxiety: Systematic review and meta-analysis.

    Science.gov (United States)

    Anderson, Naomi; Heywood-Everett, Suzanne; Siddiqi, Najma; Wright, Judy; Meredith, Jodi; McMillan, Dean

    2015-05-01

    Incorporating faith (religious or spiritual) perspectives into psychological treatments has attracted significant interest in recent years. However, previous suggestion that good psychiatric care should include spiritual components has provoked controversy. To try to address ongoing uncertainty in this field we present a systematic review and meta-analysis to assess the efficacy of faith-based adaptations of bona fide psychological therapies for depression or anxiety. A systematic review and meta-analysis of randomised controlled trials were performed. The literature search yielded 2274 citations of which 16 studies were eligible for inclusion. All studies used cognitive or cognitive behavioural models as the basis for their faith-adapted treatment (F-CBT). We identified statistically significant benefits of using F-CBT. However, quality assessment using the Cochrane risk of bias tool revealed methodological limitations that reduce the apparent strength of these findings. Whilst the effect sizes identified here were statistically significant, there were relatively a few relevant RCTs available, and those included were typically small and susceptible to significant biases. Biases associated with researcher or therapist allegiance were identified as a particular concern. Despite some suggestion that faith-adapted CBT may out-perform both standard CBT and control conditions (waiting list or "treatment as usual"), the effect sizes identified in this meta-analysis must be considered in the light of the substantial methodological limitations that affect the primary research data. Before firm recommendations about the value of faith-adapted treatments can be made, further large-scale, rigorously performed trials are required. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. A systematic review and meta-analysis of the proportion of dogs surrendered for dog-related and owner-related reasons.

    Science.gov (United States)

    Lambert, Kim; Coe, Jason; Niel, Lee; Dewey, Cate; Sargeant, Jan M

    2015-01-01

    Companion-animal relinquishment is a worldwide phenomenon that leaves companion animals homeless. Knowing why humans make the decision to end their relationship with a companion-animal can help in our understanding of this complex societal issue and can help to develop preventive strategies. A systematic review and meta-analysis was conducted to summarize reasons why dogs are surrendered, and determine if certain study characteristics were associated with the reported proportions of reasons for surrender. Articles investigating one or more reasons for dog surrender were selected from the references of a published scoping review. Two reviewers assessed the titles and abstracts of these articles, identifying 39 relevant articles. From these, 21 articles were further excluded because of ineligible study design, insufficient data available for calculating a proportion, or no data available for dogs. Data were extracted from 18 articles and meta-analysis was conducted on articles investigating reasons for dog surrender to a shelter (n=9) or dog surrender for euthanasia (n=5). Three studies were excluded from meta-analysis because they were duplicate populations. Other reasons for excluding studies from meta-analysis were, (1) the study only investigated reasons for dog re-relinquishment (n=2) and (2) the study sample size was dog surrender to a shelter and dog surrender for euthanasia. Results of meta-analysis found owner health/illness as a reason for dog surrender to a shelter had an overall estimate of 4.6% (95% CI: 4.1%, 5.2%). For all other identified reasons for surrender there was significant variation in methodology among studies preventing further meta-analysis. Univariable meta-regression was conducted to explore sources of variation among these studies. Country was identified as a significant source of variation (pdog surrender for euthanasia. The overall estimate for studies from Australia was 10% (95% CI: 8.0%, 12.0%; I(2)=15.5%), compared to 16% (95% CI

  6. Dropout from exercise randomized controlled trials among people with depression: A meta-analysis and meta regression.

    Science.gov (United States)

    Stubbs, Brendon; Vancampfort, Davy; Rosenbaum, Simon; Ward, Philip B; Richards, Justin; Soundy, Andrew; Veronese, Nicola; Solmi, Marco; Schuch, Felipe B

    2016-01-15

    Exercise has established efficacy in improving depressive symptoms. Dropouts from randomized controlled trials (RCT's) pose a threat to the validity of this evidence base, with dropout rates varying across studies. We conducted a systematic review and meta-analysis to investigate the prevalence and predictors of dropout rates among adults with depression participating in exercise RCT's. Three authors identified RCT's from a recent Cochrane review and conducted updated searches of major electronic databases from 01/2013 to 08/2015. We included RCT's of exercise interventions in people with depression (including major depressive disorder (MDD) and depressive symptoms) that reported dropout rates. A random effects meta-analysis and meta regression were conducted. Overall, 40 RCT's were included reporting dropout rates across 52 exercise interventions including 1720 people with depression (49.1 years (range=19-76 years), 72% female (range=0-100)). The trim and fill adjusted prevalence of dropout across all studies was 18.1% (95%CI=15.0-21.8%) and 17.2% (95%CI=13.5-21.7, N=31) in MDD only. In MDD participants, higher baseline depressive symptoms (β=0.0409, 95%CI=0.0809-0.0009, P=0.04) predicted greater dropout, whilst supervised interventions delivered by physiotherapists (β=-1.2029, 95%CI=-2.0967 to -0.3091, p=0.008) and exercise physiologists (β=-1.3396, 95%CI=-2.4478 to -0.2313, p=0.01) predicted lower dropout. A comparative meta-analysis (N=29) established dropout was lower in exercise than control conditions (OR=0.642, 95%CI=0.43-0.95, p=0.02). Exercise is well tolerated by people with depression and drop out in RCT's is lower than control conditions. Thus, exercise is a feasible treatment, in particular when delivered by healthcare professionals with specific training in exercise prescription. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Narcissism and Social Networking Behavior: A Meta-Analysis.

    Science.gov (United States)

    Gnambs, Timo; Appel, Markus

    2018-04-01

    The increasing popularity of social networking sites (SNS) such as Facebook and Twitter has given rise to speculations that the intensity of using these platforms is associated with narcissistic tendencies. However, recent research on this issue has been all but conclusive. We present a three-level, random effects meta-analysis including 289 effect sizes from 57 studies (total N = 25,631) on the association between trait narcissism and social networking behavior. The meta-analysis identified a small to moderate effect of ρ = .17 (τ = .11), 95% CI [.13, .21], for grandiose narcissism that replicated across different social networking platforms, respondent characteristics, and time. Moderator analyses revealed pronounced cultural differences, with stronger associations in power-distant cultures. Moreover, social networking behaviors geared toward self-presentation and the number of SNS friends exhibited stronger effects than usage durations. Overall, the study not only supported but also refined the notion of a relationship between engaging in social networking sites and narcissistic personality traits. © 2017 Wiley Periodicals, Inc.

  8. Protection from sunburn with beta-Carotene--a meta-analysis.

    Science.gov (United States)

    Köpcke, Wolfgang; Krutmann, Jean

    2008-01-01

    Nutritional protection against skin damage from sunlight is increasingly advocated to the general public, but its effectiveness is controversial. In this meta-analysis, we have systematically reviewed the existing literature on human supplementation studies on dietary protection against sunburn by beta-carotene. A review of literature until June 2007 was performed in PubMed, ISI Web of Science and EBM Cochrane library and identified a total of seven studies which evaluated the effectiveness of beta-carotene in protection against sunburn. Data were abstracted from these studies by means of a standardized data collection protocol. The subsequent meta-analysis showed that (1) beta-carotene supplementation protects against sunburn and (2) the study duration had a significant influence on the effected size. Regression plot analysis revealed that protection required a minimum of 10 weeks of supplementation with a mean increase of the protective effect of 0.5 standard deviations with every additional month of supplementation. Thus, dietary supplementation of humans with beta-carotene provides protection against sunburn in a time-dependent manner.

  9. Genetic Biomarkers of Barrett's Esophagus Susceptibility and Progression to Dysplasia and Cancer: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Findlay, John M; Middleton, Mark R; Tomlinson, Ian

    2016-01-01

    Barrett's esophagus (BE) is a common and important precursor lesion of esophageal adenocarcinoma (EAC). A third of patients with BE are asymptomatic, and our ability to predict the risk of progression of metaplasia to dysplasia and EAC (and therefore guide management) is limited. There is an urgent need for clinically useful biomarkers of susceptibility to both BE and risk of subsequent progression. This study aims to systematically identify, review, and meta-analyze genetic biomarkers reported to predict both. A systematic review of the PubMed and EMBASE databases was performed in May 2014. Study and evidence quality were appraised using the revised American Society of Clinical Oncology guidelines, and modified Recommendations for Tumor Marker Scores. Meta-analysis was performed for all markers assessed by more than one study. A total of 251 full-text articles were reviewed; 52 were included. A total of 33 germline markers of susceptibility were identified (level of evidence II-III); 17 were included. Five somatic markers of progression were identified; meta-analysis demonstrated significant associations for chromosomal instability (level of evidence II). One somatic marker of progression/relapse following photodynamic therapy was identified. However, a number of failings of methodology and reporting were identified. This is the first systematic review and meta-analysis to evaluate genetic biomarkers of BE susceptibility and risk of progression. While a number of limitations of study quality temper the utility of those markers identified, some-in particular, those identified by genome-wide association studies, and chromosomal instability for progression-appear plausible, although robust validation is required.

  10. Coffee Consumption and Risk of Biliary Tract Cancers and Liver Cancer: A Dose-Response Meta-Analysis of Prospective Cohort Studies.

    Science.gov (United States)

    Godos, Justyna; Micek, Agnieszka; Marranzano, Marina; Salomone, Federico; Rio, Daniele Del; Ray, Sumantra

    2017-08-28

    A meta-analysis was conducted to summarize the evidence from prospective cohort and case-control studies regarding the association between coffee intake and biliary tract cancer (BTC) and liver cancer risk. Eligible studies were identified by searches of PubMed and EMBASE databases from the earliest available online indexing year to March 2017. The dose-response relationship was assessed by a restricted cubic spline model and multivariate random-effect meta-regression. A stratified and subgroup analysis by smoking status and hepatitis was performed to identify potential confounding factors. We identified five studies on BTC risk and 13 on liver cancer risk eligible for meta-analysis. A linear dose-response meta-analysis did not show a significant association between coffee consumption and BTC risk. However, there was evidence of inverse correlation between coffee consumption and liver cancer risk. The association was consistent throughout the various potential confounding factors explored including smoking status, hepatitis, etc. Increasing coffee consumption by one cup per day was associated with a 15% reduction in liver cancer risk (RR 0.85; 95% CI 0.82 to 0.88). The findings suggest that increased coffee consumption is associated with decreased risk of liver cancer, but not BTC.

  11. Mutational analysis and clinical correlation of metastatic colorectal cancer.

    Science.gov (United States)

    Russo, Andrea L; Borger, Darrell R; Szymonifka, Jackie; Ryan, David P; Wo, Jennifer Y; Blaszkowsky, Lawrence S; Kwak, Eunice L; Allen, Jill N; Wadlow, Raymond C; Zhu, Andrew X; Murphy, Janet E; Faris, Jason E; Dias-Santagata, Dora; Haigis, Kevin M; Ellisen, Leif W; Iafrate, Anthony J; Hong, Theodore S

    2014-05-15

    Early identification of mutations may guide patients with metastatic colorectal cancer toward targeted therapies that may be life prolonging. The authors assessed tumor genotype correlations with clinical characteristics to determine whether mutational profiling can account for clinical similarities, differences, and outcomes. Under Institutional Review Board approval, 222 patients with metastatic colon adenocarcinoma (n = 158) and rectal adenocarcinoma (n = 64) who underwent clinical tumor genotyping were reviewed. Multiplexed tumor genotyping screened for >150 mutations across 15 commonly mutated cancer genes. The chi-square test was used to assess genotype frequency by tumor site and additional clinical characteristics. Cox multivariate analysis was used to assess the impact of genotype on overall survival. Broad-based tumor genotyping revealed clinical and anatomic differences that could be linked to gene mutations. NRAS mutations were associated with rectal cancer versus colon cancer (12.5% vs 0.6%; P colon cancer (13% vs 3%; P = .024) and older age (15.8% vs 4.6%; P = .006). TP53 mutations were associated with rectal cancer (30% vs 18%; P = .048), younger age (14% vs 28.7%; P = .007), and men (26.4% vs 14%; P = .03). Lung metastases were associated with PIK3CA mutations (23% vs 8.7%; P = .004). Only mutations in BRAF were independently associated with decreased overall survival (hazard ratio, 2.4; 95% confidence interval, 1.09-5.27; P = .029). The current study suggests that underlying molecular profiles can differ between colon and rectal cancers. Further investigation is warranted to assess whether the differences identified are important in determining the optimal treatment course for these patients. © 2014 American Cancer Society.

  12. Network meta-analysis-highly attractive but more methodological research is needed

    Directory of Open Access Journals (Sweden)

    Singh Sonal

    2011-06-01

    Full Text Available Abstract Network meta-analysis, in the context of a systematic review, is a meta-analysis in which multiple treatments (that is, three or more are being compared using both direct comparisons of interventions within randomized controlled trials and indirect comparisons across trials based on a common comparator. To ensure validity of findings from network meta-analyses, the systematic review must be designed rigorously and conducted carefully. Aspects of designing and conducting a systematic review for network meta-analysis include defining the review question, specifying eligibility criteria, searching for and selecting studies, assessing risk of bias and quality of evidence, conducting a network meta-analysis, interpreting and reporting findings. This commentary summarizes the methodologic challenges and research opportunities for network meta-analysis relevant to each aspect of the systematic review process based on discussions at a network meta-analysis methodology meeting we hosted in May 2010 at the Johns Hopkins Bloomberg School of Public Health. Since this commentary reflects the discussion at that meeting, it is not intended to provide an overview of the field.

  13. Occupational and environmental scleroderma. Systematic review and meta-analysis.

    Science.gov (United States)

    Rubio-Rivas, Manuel; Moreno, Rafael; Corbella, Xavier

    2017-03-01

    The etiology of systemic sclerosis (SSc) remains unknown; however, several occupational and environmental factors have been implicated. Our objective was to perform a meta-analysis of all studies published on SSc associated with occupational and environmental exposure. The review was undertaken by means of MEDLINE and SCOPUS from 1960 to 2014 and using the terms: "systemic," "scleroderma," or "systemic sclerosis/chemically induced" [MesH]. The Newcastle-Ottawa Scale was used for the qualifying assessment. The inverse variance-weighted method was performed. The meta-analysis of silica exposure included 15 case-control studies [overall OR 2.81 (95%CI 1.86-4.23; p < 0.001)] and 4 cohort studies [overall RR 17.52 (95%CI 5.98-51.37; p < 0.001)]; the meta-analysis of solvents exposure included 13 case-control studies (overall OR 2.00 [95%CI 1.32-3.02; p = 0.001); the meta-analysis of breast implants exposure included 4 case-control studies (overall OR 1.68 (95%CI 1.65-1.71; p < 0.001)) and 6 cohort studies (overall RR 2.13 (95%CI 0.86-5.27; p = 0.10)); the meta-analysis of epoxy resins exposure included 4 case-control studies (overall OR 2.97 (95%CI 2.31-3.83; p < 0.001)), the meta-analysis of pesticides exposure included 3 case-control studies (overall OR 1.02 (95%CI 0.78-1.32; p = 0.90)) and, finally, the meta-analysis of welding fumes exposure included 4 studies (overall OR 1.29 (95%CI 0.44-3.74; p = 0.64)). Not enough studies citing risks related to hair dyes have been published to perform an accurate meta-analysis. Silica and solvents were the two most likely substances related to the pathogenesis of SSc. While silica is involved in particular jobs, solvents are widespread and more people are at risk of having incidental contact with them.

  14. Common and distinct neural correlates of personal and vicarious reward: A quantitative meta-analysis

    Science.gov (United States)

    Morelli, Sylvia A.; Sacchet, Matthew D.; Zaki, Jamil

    2015-01-01

    Individuals experience reward not only when directly receiving positive outcomes (e.g., food or money), but also when observing others receive such outcomes. This latter phenomenon, known as vicarious reward, is a perennial topic of interest among psychologists and economists. More recently, neuroscientists have begun exploring the neuroanatomy underlying vicarious reward. Here we present a quantitative whole-brain meta-analysis of this emerging literature. We identified 25 functional neuroimaging studies that included contrasts between vicarious reward and a neutral control, and subjected these contrasts to an activation likelihood estimate (ALE) meta-analysis. This analysis revealed a consistent pattern of activation across studies, spanning structures typically associated with the computation of value (especially ventromedial prefrontal cortex) and mentalizing (including dorsomedial prefrontal cortex and superior temporal sulcus). We further quantitatively compared this activation pattern to activation foci from a previous meta-analysis of personal reward. Conjunction analyses yielded overlapping VMPFC activity in response to personal and vicarious reward. Contrast analyses identified preferential engagement of the nucleus accumbens in response to personal as compared to vicarious reward, and in mentalizing-related structures in response to vicarious as compared to personal reward. These data shed light on the common and unique components of the reward that individuals experience directly and through their social connections. PMID:25554428

  15. Statin Treatment and Mortality in Bacterial Infections – A Systematic Review and Meta-Analysis

    Science.gov (United States)

    Björkhem-Bergman, Linda; Bergman, Peter; Andersson, Jan; Lindh, Jonatan D.

    2010-01-01

    Background Several studies have reported improved survival in severe bacterial infections among statin treated patients. In addition, statins have been ascribed beneficial anti-inflammatory effects. The aim of this study was to evaluate the effect of statin-treatment on mortality in patients with bacterial infections, by means of a systematic review and a meta-analysis. Methodology and Principal Findings Studies investigating the association between statin use and mortality in patients with bacterial disease were identified in a systematic literature review and a meta-analysis was performed to calculate the overall odds ratio of mortality in statin users. The literature search identified 947 citations from which 40 relevant studies were extracted. In all, 15 studies comprising 113 910 patients were included in the final analysis. Statin use was associated with a significantly (pstatin treatment was no longer significant, with an OR of 0.79 (95% CI 0.58–1.07). Conclusion/Significance According to the meta-analysis of observational studies presented here, patients on statin therapy seem to have a better outcome in bacterial infections. However, the association did not reach statistical significance after adjustment for apparent publication bias. Thus, there is a great need for randomised controlled trials investigating the possible beneficial effect of statins in bacterial infections. PMID:20502712

  16. Survival after radiotherapy in gastric cancer: Systematic review and meta-analysis

    International Nuclear Information System (INIS)

    Valentini, Vincenzo; Cellini, Francesco; Minsky, Bruce D.; Mattiucci, Gian Carlo; Balducci, Mario; D'Agostino, Giuseppe; D'Angelo, Elisa; Dinapoli, Nicola; Nicolotti, Nicola; Valentini, Chiara; La Torre, Giuseppe

    2009-01-01

    Background and purpose: A systematic review and meta-analysis was performed to assess the impact of radiotherapy on both 3- and 5-year survival in patients with resectable gastric cancer. Methods: Randomized Clinical Trials (RCTs) in which radiotherapy, (preoperative, postoperative and/or intraoperative), was compared with surgery alone or surgery plus chemotherapy in resectable gastric cancer were identified by searching web-based databases and supplemented by manual examination of reference lists. Meta-analysis was performed using Risk Ratios (RRs). Random or fixed effects models were used to combine data. The methodological quality was evaluated by Chalmers' score. Results: Radiotherapy had a significant impact on 5-year survival. Using an intent to treat (ITT) and a Per Protocol (PP) analysis, the overall 5-year RR was 1.26 (95% CI: 1.08-1.48; NNT = 17) and 1.31 (95% CI: 1.04-1.66; NNT = 13), respectively. Although the quality of the studies was variable, the data were consistent and no clear publication bias was found. Conclusion: This meta-analysis showed a statistically significant 5-year survival benefit with the addition of radiotherapy in patients with resectable gastric cancer. Radiotherapy remains a standard component in the treatment of resectable gastric cancer and new RCTs need to address the impact of new conformal radiotherapy technologies.

  17. Weight change and all-cause mortality in older adults: A meta-analysis

    Science.gov (United States)

    This meta-analysis of observational cohort studies examined the association between weight change (weight loss, weight gain, and weight fluctuation) and all-cause mortality among older adults. We used PubMed (MEDLINE), Web of Science, and Cochrane Library to identify prospective studies published in...

  18. Meta-analysis of genome-wide association studies in celiac disease and rheumatoid arthritis identifies fourteen non-HLA shared loci.

    Directory of Open Access Journals (Sweden)

    Alexandra Zhernakova

    2011-02-01

    Full Text Available Epidemiology and candidate gene studies indicate a shared genetic basis for celiac disease (CD and rheumatoid arthritis (RA, but the extent of this sharing has not been systematically explored. Previous studies demonstrate that 6 of the established non-HLA CD and RA risk loci (out of 26 loci for each disease are shared between both diseases. We hypothesized that there are additional shared risk alleles and that combining genome-wide association study (GWAS data from each disease would increase power to identify these shared risk alleles. We performed a meta-analysis of two published GWAS on CD (4,533 cases and 10,750 controls and RA (5,539 cases and 17,231 controls. After genotyping the top associated SNPs in 2,169 CD cases and 2,255 controls, and 2,845 RA cases and 4,944 controls, 8 additional SNPs demonstrated P<5 × 10(-8 in a combined analysis of all 50,266 samples, including four SNPs that have not been previously confirmed in either disease: rs10892279 near the DDX6 gene (P(combined =  1.2 × 10(-12, rs864537 near CD247 (P(combined =  2.2 × 10(-11, rs2298428 near UBE2L3 (P(combined =  2.5 × 10(-10, and rs11203203 near UBASH3A (P(combined =  1.1 × 10(-8. We also confirmed that 4 gene loci previously established in either CD or RA are associated with the other autoimmune disease at combined P<5 × 10(-8 (SH2B3, 8q24, STAT4, and TRAF1-C5. From the 14 shared gene loci, 7 SNPs showed a genome-wide significant effect on expression of one or more transcripts in the linkage disequilibrium (LD block around the SNP. These associations implicate antigen presentation and T-cell activation as a shared mechanism of disease pathogenesis and underscore the utility of cross-disease meta-analysis for identification of genetic risk factors with pleiotropic effects between two clinically distinct diseases.

  19. Effectiveness and feasibility of hysteroscopic sterilization techniques: a systematic review and meta-analysis

    NARCIS (Netherlands)

    la Chapelle, C.F.; Veersema, S.; Brölmann, H.A.M.; Jansen, F.W.

    2015-01-01

    Objective To assess whether hysteroscopic sterilization is feasible and effective in preventing pregnancy. Secondarily, to identify risk factors for failure of hysteroscopic sterilization. Design A systematic review and meta-analysis. Setting Not applicable. Patient(s) Women undergoing hysteroscopic

  20. Mass meta-analysis in Talairach space

    DEFF Research Database (Denmark)

    Nielsen, Finn Årup

    2004-01-01

    We provide a method for mass meta-analysis in a neuroinformatics database containing stereotaxic Talairach coordinates from neuroimaging experiments. Database labels are used to group the individual experiments, e.g., according to cognitive function, and the consistent pattern of the experiments...... of experiments, and the distances to the null hypotheses are used to sort the voxels across groups of experiments. This allows for mass meta-analysis, with the construction of a list with the most prominent associations between brain areas and group labels. Furthermore, the method can be used for functional...

  1. Curcuminoids Lower Plasma Leptin Concentrations: A Meta-analysis.

    Science.gov (United States)

    Atkin, Stephen L; Katsiki, Niki; Derosa, Giuseppe; Maffioli, Pamela; Sahebkar, Amirhossein

    2017-12-01

    Curcumin is a naturally occurring polyphenol that has been suggested to improve several metabolic diseases. Leptin is an adipokine involved in metabolic status and appetite, with marked crosstalk with other systems. Available data suggest that curcumin may affect leptin levels; therefore, this meta-analysis was performed to evaluate this. A systematic review and meta-analysis were undertaken on all randomized controlled trials of curcumin studies that included the measurement of leptin. The search included PubMed-Medline, Scopus, ISI Web of Knowledge, and Google Scholar databases. Quantitative data synthesis was performed by using a random-effects model, with standardized mean difference and 95% confidence interval as summary statistics. A funnel plot, Begg's rank correlation, and Egger's weighted regression tests assessed the presence of publication bias. Four eligible articles comprising five treatment arms were selected for the meta-analysis. Meta-analysis showed a significant decrease in plasma leptin concentrations following curcumin treatment (standardized mean difference: -0.69, 95% confidence interval: -1.16, -0.23, p = 0.003; I 2  = 76.53%). There was no evidence of publication bias. This meta-analysis showed that curcumin supplementation is associated with a decrease in leptin levels that may be regarded as a potential mechanism for the metabolic effects of curcumin. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  2. The aetiological role of human papillomavirus in oesophageal squamous cell carcinoma: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Surabhi S Liyanage

    Full Text Available BACKGROUND: The aetiological role of human papillomavirus (HPV in oesophageal squamous cell carcinoma (OSCC has been widely researched for more than three decades, with conflicting findings. In the absence of a large, adequately powered single case-control study, a meta-analysis of all available case-control studies is the most rigorous way of identifying any potential association between HPV and OSCC. We present the first global meta-analysis of case-control studies investigating the role of HPV in OSCC. METHODS: Case-control studies investigating OSCC tissue for presence of HPV DNA were identified. 21 case-control studies analyzing a total of 1223 cases and 1415 controls, met our inclusion criteria. HPV detection rates were tabulated for each study and all studies were assessed for quality. The random effects method was used to pool the odds ratios (OR. RESULTS: From all OSCC specimens included in this meta-analysis, 35% (426/1223 were positive for HPV DNA. The pooled OR for an HPV-OSCC association was 3.04 (95% CI 2.20 to 4.20. Meta-regression analysis did not find a significant association between OR and any of the quality domains. Influence analysis was non-significant for the effect of individual studies on the pooled estimate. Studies conducted in countries with low to medium OSCC incidence showed a stronger relationship (OR 4.65, 95% CI 2.47 to 8.76 than regions of high OSCC incidence (OR 2.65, 95% CI 1.80 to 3.91. CONCLUSIONS: Uncertainty around the aetiological role of HPV in OSCC is due largely to the small number and scale of appropriately designed studies. Our meta-analysis of these studies suggests that HPV increases the risk of OSCC three-fold. This study provides the strongest evidence to date of an HPV-OSCC association. The importance of these findings is that prophylactic vaccination could be of public health benefit in prevention of OSCC in countries with high OSCC incidence.

  3. Natural funnel asymmetries. A simulation analysis of the three basic tools of meta analysis

    DEFF Research Database (Denmark)

    Callot, Laurent Abdelkader Francois; Paldam, Martin

    Meta-analysis studies a set of estimates of one parameter with three basic tools: The funnel diagram is the distribution of the estimates as a function of their precision; the funnel asymmetry test, FAT; and the meta average, where PET is an estimate. The FAT-PET MRA is a meta regression analysis...

  4. Cardiovascular risk associated with celecoxib or etoricoxib: a meta-analysis of randomized controlled trials which adopted comparison with placebo or naproxen

    NARCIS (Netherlands)

    Vecchis, R. De; Baldi, C.; Biase, G. Di; Ariano, C.; Cioppa, C.; Giasi, A.; Valente, L.; Cantatrione, S.

    2014-01-01

    AIM: The present meta-analysis attempted to assess whether an unfavourable cardiovascular risk profile could be identified in the case of two COX2 selective inhibitors (COXIBs), namely celecoxib and etoricoxib. Based on the data from the literature, our meta-analysis aimed to assess the probability

  5. Comparing Active Pediatric Obesity Treatments Using Meta-Analysis

    Science.gov (United States)

    Gilles, Allyson; Cassano, Michael; Shepherd, Elizabeth J.; Higgins, Diana; Hecker, Jeffrey E.; Nangle, Douglas W.

    2008-01-01

    The current meta-analysis reviews research on the treatment of pediatric obesity focusing on studies that have been published since 1994. Eleven studies (22 comparisons, 115 effect sizes, N = 447) were included in the present meta-analysis. Results indicated that comprehensive behavioral interventions may be improved in at least two ways:…

  6. Meta-analysis for evidence synthesis in plant pathology: an overview.

    Science.gov (United States)

    Madden, L V; Paul, P A

    2011-01-01

    Meta-analysis is the analysis of the results of multiple studies, which is typically performed in order to synthesize evidence from many possible sources in a formal probabilistic manner. In a simple sense, the outcome of each study becomes a single observation in the meta-analysis of all available studies. The methodology was developed originally in the social sciences by Smith, Glass, Rosenthal, Hunter, and Schmidt, based on earlier pioneering contributions in statistics by Fisher, Pearson, Yates, and Cochran, but this approach to research synthesis has now been embraced within many scientific disciplines. However, only a handful of articles have been published in plant pathology and related fields utilizing meta-analysis. After reviewing basic concepts and approaches, methods for estimating parameters and interpreting results are shown. The advantages of meta-analysis are presented in terms of prediction and risk analysis, and the high statistical power that can be achieved for detecting significant effects of treatments or significant relationships between variables. Based on power considerations, the fallacy of naïve counting of P values in a narrative review is demonstrated. Although there are many advantages to meta-analysis, results can be biased if the analysis is based on a nonrepresentative sample of study outcomes. Therefore, novel approaches for characterizing the upper bound on the bias are discussed, in order to show the robustness of meta-analysis to possible violation of assumptions.

  7. Systematic review and meta-analysis of the economic impact of smoking bans in restaurants and bars.

    Science.gov (United States)

    Cornelsen, Laura; McGowan, Yvonne; Currie-Murphy, Laura M; Normand, Charles

    2014-05-01

    To review systematically the literature on the economic impact of smoking bans in bars and restaurants and provide an estimate of the impact size using meta-analysis. Studies were identified by systematic database searches and screening references of reviews and relevant studies. Google and web-pages of tobacco control agencies were also searched. The review identified 56 studies using absolute sales, sales ratio or employment data and employing regression methods to evaluate the impact of smoking bans in the United States, Australia or in countries in South America or Europe. The meta-analysis included 39 comparable studies, with 129 cases identified based on the outcome measure, scope of the ban, type of establishment and geographical location. Methodological quality was assessed based on four pre-determined criteria. Study and case selection and data extraction were conducted independently by two researchers. Random-effects meta-analysis of all cases showed no associations between smoking bans and changes in absolute sales or employment. An increase in the share of bar and restaurant sector sales in total retail sales was associated with smoking bans [0.23 percentage-points; 95% confidence interval (CI) 0.08-0.375]. When cases were separated by business type (bars or restaurants or wider hospitality including bars and restaurants), some differential impacts emerged. Meta-analysis of the economic impact of smoking bans in hospitality sector showed overall no substantial economic gains or losses. Differential impacts were observed across individual business types and outcome variable, but at aggregate level these appear to balance out. © 2014 Society for the Study of Addiction.

  8. Meta-analysis of the association between short-term exposure to ambient ozone and respiratory hospital admissions

    International Nuclear Information System (INIS)

    Ji Meng; Bell, Michelle L; Cohan, Daniel S

    2011-01-01

    Ozone is associated with health impacts including respiratory outcomes; however, results differ across studies. Meta-analysis is an increasingly important approach to synthesizing evidence across studies. We conducted meta-analysis of short-term ozone exposure and respiratory hospitalizations to evaluate variation across studies and explore some of the challenges in meta-analysis. We identified 136 estimates from 96 studies and investigated how estimates differed by age, ozone metric, season, lag, region, disease category, and hospitalization type. Overall results indicate associations between ozone and various kinds of respiratory hospitalizations; however, study characteristics affected risk estimates. Estimates were similar, but higher, for the elderly compared to all ages and for previous day exposure compared to same day exposure. Comparison across studies was hindered by variation in definitions of disease categories, as some (e.g., asthma) were identified through ≥ 3 different sets of ICD codes. Although not all analyses exhibited evidence of publication bias, adjustment for publication bias generally lowered overall estimates. Emergency hospitalizations for total respiratory disease increased by 4.47% (95% interval: 2.48, 6.50%) per 10 ppb 24 h ozone among the elderly without adjustment for publication bias and 2.97% (1.05, 4.94%) with adjustment. Comparison of multi-city study results and meta-analysis based on single-city studies further suggested publication bias.

  9. DNA repair gene polymorphisms and risk of cutaneous melanoma: a systematic review and meta-analysis.

    Science.gov (United States)

    Mocellin, Simone; Verdi, Daunia; Nitti, Donato

    2009-10-01

    Polymorphisms of DNA repair-related genes might modulate cancer predisposition. We performed a systematic review and meta-analysis of the available evidence regarding the relationship between these polymorphisms and the risk of developing cutaneous melanoma. Relevant studies were searched using PubMed, Medline, Embase, Cancerlit, Cochrane and ISI Web of Knowledge databases. Data were gathered according to the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines. The model-free approach was adopted to perform the meta-analysis of the retrieved data. We identified 20 original reports that describe the relationship between melanoma risk and the single-nucleotide polymorphisms (SNPs) of 16 genes (cases = 4195). For seven SNPs considered in at least two studies, the findings were heterogeneous. Data were suitable for meta-analysis only in the case of the XPD/ERCC2 SNP rs13181 (cases = 2308, controls = 3698) and demonstrated that the variant C allele is associated with increased melanoma risk (odds ratio = 1.12, 95% confidence interval = 1.03-1.21, P = 0.01; population attributable risk = 9.6%). This is the first meta-analysis suggesting that XPD/ERCC2 might represent a low-penetrance melanoma susceptibility gene. Much work is still to be done before definitive conclusions can be drawn on the role of DNA repair alterations in melanomagenesis since for the other genes involved in this highly complex process, the available information is scarce or null.

  10. A Meta-analysis of Multiple Myeloma Risk Regions in African and European Ancestry Populations Identifies Putatively Functional Loci.

    Science.gov (United States)

    Rand, Kristin A; Song, Chi; Dean, Eric; Serie, Daniel J; Curtin, Karen; Sheng, Xin; Hu, Donglei; Huff, Carol Ann; Bernal-Mizrachi, Leon; Tomasson, Michael H; Ailawadhi, Sikander; Singhal, Seema; Pawlish, Karen; Peters, Edward S; Bock, Cathryn H; Stram, Alex; Van Den Berg, David J; Edlund, Christopher K; Conti, David V; Zimmerman, Todd; Hwang, Amie E; Huntsman, Scott; Graff, John; Nooka, Ajay; Kong, Yinfei; Pregja, Silvana L; Berndt, Sonja I; Blot, William J; Carpten, John; Casey, Graham; Chu, Lisa; Diver, W Ryan; Stevens, Victoria L; Lieber, Michael R; Goodman, Phyllis J; Hennis, Anselm J M; Hsing, Ann W; Mehta, Jayesh; Kittles, Rick A; Kolb, Suzanne; Klein, Eric A; Leske, Cristina; Murphy, Adam B; Nemesure, Barbara; Neslund-Dudas, Christine; Strom, Sara S; Vij, Ravi; Rybicki, Benjamin A; Stanford, Janet L; Signorello, Lisa B; Witte, John S; Ambrosone, Christine B; Bhatti, Parveen; John, Esther M; Bernstein, Leslie; Zheng, Wei; Olshan, Andrew F; Hu, Jennifer J; Ziegler, Regina G; Nyante, Sarah J; Bandera, Elisa V; Birmann, Brenda M; Ingles, Sue A; Press, Michael F; Atanackovic, Djordje; Glenn, Martha J; Cannon-Albright, Lisa A; Jones, Brandt; Tricot, Guido; Martin, Thomas G; Kumar, Shaji K; Wolf, Jeffrey L; Deming Halverson, Sandra L; Rothman, Nathaniel; Brooks-Wilson, Angela R; Rajkumar, S Vincent; Kolonel, Laurence N; Chanock, Stephen J; Slager, Susan L; Severson, Richard K; Janakiraman, Nalini; Terebelo, Howard R; Brown, Elizabeth E; De Roos, Anneclaire J; Mohrbacher, Ann F; Colditz, Graham A; Giles, Graham G; Spinelli, John J; Chiu, Brian C; Munshi, Nikhil C; Anderson, Kenneth C; Levy, Joan; Zonder, Jeffrey A; Orlowski, Robert Z; Lonial, Sagar; Camp, Nicola J; Vachon, Celine M; Ziv, Elad; Stram, Daniel O; Hazelett, Dennis J; Haiman, Christopher A; Cozen, Wendy

    2016-12-01

    Genome-wide association studies (GWAS) in European populations have identified genetic risk variants associated with multiple myeloma. We performed association testing of common variation in eight regions in 1,318 patients with multiple myeloma and 1,480 controls of European ancestry and 1,305 patients with multiple myeloma and 7,078 controls of African ancestry and conducted a meta-analysis to localize the signals, with epigenetic annotation used to predict functionality. We found that variants in 7p15.3, 17p11.2, 22q13.1 were statistically significantly (P ancestry and persons of European ancestry, and the variant in 3p22.1 was associated in European ancestry only. In a combined African ancestry-European ancestry meta-analysis, variation in five regions (2p23.3, 3p22.1, 7p15.3, 17p11.2, 22q13.1) was statistically significantly associated with multiple myeloma risk. In 3p22.1, the correlated variants clustered within the gene body of ULK4 Correlated variants in 7p15.3 clustered around an enhancer at the 3' end of the CDCA7L transcription termination site. A missense variant at 17p11.2 (rs34562254, Pro251Leu, OR, 1.32; P = 2.93 × 10 -7 ) in TNFRSF13B encodes a lymphocyte-specific protein in the TNF receptor family that interacts with the NF-κB pathway. SNPs correlated with the index signal in 22q13.1 cluster around the promoter and enhancer regions of CBX7 CONCLUSIONS: We found that reported multiple myeloma susceptibility regions contain risk variants important across populations, supporting the use of multiple racial/ethnic groups with different underlying genetic architecture to enhance the localization and identification of putatively functional alleles. A subset of reported risk loci for multiple myeloma has consistent effects across populations and is likely to be functional. Cancer Epidemiol Biomarkers Prev; 25(12); 1609-18. ©2016 AACR. ©2016 American Association for Cancer Research.

  11. Writing Characteristics of Students with Attention Deficit Hyperactive Disorder: A Meta-Analysis

    Science.gov (United States)

    Graham, Steve; Fishman, Evan J.; Reid, Robert; Hebert, Michael

    2016-01-01

    Students with Attention Deficit Hyperactivity Disorders (ADHD) frequently experience significant difficulty mastering basic academic skills. This meta-analysis focuses on one specific potential area of learning difficulties for these students: namely, writing. To identify the extent and depth of the potential writing challenges faced by students…

  12. Incidence and predictors of oral feeding intolerance in acute pancreatitis: A systematic review, meta-analysis, and meta-regression.

    Science.gov (United States)

    Bevan, Melody G; Asrani, Varsha M; Bharmal, Sakina; Wu, Landy M; Windsor, John A; Petrov, Maxim S

    2017-06-01

    Tolerance of oral food is an important criterion for hospital discharge in patients with acute pancreatitis. Patients who develop oral feeding intolerance have prolonged hospitalisation, use additional healthcare resources, and have impaired quality of life. This study aimed to quantify the incidence of oral feeding intolerance, the effect of confounders, and determine the best predictors of oral feeding intolerance. Clinical studies indexed in three electronic databases (EMBASE, MEDLINE, and the Cochrane Central Register of Controlled Trials) were reviewed. Incidence and predictor data were meta-analysed and possible confounders were investigated by meta-regression analysis. A total of 22 studies with 2024 patients met the inclusion criteria, 17 of which (with 1550 patients) were suitable for meta-analysis. The incidence of oral feeding intolerance was 16.3%, and was not affected by WHO region, age, sex, or aetiology of acute pancreatitis. Nine of the 22 studies investigated a total of 62 different predictors of oral feeding intolerance. Serum lipase level prior to refeeding, pleural effusions, (peri)pancreatic collections, Ranson score, and Balthazar score were found to be statistically significant in meta-analyses. Oral feeding intolerance affects approximately 1 in 6 patients with acute pancreatitis. Serum lipase levels of more than 2.5 times the upper limit of normal prior to refeeding is a potentially useful threshold to identify patients at high risk of developing oral feeding intolerance. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  13. Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture

    NARCIS (Netherlands)

    K. Estrada Gil (Karol); U. Styrkarsdottir (Unnur); E. Evangelou (Evangelos); Y.-H. Hsu (Yi-Hsiang); E.L. Duncan (Emma); E.E. Ntzani (Evangelia); L. Oei (Ling); O.M.E. Albagha (Omar M.); N. Amin (Najaf); J.P. Kemp (John); D.L. Koller (Daniel); G. Li (Guo); C.-T. Liu (Ching-Ti); R.L. Minster (Ryan); A. Moayyeri (Alireza); L. Vandenput (Liesbeth); D. Willner (Dana); S.-M. Xiao (Su-Mei); L.M. Yerges-Armstrong (Laura); H.-F. Zheng (Hou-Feng); N. Alonso (Nerea); J. Eriksson (Joel); C.M. Kammerer (Candace); S. Kaptoge (Stephen); P.J. Leo (Paul); G. Thorleifsson (Gudmar); S.G. Wilson (Scott); J.F. Wilson (James); V. Aalto (Ville); T.A. van Alen (Theo); A.K. Aragaki (Aaron); T. Aspelund (Thor); J.R. Center (Jacqueline); Z. Dailiana (Zoe); C. Duggan; M. Garcia (Melissa); N. Garcia-Giralt (Natàlia); S. Giroux (Sylvie); G. Hallmans (Göran); L.J. Hocking (Lynne); L.B. Husted (Lise Bjerre); K. Jameson (Karen); R. Khusainova (Rita); G.S. Kim (Ghi Su); C. Kooperberg (Charles); T. Koromila (Theodora); M. Kruk (Marcin); M. Laaksonen (Marika); A.Z. LaCroix (Andrea); S.U. Lee (Seung); P.C. Leung (Ping); J.R. Lewis (Joshua); L. Masi (Laura); S. Mencej-Bedrac (Simona); T.V. Nguyen (Tuan); X. Nogues (Xavier); M.S. Patel (Millan); J. Prezelj (Janez); L.M. Rose (Lynda); S. Scollen (Serena); K. Siggeirsdottir (Kristin); G.D. Smith; O. Svensson (Olle); S. Trompet (Stella); O. Trummer (Olivia); N.M. van Schoor (Natasja); M.M. Woo (Margaret M.); K. Zhu (Kun); S. Balcells (Susana); M.L. Brandi; B.M. Buckley (Brendan M.); S. Cheng (Sulin); C. Christiansen; C. Cooper (Charles); G.V. Dedoussis (George); I. Ford (Ian); M. Frost (Morten); D. Goltzman (David); J. González-Macías (Jesús); M. Kähönen (Mika); M. Karlsson (Magnus); E.K. Khusnutdinova (Elza); J.-M. Koh (Jung-Min); P. Kollia (Panagoula); B.L. Langdahl (Bente); W.D. Leslie (William); P. Lips (Paul); O. Ljunggren (Östen); R. Lorenc (Roman); J. Marc (Janja); D. Mellström (Dan); B. Obermayer-Pietsch (Barbara); D. Olmos (David); U. Pettersson-Kymmer (Ulrika); D.M. Reid (David); J.A. Riancho (José); P.M. Ridker (Paul); M.F. Rousseau (Francois); P.E.S. Lagboom (P Eline); N.L.S. Tang (Nelson L.); R. Urreizti (Roser); W. Van Hul (Wim); J. Viikari (Jorma); M.T. Zarrabeitia (María); Y.S. Aulchenko (Yurii); M.C. Castaño Betancourt (Martha); E. Grundberg (Elin); L. Herrera (Lizbeth); T. Ingvarsson (Torvaldur); H. Johannsdottir (Hrefna); T. Kwan (Tony); R. Li (Rui); R.N. Luben (Robert); M.C. Medina-Gomez (Carolina); S. Th Palsson (Stefan); S. Reppe (Sjur); J.I. Rotter (Jerome); G. Sigurdsson (Gunnar); J.B.J. van Meurs (Joyce); D.J. Verlaan (Dominique); F.M. Williams (Frances); A.R. Wood (Andrew); Y. Zhou (Yanhua); K.M. Gautvik (Kaare); T. Pastinen (Tomi); S. Raychaudhuri (Soumya); J.A. Cauley (Jane); D.I. Chasman (Daniel); G.R. Clark (Graeme); S. Cummings; P. Danoy (Patrick); E.M. Dennison (Elaine); R. Eastell (Richard); J.A. Eisman (John); V. Gudnason (Vilmundur); A. Hofman (Albert); R.D. Jackson (Rebecca); G. Jones (Graeme); J.W. Jukema (Jan Wouter); K-T. Khaw (Kay-Tee); T. Lehtimäki (Terho); Y. Liu (YongMei); M. Lorentzon (Mattias); E.V. McCloskey (Eugene); B.D. Mitchell (Braxton); K. Nandakumar (Kannabiran); G.C. Nicholson (Geoffrey); B.A. Oostra (Ben); M. Peacock (Munro); H.A.P. Pols (Huib); R.L. Prince (Richard); O. Raitakari (Olli); I.R. Reid (Ian); J. Robbins (John); P.N. Sambrook (Philip); P.C. Sham (Pak); A.R. Shuldiner (Alan); F.A. Tylavsky (Frances); C.M. van Duijn (Cornelia); N.J. Wareham (Nick); L.A. Cupples (Adrienne); M.J. Econs (Michael); D.M. Evans (David); T.B. Harris (Tamara); A.W.C. Kung (Annie); B.M. Psaty (Bruce); J. Reeve (Jonathan); T.D. Spector (Timothy); E.A. Streeten (Elizabeth); M.C. Zillikens (Carola); U. Thorsteinsdottir (Unnur); C. Ohlsson (Claes); D. Karasik (David); J.B. Richards (Brent); M.A. Brown (Matthew); J-A. Zwart (John-Anker); A.G. Uitterlinden (André); S.H. Ralston (Stuart); J.P.A. Ioannidis (John); D.P. Kiel (Douglas); F. Rivadeneira Ramirez (Fernando)

    2012-01-01

    textabstractBone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top

  14. Systematic review with meta-analysis

    DEFF Research Database (Denmark)

    Kimer, N; Krag, A; Møller, Søren

    2014-01-01

    BACKGROUND: Rifaximin is recommended for prevention of hepatic encephalopathy (HE). The effects of rifaximin on overt and minimal HE are debated. AIM: To perform a systematic review and meta-analysis of randomised controlled trials (RCTs) on rifaximin for HE. METHODS: We performed electronic...... and manual searches, gathered information from the U.S. Food and Drug Administration Home Page, and obtained unpublished information on trial design and outcome measures from authors and pharmaceutical companies. Meta-analyses were performed and results presented as risk ratios (RR) with 95% confidence...

  15. How acute total sleep loss affects the attending brain: a meta-analysis of neuroimaging studies.

    Science.gov (United States)

    Ma, Ning; Dinges, David F; Basner, Mathias; Rao, Hengyi

    2015-02-01

    Attention is a cognitive domain that can be severely affected by sleep deprivation. Previous neuroimaging studies have used different attention paradigms and reported both increased and reduced brain activation after sleep deprivation. However, due to large variability in sleep deprivation protocols, task paradigms, experimental designs, characteristics of subject populations, and imaging techniques, there is no consensus regarding the effects of sleep loss on the attending brain. The aim of this meta-analysis was to identify brain activations that are commonly altered by acute total sleep deprivation across different attention tasks. Coordinate-based meta-analysis of neuroimaging studies of performance on attention tasks during experimental sleep deprivation. The current version of the activation likelihood estimation (ALE) approach was used for meta-analysis. The authors searched published articles and identified 11 sleep deprivation neuroimaging studies using different attention tasks with a total of 185 participants, equaling 81 foci for ALE analysis. The meta-analysis revealed significantly reduced brain activation in multiple regions following sleep deprivation compared to rested wakefulness, including bilateral intraparietal sulcus, bilateral insula, right prefrontal cortex, medial frontal cortex, and right parahippocampal gyrus. Increased activation was found only in bilateral thalamus after sleep deprivation compared to rested wakefulness. Acute total sleep deprivation decreases brain activation in the fronto-parietal attention network (prefrontal cortex and intraparietal sulcus) and in the salience network (insula and medial frontal cortex). Increased thalamic activation after sleep deprivation may reflect a complex interaction between the de-arousing effects of sleep loss and the arousing effects of task performance on thalamic activity. © 2015 Associated Professional Sleep Societies, LLC.

  16. Joint attention in Down syndrome: A meta-analysis.

    Science.gov (United States)

    Hahn, Laura J; Loveall, Susan J; Savoy, Madison T; Neumann, Allie M; Ikuta, Toshikazu

    2018-07-01

    Some studies have indicated that joint attention may be a relative strength in Down syndrome (DS), but other studies have not. To conduct a meta-analysis of joint attention in DS to more conclusively determine if this is a relative strength or weakness when compared to children with typical development (TD), developmental disabilities (DD), and autism spectrum disorder (ASD). Journal articles published before September 13, 2016, were identified by using the search terms "Down syndrome" and "joint attention" or "coordinating attention". Identified studies were reviewed and coded for inclusion criteria, descriptive information, and outcome variables. Eleven studies (553 participants) met inclusion criteria. Children with DS showed similar joint attention as TD children and higher joint attention than children with DD and ASD. Meta-regression revealed a significant association between age and joint attention effect sizes in the DS vs. TD contrast. Joint attention appears to not be a weakness for children with DS, but may be commensurate with developmental level. Joint attention may be a relative strength in comparison to other skills associated with the DS behavioral phenotype. Early interventions for children with DS may benefit from leveraging joint attention skills. Copyright © 2018 Elsevier Ltd. All rights reserved.

  17. Evidence-based Neuro Linguistic Psychotherapy: a meta-analysis.

    Science.gov (United States)

    Zaharia, Cătălin; Reiner, Melita; Schütz, Peter

    2015-12-01

    Neuro Linguistic Programming (NLP) Framework has enjoyed enormous popularity in the field of applied psychology. NLP has been used in business, education, law, medicine and psychotherapy to identify people's patterns and alter their responses to stimuli, so they are better able to regulate their environment and themselves. NLP looks at achieving goals, creating stable relationships, eliminating barriers such as fears and phobias, building self-confidence, and self-esteem, and achieving peak performance. Neuro Linguistic Psychotherapy (NLPt) encompasses NLP as framework and set of interventions in the treatment of individuals with different psychological and/or social problems. We aimed systematically to analyse the available data regarding the effectiveness of Neuro Linguistic Psychotherapy (NLPt). The present work is a meta-analysis of studies, observational or randomized controlled trials, for evaluating the efficacy of Neuro Linguistic Programming in individuals with different psychological and/or social problems. The databases searched to identify studies in English and German language: CENTRAL in the Cochrane Library; PubMed; ISI Web of Knowledge (include results also from Medline and the Web of Science); PsycINFO (including PsycARTICLES); Psyndex; Deutschsprachige Diplomarbeiten der Psychologie (database of theses in Psychology in German language), Social SciSearch; National library of health and two NLP-specific research databases: one from the NLP Community (http://www.nlp.de/cgi-bin/research/nlprdb.cgi?action=res_entries) and one from the NLP Group (http://www.nlpgrup.com/bilimselarastirmalar/bilimsel-arastirmalar-4.html#Zweig154). From a total number of 425 studies, 350 were removed and considered not relevant based on the title and abstract. Included, in the final analysis, are 12 studies with numbers of participants ranging between 12 and 115 subjects. The vast majority of studies were prospective observational. The actual paper represents the first

  18. Effect of Metformin on Plasma Fibrinogen Concentrations: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials.

    Science.gov (United States)

    Simental-Mendia, Luis E; Pirro, Matteo; Atkin, Stephen L; Banach, Maciej; Mikhailidis, Dimitri P; Sahebkar, Amirhossein

    2018-01-01

    Fibrinogen is a key mediator of thrombosis and it has been implicated in the pathogenesis of atherosclerosis. Because metformin has shown a potential protective effect on different atherothrombotic risk factors, we assessed in this meta-analysis its effect on plasma fibrinogen concentrations. A systematic review and meta-analysis was carried out to identify randomized placebo-controlled trials evaluating the effect of metformin administration on fibrinogen levels. The search included PubMed-Medline, Scopus, ISI Web of Knowledge and Google Scholar databases (by June 2, 2017) and quality of studies was performed according to Cochrane criteria. Quantitative data synthesis was conducted using a random-effects model and sensitivity analysis by the leave-one-out method. Meta-regression analysis was performed to assess the modifiers of treatment response. Meta-analysis of data from 9 randomized placebo-controlled clinical trials with 2302 patients comprising 10 treatment arms did not suggest a significant change in plasma fibrinogen concentrations following metformin therapy (WMD: -0.25 g/L, 95% CI: -0.53, 0.04, p = 0.092). The effect size was robust in the leave-one-out sensitivity analysis and remained non-significant after omission of each single study from the meta-analysis. No significant effect of metformin on plasma fibrinogen concentrations was demonstrated in the current meta-analysis. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  19. Hypothyroidism as a risk factor for open angle glaucoma: A systematic review and meta-analysis

    Science.gov (United States)

    Liu, Yue; Zheng, Guangying

    2017-01-01

    Purpose The relationship between hypothyroidism and primary open angle glaucoma (POAG) has attracted intense interest recently, but the reported results have been controversial. This meta-analysis was carried out to determine the association between hypothyroidism and POAG. Methods The literature was identified from three databases (Web of Science, Embase, and PubMed). The meta-analyses were performed using random-effects models, with results reported as adjusted odds ratios (ORs) with 95% confidence intervals (CI 95%). Results A total of 11 studies meeting the inclusion criteria were included in the final meta-analysis. The pooled OR based on 11 risk estimates showed a statistically significant increased risk of POAG prevalence among individuals with hypothyroidism (OR = 1.64, 95% CI = 1.27–2.13). Substantial heterogeneity among these studies was detected (P hypothyroidism and POAG, which was not observed in cross-sectional studies. There was no significant publication bias in this study. Conclusions The findings of this meta-analysis indicate that individuals with hypothyroidism have an increased risk of developing POAG. PMID:29069095

  20. Automatic imitation: A meta-analysis.

    Science.gov (United States)

    Cracco, Emiel; Bardi, Lara; Desmet, Charlotte; Genschow, Oliver; Rigoni, Davide; De Coster, Lize; Radkova, Ina; Deschrijver, Eliane; Brass, Marcel

    2018-05-01

    Automatic imitation is the finding that movement execution is facilitated by compatible and impeded by incompatible observed movements. In the past 15 years, automatic imitation has been studied to understand the relation between perception and action in social interaction. Although research on this topic started in cognitive science, interest quickly spread to related disciplines such as social psychology, clinical psychology, and neuroscience. However, important theoretical questions have remained unanswered. Therefore, in the present meta-analysis, we evaluated seven key questions on automatic imitation. The results, based on 161 studies containing 226 experiments, revealed an overall effect size of g z = 0.95, 95% CI [0.88, 1.02]. Moderator analyses identified automatic imitation as a flexible, largely automatic process that is driven by movement and effector compatibility, but is also influenced by spatial compatibility. Automatic imitation was found to be stronger for forced choice tasks than for simple response tasks, for human agents than for nonhuman agents, and for goalless actions than for goal-directed actions. However, it was not modulated by more subtle factors such as animacy beliefs, motion profiles, or visual perspective. Finally, there was no evidence for a relation between automatic imitation and either empathy or autism. Among other things, these findings point toward actor-imitator similarity as a crucial modulator of automatic imitation and challenge the view that imitative tendencies are an indicator of social functioning. The current meta-analysis has important theoretical implications and sheds light on longstanding controversies in the literature on automatic imitation and related domains. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  1. Long-term outcomes of ductal carcinoma in situ of the breast: a systematic review, meta-analysis and meta-regression analysis

    International Nuclear Information System (INIS)

    Stuart, Kirsty E.; Houssami, Nehmat; Taylor, Richard; Hayen, Andrew; Boyages, John

    2015-01-01

    To summarize data on long-term ipsilateral local recurrence (LR) and breast cancer death rate (BCDR) for patients with ductal carcinoma in situ (DCIS) who received different treatments. Systematic review and study-level meta-analysis of prospective (n = 5) and retrospective (n = 21) studies of patients with pure DCIS and with median or mean follow-up time of ≥10 years. Meta-regression was performed to assess and adjust for effects of potential confounders – the average age of women, period of initial treatment, and of bias – follow-up duration on recurrence- and death-rates in each treatment group. LR and BCDR rates by local treatment used were reported. Outside of randomized trials, remaining studies were likely to have tailored patient treatment according to the clinical situation. Nine thousand four hundred and four DCIS cases in 9391 patients with 10-year follow-up were included. The adjusted meta-regression LR rate for mastectomy was 2.6 % (95 % CI, 0.8–4.5); breast-conserving surgery with radiotherapy (RT), 13.6 % (95 % CI, 9.8–17.4); breast-conserving surgery without RT, 25.5 % (95 % CI, 18.1–32.9); and biopsy-only (residual predominately low-grade DCIS following inadequate excision), 27.8 % (95 % CI, 8.4–47.1). RT + tamoxifen (TAM) in conservation surgery (CS) patients resulted in lower LR compared to one or no adjuvant treatments: LR rate for CS + RT + TAM, 9.7 %; CS + RT(no TAM), 14.1 %; CS + TAM(no RT), 24.7 %; CS(alone), 25.1 % (linear trend for treatment P < 0.0001). Compared to CS + RT + TAM, a significantly higher invasive LR was observed for CS(alone), odds ratio (OR) 2.61 (P < 0.0001); CS + TAM(no RT), OR 2.52 (P = 0.001); CS + RT(no TAM), OR 1.59 (P = 0.022). BCDR was similar for mastectomy, breast-conserving surgery with or without RT (1.3–2.0 %) and non-significantly higher for biopsy-only (2.7 %). Additionally, the 15-year follow-up was reported where all like-studies had ≥ 15-year data sets; the biopsy-only patients had a

  2. Prognostic factors in pediatric pulmonary arterial hypertension: A systematic review and meta-analysis.

    Science.gov (United States)

    Ploegstra, Mark-Jan; Zijlstra, Willemijn M H; Douwes, Johannes M; Hillege, Hans L; Berger, Rolf M F

    2015-04-01

    Despite the introduction of targeted therapies in pediatric pulmonary arterial hypertension (PAH), prognosis remains poor. For the definition of treatment strategies and guidelines, there is a high need for an evidence-based recapitulation of prognostic factors. The aim of this study was to identify and evaluate prognostic factors in pediatric PAH by a systematic review of the literature and to summarize the prognostic value of currently reported prognostic factors using meta-analysis. Medline, EMBASE and Cochrane Library were searched on April 1st 2014 to identify original studies that described predictors of mortality or lung-transplantation exclusively in children with PAH. 1053 citations were identified, of which 25 were included for further analysis. Hazard ratios (HR) and 95% confidence intervals were extracted from the papers. For variables studied in at least three non-overlapping cohorts, a combined HR was calculated using random-effects meta-analysis. WHO functional class (WHO-FC, HR 2.7), (N-terminal pro-) brain natriuretic peptide ([NT-pro]BNP, HR 3.2), mean right atrial pressure (mRAP, HR 1.1), cardiac index (HR 0.7), indexed pulmonary vascular resistance (PVRi, HR 1.3) and acute vasodilator response (HR 0.3) were identified as significant prognostic factors (p ≤ 0.001). This systematic review combined with separate meta-analyses shows that WHO-FC, (NT-pro)BNP, mRAP, PVRi, cardiac index and acute vasodilator response are consistently reported prognostic factors for outcome in pediatric PAH. These variables are useful clinical tools to assess prognosis and should be incorporated in treatment strategies and guidelines for children with PAH. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  3. A meta-analysis of the impacts of genetically modified crops.

    Directory of Open Access Journals (Sweden)

    Wilhelm Klümper

    Full Text Available Despite the rapid adoption of genetically modified (GM crops by farmers in many countries, controversies about this technology continue. Uncertainty about GM crop impacts is one reason for widespread public suspicion.We carry out a meta-analysis of the agronomic and economic impacts of GM crops to consolidate the evidence.Original studies for inclusion were identified through keyword searches in ISI Web of Knowledge, Google Scholar, EconLit, and AgEcon Search.Studies were included when they build on primary data from farm surveys or field trials anywhere in the world, and when they report impacts of GM soybean, maize, or cotton on crop yields, pesticide use, and/or farmer profits. In total, 147 original studies were included.Analysis of mean impacts and meta-regressions to examine factors that influence outcomes.On average, GM technology adoption has reduced chemical pesticide use by 37%, increased crop yields by 22%, and increased farmer profits by 68%. Yield gains and pesticide reductions are larger for insect-resistant crops than for herbicide-tolerant crops. Yield and profit gains are higher in developing countries than in developed countries.Several of the original studies did not report sample sizes and measures of variance.The meta-analysis reveals robust evidence of GM crop benefits for farmers in developed and developing countries. Such evidence may help to gradually increase public trust in this technology.

  4. Acupuncture for Acne Vulgaris: A Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Suzi S. Y. Mansu

    2018-01-01

    Full Text Available Purpose. To conduct a systematic review and meta-analysis to determine the current best available evidence of the efficacy and safety of acupuncture and related therapies for acne vulgaris. Methods. Eleven English and Chinese databases were searched to identify randomized controlled trials (RCTs of acne vulgaris compared to pharmacotherapies, no treatment, and sham or placebo acupuncture. Methodological quality was assessed using Cochrane Collaboration’s risk of bias tool. Meta-analysis was conducted using RevMan software. Results. Twelve RCTs were included in the qualitative review and 10 RCTs were included in meta-analysis. Methodological quality of trials was generally low. The chance of achieving ≥30% change in lesion count in the acupuncture group was no different to the pharmacotherapy group (RR: 1.07 [95% CI 0.98, 1.17]; I2=8% and ≥50% change in lesion count in the acupuncture group was not statistically different to the pharmacotherapy group (RR: 1.07 [95% CI 0.98, 1.17]; I2=50%. Conclusions. While caution should be exercised due to quality of the included studies, acupuncture and auricular acupressure were not statistically different to guideline recommended treatments but were with fewer side effects and may be a treatment option. Future trials should address the methodological weaknesses and meet standard reporting requirements stipulated in STRICTA.

  5. Transcranial Direct Current Stimulation in Tinnitus Patients: A Systemic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Jae-Jin Song

    2012-01-01

    Full Text Available Although transcranial direct current stimulation (tDCS has already been used to manage tinnitus patients, paucity of reports and variations in protocols preclude a comprehensive understanding. Hence, we conducted a meta-analysis based on systemic review to assess effectiveness of tDCS in tinnitus management and to compare stimulation parameters. PubMed was searched for tDCS studies in tinnitus. For randomized controlled trials (RCTs, a meta-analysis was performed. A total of 17 studies were identified and 6 of them were included in the systemic review and 2 RCTs were included in the meta-analysis. Overall 39.5% responded to active tDCS with a mean tinnitus intensity reduction of 13.5%. Additionally, left temporal area (LTA and bifrontal tDCS indicated comparable results. Active tDCS was found to be more effective than sham tDCS for tinnitus intensity reduction (Hedges' g=.77, 95% confidence interval 0.23–1.31. The efficacy of tDCS in tinnitus could not be fully confirmed by the current study because of the limited number of studies, but all studies included in the current systemic review and meta-analysis demonstrated significant tinnitus intensity improvement. Therefore, tDCS may be a promising tool for tinnitus management. Future RCTs in a large series regarding the efficacy as well as the comparison between LTA- and bifrontal tDCS are recommended.

  6. Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture

    DEFF Research Database (Denmark)

    Estrada, Karol; Styrkarsdottir, Unnur; Evangelou, Evangelos

    2012-01-01

    Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associ...

  7. C-reactive protein gene polymorphisms and myocardial infarction risk: a meta-analysis and meta-regression.

    Science.gov (United States)

    Zhu, Yanbin; Liu, Tongku; He, Haitao; Sun, Yuqing; Zhuo, Fengling

    2013-12-01

    C-reactive protein (CRP), the classic acute-phase protein, plays an important role in the etiology of myocardial infarction (MI). Emerging evidence has shown that the common polymorphisms in the CRP gene may influence an individual's susceptibility to MI; but individually published studies showed inconclusive results. This meta-analysis aimed to derive a more precise estimation of the associations between CRP gene polymorphisms and MI risk. A literature search of PubMed, Embase, Web of Science, and China BioMedicine (CBM) databases was conducted on articles published before June 1st, 2013. Crude odds ratio (OR) with 95% confidence interval (CI) were calculated. Nine case-control studies were included with a total of 2992 MI patients and 4711 healthy controls. The meta-analysis results indicated that CRP rs3093059 (T>C) polymorphism was associated with decreased risk of MI, especially among Asian populations. However, similar associations were not observed in CRP rs1800947 (G>C) and rs2794521 (G>A) polymorphisms (all p>0.05) among both Asian and Caucasian populations. Univariate and multivariate meta-regression analyses showed that ethnicity may be a major source of heterogeneity. No publication bias was detected in this meta-analysis. In conclusion, the current meta-analysis indicates that CRP rs3093059 (T>C) polymorphism may be associated with decreased risk of MI, especially among Asian populations.

  8. Acupuncture for Alcohol Use Disorder: A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Na Young Shin

    2017-01-01

    Full Text Available Empirical research has produced mixed results regarding the effects of acupuncture on the treatment of alcohol use disorder in humans. Few studies have provided a comprehensive review or a systematic overview of the magnitude of the treatment effect of acupuncture on alcoholism. This study investigated the effects of acupuncture on alcohol-related symptoms and behaviors in patients with this disorder. The PubMed database was searched until 23 August 2016, and reference lists from review studies were also reviewed. Seventeen studies were identified for a full-text inspection, and seven (243 patients of these met our inclusion criteria. The outcomes assessed at the last posttreatment point and any available follow-up data were extracted from each of the studies. Our meta-analysis demonstrated that an acupuncture intervention had a stronger effect on reducing alcohol-related symptoms and behaviors than did the control intervention (g=0.67. A beneficial but weak effect of acupuncture treatment was also found in the follow-up data (g=0.29. Although our analysis showed a significant difference between acupuncture and the control intervention in patients with alcohol use disorder, this meta-analysis is limited by the small number of studies included. Thus, a larger cohort study is required to provide a firm conclusion.

  9. The Effect of Hypnosis on Anxiety in Patients With Cancer: A Meta-Analysis.

    Science.gov (United States)

    Chen, Pei-Ying; Liu, Ying-Mei; Chen, Mei-Ling

    2017-06-01

    Anxiety is a common form of psychological distress in patients with cancer. One recognized nonpharmacological intervention to reduce anxiety for various populations is hypnotherapy or hypnosis. However, its effect in reducing anxiety in cancer patients has not been systematically evaluated. This meta-analysis was designed to synthesize the immediate and sustained effects of hypnosis on anxiety of cancer patients and to identify moderators for these hypnosis effects. Qualified studies including randomized controlled trials (RCT) and pre-post design studies were identified by searching seven electronic databases: Scopus, Medline Ovidsp, PubMed, PsycInfo-Ovid, Academic Search Premier, CINAHL Plus with FT-EBSCO, and SDOL. Effect size (Hedges' g) was computed for each study. Random-effect modeling was used to combine effect sizes across studies. All statistical analyses were conducted with Comprehensive Meta-Analysis, version 2 (Biostat, Inc., Englewood, NJ, USA). Our meta-analysis of 20 studies found that hypnosis had a significant immediate effect on anxiety in cancer patients (Hedges' g: 0.70-1.41, p Hypnosis delivered by a therapist was significantly more effective than self-hypnosis. Hypnosis can reduce anxiety of cancer patients, especially for pediatric cancer patients who experience procedure-related stress. We recommend therapist-delivered hypnosis should be preferred until more effective self-hypnosis strategies are developed. © 2017 Sigma Theta Tau International.

  10. Meta-analysis of lipid-traits in Hispanics identifies novel loci, population-specific effects, and tissue-specific enrichment of eQTLs

    NARCIS (Netherlands)

    Below, Jennifer E.; Parra, Esteban J.; Gamazon, Eric R.; Torres, Jason; Krithika, S.; Candille, Sophie; Lu, Yingchang; Manichakul, Ani; Peralta-Romero, Jesus; Duan, Qing; Li, Yun; Morris, Andrew P.; Gottesman, Omri; Bottinger, Erwin; Wang, Xin-Qun; Taylor, Kent D.; Ida Chen, Y.-D.; Rotter, Jerome I.; Rich, Stephen S.; Loos, Ruth J. F.; Tang, Hua; Cox, Nancy J.; Cruz, Miguel; Hanis, Craig L.; Valladares-Salgado, Adan

    2016-01-01

    We performed genome-wide meta-analysis of lipid traits on three samples of Mexican and Mexican American ancestry comprising 4,383 individuals, and followed up significant and highly suggestive associations in three additional Hispanic samples comprising 7,876 individuals. Genome-wide significant

  11. The effects of aromatherapy on sleep improvement: a systematic literature review and meta-analysis.

    Science.gov (United States)

    Hwang, Eunhee; Shin, Sujin

    2015-02-01

    To evaluate the existing data on aromatherapy interventions for improvement of sleep quality. Systematic literature review and meta-analysis on the effects of aromatherapy. Study Sources: Electronic databases, including the Korea Education and Research Information Service (KERIS), Korean studies Information Service System (KISS), National Assembly Library, and eight academies within the Korean Society of Nursing Science, were searched to identify studies published between 2000 and August 2013. Randomized controlled and quasi-experimental trials that included aromatherapy for the improvement of sleep quality. Of the 245 publications identified, 13 studies met the inclusion and exclusion criteria, and 12 studies were used in the meta-analysis. Meta-analysis of the 12 studies using a random-effects model revealed that the use of aromatherapy was effective in improving sleep quality (95% confidence interval [CI], 0.540-1.745; Z=3.716). Subgroup analysis revealed that inhalation aromatherapy (95% CI, 0.792-1.541; Z=6.107) was more effective than massage therapy (95% CI, 0.128-2.166; Z=2.205) in unhealthy (95% CI, 0.248-1.100; Z=3.100) and healthy (95% CI, 0.393-5.104; Z=2.287) participants, respectively. Readily available aromatherapy treatments appear to be effective and promote sleep. Thus, it is essential to develop specific guidelines for the efficient use of aromatherapy.

  12. Exosomes from metastatic cancer cells transfer amoeboid phenotype to non-metastatic cells and increase endothelial permeability: their emerging role in tumor heterogeneity.

    Science.gov (United States)

    Schillaci, Odessa; Fontana, Simona; Monteleone, Francesca; Taverna, Simona; Di Bella, Maria Antonietta; Di Vizio, Dolores; Alessandro, Riccardo

    2017-07-05

    The goal of this study was to understand if exosomes derived from high-metastatic cells may influence the behavior of less aggressive cancer cells and the properties of the endothelium. We found that metastatic colon cancer cells are able to transfer their amoeboid phenotype to isogenic primary cancer cells through exosomes, and that this morphological transition is associated with the acquisition of a more aggressive behavior. Moreover, exosomes from the metastatic line (SW620Exos) exhibited higher ability to cause endothelial hyperpermeability than exosomes from the non metastatic line (SW480Exos). SWATH-based quantitative proteomic analysis highlighted that SW620Exos are significantly enriched in cytoskeletal-associated proteins including proteins activating the RhoA/ROCK pathway, known to induce amoeboid properties and destabilization of endothelial junctions. In particular, thrombin was identified as a key mediator of the effects induced by SW620Exos in target cells, in which we also found a significant increase of RhoA activity. Overall, our results demonstrate that in a heterogeneous context exosomes released by aggressive sub-clones can contribute to accelerate tumor progression by spreading malignant properties that affect both the tumor cell plasticity and the endothelial cell behavior.

  13. Neuroanatomic changes and their association with cognitive decline in mild cognitive impairment: a meta-analysis

    OpenAIRE

    Nickl-Jockschat, Thomas; Kleiman, Alexandra; Schulz, Jörg B.; Schneider, Frank; Laird, Angela R.; Fox, Peter T.; Eickhoff, Simon B.; Reetz, Kathrin

    2011-01-01

    Mild cognitive impairment (MCI) is an acquired syndrome characterised by cognitive decline not affecting activities of daily living. Using a quantitative meta-analytic approach, we aimed to identify consistent neuroanatomic correlates of MCI and how they are related to cognitive dysfunction. The meta-analysis enrols 22 studies, involving 917 MCI (848 amnestic MCI) patients and 809 healthy controls. Only studies investigating local changes in grey matter and reporting whole-brain results in st...

  14. Hypothyroidism as a risk factor for open angle glaucoma: A systematic review and meta-analysis

    OpenAIRE

    Wang, Shiming; Liu, Yue; Zheng, Guangying

    2017-01-01

    Purpose The relationship between hypothyroidism and primary open angle glaucoma (POAG) has attracted intense interest recently, but the reported results have been controversial. This meta-analysis was carried out to determine the association between hypothyroidism and POAG. Methods The literature was identified from three databases (Web of Science, Embase, and PubMed). The meta-analyses were performed using random-effects models, with results reported as adjusted odds ratios (ORs) with 95% co...

  15. Graphics and Statistics for Cardiology: Data visualisation for meta-analysis.

    Science.gov (United States)

    Kiran, Amit; Crespillo, Abel Pérez; Rahimi, Kazem

    2017-01-01

    Graphical displays play a pivotal role in understanding data sets and disseminating results. For meta-analysis, they are instrumental in presenting findings from multiple studies. This report presents guidance to authors wishing to submit graphical displays as part of their meta-analysis to a clinical cardiology journal, such as HeartWhen using graphical displays for meta-analysis, we recommend the following: Use a flow diagram to describe the number of studies returned from the initial search, the inclusion/exclusion criteria applied and the final number of studies used in the meta-analysis.Present results from the meta-analysis using a figure that incorporates a forest plot and underlying (tabulated) statistics, including test for heterogeneity.Use displays such as funnel plot (minimum 10 studies) and Galbraith plot to visually present distribution of effect sizes or associations in order to evaluate small-study effects and publication bias).For meta-regression, the bubble plot is a useful display for assessing associations by study-level factors.Final checks on graphs, such as appropriate use of axis scale, line pattern, text size and graph resolution, should always be performed. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  16. Cancer Incidence in Patients with Acromegaly: A cohort study and meta-analysis of the literature

    DEFF Research Database (Denmark)

    Dal, Jakob; Leisner, Michelle Z; Hermansen, Kasper

    2018-01-01

    -2010) including 529 acromegaly cases was performed. Incident cancer diagnoses and mortality were compared to national rates estimating standardized incidence ratios (SIRs). A meta-analysis of cancer SIRs from 23 studies (including the present one) was performed. Results: The cohort study identified 81 cases...... in acromegaly (SIR 1.3 [95% CI: 1.1-1.6]), cancer-specific mortality was not. The meta-analysis yielded a SIR of overall cancer of 1.5 [95% CI: 1.2-1.8]. SIRs were elevated for colorectal cancer: 2.6 [95% CI: 1.7-4.0], thyroid cancer: 9.2 [95% CI: 4.2-19.9], breast cancer: 1.6 [1.1-2.3], gastric cancer: 2.0 [95......% CI: 1.4-2.9], and urinary tract cancer: 1.5 [95% CI: 1.0-2.3]). In general, cancer SIR was higher in single-center studies and in studies with meta-analysis...

  17. Road safety effects of roundabouts: A meta-analysis.

    Science.gov (United States)

    Elvik, Rune

    2017-02-01

    This paper presents a meta-analysis of the road safety effects of converting junctions to roundabouts. 44 studies containing a total of 154 estimates of effect were included. Based on a meta-regression analysis, converting junctions to roundabouts is associated with a reduction of fatal accidents of about 65% and a reduction of injury accidents of about 40%. The mean effect on property-damage-only accidents is ambiguous. Summary estimates of effect are robust for fatal and injury accidents, but vary depending on the model of meta-analysis and the treatment of outlying data points for property-damage-only accidents. A trim-and-fill analysis suggests a weak tendency for publication bias, with modest influence on summary estimates of effect. It is concluded that roundabouts are very effective in reducing traffic fatalities. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Systematic reviews with meta-analysis: Why, when, and how?

    NARCIS (Netherlands)

    Crocetti, E.

    2016-01-01

    Systematic reviews with meta-analysis represent the gold standard for conducting reliable and transparent reviews of the literature. The purpose of this article is threefold: (a) to address why and when it is worthwhile to conduct a systematic review with meta-analysis, covering advantages of this

  19. Association between periodontitis and ischemic stroke: a systematic review and meta-analysis

    International Nuclear Information System (INIS)

    Leira, Yago; Seoane, Juan; Blanco, Miguel; Rodríguez-Yáñez, Manuel; Takkouche, Bahi; Blanco, Juan; Castillo, José

    2017-01-01

    Several observational studies have suggested an association between periodontitis and cerebral ischemia. This meta-analysis aimed to investigate whether this link exists, and if so, the degree to which it is significant. The Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guideline for systematic review was used. The search strategy included using electronic databases and hand searching works published up to March 2015. MEDLINE via PubMed, EMBASE, Proceedings Web of Science and Current Contents Connect were searched by two independent reviewers. Case-control, cross-sectional or cohort studies including patients with measures of periodontitis and ischemic stroke were eligible to be included in the analysis. Quality assessments of selected studies were performed. From a total of 414 titles and abstracts, 57 potentially relevant full text papers were identified. After inclusion criteria were applied, 8 studies were included in the present systematic review (5 case-control and 3 cohort studies). Although it was not the intention, cross-sectional studies were excluded due to eligibility criteria were not accomplished. Therefore, meta-analyses were conducted with data retrieved from the 8 studies included. These meta-analyses showed statistically significant association between periodontitis and ischemic stroke in both cohort pooled relative risks at 2.52 (1.77–3.58), and case-control studies pooled relative risks at 3.04 (1.10–8.43). In conclusion, the present meta-analysis demonstrated an association between periodontitis and ischemic stroke. However, well-designed prospective studies should be carried out to provide robust evidence of the link between both diseases. In regards to ischemic stroke subtypes, further case-control studies should be carried out to investigate whether there is any association between the different subtypes of cerebral infarcts and periodontitis.

  20. Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis

    DEFF Research Database (Denmark)

    Voight, Benjamin F; Scott, Laura J; Steinthorsdottir, Valgerdur

    2010-01-01

    By combining genome-wide association data from 8,130 individuals with type 2 diabetes (T2D) and 38,987 controls of European descent and following up previously unidentified meta-analysis signals in a further 34,412 cases and 59,925 controls, we identified 12 new T2D association signals...

  1. Hypothyroidism and carpal tunnel syndrome: a meta-analysis.

    Science.gov (United States)

    Shiri, Rahman

    2014-12-01

    This study aimed to assess the magnitude of the association between hypothyroidism and carpal tunnel syndrome (CTS). Eighteen studies were included in a random-effects meta-analysis. A meta-analysis of the studies that did not control their estimates for any confounder showed an association between a thyroid disease (hypo- or hyperthyroidism) and CTS (N = 9,573, effect size [ES] = 1.32 (95% confidence interval [CI], 1.04-1.68) and between hypothyroidism and CTS (N = 64,531, ES = 2.15 [95% CI, 1.64-2.83]). When a meta-analysis limited to the studies that controlled their estimates for some potential confounders, the association between a thyroid disease and CTS disappeared (N = 4,799, ES = 1.17 [95% CI, 0.71-1.92], I(2) = 0%), and the effect size for hypothyroidism largely attenuated (N = 71,133, ES = 1.44 [95% CI, 1.27-1.63], I(2) = 0%). Moreover, there was evidence of publication bias. This meta-analysis found only a modest association between hypothyroidism and CTS. Confounding and publication bias may still account for part of the remaining excess risk. © 2014 Wiley Periodicals, Inc.

  2. A Bayesian network meta-analysis on second-line systemic therapy in advanced gastric cancer.

    Science.gov (United States)

    Zhu, Xiaofu; Ko, Yoo-Joung; Berry, Scott; Shah, Keya; Lee, Esther; Chan, Kelvin

    2017-07-01

    It is unclear which regimen is the most efficacious among the available therapies for advanced gastric cancer in the second-line setting. We performed a network meta-analysis to determine their relative benefits. We conducted a systematic review of randomized controlled trials (RCTs) through the MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases and American Society of Clinical Oncology abstracts up to June 2014 to identify phase III RCTs on advanced gastric cancer in the second-line setting. Overall survival (OS) data were the primary outcome of interest. Hazard ratios (HRs) were extracted from the publications on the basis of reported values or were extracted from survival curves by established methods. A Bayesian network meta-analysis was performed with WinBUGS to compare all regimens simultaneously. Eight RCTs (2439 patients) were identified and contained extractable data for quantitative analysis. Network meta-analysis showed that paclitaxel plus ramucirumab was superior to single-agent ramucirumab [OS HR 0.51, 95 % credible region (CR) 0.30-0.86], paclitaxel (OS HR 0.81, 95 % CR 0.68-0.96), docetaxel (OS HR 0.56, 95 % CR 0.33-0.94), and irinotecan (OS HR 0.71, 95 % CR 0.52-0.99). Paclitaxel plus ramucirumab also had an 89 % probability of being the best regimen among all these regimens. Single-agent ramucirumab, paclitaxel, docetaxel, and irinotecan were comparable to each other with respect to OS and were superior to best supportive care. This is the first network meta-analysis to compare all second-line regimens reported in phase III gastric cancer trials. The results suggest the paclitaxel plus ramucirumab combination is the most effective therapy and should be the reference regimen for future comparative trials.

  3. Methotrexate for the Treatment of Pediatric Crohn's Disease: A Systematic Review and Meta-analysis.

    Science.gov (United States)

    Colman, Ruben J; Lawton, Rachel C; Dubinsky, Marla C; Rubin, David T

    2018-04-23

    Methotrexate (MTX) is an immunomodulator used for the treatment of pediatric inflammatory bowel disease (IBD). There are currently no RCTs that assess the treatment efficacy of methotrexate within the pediatric IBD patient population. This systematic review and meta-analysis assesses the efficacy of MTX therapy among the existing pediatric literature. A systematic literature search was performed using MEDLINE and the Cochrane library from inception until March 2016. Synonyms for 'pediatric', 'methotrexate' and 'IBD' were utilized as both free text and MESH search terms. The studies included contained clinical remission (CR) rates for MTX treatment of pediatric IBD patients 18 yrs old, as mono- or combination therapy. Case studies with <10 patients were excluded. Quality assessment was performed with the Newcastle-Ottawa Scale. Meta-analysis calculated pooled CR rates. A random-effects meta-analysis with forest plots was performed using R. Fourteen (11 monotherapy, 1 combination therapy, 2 both; n = 886 patients) observational studies were eligible out of 202 studies. No interventional studies were identified. The pooled achieved CR rate for pediatric CD patients on monotherapy within 3-6 months was 57.7% (95% CI 48.2-66.6%), (P =0.22; I2 = 29.8%). The CR was 37.1% (95% CI 29.5-45.5%), (P = 0.20; I2 = 37.4%) for maintenance therapy at 12 months. Sub-analysis could not identify CR differences between MTX administration types, thiopurine exposure. This meta-analysis demonstrated that, over 50% of pediatric Crohn's disease patients induced with methotrexate achieved clinical remission, while 12-month remission rate was only 37%. Prospective controlled interventional trials should assess treatment efficacy among patient subgroups. 10.1093/ibd/izy078_video1izy078.video15774883936001.

  4. Moyer's method of mixed dentition analysis: a meta-analysis ...

    African Journals Online (AJOL)

    The applicability of tables derived from the data Moyer used to other ethnic groups has ... This implies that Moyer's method of prediction may have population variations. ... Key Words: meta-analysis, mixed dentition analysis, Moyer's method

  5. HIV-Associated Cognitive Impairment in Perinatally Infected Children: A Meta-analysis.

    Science.gov (United States)

    Phillips, Nicole; Amos, Taryn; Kuo, Caroline; Hoare, Jacqueline; Ipser, Jonathan; Thomas, Kevin G F; Stein, Dan J

    2016-11-01

    Research shows, conclusively, that perinatal HIV infection has negative effects on cognitive functioning of children and adolescents. However, the extent of these cognitive impairments is unknown. Current literature does not document specific cognitive domains most affected in HIV-infected children and adolescents. To systematically review and meta-analyze the degree of cognitive impairment, and the specific cognitive domains affected, in children and adolescents with perinatally acquired HIV infection. We systematically searched 5 electronic bibliographic databases, namely: PubMed, PsychINFO, Academic Search Premier, Scopus, and WorldCat, by using a search protocol specifically designed for this study. Studies were selected on the basis of set a priori eligibility criteria. Titles, abstracts, and full texts were assessed by 2 independent reviewers. Data from included studies were extracted into Microsoft Excel by 2 independent reviewers. Twenty-two studies were identified for inclusion in the systematic review and of this, 6 studies were included in the meta-analysis. Results from the meta-analysis indicated that working memory and executive function were the domains most affected by the HIV virus. Only 27% of the included studies were suitable to enter into the meta-analysis. There was significant geographic bias in published studies, with only 32% (7/22) of included studies from sub-Saharan Africa. The evidence supports an association between HIV infection in children and adolescents and cognitive impairment in the domains of working memory, executive function and processing speed, with effect size estimates also providing some support for deficits in visual memory and visual-spatial ability. Copyright © 2016 by the American Academy of Pediatrics.

  6. Meta-analysis of the relative sensitivity of semi-natural vegetation species to ozone

    International Nuclear Information System (INIS)

    Hayes, F.; Jones, M.L.M.; Mills, G.; Ashmore, M.

    2007-01-01

    This study identified 83 species from existing publications suitable for inclusion in a database of sensitivity of species to ozone (OZOVEG database). An index, the relative sensitivity to ozone, was calculated for each species based on changes in biomass in order to test for species traits associated with ozone sensitivity. Meta-analysis of the ozone sensitivity data showed a wide inter-specific range in response to ozone. Some relationships in comparison to plant physiological and ecological characteristics were identified. Plants of the therophyte lifeform were particularly sensitive to ozone. Species with higher mature leaf N concentration were more sensitive to ozone than those with lower leaf N concentration. Some relationships between relative sensitivity to ozone and Ellenberg habitat requirements were also identified. In contrast, no relationships between relative sensitivity to ozone and mature leaf P concentration, Grime's CSR strategy, leaf longevity, flowering season, stomatal density and maximum altitude were found. The relative sensitivity of species and relationships with plant characteristics identified in this study could be used to predict sensitivity to ozone of untested species and communities. - Meta-analysis of the relative sensitivity of semi-natural vegetation species to ozone showed some relationships with physiological and ecological characteristics

  7. Affective mapping: An activation likelihood estimation (ALE) meta-analysis.

    Science.gov (United States)

    Kirby, Lauren A J; Robinson, Jennifer L

    2017-11-01

    Functional neuroimaging has the spatial resolution to explain the neural basis of emotions. Activation likelihood estimation (ALE), as opposed to traditional qualitative meta-analysis, quantifies convergence of activation across studies within affective categories. Others have used ALE to investigate a broad range of emotions, but without the convenience of the BrainMap database. We used the BrainMap database and analysis resources to run separate meta-analyses on coordinates reported for anger, anxiety, disgust, fear, happiness, humor, and sadness. Resultant ALE maps were compared to determine areas of convergence between emotions, as well as to identify affect-specific networks. Five out of the seven emotions demonstrated consistent activation within the amygdala, whereas all emotions consistently activated the right inferior frontal gyrus, which has been implicated as an integration hub for affective and cognitive processes. These data provide the framework for models of affect-specific networks, as well as emotional processing hubs, which can be used for future studies of functional or effective connectivity. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. CrossFit Overview: Systematic Review and Meta-analysis.

    Science.gov (United States)

    Claudino, João Gustavo; Gabbett, Tim J; Bourgeois, Frank; Souza, Helton de Sá; Miranda, Rafael Chagas; Mezêncio, Bruno; Soncin, Rafael; Cardoso Filho, Carlos Alberto; Bottaro, Martim; Hernandez, Arnaldo Jose; Amadio, Alberto Carlos; Serrão, Julio Cerca

    2018-02-26

    CrossFit is recognized as one of the fastest growing high-intensity functional training modes in the world. However, scientific data regarding the practice of CrossFit is sparse. Therefore, the objective of this study is to analyze the findings of scientific literature related to CrossFit via systematic review and meta-analysis. Systematic searches of the PubMed, Web of Science, Scopus, Bireme/MedLine, and SciELO online databases were conducted for articles reporting the effects of CrossFit training. The systematic review followed the PRISMA guidelines. The Oxford Levels of Evidence was used for all included articles, and only studies that investigated the effects of CrossFit as a training program were included in the meta-analysis. For the meta-analysis, effect sizes (ESs) with 95% confidence interval (CI) were calculated and heterogeneity was assessed using a random-effects model. Thirty-one articles were included in the systematic review and four were included in the meta-analysis. However, only two studies had a high level of evidence at low risk of bias. Scientific literature related to CrossFit has reported on body composition, psycho-physiological parameters, musculoskeletal injury risk, life and health aspects, and psycho-social behavior. In the meta-analysis, significant results were not found for any variables. The current scientific literature related to CrossFit has few studies with high level of evidence at low risk of bias. However, preliminary data has suggested that CrossFit practice is associated with higher levels of sense of community, satisfaction, and motivation.

  9. Meta-analysis of expression and function of neprilysin in Alzheimer's disease.

    Science.gov (United States)

    Zhang, Huifeng; Liu, Dan; Wang, Yixing; Huang, Huanhuan; Zhao, Yujia; Zhou, Hui

    2017-09-14

    Neprilysin (NEP) is one of the most important Aβ-degrading enzymes, and its expression and activity in Alzheimer's brain have been widely reported, but the results remain debatable. Thus, the meta-analysis was performed to elucidate the role of NEP in Alzheimer's disease (AD). The relevant case-control or cohort studies were retrieved according to our inclusion/exclusion criteria. Six studies with 123 controls and 141 AD cases, seven studies with 102 controls and 90 AD cases, and four studies with 93 controls and 132 AD cases were included in meta-analysis of NEP's protein, mRNA, and enzyme activity respectively. We conducted Meta regression to detect the sources of heterogeneity and further performed cumulative meta-analysis or subgroup analysis. Our meta-analysis revealed a significantly lower level of NEP mRNA (SMD=-0.44, 95%CI: -0.87, -0.00, p=0.049) in AD cases than in non-AD cases, and such pattern was not altered over time in the cumulative meta-analysis. However, the decrease of NEP protein (SMD=-0.18, 95%CI: -0.62, 0.25) and enzyme activity (SMD=-0.35, 95%CI: -1.03, 0.32) in AD cases did not pass the significance check, while the cumulative meta-analysis by average age showed the pooled effect became insignificant as adding the studies with younger subjects, which indicates that the protein expression and enzyme activity of NEP in the cortex are affected by age. Therefore, the present meta-analysis suggests the need of further investigation of roles of NEP in AD pathogenesis and treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Meta-analysis in a nutshell: Techniques and general findings

    DEFF Research Database (Denmark)

    Paldam, Martin

    2015-01-01

    The purpose of this article is to introduce the technique and main findings of meta-analysis to the reader, who is unfamiliar with the field and has the usual objections. A meta-analysis is a quantitative survey of a literature reporting estimates of the same parameter. The funnel showing...

  11. Regional variation in the prevalence of E. coli O157 in cattle: a meta-analysis and meta-regression.

    Science.gov (United States)

    Islam, Md Zohorul; Musekiwa, Alfred; Islam, Kamrul; Ahmed, Shahana; Chowdhury, Sharmin; Ahad, Abdul; Biswas, Paritosh Kumar

    2014-01-01

    Escherichia coli O157 (EcO157) infection has been recognized as an important global public health concern. But information on the prevalence of EcO157 in cattle at the global and at the wider geographical levels is limited, if not absent. This is the first meta-analysis to investigate the point prevalence of EcO157 in cattle at the global level and to explore the factors contributing to variation in prevalence estimates. Seven electronic databases- CAB Abstracts, PubMed, Biosis Citation Index, Medline, Web of Knowledge, Scirus and Scopus were searched for relevant publications from 1980 to 2012. A random effect meta-analysis model was used to produce the pooled estimates. The potential sources of between study heterogeneity were identified using meta-regression. A total of 140 studies consisting 220,427 cattle were included in the meta-analysis. The prevalence estimate of EcO157 in cattle at the global level was 5.68% (95% CI, 5.16-6.20). The random effects pooled prevalence estimates in Africa, Northern America, Oceania, Europe, Asia and Latin America-Caribbean were 31.20% (95% CI, 12.35-50.04), 7.35% (95% CI, 6.44-8.26), 6.85% (95% CI, 2.41-11.29), 5.15% (95% CI, 4.21-6.09), 4.69% (95% CI, 3.05-6.33) and 1.65% (95% CI, 0.77-2.53), respectively. Between studies heterogeneity was evidenced in most regions. World region (p<0.001), type of cattle (p<0.001) and to some extent, specimens (p = 0.074) as well as method of pre-enrichment (p = 0.110), were identified as factors for variation in the prevalence estimates of EcO157 in cattle. The prevalence of the organism seems to be higher in the African and Northern American regions. The important factors that might have influence in the estimates of EcO157 are type of cattle and kind of screening specimen. Their roles need to be determined and they should be properly handled in any survey to estimate the true prevalence of EcO157.

  12. Differential Identification of Females and Males with Reading Difficulties: A Meta-Analysis

    Science.gov (United States)

    Quinn, Jamie M.

    2018-01-01

    Males are more likely than females to be identified as having reading difficulties, but it is unclear if this is a result of sample ascertainment or identification bias. The purpose of this meta-analysis was to determine the magnitude of gender differences in reading difficulties using available studies in which researchers investigated this…

  13. Meta-analysis reveals host-dependent nitrogen recycling as a mechanism of symbiont control in Aiptasia

    KAUST Repository

    Cui, Guoxin; Liew, Yi Jin; Li, Yong; Kharbatia, Najeh M.; Zahran, Noura Ibrahim Omar; Emwas, Abdul-Hamid M.; Eguí luz, Ví ctor M; Aranda, Manuel

    2018-01-01

    in the emerging model organism Aiptasia. However, previous studies identified thousands of putatively symbiosis-related genes, making it difficult to disentangle symbiosis-induced responses from undesired experimental parameters. Using a meta-analysis approach, we

  14. Memory training interventions for older adults: a meta-analysis.

    Science.gov (United States)

    Gross, Alden L; Parisi, Jeanine M; Spira, Adam P; Kueider, Alexandra M; Ko, Jean Y; Saczynski, Jane S; Samus, Quincy M; Rebok, George W

    2012-01-01

    A systematic review and meta-analysis of memory training research was conducted to characterize the effect of memory strategies on memory performance among cognitively intact, community-dwelling older adults, and to identify characteristics of individuals and of programs associated with improved memory. The review identified 402 publications, of which 35 studies met criteria for inclusion. The overall effect size estimate, representing the mean standardized difference in pre-post change between memory-trained and control groups, was 0.31 standard deviations (SD; 95% confidence interval (CI): 0.22, 0.39). The pre-post training effect for memory-trained interventions was 0.43 SD (95% CI: 0.29, 0.57) and the practice effect for control groups was 0.06 SD (95% CI: 0.05, 0.16). Among 10 distinct memory strategies identified in studies, meta-analytic methods revealed that training multiple strategies was associated with larger training gains (p=0.04), although this association did not reach statistical significance after adjusting for multiple comparisons. Treatment gains among memory-trained individuals were not better after training in any particular strategy, or by the average age of participants, session length, or type of control condition. These findings can inform the design of future memory training programs for older adults.

  15. Does chocolate reduce blood pressure? A meta-analysis

    Directory of Open Access Journals (Sweden)

    Ried Karin

    2010-06-01

    Full Text Available Abstract Background Dark chocolate and flavanol-rich cocoa products have attracted interest as an alternative treatment option for hypertension, a known risk factor for cardiovascular disease. Previous meta-analyses concluded that cocoa-rich foods may reduce blood pressure. Recently, several additional trials have been conducted with conflicting results. Our study summarises current evidence on the effect of flavanol-rich cocoa products on blood pressure in hypertensive and normotensive individuals. Methods We searched Medline, Cochrane and international trial registries between 1955 and 2009 for randomised controlled trials investigating the effect of cocoa as food or drink compared with placebo on systolic and diastolic blood pressure (SBP/DBP for a minimum duration of 2 weeks. We conducted random effects meta-analysis of all studies fitting the inclusion criteria, as well as subgroup analysis by baseline blood pressure (hypertensive/normotensive. Meta-regression analysis explored the association between type of treatment, dosage, duration or baseline blood pressure and blood pressure outcome. Statistical significance was set at P Results Fifteen trial arms of 13 assessed studies met the inclusion criteria. Pooled meta-analysis of all trials revealed a significant blood pressure-reducing effect of cocoa-chocolate compared with control (mean BP change ± SE: SBP: -3.2 ± 1.9 mmHg, P = 0.001; DBP: -2.0 ± 1.3 mmHg, P = 0.003. However, subgroup meta-analysis was significant only for the hypertensive or prehypertensive subgroups (SBP: -5.0 ± 3.0 mmHg; P = 0.0009; DBP: -2.7 ± 2.2 mm Hg, P = 0.01, while BP was not significantly reduced in the normotensive subgroups (SBP: -1.6 ± 2.3 mmHg, P = 0.17; DBP: -1.3 ± 1.6 mmHg, P = 0.12. Nine trials used chocolate containing 50% to 70% cocoa compared with white chocolate or other cocoa-free controls, while six trials compared high- with low-flavanol cocoa products. Daily flavanol dosages ranged from 30

  16. Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis

    NARCIS (Netherlands)

    B.F. Voight (Benjamin); L.J. Scott (Laura); V. Steinthorsdottir (Valgerdur); A.D. Morris (Andrew); C. Dina (Christian); R.P. Welch (Ryan); E. Zeggini (Eleftheria); C. Huth (Cornelia); Y.S. Aulchenko (Yurii); G. Thorleifsson (Gudmar); L.J. McCulloch (Laura); T. Ferreira (Teresa); H. Grallert (Harald); N. Amin (Najaf); G. Wu (Guanming); C.J. Willer (Cristen); S. Raychaudhuri (Soumya); S.A. McCarroll (Steven); C. Langenberg (Claudia); O.M. Hofmann (Oliver); J. Dupuis (Josée); L. Qi (Lu); A.V. Segrè (Ayellet); M. van Hoek (Mandy); P. Navarro (Pau); K.G. Ardlie (Kristin); B. Balkau (Beverley); R. Benediktsson (Rafn); A.J. Bennett (Amanda); R. Blagieva (Roza); E.A. Boerwinkle (Eric); L.L. Bonnycastle (Lori); K.B. Boström (Kristina Bengtsson); B. Bravenboer (Bert); S. Bumpstead (Suzannah); N.P. Burtt (Noël); G. Charpentier (Guillaume); P.S. Chines (Peter); M. Cornelis (Marilyn); D.J. Couper (David); G. Crawford (Gabe); A.S.F. Doney (Alex); K.S. Elliott (Katherine); M.R. Erdos (Michael); C.S. Fox (Caroline); C.S. Franklin (Christopher); M. Ganser (Martha); C. Gieger (Christian); N. Grarup (Niels); T. Green (Todd); S. Griffin (Simon); C.J. Groves (Christopher); C. Guiducci (Candace); S. Hadjadj (Samy); N. Hassanali (Neelam); C. Herder (Christian); B. Isomaa (Bo); A.U. Jackson (Anne); P.R.V. Johnson (Paul); T. Jørgensen (Torben); W.H.L. Kao (Wen); N. Klopp (Norman); A. Kong (Augustine); P. Kraft (Peter); J. Kuusisto (Johanna); T. Lauritzen (Torsten); M. Li (Man); A. Lieverse (Aloysius); C.M. Lindgren (Cecilia); V. Lyssenko (Valeriya); M. Marre (Michel); T. Meitinger (Thomas); K. Midthjell (Kristian); M.A. Morken (Mario); N. Narisu (Narisu); P. Nilsson (Peter); K.R. Owen (Katharine); F. Payne (Felicity); J.R.B. Perry (John); A.K. Petersen; C. Platou (Carl); C. Proença (Christine); I. Prokopenko (Inga); W. Rathmann (Wolfgang); N.W. Rayner (Nigel William); N.R. Robertson (Neil); G. Rocheleau (Ghislain); M. Roden (Michael); M.J. Sampson (Michael); R. Saxena (Richa); B.M. Shields (Beverley); P. Shrader (Peter); G. Sigurdsson (Gunnar); T. Sparsø (Thomas); K. Strassburger (Klaus); H.M. Stringham (Heather); Q. Sun (Qi); A.J. Swift (Amy); B. Thorand (Barbara); J. Tichet (Jean); T. Tuomi (Tiinamaija); R.M. van Dam (Rob); T.W. van Haeften (Timon); T.W. van Herpt (Thijs); J.V. van Vliet-Ostaptchouk (Jana); G.B. Walters (Bragi); M.N. Weedon (Michael); C. Wijmenga (Cisca); J.C.M. Witteman (Jacqueline); R.N. Bergman (Richard); S. Cauchi (Stephane); F.S. Collins (Francis); A.L. Gloyn (Anna); U. Gyllensten (Ulf); T. Hansen (Torben); W.A. Hide (Winston); G.A. Hitman (Graham); A. Hofman (Albert); D. Hunter (David); K. Hveem (Kristian); M. Laakso (Markku); K.L. Mohlke (Karen); C.N.A. Palmer (Colin); P.P. Pramstaller (Peter Paul); I. Rudan (Igor); E.J.G. Sijbrands (Eric); L.D. Stein (Lincoln); J. Tuomilehto (Jaakko); A.G. Uitterlinden (André); M. Walker (Mark); N.J. Wareham (Nick); G.R. Abecasis (Gonçalo); B.O. Boehm (Bernhard); H. Campbell (Harry); M.J. Daly (Mark); A.T. Hattersley (Andrew); F.B. Hu (Frank); J.B. Meigs (James); J.S. Pankow (James); O. Pedersen (Oluf); H.E. Wichmann (Erich); I.E. Barroso (Inês); J.C. Florez (Jose); T.M. Frayling (Timothy); L. Groop (Leif); R. Sladek (Rob); U. Thorsteinsdottir (Unnur); J.F. Wilson (James); T. Illig (Thomas); P. Froguel (Philippe); P. Tikka-Kleemola (Päivi); J-A. Zwart (John-Anker); D. Altshuler (David); M. Boehnke (Michael); M.I. McCarthy (Mark); R.M. Watanabe (Richard)

    2010-01-01

    textabstractBy combining genome-wide association data from 8,130 individuals with type 2 diabetes (T2D) and 38,987 controls of European descent and following up previously unidentified meta-analysis signals in a further 34,412 cases and 59,925 controls, we identified 12 new T2D association signals

  17. Meta-analysis in epidemiology | Yach | South African Medical Journal

    African Journals Online (AJOL)

    Meta-analysis is the structured and systematic qualitative and quantitative integration of the results of several independent studies (Le. the epidemiology of results). As in any epidemiological study, a meta-analysis needs to start with clearly stated aims and objectives. Attention needs to be paid to selection bias in selecting ...

  18. Genome-Wide Meta-Analysis of Sciatica in Finnish Population.

    Science.gov (United States)

    Lemmelä, Susanna; Solovieva, Svetlana; Shiri, Rahman; Benner, Christian; Heliövaara, Markku; Kettunen, Johannes; Anttila, Verneri; Ripatti, Samuli; Perola, Markus; Seppälä, Ilkka; Juonala, Markus; Kähönen, Mika; Salomaa, Veikko; Viikari, Jorma; Raitakari, Olli T; Lehtimäki, Terho; Palotie, Aarno; Viikari-Juntura, Eira; Husgafvel-Pursiainen, Kirsti

    2016-01-01

    Sciatica or the sciatic syndrome is a common and often disabling low back disorder in the working-age population. It has a relatively high heritability but poorly understood molecular mechanisms. The Finnish population is a genetic isolate where small founder population and bottleneck events have led to enrichment of certain rare and low frequency variants. We performed here the first genome-wide association (GWAS) and meta-analysis of sciatica. The meta-analysis was conducted across two GWAS covering 291 Finnish sciatica cases and 3671 controls genotyped and imputed at 7.7 million autosomal variants. The most promising loci (psciatica patients and 18,489 controls. We identified five intragenic variants, with relatively low frequencies, at two novel loci associated with sciatica at genome-wide significance. These included chr9:14344410:I (rs71321981) at 9p22.3 (NFIB gene; p = 1.30x10-8, MAF = 0.08) and four variants at 15q21.2: rs145901849, rs80035109, rs190200374 and rs117458827 (MYO5A; p = 1.34x10-8, MAF = 0.06; p = 2.32x10-8, MAF = 0.07; p = 3.85x10-8, MAF = 0.06; p = 4.78x10-8, MAF = 0.07, respectively). The most significant association in the meta-analysis, a single base insertion rs71321981 within the regulatory region of the transcription factor NFIB, replicated in an independent Finnish population sample (p = 0.04). Despite identifying 15q21.2 as a promising locus, we were not able to replicate it. It was differentiated; the lead variants within 15q21.2 were more frequent in Finland (6-7%) than in other European populations (1-2%). Imputation accuracies of the three significantly associated variants (chr9:14344410:I, rs190200374, and rs80035109) were validated by genotyping. In summary, our results suggest a novel locus, 9p22.3 (NFIB), which may be involved in susceptibility to sciatica. In addition, another locus, 15q21.2, emerged as a promising one, but failed to replicate.

  19. Association of XPC polymorphisms and lung cancer risk: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Bo Jin

    Full Text Available BACKGROUND: Xeroderma pigmentosum complementation group C gene (XPC is a key member of nucleotide excision repair pathway and plays an important role in human DNA repair system. It is reported that several common polymorphisms of XPC are associated with susceptibility to lung cancer. However, the conclusion is still elusive. METHOD: This meta-analysis was performed to determine the relationship between XPC polymorphisms (Lys939Gln, Ala499Val, and PAT and lung cancer risk. Published literatures were identified by searching online databases and reference lists of relevant studies. Odds ratios (ORs and 95% confidence intervals (CIs were calculated to estimate the association strength. Publication bias were detected by Egger's and Begg's test. RESULT: After strict screening, we identified 14 eligible studies in this meta-analysis, including 5647 lung cancer cases and 6908 controls. By pooling all eligible studies, we found that the homozygote Gln939Gln genotype was associated with a significantly increased risk of lung cancer in Asian population (GlnGln vs LysLys, OR=1.229, 95% CI: 1.000-1.510; GlnGln vs LysLys/LysGln, OR=1.257, 95% CI: 1.038-1.522. As for the PAT polymorphism, in Caucasian population, we found carriers of the -/- genotype were associated significantly reduced risk of lung cancer in homozygote comparison model (-/- vs +/+, OR=0.735, 95% CI: 0.567-0.952. CONCLUSION: In this meta-analysis we found that Gln939Gln genotype was associated with significantly increased risk of lung cancer in Asian population; the PAT -/- genotype significantly reduced susceptibility to lung cancer in Caucasian population; while the XPC Ala499Val polymorphism was not associated with lung cancer risk.

  20. Vitamin D and depression: a systematic review and meta-analysis comparing studies with and without biological flaws.

    Science.gov (United States)

    Spedding, Simon

    2014-04-11

    Efficacy of Vitamin D supplements in depression is controversial, awaiting further literature analysis. Biological flaws in primary studies is a possible reason meta-analyses of Vitamin D have failed to demonstrate efficacy. This systematic review and meta-analysis of Vitamin D and depression compared studies with and without biological flaws. The systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The literature search was undertaken through four databases for randomized controlled trials (RCTs). Studies were critically appraised for methodological quality and biological flaws, in relation to the hypothesis and study design. Meta-analyses were performed for studies according to the presence of biological flaws. The 15 RCTs identified provide a more comprehensive evidence-base than previous systematic reviews; methodological quality of studies was generally good and methodology was diverse. A meta-analysis of all studies without flaws demonstrated a statistically significant improvement in depression with Vitamin D supplements (+0.78 CI +0.24, +1.27). Studies with biological flaws were mainly inconclusive, with the meta-analysis demonstrating a statistically significant worsening in depression by taking Vitamin D supplements (-1.1 CI -0.7, -1.5). Vitamin D supplementation (≥800 I.U. daily) was somewhat favorable in the management of depression in studies that demonstrate a change in vitamin levels, and the effect size was comparable to that of anti-depressant medication.

  1. Reference values for muscle strength: a systematic review with a descriptive meta-analysis.

    Science.gov (United States)

    Benfica, Poliana do Amaral; Aguiar, Larissa Tavares; Brito, Sherindan Ayessa Ferreira de; Bernardino, Luane Helena Nunes; Teixeira-Salmela, Luci Fuscaldi; Faria, Christina Danielli Coelho de Morais

    2018-05-03

    Muscle strength is an important component of health. To describe and evaluate the studies which have established the reference values for muscle strength on healthy individuals and to synthesize these values with a descriptive meta-analysis approach. A systematic review was performed in MEDLINE, LILACS, and SciELO databases. Studies that investigated the reference values for muscle strength of two or more appendicular/axial muscle groups of health individuals were included. Methodological quality, including risk of bias was assessed by the QUADAS-2. Data extracted included: country of the study, sample size, population characteristics, equipment/method used, and muscle groups evaluated. Of the 414 studies identified, 46 were included. Most of the studies had adequate methodological quality. Included studies evaluated: appendicular (80.4%) and axial (36.9%) muscles; adults (78.3%), elderly (58.7%), adolescents (43.5%), children (23.9%); isometric (91.3%) and isokinetic (17.4%) strength. Six studies (13%) with similar procedures were synthesized with meta-analysis. Generally, the coefficient of variation values that resulted from the meta-analysis ranged from 20.1% to 30% and were similar to those reported by the original studies. The meta-analysis synthesized the reference values of isometric strength of 14 muscle groups of the dominant/non-dominant sides of the upper/lower limbs of adults/elderly from developed countries, using dynamometers/myometer. Most of the included studies had adequate methodological quality. The meta-analysis provided reference values for the isometric strength of 14 appendicular muscle groups of the dominant/non-dominant sides, measured with dynamometers/myometers, of men/women, of adults/elderly. These data may be used to interpret the results of the evaluations and establish appropriate treatment goals. Copyright © 2018 Associação Brasileira de Pesquisa e Pós-Graduação em Fisioterapia. Publicado por Elsevier Editora Ltda. All rights

  2. Meta-analysis of genome-wide studies identifies WNT16 and ESR1 SNPs associated with bone mineral density in premenopausal women.

    Science.gov (United States)

    Koller, Daniel L; Zheng, Hou-Feng; Karasik, David; Yerges-Armstrong, Laura; Liu, Ching-Ti; McGuigan, Fiona; Kemp, John P; Giroux, Sylvie; Lai, Dongbing; Edenberg, Howard J; Peacock, Munro; Czerwinski, Stefan A; Choh, Audrey C; McMahon, George; St Pourcain, Beate; Timpson, Nicholas J; Lawlor, Debbie A; Evans, David M; Towne, Bradford; Blangero, John; Carless, Melanie A; Kammerer, Candace; Goltzman, David; Kovacs, Christopher S; Prior, Jerilynn C; Spector, Tim D; Rousseau, Francois; Tobias, Jon H; Akesson, Kristina; Econs, Michael J; Mitchell, Braxton D; Richards, J Brent; Kiel, Douglas P; Foroud, Tatiana

    2013-03-01

    Previous genome-wide association studies (GWAS) have identified common variants in genes associated with variation in bone mineral density (BMD), although most have been carried out in combined samples of older women and men. Meta-analyses of these results have identified numerous single-nucleotide polymorphisms (SNPs) of modest effect at genome-wide significance levels in genes involved in both bone formation and resorption, as well as other pathways. We performed a meta-analysis restricted to premenopausal white women from four cohorts (n = 4061 women, aged 20 to 45 years) to identify genes influencing peak bone mass at the lumbar spine and femoral neck. After imputation, age- and weight-adjusted bone-mineral density (BMD) values were tested for association with each SNP. Association of an SNP in the WNT16 gene (rs3801387; p = 1.7 × 10(-9) ) and multiple SNPs in the ESR1/C6orf97 region (rs4870044; p = 1.3 × 10(-8) ) achieved genome-wide significance levels for lumbar spine BMD. These SNPs, along with others demonstrating suggestive evidence of association, were then tested for association in seven replication cohorts that included premenopausal women of European, Hispanic-American, and African-American descent (combined n = 5597 for femoral neck; n = 4744 for lumbar spine). When the data from the discovery and replication cohorts were analyzed jointly, the evidence was more significant (WNT16 joint p = 1.3 × 10(-11) ; ESR1/C6orf97 joint p = 1.4 × 10(-10) ). Multiple independent association signals were observed with spine BMD at the ESR1 region after conditioning on the primary signal. Analyses of femoral neck BMD also supported association with SNPs in WNT16 and ESR1/C6orf97 (p women. These data support the hypothesis that variants in these genes of known skeletal function also affect BMD during the premenopausal period. Copyright © 2013 American Society for Bone and Mineral Research.

  3. A Meta-Analysis of Mathematics and Working Memory: Moderating Effects of Working Memory Domain, Type of Mathematics Skill, and Sample Characteristics

    Science.gov (United States)

    Peng, Peng; Namkung, Jessica; Barnes, Marcia; Sun, Congying

    2016-01-01

    The purpose of this meta-analysis was to determine the relation between mathematics and working memory (WM) and to identify possible moderators of this relation including domains of WM, types of mathematics skills, and sample type. A meta-analysis of 110 studies with 829 effect sizes found a significant medium correlation of mathematics and WM, r…

  4. A Meta-analysis on Resting State High-frequency Heart Rate Variability in Bulimia Nervosa.

    Science.gov (United States)

    Peschel, Stephanie K V; Feeling, Nicole R; Vögele, Claus; Kaess, Michael; Thayer, Julian F; Koenig, Julian

    2016-09-01

    Autonomic nervous system function is altered in eating disorders. We aimed to quantify differences in resting state vagal activity, indexed by high-frequency heart rate variability comparing patients with bulimia nervosa (BN) and healthy controls. A systematic search of the literature to identify studies eligible for inclusion and meta-analytical methods were applied. Meta-regression was used to identify potential covariates. Eight studies reporting measures of resting high-frequency heart rate variability in individuals with BN (n = 137) and controls (n = 190) were included. Random-effects meta-analysis revealed a sizeable main effect (Z = 2.22, p = .03; Hedge's g = 0.52, 95% CI [0.06;0.98]) indicating higher resting state vagal activity in individuals with BN. Meta-regression showed that body mass index and medication intake are significant covariates. Findings suggest higher vagal activity in BN at rest, particularly in unmedicated samples with lower body mass index. Potential mechanisms underlying these findings and implications for routine clinical care are discussed. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association.

  5. Multiplex flow cytometry barcoding and antibody arrays identify surface antigen profiles of primary and metastatic colon cancer cell lines.

    Directory of Open Access Journals (Sweden)

    Kumar Sukhdeo

    Full Text Available Colon cancer is a deadly disease affecting millions of people worldwide. Current treatment challenges include management of disease burden as well as improvements in detection and targeting of tumor cells. To identify disease state-specific surface antigen signatures, we combined fluorescent cell barcoding with high-throughput flow cytometric profiling of primary and metastatic colon cancer lines (SW480, SW620, and HCT116. Our multiplexed technique offers improvements over conventional methods by permitting the simultaneous and rapid screening of cancer cells with reduced effort and cost. The method uses a protein-level analysis with commercially available antibodies on live cells with intact epitopes to detect potential tumor-specific targets that can be further investigated for their clinical utility. Multiplexed antibody arrays can easily be applied to other tumor types or pathologies for discovery-based approaches to target identification.

  6. Statin treatment and functional outcome after ischemic stroke: case-control and meta-analysis.

    Science.gov (United States)

    Biffi, Alessandro; Devan, William J; Anderson, Christopher D; Cortellini, Lynelle; Furie, Karen L; Rosand, Jonathan; Rost, Natalia S

    2011-05-01

    Multiple studies suggest that statin use before acute ischemic stroke is associated with improved functional outcome. However, available evidence is conflicting, and several published reports are limited by small sample sizes. We therefore investigated the effect of antecedent use of statins on stroke outcome by performing a meta-analysis of all results from published studies as well as our own unpublished data. We performed a systematic literature search and meta-analysis of studies investigating the association between prestroke statin use and clinical outcome and included additional data from 126 prestroke statin users and 767 nonusers enrolled at our institution. A total of 12 studies, comprising 2013 statin users and 9682 nonusers, was meta-analyzed using a random effects model. We also meta-analyzed results for individual Trial of ORG 10172 in Acute Stroke Treatment stroke subtypes to determine whether the effect of statin use differed across subtypes using the Breslow-Day test. Meta-analysis of all available data identified an association between prestroke statin use and improved functional outcome (OR, 1.62; 95% CI, 1.39 to 1.88), but we uncovered evidence of publication bias. The effect of statin use on functional outcome was found to be larger for small vessel strokes compared with other subtypes (Breslow-Day P=0.008). Antecedent use of statins is associated with improved outcome in patients with acute ischemic stroke. This association appears to be stronger in patients with small vessel stroke subtype. However, evidence of publication bias in the existing literature suggests these findings should be interpreted with caution.

  7. Pesticide exposure and risk of Alzheimer’s disease: a systematic review and meta-analysis

    Science.gov (United States)

    Yan, Dandan; Zhang, Yunjian; Liu, Liegang; Yan, Hong

    2016-09-01

    Evidence suggests that lifelong cumulative exposure to pesticides may generate lasting toxic effects on the central nervous system and contribute to the development of Alzheimer’s disease (AD). A number of reports indicate a potential association between long-term/low-dose pesticide exposure and AD, but the results are inconsistent. Therefore, we conducted a meta-analysis to clarify this association. Relevant studies were identified according to inclusion criteria. Summary odds ratios (ORs) were calculated using fixed-effects models. A total of seven studies were included in our meta-analysis. A positive association was observed between pesticide exposure and AD (OR = 1.34 95% confidence interval [CI] = 1.08, 1.67; n = 7). The summary ORs with 95% CIs from the crude and adjusted effect size studies were 1.14 (95% CI = 0.94, 1.38; n = 7) and 1.37 (95% CI = 1.09, 1.71; n = 5), respectively. The sensitivity analyses of the present meta-analysis did not substantially modify the association between pesticide exposure and AD. Subgroup analyses revealed that high-quality studies tended to show significant relationships. The present meta-analysis suggested a positive association between pesticide exposure and AD, confirming the hypothesis that pesticide exposure is a risk factor for AD. Further high-quality cohort and case-control studies are required to validate a causal relationship.

  8. Discrimination against Latina/os: A Meta-Analysis of Individual-Level Resources and Outcomes

    Science.gov (United States)

    Lee, Debbiesiu L.; Ahn, Soyeon

    2012-01-01

    This meta-analysis synthesizes the findings of 60 independent samples from 51 studies examining racial/ethnic discrimination against Latina/os in the United States. The purpose was to identify individual-level resources and outcomes that most strongly relate to discrimination. Discrimination against Latina/os significantly results in outcomes…

  9. Follicular flushing during oocyte retrieval: a systematic review and meta-analysis.

    Science.gov (United States)

    Roque, Matheus; Sampaio, Marcos; Geber, Selmo

    2012-11-01

    The purpose of this systematic review and meta-analysis was to examine the literature and identify randomized controlled trials (RCTs), in order to answer if performing follicular flushing during the oocyte retrieval may improve the assisted reproductive technologies (ART) outcomes. An exhaustive electronic search was performed using MEDLINE and EMBASE databases. Only RCTs comparing follicular flushing to aspiration only during ART, were included. We included 5 trials, with a total of 482 patients randomized, with median ages ranging from 30.5 to 37.1. The data analyses did not show significant differences regarding live birth rate, clinical pregnancies rates, and the number of oocytes retrieved. The duration of oocyte retrieval was significantly increased in the follicular flushing group. The results from this systematic review and meta-analysis suggest that there is no advantage to use of routine follicular flushing during OR in an unselected group of patients.

  10. Meta-analysis on the efficacy of foot-and-mouth disease emergency vaccination

    DEFF Research Database (Denmark)

    Hisham Beshara Halasa, Tariq; Boklund, Anette; Cox, S.

    2012-01-01

    The objectives of this study were to provide a summary quantification of the efficacy of FMD emergency vaccination based on a systematic review and a meta-analysis of available literature, and to further discuss the suitability of this review and meta-analysis to summarize and further interpret...... of clinical signs including FMD lesions and fever, while the virological protection parameter was estimated based on the outcome of laboratory tests that were used to diagnose FMD infection. A meta-analysis relative risk was calculated per protection parameter. Results of the meta-analyses were examined using...... vaccine. Fortunately, no significant bias that would alter the conclusions was encountered in the analysis. Meta-analysis showed to be a useful tool to summarize literature results from a systematic review of the efficacy of foot and mouth disease emergency vaccination....

  11. Risk factors for new onset diabetes mellitus after liver transplantation: A meta-analysis.

    Science.gov (United States)

    Li, Da-Wei; Lu, Tian-Fei; Hua, Xiang-Wei; Dai, Hui-Juan; Cui, Xiao-Lan; Zhang, Jian-Jian; Xia, Qiang

    2015-05-28

    To determine the risk factors for new-onset diabetes mellitus (NODM) after liver transplantation by conducting a systematic review and meta-analysis. We electronically searched the databases of MEDLINE, EMBASE and the Cochrane Library from January 1980 to December 2013 to identify relevant studies reporting risk factors for NODM after liver transplantation. Two authors independently assessed the trials for inclusion and extracted the data. Discrepancies were resolved in consultation with a third reviewer. All statistical analyses were performed with the RevMan5.0 software (The Cochrane Collaboration, Oxford, United Kingdom). Pooled odds ratios (OR) or weighted mean differences (WMD) with 95% confidence intervals (CIs) were calculated using either a fixed effects or a random effects model, based on the presence (I (2) 50%) of significant heterogeneity. Twenty studies with 4580 patients were included in the meta-analysis, all of which were retrospective. The meta-analysis identified the following significant risk factors: hepatitis C virus (HCV) infection (OR = 2.68; 95%CI: 1.92-3.72); a family history of diabetes (OR = 1.69, 95%CI: 1.09-2.63, P diabetes (OR = 1.69; 95%CI: 1.09-2.63; P = 0.02); use of tacrolimus (OR = 1.34; 95%CI: 1.03-1.76; P = 0.03) and body mass index (BMI)(WMD = 1.19, 95%CI: 0.69-1.68, P diabetes, male gender, tacrolimus and BMI are risk factors for NODM after liver transplantation.

  12. Optimal patient education for cancer pain: a systematic review and theory-based meta-analysis.

    Science.gov (United States)

    Marie, N; Luckett, T; Davidson, P M; Lovell, M; Lal, S

    2013-12-01

    Previous systematic reviews have found patient education to be moderately efficacious in decreasing the intensity of cancer pain, but variation in results warrants analysis aimed at identifying which strategies are optimal. A systematic review and meta-analysis was undertaken using a theory-based approach to classifying and comparing educational interventions for cancer pain. The reference lists of previous reviews and MEDLINE, PsycINFO, and CENTRAL were searched in May 2012. Studies had to be published in a peer-reviewed English language journal and compare the effect on cancer pain intensity of education with usual care. Meta-analyses used standardized effect sizes (ES) and a random effects model. Subgroup analyses compared intervention components categorized using the Michie et al. (Implement Sci 6:42, 2011) capability, opportunity, and motivation behavior (COM-B) model. Fifteen randomized controlled trials met the criteria. As expected, meta-analysis identified a small-moderate ES favoring education versus usual care (ES, 0.27 [-0.47, -0.07]; P = 0.007) with substantial heterogeneity (I² = 71 %). Subgroup analyses based on the taxonomy found that interventions using "enablement" were efficacious (ES, 0.35 [-0.63, -0.08]; P = 0.01), whereas those lacking this component were not (ES, 0.18 [-0.46, 0.10]; P = 0.20). However, the subgroup effect was nonsignificant (P = 0.39), and heterogeneity was not reduced. Factoring in the variable of individualized versus non-individualized influenced neither efficacy nor heterogeneity. The current meta-analysis follows a trend in using theory to understand the mechanisms of complex interventions. We suggest that future efforts focus on interventions that target patient self-efficacy. Authors are encouraged to report comprehensive details of interventions and methods to inform synthesis, replication, and refinement.

  13. A Meta-Analysis on Prehypertension and Chronic Kidney Disease.

    Directory of Open Access Journals (Sweden)

    Yang Li

    Full Text Available Recent studies have demonstrated that there is an association between prehypertension and an increased risk of end-stage renal disease. However, there is conflicting evidence regarding the relationship between prehypertension and chronic kidney disease (CKD. This meta-analysis aimed to demonstrate the association between prehypertension and the incidence of CKD and identify the impacts of gender and ethnic differences.MEDLINE, EMBASE, Cochrane Library (from inception through March 2016 and article reference lists were searched for relevant studies regarding blood pressure and CKD. Blood pressure (BP measurements were classified as follows: optimal BP (less than 120/80 mmHg, prehypertension (120-139/80-89 mmHg and hypertension (over 140/90 mmHg. CKD was defined by estimated glomerular filtration rate (eGFR<60 ml/min/1.73 m2 or proteinuria. Two investigators independently extracted the data and assessed the quality of studies enrolled in this meta-analysis using the Newcastle-Ottawa Scale (NOS. We performed the meta-analysis using Stata/SE 12.0 (StataCorp LP. The random-effect models were used in the heterogeneous analyses.After retrieving data from 4,537 potentially relevant articles, we identified 7 cohort studies including 261,264 subjects, according to the predefined selection criteria. Five studies were conducted in Mongolians from East Asia, and the other two studies were performed in Indo-Europeans from Austria and Iran. The participants ranged in age from 20 to 89 years, and the proportion of females ranged from 27.2% to 63.8%. The follow-up period ranged from 2 to 11 years. Compared with the optimal BP values, prehypertension showed an increased risk of CKD (pooled RR = 1.28; 95% CI = 1.13-1.44; P = 0.000; I2 = 77.9%. In the sex-stratified analysis, we found a similar trend in women (pooled RR = 1.29; 95% CI = 1.01-1.63; P = 0.039; I2 = 76.1% but not in men. This effect was observed only in Mongolians from East Asia (pooled RR = 1.37; 95

  14. ABERRANT RESTING-STATE BRAIN ACTIVITY IN POSTTRAUMATIC STRESS DISORDER: A META-ANALYSIS AND SYSTEMATIC REVIEW.

    Science.gov (United States)

    Koch, Saskia B J; van Zuiden, Mirjam; Nawijn, Laura; Frijling, Jessie L; Veltman, Dick J; Olff, Miranda

    2016-07-01

    About 10% of trauma-exposed individuals develop PTSD. Although a growing number of studies have investigated resting-state abnormalities in PTSD, inconsistent results suggest a need for a meta-analysis and a systematic review. We conducted a systematic literature search in four online databases using keywords for PTSD, functional neuroimaging, and resting-state. In total, 23 studies matched our eligibility criteria. For the meta-analysis, we included 14 whole-brain resting-state studies, reporting data on 663 participants (298 PTSD patients and 365 controls). We used the activation likelihood estimation approach to identify concurrence of whole-brain hypo- and hyperactivations in PTSD patients during rest. Seed-based studies could not be included in the quantitative meta-analysis. Therefore, a separate qualitative systematic review was conducted on nine seed-based functional connectivity studies. The meta-analysis showed consistent hyperactivity in the ventral anterior cingulate cortex and the parahippocampus/amygdala, but hypoactivity in the (posterior) insula, cerebellar pyramis and middle frontal gyrus in PTSD patients, compared to healthy controls. Partly concordant with these findings, the systematic review on seed-based functional connectivity studies showed enhanced salience network (SN) connectivity, but decreased default mode network (DMN) connectivity in PTSD. Combined, these altered resting-state connectivity and activity patterns could represent neurobiological correlates of increased salience processing and hypervigilance (SN), at the cost of awareness of internal thoughts and autobiographical memory (DMN) in PTSD. However, several discrepancies between findings of the meta-analysis and systematic review were observed, stressing the need for future studies on resting-state abnormalities in PTSD patients. © 2016 Wiley Periodicals, Inc.

  15. Systematic Review and Meta-Analysis of Tacrolimus versus Ciclosporin as Primary Immunosuppression After Liver Transplant.

    Directory of Open Access Journals (Sweden)

    Gorden Muduma

    Full Text Available Several meta-analyses comparing ciclosporin with tacrolimus have been conducted since the 1994 publication of the tacrolimus registration trials, but most captured data from randomized controlled trials (RCTs predating recent improvements in waiting list prioritization, induction protocols and concomitant medications. The present study comprised a systematic review and meta-analysis of ciclosporin and tacrolimus in liver transplant recipients using studies published since January 2000.Searches of PubMed, the Cochrane Library and EMBASE identified RCTs of tacrolimus and ciclosporin as the immunosuppressant in adult primary liver transplant recipients, published between January 2000 and August 6, 2014. A random effects meta-analysis was conducted to evaluate the relative risk of death, graft loss, acute rejection (AR, new-onset diabetes after transplantation (NODAT and hypertension with tacrolimus relative to ciclosporin at 12 months.The literature search identified 11 RCTs comparing ciclosporin with tacrolimus. Relative to ciclosporin, tacrolimus was associated with significantly improved outcomes in terms of patient mortality (risk ratio [RR] with ciclosporin of 1.26; 95% confidence interval [95%CI] 1.01-1.58. Tacrolimus was superior to ciclosporin in terms of hypertension (RR with ciclosporin 1.26; 95%CI 1.07-1.47, but inferior in terms of NODAT (RR with ciclosporin 0.60; 95%CI 0.47-0.77. There were no significant differences between ciclosporin and tacrolimus in terms of graft loss or AR.Meta-analysis of RCTs published since 2000 showed tacrolimus to be superior to ciclosporin in terms of patient mortality and hypertension, while ciclosporin was superior in terms of NODAT. No significant differences were identified in terms of graft loss or AR. These findings provide further evidence supporting the use of tacrolimus as the cornerstone of immunosuppressive therapy in liver transplant recipients.

  16. Psychotherapy for chronic major depression and dysthymia: A meta analysis.

    NARCIS (Netherlands)

    Cuijpers, P.; Straten, van A.; Schuurmans, J.; Oppen, van P.C.; Hollon, S.D.; Andersson, G.

    2009-01-01

    Abstract Although several studies have examined the effects of psychotherapy on chronic depression and dysthymia, no meta-analysis has been conducted to integrate results of these studies. We conducted a meta-analysis of 16 randomized trials examining the effects of psychotherapy on chronic

  17. Patient characteristics and stratification in medical treatment studies for metastatic colorectal cancer: a proposal for standardization of patient characteristic reporting and stratification.

    Science.gov (United States)

    Sorbye, H; Köhne, C-H; Sargent, D J; Glimelius, B

    2007-10-01

    Prognostic factors have the potential to determine the survival of patients to a greater extent than current antineoplastic agents. Despite this knowledge, there is no consensus on, first, what patient characteristics to report and, second, what stratification factors to use in metastatic colorectal cancer trials. Seven leading oncology and medical journals were reviewed for phase II and III publications reporting on medical treatment of metastatic colorectal cancer patients during 2001-2005. One hundred and forty-three studies with 21 214 patients were identified. The reporting of patient characteristics and use of stratification was noted. Age, gender, performance status, metastases location, sites and adjuvant chemotherapy were often reported (99-63%). Laboratory values as alkaline phosphatase, lactate dehydrogenase and white blood cell count, repeatedly found to be of prognostic relevance, were rarely reported (5-9%). Stratification was used in all phase III trials; however, only study centre was used with any consistency. There is considerable inconsistency in the reporting of patient characteristics and use of stratification factors in metastatic colorectal cancer trials. We propose a standardization of patient characteristics reporting and stratification factors. A common set of characteristics and strata will aid in trial reporting, interpretation and future meta-analyses.

  18. Periodontal disease and risk of chronic obstructive pulmonary disease: a meta-analysis of observational studies.

    Directory of Open Access Journals (Sweden)

    Xian-Tao Zeng

    Full Text Available BACKGROUND: Many epidemiological studies have found a positive association between periodontal disease (PD and risk of chronic obstructive pulmonary disease (COPD, but this association is varied and even contradictory among studies. We performed a meta-analysis to ascertain the relationship between PD and COPD. METHODS: PubMed and Embase database were searched up to January 10, 2012, for relevant observational studies on the association between PD and risk of COPD. Data from the studies selected were extracted and analyzed independently by two authors. The meta-analysis was performed using the Comprehensive Meta-Analysis software. RESULTS: Fourteen observational studies (one nested case-control, eight case-control, and five cross-sectional involving 3,988 COPD patients were yielded. Based on random-effects meta-analysis, a significant association between PD and COPD was identified (odds ratio = 2.08, 95% confidence interval = 1.48-2.91; P<0.001, with sensitivity analysis showing that the result was robust. Subgroups analyses according to study design, ethnicity, assessment of PD/COPD, and adjusted/unadjusted odds ratios also revealed a significant association. Publication bias was detected. CONCLUSIONS: Based on current evidence, PD is a significant and independent risk factor of COPD. However, whether a causal relationships exists remains unclear. Morever, we suggest performing randomized controlled trails to explore whether periodontal interventions are beneficial in regulating COPD pathogenesis and progression.

  19. Meta-Analysis for Sociology – A Measure-Driven Approach

    Science.gov (United States)

    Roelfs, David J.; Shor, Eran; Falzon, Louise; Davidson, Karina W.; Schwartz, Joseph E.

    2013-01-01

    Meta-analytic methods are becoming increasingly important in sociological research. In this article we present an approach for meta-analysis which is especially helpful for sociologists. Conventional approaches to meta-analysis often prioritize “concept-driven” literature searches. However, in disciplines with high theoretical diversity, such as sociology, this search approach might constrain the researcher’s ability to fully exploit the entire body of relevant work. We explicate a “measure-driven” approach, in which iterative searches and new computerized search techniques are used to increase the range of publications found (and thus the range of possible analyses) and to traverse time and disciplinary boundaries. We demonstrate this measure-driven search approach with two meta-analytic projects, examining the effects of various social variables on all-cause mortality. PMID:24163498

  20. Identification of conserved drought-adaptive genes using a cross-species meta-analysis approach.

    Science.gov (United States)

    Shaar-Moshe, Lidor; Hübner, Sariel; Peleg, Zvi

    2015-05-03

    Drought is the major environmental stress threatening crop-plant productivity worldwide. Identification of new genes and metabolic pathways involved in plant adaptation to progressive drought stress at the reproductive stage is of great interest for agricultural research. We developed a novel Cross-Species meta-Analysis of progressive Drought stress at the reproductive stage (CSA:Drought) to identify key drought adaptive genes and mechanisms and to test their evolutionary conservation. Empirically defined filtering criteria were used to facilitate a robust integration of 17 deposited microarray experiments (148 arrays) of Arabidopsis, rice, wheat and barley. By prioritizing consistency over intensity, our approach was able to identify 225 differentially expressed genes shared across studies and taxa. Gene ontology enrichment and pathway analyses classified the shared genes into functional categories involved predominantly in metabolic processes (e.g. amino acid and carbohydrate metabolism), regulatory function (e.g. protein degradation and transcription) and response to stimulus. We further investigated drought related cis-acting elements in the shared gene promoters, and the evolutionary conservation of shared genes. The universal nature of the identified drought-adaptive genes was further validated in a fifth species, Brachypodium distachyon that was not included in the meta-analysis. qPCR analysis of 27, randomly selected, shared orthologs showed similar expression pattern as was found by the CSA:Drought.In accordance, morpho-physiological characterization of progressive drought stress, in B. distachyon, highlighted the key role of osmotic adjustment as evolutionary conserved drought-adaptive mechanism. Our CSA:Drought strategy highlights major drought-adaptive genes and metabolic pathways that were only partially, if at all, reported in the original studies included in the meta-analysis. These genes include a group of unclassified genes that could be involved

  1. Conventional vs. e-learning in nursing education: A systematic review and meta-analysis.

    Science.gov (United States)

    Voutilainen, Ari; Saaranen, Terhi; Sormunen, Marjorita

    2017-03-01

    By and large, in health professions training, the direction of the effect of e-learning, positive or negative, strongly depends on the learning outcome in question as well as on learning methods which e-learning is compared to. In nursing education, meta-analytically generated knowledge regarding the comparisons between conventional and e-learning is scarce. The aim of this review is to discover the size of the effect of e-learning on learning outcomes in nursing education and to assess the quality of studies in which e-learning has been compared to conventional learning. A systematic search of six electronic databases, PubMed, Ovid MEDLINE®, CINAHL (EBSCOhost), Cochrane Library, PsycINFO, and ERIC, was conducted in order to identify relevant peer-reviewed English language articles published between 2011 and 2015. The quality of the studies included as well as the risk of bias in each study was assessed. A random-effects meta-analysis was performed to generate a pooled mean difference in the learning outcome. Altogether, 10 studies were eligible for the quality assessment and meta-analysis. Nine studies were evaluated as good quality studies, but not without a risk of bias. Performance bias caused a high risk in nearly all the studies. In the meta-analysis, an e-learning method resulted in test scores that were, on average, five points higher than a conventional method on a 0-100 scale. Heterogeneity between the studies was very large. The size and direction of the effect of a learning method on learning outcomes appeared to be strongly situational. We suggest that meta-regressions should be performed instead of basic meta-analyses in order to reveal factors that cause variation in the learning outcomes of nursing education. It might be necessary to perform separate meta-analyses between e-learning interventions aimed at improving nursing knowledge and those aimed at improving nursing skills. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Clinical efficacy of including capecitabine in neoadjuvant chemotherapy for breast cancer: a systematic review and meta-analysis of randomized controlled trials.

    Directory of Open Access Journals (Sweden)

    Qiuyun Li

    Full Text Available BACKGROUND: Capecitabine has proven effective as a chemotherapy for metastatic breast cancer. Though several Phase II/III studies of capecitabine as neoadjuvant chemotherapy have been conducted, the results still remain inconsistent. Therefore, we performed a meta-analysis to obtain more precise understanding of the role of capecitabine in neoadjuvant chemotherapy for breast cancer patients. METHODS: The electronic database PubMed and online abstracts from ASCO and SABCS were searched to identify randomized clinical trials comparing neoadjuvant chemotherapy with or without capecitabine in early/operable breast cancer patients without distant metastasis. Risk ratios were used to estimate the association between capecitabine in neoadjuvant chemotherapy and various efficacy outcomes. Fixed- or random-effect models were adopted to pool data in RevMan 5.1. RESULTS: Five studies were included in the meta-analysis. Neoadjuvant use of capecitabine with anthracycline and/or taxane based therapy was not associated with significant improvement in clinical outcomes including: pathologic complete response in breast (pCR; RR = 1.10, 95% CI 0.87-1.40, p = 0.43, pCR in breast tumor and nodes (tnpCR RR = 0.99, 95% CI 0.83-1.18, p = 0.90, overall response rate (ORR; RR = 1.00, 95% CI 0.94-1.07, p = 0.93, or breast-conserving surgery (BCS; RR = 0.98, 95% CI 0.93-1.04, p = 0.49. CONCLUSIONS: Neoadjuvant treatment of breast cancer involving capecitabine did not significantly improve pCR, tnpCR, BCS or ORR. Thus adding capecitabine to neoadjuvant chemotherapy regimes is unlikely to improve outcomes in breast cancer patients without distant metastasis. Further research is required to establish the condition that capecitabine may be useful in breast cancer neoadjuvant chemotherapy.

  3. Gastrointestinal adverse effects of cyclin-dependent kinase 4 and 6 inhibitors in breast cancer patients: a systematic review and meta-analysis.

    Science.gov (United States)

    Shohdy, Kyrillus S; Lasheen, Shaimaa; Kassem, Loay; Abdel-Rahman, Omar

    2017-11-01

    Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors show promising results in metastatic breast cancer. However, an increased incidence of adverse events is remarkable. Among others, gastrointestinal (GI) involvement is of momentous impact on patients and their quality of life. Our search included PubMed, ASCO, ESMO and SABCS databases. Randomized phase II/III trials in metastatic breast cancer receiving CDK4/6 inhibitors were identified and considered relevant based on providing a sufficient safety profile on the incidence of adverse GI effects. Of the 999 records initially screened for relevance, 33 articles were found relevant and 4 studies were finally eligible for meta-analysis with a total of 2007 patients. The relative risk (RR) for all-grade nausea was 1.48 [95% confidence interval (CI): 1.12-1.93, p = 0.005], vomiting was 1.74 (95% CI: 1.09-2.76, p = 0.02), decreased appetite was 1.42 (95% CI: 1.07-1.88, p = 0.02), and for diarrhea it was 1.44 (95% CI: 1.19-1.74, p = 0.0002). Meanwhile, the RR for high-grade nausea was 1.10 (95% CI: 0.29-4.13, p = 0.89), vomiting was 1.38 (95% CI: 0.25-7.75, p = 0.72), decreased appetite was 4.00 (95% CI: 0.87-18.37, p = 0.07), and high-grade diarrhea was 1.19 (95% CI: 0.44-3.21, p = 0.73). Selective CDK4/6 inhibitors were not associated with higher-grade GI toxicities reflecting a well-tolerated safety profile. Regarding the increase in all-grade GI toxicities, it needs further caution with addition of cytotoxic chemotherapy.

  4. Genome-wide linkage meta-analysis identifies susceptibility loci at 2q34 and 13q31.3 for genetic generalized epilepsies

    DEFF Research Database (Denmark)

    Leu, Costin; de Kovel, Carolien G F; Zara, Federico

    2012-01-01

    Purpose: Genetic generalized epilepsies (GGEs) have a lifetime prevalence of 0.3% with heritability estimates of 80%. A considerable proportion of families with siblings affected by GGEs presumably display an oligogenic inheritance. The present genome-wide linkage meta-analysis aimed to map: (1) ...

  5. Meta-Analysis of Biofeedback for Tension-Type Headache: Efficacy, Specificity, and Treatment Moderators

    Science.gov (United States)

    Nestoriuc, Yvonne; Rief, Winfried; Martin, Alexandra

    2008-01-01

    The aims of the present meta-analysis were to investigate the short- and long-term efficacy, multidimensional outcome, and treatment moderators of biofeedback as a behavioral treatment option for tension-type headache. A literature search identified 74 outcome studies, of which 53 were selected according to predefined inclusion criteria.…

  6. Meta-Analysis: Risk of Tics Associated With Psychostimulant Use in Randomized, Placebo-Controlled Trials.

    Science.gov (United States)

    Cohen, Stephanie C; Mulqueen, Jilian M; Ferracioli-Oda, Eduardo; Stuckelman, Zachary D; Coughlin, Catherine G; Leckman, James F; Bloch, Michael H

    2015-09-01

    Clinical practice currently restricts the use of psychostimulant medications in children with tics or a family history of tics for fear that tics will develop or worsen as a side effect of treatment. Our goal was to conduct a meta-analysis to examine the risk of new onset or worsening of tics as an adverse event of psychostimulants in randomized, placebo-controlled trials. We conducted a PubMed search to identify all double-blind, randomized, placebo-controlled trials examining the efficacy of psychostimulant medications in the treatment of children with attention-deficit/hyperactivity disorder (ADHD). We used a fixed effects meta-analysis with risk ratio of new onset or worsening tics in children treated with psychostimulants compared to placebo. We used stratified subgroup analysis and meta-regression to examine the effects of stimulant type, dose, duration of treatment, recorder of side effect data, trial design, and mean age of participants on the measured risk of tics. We identified 22 studies involving 2,385 children with ADHD for inclusion in our meta-analysis. New onset tics or worsening of tic symptoms were commonly reported in the psychostimulant (event rate = 5.7%, 95% CI = 3.7%-8.6%) and placebo groups (event rate = 6.5%, 95% CI = 4.4%-9.5%). The risk of new onset or worsening of tics associated with psychostimulant treatment was similar to that observed with placebo (risk ratio = 0.99, 95% CI = 0.78-1.27, z = -0.05, p = .962). Type of psychostimulant, dose, duration of treatment, recorder, and participant age did not affect risk of new onset or worsening of tics. Crossover studies were associated with a significantly greater measured risk of tics with psychostimulant use compared to parallel group trials. Meta-analysis of controlled trials does not support an association between new onset or worsening of tics and psychostimulant use. Clinicians may want to consider rechallenging children who report new onset or worsening of tics with psychostimulant

  7. Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia

    NARCIS (Netherlands)

    Berndt, Sonja I; Camp, Nicola J; Skibola, Christine F; Vijai, Joseph; Wang, Zhaoming; Gu, Jian; Nieters, Alexandra; Kelly, Rachel S; Smedby, Karin E; Monnereau, Alain; Cozen, Wendy; Cox, Angela; Wang, Sophia S; Lan, Qing; Teras, Lauren R; Machado, Moara; Yeager, Meredith; Brooks-Wilson, Angela R; Hartge, Patricia; Purdue, Mark P; Birmann, Brenda M; Vajdic, Claire M; Cocco, Pierluigi; Zhang, Yawei; Giles, Graham G; Zeleniuch-Jacquotte, Anne; Lawrence, Charles; Montalvan, Rebecca; Burdett, Laurie; Hutchinson, Amy; Ye, Yuanqing; Call, Timothy G; Shanafelt, Tait D; Novak, Anne J; Kay, Neil E; Liebow, Mark; Cunningham, Julie M; Allmer, Cristine; Hjalgrim, Henrik; Adami, Hans-Olov; Melbye, Mads; Glimelius, Bengt; Chang, Ellen T; Glenn, Martha; Curtin, Karen; Cannon-Albright, Lisa A; Diver, W Ryan; Link, Brian K; Weiner, George J; Conde, Lucia; Bracci, Paige M; Riby, Jacques; Arnett, Donna K; Zhi, Degui; Leach, Justin M; Holly, Elizabeth A; Jackson, Rebecca D; Tinker, Lesley F; Benavente, Yolanda; Sala, Núria; Casabonne, Delphine; Becker, Nikolaus; Boffetta, Paolo; Brennan, Paul; Foretova, Lenka; Maynadie, Marc; McKay, James; Staines, Anthony; Chaffee, Kari G; Achenbach, Sara J; Vachon, Celine M; Goldin, Lynn R; Strom, Sara S; Leis, Jose F; Weinberg, J Brice; Caporaso, Neil E; Norman, Aaron D; De Roos, Anneclaire J; Morton, Lindsay M; Severson, Richard K; Riboli, Elio; Vineis, Paolo; Kaaks, Rudolph; Masala, Giovanna; Weiderpass, Elisabete; Chirlaque, María-Dolores; Vermeulen, Roel C H|info:eu-repo/dai/nl/216532620; Travis, Ruth C; Southey, Melissa C; Milne, Roger L; Albanes, Demetrius; Virtamo, Jarmo; Weinstein, Stephanie; Clavel, Jacqueline; Zheng, Tongzhang; Holford, Theodore R; Villano, Danylo J; Maria, Ann; Spinelli, John J; Gascoyne, Randy D; Connors, Joseph M; Bertrand, Kimberly A; Giovannucci, Edward; Kraft, Peter; Kricker, Anne; Turner, Jenny; Ennas, Maria Grazia; Ferri, Giovanni M; Miligi, Lucia; Liang, Liming; Ma, Baoshan; Huang, Jinyan; Crouch, Simon; Park, Ju-Hyun; Chatterjee, Nilanjan; North, Kari E; Snowden, John A; Wright, Josh; Fraumeni, Joseph F; Offit, Kenneth; Wu, Xifeng; de Sanjose, Silvia; Cerhan, James R; Chanock, Stephen J; Rothman, Nathaniel; Slager, Susan L

    2016-01-01

    Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy with strong heritability. To further understand the genetic susceptibility for CLL and identify common loci associated with risk, we conducted a meta-analysis of four genome-wide association studies (GWAS) composed of 3,100 cases and

  8. Effective self-regulation change techniques to promote mental wellbeing among adolescents: a meta-analysis

    NARCIS (Netherlands)

    Genugten, L. van; Dusseldorp, E.; Massey, E.K.; Empelen, P. van

    2017-01-01

    Mental wellbeing is influenced by self-regulation processes. However, little is known on the efficacy of change techniques based on self-regulation to promote mental wellbeing. The aim of this meta-analysis is to identify effective self-regulation techniques (SRTs) in primary and secondary

  9. Risk of malignancy in ankylosing spondylitis: a systematic review and meta-analysis.

    Science.gov (United States)

    Deng, Chuiwen; Li, Wenli; Fei, Yunyun; Li, Yongzhe; Zhang, Fengchun

    2016-08-18

    Current knowledge about the overall and site-specific risk of malignancy associated with ankylosing spondylitis (AS) is inconsistent. We conducted a systematic review and meta-analysis to address this knowledge gap. Five databases (PubMed, EMBASE, Web of Science, the Cochrane library and the virtual health library) were systematically searched. A manual search of publications within the last 2 years in key journals in the field (Annals of the Rheumatic Diseases, Rheumatology and Arthritis &rheumatology) was also performed. STATA 11.2 software was used to conduct the meta-analysis. After screening, twenty-three studies, of different designs, were eligible for meta-analysis. AS is associated with a 14% (pooled RR 1.14; 95% CI 1.03-1.25) increase in the overall risk for malignancy. Compared to controls, patients with AS are at a specific increased risk for malignancy of the digestive system (pooled RR 1.20; 95% CI 1.01 to 1.42), multiple myelomas (pooled RR 1.92; 95% CI 1.37 to 3.69) and lymphomas (pooled RR 1.32; 95% CI 1.11 to 1.57). On subgroup analysis, evidence from high quality cohort studies indicated that AS patients from Asia are at highest risk for malignancy overall. Confirmation of findings from large-scale longitudinal studies is needed to identify specific risk factors and to evaluate treatment effects.

  10. Meta-analysis: Serum creatinine changes following contrast enhanced CT imaging

    International Nuclear Information System (INIS)

    Kooiman, Judith; Pasha, Sharif M.; Zondag, Wendy; Sijpkens, Yvo W.J.; Molen, Aart J. van der; Huisman, Menno V.; Dekkers, Olaf M.

    2012-01-01

    Purpose: Contrast induced nephropathy (CIN) is defined as a decrease in renal function following administration of contrast media. The aim of this meta-analysis was to asses the overall risk of CIN, chronic loss of kidney function and the need for renal replacement therapy (RRT) after intravenous contrast enhanced CT-scan. Secondly, we aimed to identify subgroups at increased risk for CIN. Materials and methods: A literature search in Pubmed, Medline, Embase and Cochrane databases was performed. Data extraction was carried out independently by two reviewers. Meta-analysis and meta-regression were performed using an exact likelihood approach. Results: Forty studies evaluating the incidence of CIN after CT were included. The pooled incidence of CIN was 6.4% (95% CI 5.0–8.1). The risk of RRT after CIN was low, 0.06% (95% CI 0.01–0.4). The decline in renal function persisted in 1.1% of patients (95% CI 0.6–2.1%). Patients with chronic kidney disease (odds ratio 2.26, p < 0.001) or diabetes mellitus (odds ratio 3.10, p < 0.001) were at increased risk for the development of CIN. Conclusion: CIN occurred in 6% of patients after contrast enhanced CT. In 1% of all patients undergoing contrast enhanced CT the decline in renal function persisted

  11. Meta-analysis: Serum creatinine changes following contrast enhanced CT imaging

    Energy Technology Data Exchange (ETDEWEB)

    Kooiman, Judith, E-mail: j.kooiman@lumc.nl [Department of Thrombosis and Haemostasis, LUMC, Leiden (Netherlands); Pasha, Sharif M., E-mail: s.m.pasha@lumc.nl [Department of Thrombosis and Haemostasis, LUMC, Leiden (Netherlands); Zondag, Wendy, E-mail: w.zondag@lumc.nl [Department of Thrombosis and Haemostasis, LUMC, Leiden (Netherlands); Sijpkens, Yvo W.J., E-mail: ysijpens@bronovo.nl [Department of Nephrology, Bronovo Hospital, The Hague (Netherlands); Molen, Aart J. van der, E-mail: molen@lumc.nl [Department of Radiology, LUMC, Leiden (Netherlands); Huisman, Menno V., E-mail: m.v.huisman@lumc.nl [Department of Thrombosis and Haemostasis, LUMC, Leiden (Netherlands); Dekkers, Olaf M., E-mail: o.m.dekkers@lumc.nl [Department of Clinical Epidemiology and Department of Endocrinology, LUMC, Leiden (Netherlands)

    2012-10-15

    Purpose: Contrast induced nephropathy (CIN) is defined as a decrease in renal function following administration of contrast media. The aim of this meta-analysis was to asses the overall risk of CIN, chronic loss of kidney function and the need for renal replacement therapy (RRT) after intravenous contrast enhanced CT-scan. Secondly, we aimed to identify subgroups at increased risk for CIN. Materials and methods: A literature search in Pubmed, Medline, Embase and Cochrane databases was performed. Data extraction was carried out independently by two reviewers. Meta-analysis and meta-regression were performed using an exact likelihood approach. Results: Forty studies evaluating the incidence of CIN after CT were included. The pooled incidence of CIN was 6.4% (95% CI 5.0–8.1). The risk of RRT after CIN was low, 0.06% (95% CI 0.01–0.4). The decline in renal function persisted in 1.1% of patients (95% CI 0.6–2.1%). Patients with chronic kidney disease (odds ratio 2.26, p < 0.001) or diabetes mellitus (odds ratio 3.10, p < 0.001) were at increased risk for the development of CIN. Conclusion: CIN occurred in 6% of patients after contrast enhanced CT. In 1% of all patients undergoing contrast enhanced CT the decline in renal function persisted.

  12. Z-drug for schizophrenia: A systematic review and meta-analysis.

    Science.gov (United States)

    Kishi, Taro; Inada, Ken; Matsui, Yuki; Iwata, Nakao

    2017-10-01

    No systematic reviews and meta-analyses on the use of Z-drug for schizophrenia are available. Randomized, placebo-controlled, or non-pharmacological intervention-controlled trials published before 03/20/2017 were retrieved from major healthcare databases and clinical trial registries. A meta-analysis including only randomized, placebo-controlled trials was performed. Efficacy outcomes were measured as improvement in overall schizophrenia symptoms, total sleep time, and wake after sleep onset. Safety/acceptability outcomes were discontinuation rate and individual adverse events. Four trials [1 alpidem placebo-controlled study (n=66), 2 eszopiclone placebo-controlled studies (n=60), and 1 eszopiclone, shallow needling-controlled study (n=96)] were identified. The meta-analysis showed no significant differences in any outcome between pooled Z-drug and placebo treatment groups. For individual studies, alpidem was superior to placebo in improving the overall schizophrenia symptoms. One of the eszopiclone studies showed that eszopiclone was superior to placebo in improving the Insomnia Severity Index scores. Another eszopiclone study showed that eszopiclone did not differ from shallow needling therapy in improving both schizophrenia- and insomnia-related symptoms. Although this study failed to show significant benefits for the use of Z-drug in the treatment of schizophrenia, it showed that short-term use of eszopiclone is an acceptable method for treating persistent insomnia among these patients. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Scientists Admitting to Plagiarism: A Meta-analysis of Surveys.

    Science.gov (United States)

    Pupovac, Vanja; Fanelli, Daniele

    2015-10-01

    We conducted a systematic review and meta-analysis of anonymous surveys asking scientists whether they ever committed various forms of plagiarism. From May to December 2011 we searched 35 bibliographic databases, five grey literature databases and hand searched nine journals for potentially relevant studies. We included surveys that asked scientists if, in a given recall period, they had committed or knew of a colleague who committed plagiarism, and from each survey extracted the proportion of those who reported at least one case. Studies that focused on academic (i.e. student) plagiarism were excluded. Literature searches returned 12,460 titles from which 17 relevant survey studies were identified. Meta-analysis of studies reporting committed (N = 7) and witnessed (N = 11) plagiarism yielded a pooled estimate of, respectively, 1.7% (95% CI 1.2-2.4) and 30% (95% CI 17-46). Basic methodological factors, including sample size, year of survey, delivery method and whether survey questions were explicit rather than indirect made a significant difference on survey results. Even after controlling for these methodological factors, between-study differences in admission rates were significantly above those expected by sampling error alone and remained largely unexplained. Despite several limitations of the data and of this meta-analysis, we draw three robust conclusions: (1) The rate at which scientists report knowing a colleague who committed plagiarism is higher than for data fabrication and falsification; (2) The rate at which scientists report knowing a colleague who committed plagiarism is correlated to that of fabrication and falsification; (3) The rate at which scientists admit having committed either form of misconduct (i.e. fabrication, falsification and plagiarism) in surveys has declined over time.

  14. Consumption of garlic and risk of colorectal cancer: an updated meta-analysis of prospective studies.

    Science.gov (United States)

    Hu, Ji-Yi; Hu, Yi-Wang; Zhou, Jiao-Jiao; Zhang, Meng-Wen; Li, Dan; Zheng, Shu

    2014-11-07

    To conduct an updated meta-analysis of prospective studies addressing the association between garlic consumption and colorectal cancer. Eligible cohort studies were identified by searching MEDLINE (PubMed) and screening the references of related articles published up to October 2013. Meta-analyses were conducted for colorectal cancer in relation to consumption of raw and cooked (RC) garlic and garlic supplements, separately. The summary relative risks (RR) with 95%CI were calculated using fixed-effects or random-effects model depending on the heterogeneity among studies. A total of 5 prospective cohort studies were identified. In contrast to the previous meta-analysis, no significant associations were found between consumption of RC garlic (RR: 1.06; 95%CI: 0.95-1.19) or garlic supplements (RR: 1.12; 95%CI: 0.96-1.31) and risk of colorectal cancer. A non-significant protective effect of garlic supplement intake against colorectal cancer was observed in females (RR: 0.84; 95%CI: 0.64-1.11), but the opposite was the case in males (RR: 1.24; 95%CI: 0.96-1.59). Consumption of RC garlic or garlic supplements is not significantly associated with reduced colorectal cancer risk.

  15. Simpson's paradox visualized: The example of the Rosiglitazone meta-analysis

    Directory of Open Access Journals (Sweden)

    Schumacher Martin

    2008-05-01

    Full Text Available Abstract Background Simpson's paradox is sometimes referred to in the areas of epidemiology and clinical research. It can also be found in meta-analysis of randomized clinical trials. However, though readers are able to recalculate examples from hypothetical as well as real data, they may have problems to easily figure where it emerges from. Method First, two kinds of plots are proposed to illustrate the phenomenon graphically, a scatter plot and a line graph. Subsequently, these can be overlaid, resulting in a overlay plot. The plots are applied to the recent large meta-analysis of adverse effects of rosiglitazone on myocardial infarction and to an example from the literature. A large set of meta-analyses is screened for further examples. Results As noted earlier by others, occurrence of Simpson's paradox in the meta-analytic setting, if present, is associated with imbalance of treatment arm size. This is well illustrated by the proposed plots. The rosiglitazone meta-analysis shows an effect reversion if all trials are pooled. In a sample of 157 meta-analyses, nine showed an effect reversion after pooling, though non-significant in all cases. Conclusion The plots give insight on how the imbalance of trial arm size works as a confounder, thus producing Simpson's paradox. Readers can see why meta-analytic methods must be used and what is wrong with simple pooling.

  16. Lysergic acid diethylamide (LSD) for alcoholism: meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Krebs, Teri S; Johansen, Pål-Ørjan

    2012-07-01

    Assessments of lysergic acid diethylamide (LSD) in the treatment of alcoholism have not been based on quantitative meta-analysis. Hence, we performed a meta-analysis of randomized controlled trials in order to evaluate the clinical efficacy of LSD in the treatment of alcoholism. Two reviewers independently extracted the data, pooling the effects using odds ratios (ORs) by a generic inverse variance, random effects model. We identified six eligible trials, including 536 participants. There was evidence for a beneficial effect of LSD on alcohol misuse (OR, 1.96; 95% CI, 1.36-2.84; p = 0.0003). Between-trial heterogeneity for the treatment effects was negligible (I² = 0%). Secondary outcomes, risk of bias and limitations are discussed. A single dose of LSD, in the context of various alcoholism treatment programs, is associated with a decrease in alcohol misuse.

  17. Psychotherapy for chronic major depression and dysthymia: A meta analysis

    NARCIS (Netherlands)

    Cuijpers, P.; van Straten, A.; Schuurmans, J.; van Oppen, P.C.; Hollon, S.D.; Andersson, G.

    2010-01-01

    Although several studies have examined the effects of psychotherapy on chronic depression and dysthymia, no meta-analysis has been conducted to integrate results of these studies. We conducted a meta-analysis of 16 randomized trials examining the effects of psychotherapy on chronic depression and

  18. Psychotherapy for chronic major depression and dysthymia: A meta analysis.

    NARCIS (Netherlands)

    Cuijpers, P.; van Straten, A.; Schuurmans, J.; van Oppen, P.C.; Hollon, S.D.; Andersson, G.

    2009-01-01

    Although several studies have examined the effects of psychotherapy on chronic depression and dysthymia, no meta-analysis has been conducted to integrate results of these studies. We conducted a meta-analysis of 16 randomized trials examining the effects of psychotherapy on chronic depression and

  19. Does chocolate reduce blood pressure? A meta-analysis.

    Science.gov (United States)

    Ried, Karin; Sullivan, Thomas; Fakler, Peter; Frank, Oliver R; Stocks, Nigel P

    2010-06-28

    Dark chocolate and flavanol-rich cocoa products have attracted interest as an alternative treatment option for hypertension, a known risk factor for cardiovascular disease. Previous meta-analyses concluded that cocoa-rich foods may reduce blood pressure. Recently, several additional trials have been conducted with conflicting results. Our study summarises current evidence on the effect of flavanol-rich cocoa products on blood pressure in hypertensive and normotensive individuals. We searched Medline, Cochrane and international trial registries between 1955 and 2009 for randomised controlled trials investigating the effect of cocoa as food or drink compared with placebo on systolic and diastolic blood pressure (SBP/DBP) for a minimum duration of 2 weeks. We conducted random effects meta-analysis of all studies fitting the inclusion criteria, as well as subgroup analysis by baseline blood pressure (hypertensive/normotensive). Meta-regression analysis explored the association between type of treatment, dosage, duration or baseline blood pressure and blood pressure outcome. Statistical significance was set at P chocolate compared with control (mean BP change +/- SE: SBP: -3.2 +/- 1.9 mmHg, P = 0.001; DBP: -2.0 +/- 1.3 mmHg, P = 0.003). However, subgroup meta-analysis was significant only for the hypertensive or prehypertensive subgroups (SBP: -5.0 +/- 3.0 mmHg; P = 0.0009; DBP: -2.7 +/- 2.2 mm Hg, P = 0.01), while BP was not significantly reduced in the normotensive subgroups (SBP: -1.6 +/- 2.3 mmHg, P = 0.17; DBP: -1.3 +/- 1.6 mmHg, P = 0.12). Nine trials used chocolate containing 50% to 70% cocoa compared with white chocolate or other cocoa-free controls, while six trials compared high- with low-flavanol cocoa products. Daily flavanol dosages ranged from 30 mg to 1000 mg in the active treatment groups, and interventions ran for 2 to 18 weeks. Meta-regression analysis found study design and type of control to be borderline significant but possibly indirect predictors

  20. Meta-análise em pesquisas científicas: enfoque em metodologias Meta analysis in scientific research: a methodological approach

    Directory of Open Access Journals (Sweden)

    P.A. Lovatto

    2007-07-01

    Full Text Available Este texto descreve os princípios básicos de sistematização com enfoque em meta-análise. É apresentado o estado da arte da meta-análise, recuperando informações de sua evolução e metodologias básicas para sua realização. São descritos seus antecedentes históricos, os limites das abordagens clássicas de revisão de literatura, as bases conceituais, os objetivos e justificativas. É indicada uma metodologia geral para realização da meta-análise. São apresentados os critérios para a definição dos objetivos. São descritos os procedimentos de sistematização das informações e gestão de base bibliográfica de dados destinada aos estudos meta-analíticos (seleção, codificação, filtragem de dados. São apresentadas as análises mais comuns (gráfica, ponderações, a escolha do modelo estatístico (um fator explicativo qualitativo, um efeito qualitativo ou quantitativo, os fatores de interferência, os procedimentos pós-analíticos (variações residuais, heterogeneidade entre resultados. Em síntese, este texto mostra que a meta-análise é superior às formas tradicionais de revisão de literatura por estimar com maior precisão os efeitos dos tratamentos, ajustando-os para a heterogeneidade experimental. No entanto, a meta-análise exige os efeitos na sistematização e análise dos resultados da pesquisa.This text describes a basic approach of systematization with focus on meta-analysis. It is presented the art state of the meta-analysis, recovering information of its evolution and basic methodologies for its accomplishment. In this text are described the historical antecedents of meta-analysis, the limits of the classic approaches of literature review, the conceptual bases and the objectives. It is indicated a general methodology for meta-analysis procedures. The criteria for the definition of the objectives are presented. The procedures of the systematization and management of bibliographical data base selected to

  1. Higher-Than-Conventional Radiation Doses in Localized Prostate Cancer Treatment: A Meta-analysis of Randomized, Controlled Trials

    International Nuclear Information System (INIS)

    Viani, Gustavo Arruda; Stefano, Eduardo Jose; Afonso, Sergio Luis

    2009-01-01

    Purpose: To determine in a meta-analysis whether the outcomes in men with localized prostate cancer treated with high-dose radiotherapy (HDRT) are better than those in men treated with conventional-dose radiotherapy (CDRT), by quantifying the effect of the total dose of radiotherapy on biochemical control (BC). Methods and Materials: The MEDLINE, EMBASE, CANCERLIT, and Cochrane Library databases, as well as the proceedings of annual meetings, were systematically searched to identify randomized, controlled studies comparing HDRT with CDRT for localized prostate cancer. To evaluate the dose-response relationship, we conducted a meta-regression analysis of BC ratios by means of weighted linear regression. Results: Seven RCTs with a total patient population of 2812 were identified that met the study criteria. Pooled results from these RCTs showed a significant reduction in the incidence of biochemical failure in those patients with prostate cancer treated with HDRT (p 2 gastrointestinal toxicity after HDRT than after CDRT. In the subgroup analysis, patients classified as being at low (p = 0.007), intermediate (p < 0.0001), and high risk (p < 0.0001) of biochemical failure all showed a benefit from HDRT. The meta-regression analysis also detected a linear correlation between the total dose of radiotherapy and biochemical failure (BC = -67.3 + [1.8 x radiotherapy total dose in Gy]; p = 0.04). Conclusions: Our meta-analysis showed that HDRT is superior to CDRT in preventing biochemical failure in low-, intermediate-, and high-risk prostate cancer patients, suggesting that this should be offered as a treatment for all patients, regardless of their risk status.

  2. Meta-analysis of high-latitude nitrogen-addition and warming studies implies ecological mechanisms overlooked by land models

    Science.gov (United States)

    Bouskill, N. J.; Riley, W. J.; Tang, J. Y.

    2014-12-01

    Accurate representation of ecosystem processes in land models is crucial for reducing predictive uncertainty in energy and greenhouse gas feedbacks with the climate. Here we describe an observational and modeling meta-analysis approach to benchmark land models, and apply the method to the land model CLM4.5 with two versions of belowground biogeochemistry. We focused our analysis on the aboveground and belowground responses to warming and nitrogen addition in high-latitude ecosystems, and identified absent or poorly parameterized mechanisms in CLM4.5. While the two model versions predicted similar soil carbon stock trajectories following both warming and nitrogen addition, other predicted variables (e.g., belowground respiration) differed from observations in both magnitude and direction, indicating that CLM4.5 has inadequate underlying mechanisms for representing high-latitude ecosystems. On the basis of observational synthesis, we attribute the model-observation differences to missing representations of microbial dynamics, aboveground and belowground coupling, and nutrient cycling, and we use the observational meta-analysis to discuss potential approaches to improving the current models. However, we also urge caution concerning the selection of data sets and experiments for meta-analysis. For example, the concentrations of nitrogen applied in the synthesized field experiments (average = 72 kg ha-1 yr-1) are many times higher than projected soil nitrogen concentrations (from nitrogen deposition and release during mineralization), which precludes a rigorous evaluation of the model responses to likely nitrogen perturbations. Overall, we demonstrate that elucidating ecological mechanisms via meta-analysis can identify deficiencies in ecosystem models and empirical experiments.

  3. Vitamin D and Depression: A Systematic Review and Meta-Analysis Comparing Studies with and without Biological Flaws

    Directory of Open Access Journals (Sweden)

    Simon Spedding

    2014-04-01

    Full Text Available Efficacy of Vitamin D supplements in depression is controversial, awaiting further literature analysis. Biological flaws in primary studies is a possible reason meta-analyses of Vitamin D have failed to demonstrate efficacy. This systematic review and meta-analysis of Vitamin D and depression compared studies with and without biological flaws. The systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA guidelines. The literature search was undertaken through four databases for randomized controlled trials (RCTs. Studies were critically appraised for methodological quality and biological flaws, in relation to the hypothesis and study design. Meta-analyses were performed for studies according to the presence of biological flaws. The 15 RCTs identified provide a more comprehensive evidence-base than previous systematic reviews; methodological quality of studies was generally good and methodology was diverse. A meta-analysis of all studies without flaws demonstrated a statistically significant improvement in depression with Vitamin D supplements (+0.78 CI +0.24, +1.27. Studies with biological flaws were mainly inconclusive, with the meta-analysis demonstrating a statistically significant worsening in depression by taking Vitamin D supplements (−1.1 CI −0.7, −1.5. Vitamin D supplementation (≥800 I.U. daily was somewhat favorable in the management of depression in studies that demonstrate a change in vitamin levels, and the effect size was comparable to that of anti-depressant medication.

  4. Risk factors for chronic and recurrent otitis media-a meta-analysis.

    Science.gov (United States)

    Zhang, Yan; Xu, Min; Zhang, Jin; Zeng, Lingxia; Wang, Yanfei; Zheng, Qing Yin

    2014-01-01

    Risk factors associated with chronic otitis media (COM) and recurrent otitis media (ROM) have been investigated in previous studies. The objective of this study was to integrate the findings and determine the possible risk factors for COM/ROM based on our meta-analysis. A comprehensive search of electronic bibliographic databases (PubMed, Embase, CNKI and Wanfang database) from 1964 to Dec 2012, as well as a manual search of references of articles, was performed. A total of 2971 articles were searched, and 198 full-text articles were assessed for eligibility; 24 studies were eligible for this meta-analysis. Regarding risk factors for COM/ROM, there were two to nine different studies from which the odds ratios (ORs) could be pooled. The presence of allergy or atopy increased the risk of COM/ROM (OR, 1.36; 95% CI, 1.13-1.64; P = 0.001). An upper respiratory tract infection (URTI) significantly increased the risk of COM/ROM (OR, 6.59; 95% CI, 3.13-13.89; Pmedia (AOM)/ROM increased the risk of COM/ROM (OR, 11.13; 95% CI, 1.06-116.44; P = 0.04). Passive smoke significantly increased the risk of COM/ROM (OR, 1.39; 95% CI, 1.02-1.89 P = 0.04). Low social status appeared to be a risk factor for COM/ROM (OR, 3.82; 95% CI, 1.11-13.15; P = 0.03). Our meta-analysis identified reliable conclusions that allergy/atopy, URTI, snoring, previous history of AOM/ROM, Second-hand smoke and low social status are important risk factors for COM/ROM. Other unidentified risk factors need to be identified in further studies with critical criteria.

  5. Developmental defects of enamel and dental caries in the primary dentition: A systematic review and meta-analysis.

    Science.gov (United States)

    Costa, Francine S; Silveira, Ethieli R; Pinto, Gabriela S; Nascimento, Gustavo G; Thomson, William Murray; Demarco, Flávio F

    2017-05-01

    This systematic review and meta-analysis evaluated the association between developmental defects of enamel and dental caries in the primary dentition. Electronic searches were performed in PubMed, Web of Knowledge, Scopus and Scielo for the identification of relevant studies. Observational studies that examined the association between developmental defects of enamel and dental caries in the deciduous dentition were included. Additionally, meta-analysis, funnel plots and sensitivity analysis were employed to synthesize the available evidence. Multivariable meta-regression analysis was performed to explore heterogeneity among studies. A total of 318 articles were identified in the electronic searches. Of those, 16 studies were included in the meta-analysis. Pooled estimates revealed that children with developmental defects of enamel had higher odds of having dental caries (OR 3.32; 95%CI 2.41-4.57), with high heterogeneity between studies (I 2 80%). Methodological characteristic of the studies, such as where it was conducted, the examined teeth and the quality of the study explained about 30% of the variability. Concerning type of defect, children with hypoplasia and diffuse opacities had higher odds of having dental caries (OR 4.28; 95%CI 2.24-8.15; OR1.42; 95%CI 1.15-1.76, respectively). This systematic review and meta-analysis demonstrates a clear association between developmental defects of enamel and dental caries in the primary dentition. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Design Parameters of Vortex Pumps: A Meta-Analysis of Experimental Studies

    Directory of Open Access Journals (Sweden)

    Angela Gerlach

    2017-01-01

    Full Text Available Vortex pumps can impel solid-containing fluids and are therefore widely applied, from wastewater transport to the food industry. Despite constant efforts to improve vortex pumps, however, they have remained relatively inefficient compared to conventional centrifugal pumps. To find an optimized design of vortex pumps, this paper provides a systematic analysis on experimental studies that investigated how variations in geometric parameters influence vortex pump characteristics, in particular the pump head, the pressure coefficient and the efficiency for best point operation. To this end, an extensive literature search was conducted, and eighteen articles with 53 primary investigations were identified and meta-integrated. This showed that it is not yet clarified how vortex pumps operate. Two different assumptions of the underlying operating principle of a vortex pump lead to diverging design principles. From the results of this meta-analysis, we deduce recommendations for a more efficient design of a vortex pump and emphasize further aspects on the underlying operating principle of a vortex pump.

  7. Alcohol and the risk of sleep apnoea: a systematic review and meta-analysis.

    Science.gov (United States)

    Simou, Evangelia; Britton, John; Leonardi-Bee, Jo

    2018-02-01

    A systematic review and meta-analysis of the association between alcohol consumption and risk of sleep apnoea in adults. We searched Medline, EMBASE and Web of Science databases from 1985 to 2015 for comparative epidemiological studies assessing the relation between alcohol consumption and sleep apnoea. Two authors independently screened and extracted data. Random effects meta-analysis was used to estimate pooled effect sizes with 95% confidence intervals (CI). Heterogeneity was quantified using I 2 and explored using subgroup analyses based on study exposure and outcome measures, quality, design, adjustment for confounders and geographical location. Publication bias was assessed using a funnel plot and Egger's test. We identified 21 studies from which estimates of relative risk could be obtained. Meta-analysis of these estimates demonstrated that higher levels of alcohol consumption increased the risk of sleep apnoea by 25% (RR 1.25, 95%CI 1.13-1.38, I 2  = 82%, p Country locations. We detected evidence of publication bias (p = 0.001). A further eight included studies reported average alcohol consumption in people with and without sleep apnoea. Meta-analysis revealed that mean alcohol intake was two units/week higher in those with sleep apnoea, but this difference was not statistically significant (p = 0.41). These findings suggest that alcohol consumption is associated with a higher risk of sleep apnoea, further supporting evidence that reducing alcohol intake is of potential therapeutic and preventive value in this condition. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  8. Medical Student Research: An Integrated Mixed-Methods Systematic Review and Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Mohamed Amgad

    Full Text Available Despite the rapidly declining number of physician-investigators, there is no consistent structure within medical education so far for involving medical students in research.To conduct an integrated mixed-methods systematic review and meta-analysis of published studies about medical students' participation in research, and to evaluate the evidence in order to guide policy decision-making regarding this issue.We followed the PRISMA statement guidelines during the preparation of this review and meta-analysis. We searched various databases as well as the bibliographies of the included studies between March 2012 and September 2013. We identified all relevant quantitative and qualitative studies assessing the effect of medical student participation in research, without restrictions regarding study design or publication date. Prespecified outcome-specific quality criteria were used to judge the admission of each quantitative outcome into the meta-analysis. Initial screening of titles and abstracts resulted in the retrieval of 256 articles for full-text assessment. Eventually, 79 articles were included in our study, including eight qualitative studies. An integrated approach was used to combine quantitative and qualitative studies into a single synthesis. Once all included studies were identified, a data-driven thematic analysis was performed.Medical student participation in research is associated with improved short- and long- term scientific productivity, more informed career choices and improved knowledge about-, interest in- and attitudes towards research. Financial worries, gender, having a higher degree (MSc or PhD before matriculation and perceived competitiveness of the residency of choice are among the factors that affect the engagement of medical students in research and/or their scientific productivity. Intercalated BSc degrees, mandatory graduation theses and curricular research components may help in standardizing research education during

  9. Memory and Obstructive Sleep Apnea: A Meta-Analysis

    Science.gov (United States)

    Wallace, Anna; Bucks, Romola S.

    2013-01-01

    Study Objectives: To examine episodic memory performance in individuals with obstructive sleep apnea (OSA). Design Meta-analysis was used to synthesize results from individual studies examining the impact of OSA on episodic memory performance. The performance of individuals with OSA was compared to healthy controls or normative data. Participants Forty-two studies were included, comprising 2,294 adults with untreated OSA and 1,364 healthy controls. Studies that recorded information about participants at baseline prior to treatment interventions were included in the analysis. Measurements Participants were assessed with tasks that included a measure of episodic memory: immediate recall, delayed recall, learning, and/or recognition memory. Results: The results of the meta-analyses provide evidence that individuals with OSA are significantly impaired when compared to healthy controls on verbal episodic memory (immediate recall, delayed recall, learning, and recognition) and visuo-spatial episodic memory (immediate and delayed recall), but not visual immediate recall or visuo-spatial learning. When patients were compared to norms, negative effects of OSA were found only in verbal immediate and delayed recall. Conclusions: This meta-analysis contributes to understanding of the nature of episodic memory deficits in individuals with OSA. Impairments to episodic memory are likely to affect the daily functioning of individuals with OSA. Citation Wallace A; Bucks RS. Memory and obstructive sleep apnea: a meta-analysis. SLEEP 2013;36(2):203-220. PMID:23372268

  10. How can interventions increase motivation for physical activity? A systematic review and meta-analysis

    OpenAIRE

    Crutzen, Rik; Nurmi, Johanna; Beattie, Marguerite; Dombrowski, Stephan; Knittle, Keegan; Hankonen, Nelli

    2018-01-01

    Motivation is a proximal determinant of behavior in many psychological theories, and increasing motivation is central to most behavior change interventions. This systematic review and meta-analysis sought to fill a gap in the literature by identifying features of behavior change interventions associated with favorable changes in three prominent motivational constructs: intention, stage of change and autonomous motivation. A systematic literature search identified 88 intervention studies (N = ...

  11. Caffeine ingestion enhances Wingate performance: a meta-analysis.

    Science.gov (United States)

    Grgic, Jozo

    2018-03-01

    The positive effects of caffeine ingestion on aerobic performance are well-established; however, recent findings are suggesting that caffeine ingestion might also enhance components of anaerobic performance. A commonly used test of anaerobic performance and power output is the 30-second Wingate test. Several studies explored the effects of caffeine ingestion on Wingate performance, with equivocal findings. To elucidate this topic, this paper aims to determine the effects of caffeine ingestion on Wingate performance using meta-analytic statistical techniques. Following a search through PubMed/MEDLINE, Scopus, and SportDiscus ® , 16 studies were found meeting the inclusion criteria (pooled number of participants = 246). Random-effects meta-analysis of standardized mean differences (SMD) for peak power output and mean power output was performed. Study quality was assessed using the modified version of the PEDro checklist. Results of the meta-analysis indicated a significant difference (p = .005) between the placebo and caffeine trials on mean power output with SMD values of small magnitude (0.18; 95% confidence interval: 0.05, 0.31; +3%). The meta-analysis performed for peak power output indicated a significant difference (p = .006) between the placebo and caffeine trials (SMD = 0.27; 95% confidence interval: 0.08, 0.47 [moderate magnitude]; +4%). The results from the PEDro checklist indicated that, in general, studies are of good and excellent methodological quality. This meta-analysis adds on to the current body of evidence showing that caffeine ingestion can also enhance components of anaerobic performance. The results presented herein may be helpful for developing more efficient evidence-based recommendations regarding caffeine supplementation.

  12. A Meta-Analysis of the Relationship between Testicular Microlithiasis and Incidence of Testicular Cancer.

    Science.gov (United States)

    Wang, Tao; Liu, LuHao; Luo, JinTai; Liu, TaiSheng; Wei, AnYang

    2015-04-29

    There are many recent observational studies on testicular microlithiasis (TM) and risk of testicular cancer. Whether TM increases the risk of testicular cancer is still inconclusive. The objective of this updated meta-analysis was to synthesize evidence from clinical observational studies that evaluated the association between TM and testicular cancer. We identified eligible studies by searching the PubMed, Embase and Cochrane Library before March 2014. Adjusted relative risks (RR) with 95% confidence interval (CI) were calculated using random-or fixed-model. A total of 14 studies involving 35,578 participants were included in the meta-analysis. On the basis of the Newcastle Ottawa Scale systematic review, eleven studies were identified as relatively high-quality. TM was strong association with an increased incidence of testicular cancer (RR = 12.70, 95% CI: 8.18-19.71, P testicular cancer. More researches are warranted to clarify an understanding of the association between TM and risk of testicular cancer.

  13. Risk of herpes zoster and family history: A Meta-analysis of case–control studies

    Directory of Open Access Journals (Sweden)

    Yi Chun Lai

    2016-01-01

    Full Text Available Background: Herpes zoster (HZ results from the reactivation of latent varicella zoster virus (VZV residing in dorsal root and cranial nerve ganglia. Advanced age and dysfunctional cell-mediated immune responses are well-established risk factors for VZV reactivation. There have been recent interests in whether there is an increased risk of the disease associated with a positive family history. Aims and Objectives: We aimed to conduct a meta-analysis to evaluate the association between HZ infection and family history. In addition, we investigated the dose-response relationship between HZ infection and the number of relatives with a history of HZ. Materials and Methods: Observational studies were searched from MEDLINE, EMBASE, and Cochrane Central Register from inception to April 15, 2015. The Meta-analysis of Observational Studies in Epidemiology guidelines were followed in conducting this study. To estimate the pooled odds ratio, random-effects model of DerSimonian and Laird was used. Heterogeneity between studies was assessed using the I2 statistic. A dose-response meta-analysis with studies that reported appropriate data were done using the generalized least squares for trend method. Results: Five studies, yielding a total of 4169 subjects, were identified for meta-analysis. Cases with HZ were 3.03 (95% confidence interval [CI]: 1.86–4.94, P < 0.001 and 3.27 (95% CI: 1.75–6.10, P < 0.001 times more likely to report the first-degree relatives and total relatives with a history of HZ, respectively. A significant positive dose-response relationship between the risk of HZ infection and the number of relatives with a history of HZ was also demonstrated (P < 0.001. Conclusions: This meta-analysis demonstrated that family history is a significant risk factor for HZ infection. This risk has a dose-response relationship with the number of relatives with a history of HZ.

  14. Association between TYK2 polymorphisms and susceptibility to autoimmune rheumatic diseases: a meta-analysis.

    Science.gov (United States)

    Lee, Y H; Bae, S-C

    2016-10-01

    This study aimed to explore whether TYK2 polymorphisms are associated with susceptibility to autoimmune rheumatic diseases. We conducted a meta-analysis on the association between TYK2 polymorphisms and autoimmune rheumatic diseases. Twelve studies with a total of 16,335 patients and 30,065 controls were included in the meta-analysis. Meta-analysis revealed an association between rheumatic diseases and the 2 allele of the TYK2 rs2304256 (OR = 0.885, 95% CI = 0.802-0.978, p = 0.016). Furthermore, stratification by ethnicity identified a significant association between this polymorphism and rheumatic diseases in Caucasians (OR = 0.822, 95% CI = 0.706-0.889, p = 9.5 × 10(-7)), but not in Asians (OR = 1.127, 95% CI = 0.835-1.522, p = 0.434). Meta-analysis by rheumatic disease type revealed a significant association between the 2 allele of the TYK2 rs2304256 and SLE in Caucasians (OR = 0.737, 95% CI = 0.673-0.808, p rheumatic diseases in Caucasians (OR = 0.812, 95% CI = 0.661-0.997, p = 0.046) but not in Asians. Interestingly, the rs280519 polymorphism was significantly associated with susceptibility to SLE both in Caucasians and Asians. However, no associations were found between the rs12720270, rs280500, rs280523 and rs8108236 polymorphisms and susceptibility to rheumatic diseases. This meta-analysis demonstrates that the TYK2 rs2304256 and rs12720356 polymorphisms are associated with susceptibility to rheumatic diseases, rs2304256 polymorphism is associated with SLE in Caucasians, and rs280519 polymorphism is associated with SLE in Caucasians and Asians. © The Author(s) 2016.

  15. Systematic review and meta-analysis in cardiac surgery: a primer.

    Science.gov (United States)

    Yanagawa, Bobby; Tam, Derrick Y; Mazine, Amine; Tricco, Andrea C

    2018-03-01

    The purpose of this article is to review the strengths and weaknesses of systematic reviews and meta-analyses to inform our current understanding of cardiac surgery. A systematic review and meta-analysis of a focused topic can provide a quantitative estimate for the effect of a treatment intervention or exposure. In cardiac surgery, observational studies and small, single-center prospective trials provide most of the clinical outcomes that form the evidence base for patient management and guideline recommendations. As such, meta-analyses can be particularly valuable in synthesizing the literature for a particular focused surgical question. Since the year 2000, there are over 800 meta-analysis-related publications in our field. There are some limitations to this technique, including clinical, methodological and statistical heterogeneity, among other challenges. Despite these caveats, results of meta-analyses have been useful in forming treatment recommendations or in providing guidance in the design of future clinical trials. There is a growing number of meta-analyses in the field of cardiac surgery. Knowledge translation via meta-analyses will continue to guide and inform cardiac surgical practice and our practice guidelines.

  16. Trial sequential analyses of meta-analyses of complications in laparoscopic vs. small-incision cholecystectomy: more randomized patients are needed

    DEFF Research Database (Denmark)

    Keus, Frederik; Wetterslev, Jørn; Gluud, Christian

    2010-01-01

    Conclusions based on meta-analyses of randomized trials carry a status of "truth." Methodological components may identify trials with systematic errors ("bias"). Trial sequential analysis (TSA) evaluates random errors in meta-analysis. We analyzed meta-analyses on laparoscopic vs. small-incision ......Conclusions based on meta-analyses of randomized trials carry a status of "truth." Methodological components may identify trials with systematic errors ("bias"). Trial sequential analysis (TSA) evaluates random errors in meta-analysis. We analyzed meta-analyses on laparoscopic vs. small...

  17. Migraine Headache and Ischemic Stroke Risk: An Updated Meta-analysis

    Science.gov (United States)

    Spector, June T.; Kahn, Susan R.; Jones, Miranda R.; Jayakumar, Monisha; Dalal, Deepan; Nazarian, Saman

    2010-01-01

    Background Observational studies, including recent large cohort studies which were unavailable for prior meta-analysis, have suggested an association between migraine headache and ischemic stroke. We performed an updated meta-analysis to quantitatively summarize the strength of association between migraine and ischemic stroke risk. Methods We systematically searched electronic databases, including MEDLINE and EMBASE, through February 2009 for studies of human subjects in the English language. Study selection using a priori selection criteria, data extraction, and assessment of study quality were conducted independently by reviewer pairs using standardized forms. Results Twenty-one (60%) of 35 studies met the selection criteria, for a total of 622,381 participants (13 case-control, 8 cohort studies) included in the meta-analysis. The pooled adjusted odds ratio of ischemic stroke comparing migraineurs to non-migraineurs using a random effects model was 2.30 (95% confidence interval [CI], 1.91-2.76). The pooled adjusted effect estimates for studies that reported relative risks and hazard ratios, respectively, were 2.41 (95% CI, 1.81-3.20) and 1.52 (95% CI, 0.99-2.35). The overall pooled effect estimate was 2.04 (95% CI, 1.72-2.43). Results were robust to sensitivity analyses excluding lower quality studies. Conclusions Migraine is associated with increased ischemic stroke risk. These findings underscore the importance of identifying high-risk migraineurs with other modifiable stroke risk factors. Future studies of the effect of migraine treatment and modifiable risk factor reduction on stroke risk in migraineurs are warranted. PMID:20493462

  18. Meta-analysis of skeletal mandibular changes during Frankel appliance treatment.

    Science.gov (United States)

    Perillo, Letizia; Cannavale, Rosangela; Ferro, Fabrizia; Franchi, Lorenzo; Masucci, Caterina; Chiodini, Paolo; Baccetti, Tiziano

    2011-02-01

    The purpose of this study was to perform a meta-analysis of articles to verify the mandibular changes produced by the Fränkel-2 (FR-2) appliance during the treatment of growing patients with Class II malocclusions when compared with untreated growing Class II subjects. The literature published from January 1966 to January 2009 was reviewed with search engines. A quality analysis was performed. The effects on primary end points were calculated with random-effect models. Heterogeneity was assessed using Q statistic and investigated using study-level meta-regression. A total of nine articles were identified. The quality of the studies ranged from low to medium. Meta-analysis showed that the FR-2 was associated with enhancement of mandibular body length [0.4 mm/year 95 per cent confidence interval (CI) 0.182-0.618], total mandibular length (1.069 mm/year, 95 per cent CI 0.683-1.455), and mandibular ramus height (0.654 mm/year, 95 per cent CI 0.244-1.064). A consistent heterogeneity among studies was found for all the considered linear measurements. The FR-2 appliance had a statistically significant effect on mandibular growth. Nevertheless, the heterogeneity of the FR-2 effects, the quality of studies, the differences in age, skeletal age, treatment duration, and the inconsistent initial diagnosis seem to overstate the benefits of the FR-2 appliance. An evidence-based approach to the orthodontic outcomes of FR-2 appliance is needed, by selecting and comparing groups of children with the same cephalometric characteristics with and without treatment.

  19. Sensitivity analysis for publication bias in meta-analysis of diagnostic studies for a continuous biomarker.

    Science.gov (United States)

    Hattori, Satoshi; Zhou, Xiao-Hua

    2018-02-10

    Publication bias is one of the most important issues in meta-analysis. For standard meta-analyses to examine intervention effects, the funnel plot and the trim-and-fill method are simple and widely used techniques for assessing and adjusting for the influence of publication bias, respectively. However, their use may be subjective and can then produce misleading insights. To make a more objective inference for publication bias, various sensitivity analysis methods have been proposed, including the Copas selection model. For meta-analysis of diagnostic studies evaluating a continuous biomarker, the summary receiver operating characteristic (sROC) curve is a very useful method in the presence of heterogeneous cutoff values. To our best knowledge, no methods are available for evaluation of influence of publication bias on estimation of the sROC curve. In this paper, we introduce a Copas-type selection model for meta-analysis of diagnostic studies and propose a sensitivity analysis method for publication bias. Our method enables us to assess the influence of publication bias on the estimation of the sROC curve and then judge whether the result of the meta-analysis is sufficiently confident or should be interpreted with much caution. We illustrate our proposed method with real data. Copyright © 2017 John Wiley & Sons, Ltd.

  20. Prevalence of posttraumatic stress disorder among road traffic accident survivors: A PRISMA-compliant meta-analysis.

    Science.gov (United States)

    Lin, Wanli; Gong, Lina; Xia, Miaojuan; Dai, Wenjie

    2018-01-01

    Involvement in road traffic accidents (RTAs) may put individuals at increased risk for a wide range of psychiatric disorders, among which posttraumatic stress disorder (PTSD) presents a public health issue. However, a great disparity was observed among studies exploring the prevalence of PTSD among RTA survivors. This meta-analysis aimed to explore the pooled prevalence of PTSD among RTA survivors. Electronic databases of PubMed, Embase, Web of Science, PsycARTICLES, PsycINFO, and CINAHL were searched to identify relevant studies. Study selection and data extraction were conducted independently by 2 investigators, and a meta-analysis was performed to synthesize the data. Heterogeneity among studies was evaluated using the Cochran Q test and quantified using the I statistic. Subgroup analyses were performed to identify the source of the heterogeneity. The possibility of publication bias was assessed using Egger linear test. Fifteen eligible studies containing 6804 RTA survivors were identified in this meta-analysis, of which 1489 were identified with PTSD. The pooled prevalence of PTSD among RTA survivors was 22.25% (95% confidence interval: 16.71%-28.33%). A high degree of heterogeneity was observed across studies (I = 97.1%, P < .001), with reported PTSD prevalence ranging from 6.3% to 58.3%. Subgroup analyses found that the prevalence of PTSD among RTA survivors varied significantly across studies in relation to the instrument used to assess PTSD, country, race, gender, and education level (P < .05). The high pooled prevalence of PTSD among RTA survivors found in this study significantly underscores the need for providing timely and effective intervention strategies for RTA survivors. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

  1. Mismatch Negativity in Han Chinese Patients with Schizophrenia: A Meta-Analysis.

    Science.gov (United States)

    Xiong, Yanbing; Ll, Xianbin; Zhao, Lei; Wang, Chuanyue

    2017-10-25

    Previous meta-analysis revealed that mismatch negativity(MMN) amplitude decreased in patients with schizophrenia compared with healthy controls (Cohen's d, d about 1), leading to the possibility of mismatch negativity being used as a biomarker for schizophrenia. However, it is unknown whether MMN is reliably changed in Chinese patients. It is necessary to carry out a meta-analysis on MMN of Han Chinese patients with schizophrenia. To investigate whether MMN could be used as a biomarker for Han Chinese patients with schizophrenia. A literature search was conducted to identify clinical trials on MMN in Han Chinese schizophrenia patients published before May 8, 2017, by searching the Chinese language databases CNKI, WanFang Data, VIP Data and PubMed. The effects of MMN deficits were evaluated for MMN amplitude by calculating standard mean difference (SMDs) between schizophrenia patient groups and healthy control groups. A total of 11 studies were included in the analysis. The total quality of all the studies were more than 6 as evaluated by Newcastle-Ottawa Scale (NOS). Meta-analysis of data from these studies had a pooled sample of 432 patients with schizophrenia and 392 healthy controls. There exists significant MMN deficit in schizophrenia patients compared to healthy controls (Cohen's d =1.004). When studies were excluded due to heterogeneity, the pooled effect size of the MMN differences between the patient group and healthy controls dropped to 0.79 (Cohen's d =0.79). Subgroup analysis showed that MMN amplitude deficits of schizophrenia over three years had the pooled effect size of 0.95, and less than three years had the pooled effect size of 0.77. Publication bias conducted via Egger regression test ( t = 1.83; p = 0.101), suggested that there was no publication bias. The effect size of MMN amplitude between Chinese patients with schizophrenia and healthy controls is consistent with other meta-analyses published on this topic, suggesting that Han Chinese

  2. Evaluation of Open and Minimally Invasive Adrenalectomy: A Systematic Review and Network Meta-analysis.

    Science.gov (United States)

    Heger, Patrick; Probst, Pascal; Hüttner, Felix J; Gooßen, Käthe; Proctor, Tanja; Müller-Stich, Beat P; Strobel, Oliver; Büchler, Markus W; Diener, Markus K

    2017-11-01

    Adrenalectomy can be performed via open and various minimally invasive approaches. The aim of this systematic review was to summarize the current evidence on surgical techniques of adrenalectomy. Systematic literature searches (MEDLINE, EMBASE, Web of Science, Cochrane Library) were conducted to identify randomized controlled trials (RCTs) and controlled clinical trials (CCTs) comparing at least two surgical procedures for adrenalectomy. Statistical analyses were performed, and meta-analyses were conducted. Furthermore, an indirect comparison of RCTs and a network meta-analysis of CCTs were carried out for each outcome. Twenty-six trials (1710 patients) were included. Postoperative complication rates did not show differences for open and minimally invasive techniques. Operation time was significantly shorter for open adrenalectomy than for the robotic approach (p meta-analysis showed open adrenalectomy to be the fastest technique. Blood loss was significantly reduced in the robotic arm compared with open and laparoscopic adrenalectomy (p = 0.01). Length of hospital stay (LOS) was significantly lower after conventional laparoscopy than open adrenalectomy in CCTs (p meta-analysis revealed the lowest LOS after retroperitoneoscopic adrenalectomy. Minimally invasive adrenalectomy is safe and should be preferred over open adrenalectomy due to shorter LOS, lower blood loss, and equivalent complication rates. The retroperitoneoscopic access features the shortest LOS and operating time. Further high-quality RCTs are warranted, especially to compare the posterior retroperitoneoscopic and the transperitoneal robotic approach.

  3. Quantifying the dose-response of walking in reducing coronary heart disease risk: meta-analysis.

    Science.gov (United States)

    Zheng, Henry; Orsini, Nicola; Amin, Janaki; Wolk, Alicja; Nguyen, Van Thi Thuy; Ehrlich, Fred

    2009-01-01

    The evidence for the efficacy of walking in reducing the risk of and preventing coronary heart disease (CHD) is not completely understood. This meta-analysis aimed to quantify the dose-response relationship between walking and CHD risk reduction for both men and women in the general population. Studies on walking and CHD primary prevention between 1954 and 2007 were identified through Medline, SportDiscus and the Cochrane Database of Systematic Reviews. Random-effect meta-regression models were used to pool the relative risks from individual studies. A total of 11 prospective cohort studies and one randomized control trial study met the inclusion criteria, with 295,177 participants free of CHD at baseline and 7,094 cases at follow-up. The meta-analysis indicated that an increment of approximately 30 min of normal walking a day for 5 days a week was associated with 19% CHD risk reduction (95% CI = 14-23%; P-heterogeneity = 0.56; I (2) = 0%). We found no evidence of heterogeneity between subgroups of studies defined by gender (P = 0.67); age of the study population (P = 0.52); or follow-up duration (P = 0.77). The meta-analysis showed that the risk for developing CHD decreases as walking dose increases. Walking should be prescribed as an evidence-based effective exercise modality for CHD prevention in the general population.

  4. Working after a metastatic cancer diagnosis: Factors affecting employment in the metastatic setting from ECOG-ACRIN's Symptom Outcomes and Practice Patterns study.

    Science.gov (United States)

    Tevaarwerk, Amye J; Lee, Ju-Whei; Terhaar, Abigail; Sesto, Mary E; Smith, Mary Lou; Cleeland, Charles S; Fisch, Michael J

    2016-02-01

    Improved survival for individuals with metastatic cancer accentuates the importance of employment for cancer survivors. A better understanding of how metastatic cancer affects employment is a necessary step toward the development of tools for assisting survivors in this important realm. The ECOG-ACRIN Symptom Outcomes and Practice Patterns study was analyzed to investigate what factors were associated with the employment of 680 metastatic cancer patients. Univariate and multivariate logistic regression analyses were conducted to compare patients stably working with patients no longer working. There were 668 metastatic working-age participants in the analysis: 236 (35%) worked full- or part-time, whereas 302 (45%) had stopped working because of illness. Overall, 58% reported some change in employment due to illness. A better performance status and non-Hispanic white ethnicity/race were significantly associated with continuing to work despite a metastatic cancer diagnosis in the multivariate analysis. The disease type, time since metastatic diagnosis, number of metastatic sites, location of metastatic disease, and treatment status had no significant impact. Among the potentially modifiable factors, receiving hormonal treatment (if a viable option) and decreasing symptom interference were associated with continuing to work. A significant percentage of the metastatic patients remained employed; increased symptom burden was associated with a change to no longer working. Modifiable factors resulting in work interference should be minimized so that patients with metastatic disease may continue working if this is desired. Improvements in symptom control and strategies developed to help address workplace difficulties have promise for improving this aspect of survivorship. © 2015 American Cancer Society.

  5. Exercise and Bone Density: Meta-Analysis

    National Research Council Canada - National Science Library

    Kelley, George A; Sharpe-Kelley, Kristi

    2007-01-01

    .... Since no meta-analysis had existed using individual patient data (IPD) to examine the effects of exercise on BMD, our second two-year period of funding was devoted to examining the feasibility...

  6. Meta-analysis in plant pathology: synthesizing research results.

    Science.gov (United States)

    Rosenberg, M S; Garrett, K A; Su, Z; Bowden, R L

    2004-09-01

    ABSTRACT Meta-analysis is a set of statistical procedures for synthesizing research results from a number of different studies. An estimate of a statistical effect, such as the difference in disease severity for plants with or without a management treatment, is collected from each study along with a measure of the variance of the estimate of the effect. Combining results from different studies will generally result in increased statistical power so that it is easier to detect small effects. Combining results from different studies may also make it possible to compare the size of the effect as a function of other predictor variables such as geographic region or pathogen species. We present a review of the basic methodology for meta-analysis. We also present an example of meta-analysis of the relationship between disease severity and yield loss for foliar wheat diseases, based on data collected from a decade of fungicide and nematicide test results.

  7. Exploratory Network Meta Regression Analysis of Stroke Prevention in Atrial Fibrillation Fails to Identify Any Interactions with Treatment Effect.

    Science.gov (United States)

    Batson, Sarah; Sutton, Alex; Abrams, Keith

    2016-01-01

    Patients with atrial fibrillation are at a greater risk of stroke and therefore the main goal for treatment of patients with atrial fibrillation is to prevent stroke from occurring. There are a number of different stroke prevention treatments available to include warfarin and novel oral anticoagulants. Previous network meta-analyses of novel oral anticoagulants for stroke prevention in atrial fibrillation acknowledge the limitation of heterogeneity across the included trials but have not explored the impact of potentially important treatment modifying covariates. To explore potentially important treatment modifying covariates using network meta-regression analyses for stroke prevention in atrial fibrillation. We performed a network meta-analysis for the outcome of ischaemic stroke and conducted an exploratory regression analysis considering potentially important treatment modifying covariates. These covariates included the proportion of patients with a previous stroke, proportion of males, mean age, the duration of study follow-up and the patients underlying risk of ischaemic stroke. None of the covariates explored impacted relative treatment effects relative to placebo. Notably, the exploration of 'study follow-up' as a covariate supported the assumption that difference in trial durations is unimportant in this indication despite the variation across trials in the network. This study is limited by the quantity of data available. Further investigation is warranted, and, as justifying further trials may be difficult, it would be desirable to obtain individual patient level data (IPD) to facilitate an effort to relate treatment effects to IPD covariates in order to investigate heterogeneity. Observational data could also be examined to establish if there are potential trends elsewhere. The approach and methods presented have potentially wide applications within any indication as to highlight the potential benefit of extending decision problems to include additional

  8. Exploratory Network Meta Regression Analysis of Stroke Prevention in Atrial Fibrillation Fails to Identify Any Interactions with Treatment Effect.

    Directory of Open Access Journals (Sweden)

    Sarah Batson

    Full Text Available Patients with atrial fibrillation are at a greater risk of stroke and therefore the main goal for treatment of patients with atrial fibrillation is to prevent stroke from occurring. There are a number of different stroke prevention treatments available to include warfarin and novel oral anticoagulants. Previous network meta-analyses of novel oral anticoagulants for stroke prevention in atrial fibrillation acknowledge the limitation of heterogeneity across the included trials but have not explored the impact of potentially important treatment modifying covariates.To explore potentially important treatment modifying covariates using network meta-regression analyses for stroke prevention in atrial fibrillation.We performed a network meta-analysis for the outcome of ischaemic stroke and conducted an exploratory regression analysis considering potentially important treatment modifying covariates. These covariates included the proportion of patients with a previous stroke, proportion of males, mean age, the duration of study follow-up and the patients underlying risk of ischaemic stroke.None of the covariates explored impacted relative treatment effects relative to placebo. Notably, the exploration of 'study follow-up' as a covariate supported the assumption that difference in trial durations is unimportant in this indication despite the variation across trials in the network.This study is limited by the quantity of data available. Further investigation is warranted, and, as justifying further trials may be difficult, it would be desirable to obtain individual patient level data (IPD to facilitate an effort to relate treatment effects to IPD covariates in order to investigate heterogeneity. Observational data could also be examined to establish if there are potential trends elsewhere. The approach and methods presented have potentially wide applications within any indication as to highlight the potential benefit of extending decision problems to

  9. Effectiveness of Mobile Devices on Vocabulary Learning: A Meta-Analysis

    Science.gov (United States)

    Mahdi, Hassan Saleh

    2018-01-01

    Mobile devices are considered as the most widely used information and communication technologies. They have provided great advantages in language learning. This study reports a meta-analysis of the effectiveness of using mobile devices on vocabulary learning. A meta-analysis was conducted on research that compared the outcomes from students…

  10. Wood dust exposure and lung cancer risk: a meta-analysis.

    Science.gov (United States)

    Hancock, David G; Langley, Mary E; Chia, Kwan Leung; Woodman, Richard J; Shanahan, E Michael

    2015-12-01

    Occupational lung cancers represent a major health burden due to their increasing prevalence and poor long-term outcomes. While wood dust is a confirmed human carcinogen, its association with lung cancer remains unclear due to inconsistent findings in the literature. We aimed to clarify this association using meta-analysis. We performed a search of 10 databases to identify studies published until June 2014. We assessed the lung cancer risk associated with wood dust exposure as the primary outcome and with wood dust-related occupations as a secondary outcome. Random-effects models were used to pool summary risk estimates. 85 publications were included in the meta-analysis. A significantly increased risk for developing lung cancer was observed among studies that directly assessed wood dust exposure (RR 1.21, 95% CI 1.05 to 1.39, n=33) and that assessed wood dust-related occupations (RR 1.15, 95% CI 1.07 to 1.23, n=59). In contrast, a reduced risk for lung cancer was observed among wood dust (RR 0.63, 95% CI 0.39 to 0.99, n=5) and occupation (RR 0.96, 95% CI 0.95 to 0.98, n=1) studies originating in Nordic countries, where softwood dust is the primary exposure. These results were independent of the presence of adjustment for smoking and exposure classification methods. Only minor differences in risk between the histological subtypes were identified. This meta-analysis provides strong evidence for an association between wood dust and lung cancer, which is critically influenced by the geographic region of the study. The reasons for this region-specific effect estimates remain to be clarified, but may suggest a differential effect for hardwood and softwood dusts. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  11. Poor Gait Performance and Prediction of Dementia: Results From a Meta-Analysis.

    Science.gov (United States)

    Beauchet, Olivier; Annweiler, Cédric; Callisaya, Michele L; De Cock, Anne-Marie; Helbostad, Jorunn L; Kressig, Reto W; Srikanth, Velandai; Steinmetz, Jean-Paul; Blumen, Helena M; Verghese, Joe; Allali, Gilles

    2016-06-01

    Poor gait performance predicts risk of developing dementia. No structured critical evaluation has been conducted to study this association yet. The aim of this meta-analysis was to systematically examine the association of poor gait performance with incidence of dementia. An English and French Medline search was conducted in June 2015, with no limit of date, using the medical subject headings terms "Gait" OR "Gait Disorders, Neurologic" OR "Gait Apraxia" OR "Gait Ataxia" AND "Dementia" OR "Frontotemporal Dementia" OR "Dementia, Multi-Infarct" OR "Dementia, Vascular" OR "Alzheimer Disease" OR "Lewy Body Disease" OR "Frontotemporal Dementia With Motor Neuron Disease" (Supplementary Concept). Poor gait performance was defined by standardized tests of walking, and dementia was diagnosed according to international consensus criteria. Four etiologies of dementia were identified: any dementia, Alzheimer disease (AD), vascular dementia (VaD), and non-AD (ie, pooling VaD, mixed dementias, and other dementias). Fixed effects meta-analyses were performed on the estimates in order to generate summary values. Of the 796 identified abstracts, 12 (1.5%) were included in this systematic review and meta-analysis. Poor gait performance predicted dementia [pooled hazard ratio (HR) combined with relative risk and odds ratio = 1.53 with P analysis provides evidence that poor gait performance predicts dementia. This association depends on the type of dementia; poor gait performance is a stronger predictor of non-AD dementias than AD. Copyright © 2016 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

  12. The efficacy of topical tranexamic acid in total hip arthroplasty: a meta-analysis.

    Science.gov (United States)

    Chen, Shubiao; Wu, Kezhou; Kong, Gengbin; Feng, Weili; Deng, Zhihua; Wang, Hu

    2016-02-16

    Topical tranexamic acid (TXA) has been shown to be effective in reducing blood loss and the need for transfusion after total knee arthroplasty. However, the effectiveness of topical TXA use in total hip arthroplasty (THA) still remains unclear. The purpose of this meta-analysis is to examine the safety and efficacy of topical use of TXA following THA. Topical TXA reduces blood loss and transfusion rates without increasing risk of deep vein thrombosis in patients with THA. An electronic literature search of PubMed, Embase, the Cochrane Library, Web of Science and Chinese Biomedical Database was performed, to identify studies published before February 2015. All randomized controlled trials and cohort studies evaluating the efficacy of topical TXA during THA were included. Two independent authors identified the eligible studies, assessed their methodological quality, and extracted data. The data were using fixed-effects or random-effects models with (standard) mean differences and risk ratios for continuous and dichotomous variables, respectively. Data were analysed using RevMan 5.3 software. Fourteen studies encompassing 2594 patients met the inclusion criteria for our meta-analysis. Our meta-analysis indicated that when compared with the placebo group, topical use of TXA significantly reduced total blood loss (MD = -297.65 ml, 95 % CI -371.68 ml, 116.08 ml; P level (SMD = -0.66, 95 % CI -0.91, -0.41; P Topical TXA could significantly reduce total blood loss, drainage loss, transfusion rates and decrease haemoglobin level following THA, without increasing risk of venous thromboembolisms.

  13. Bullying and Suicidal Ideation and Behaviors: A Meta-Analysis

    Science.gov (United States)

    Holt, Melissa K.; Vivolo-Kantor, Alana M.; Polanin, Joshua R.; Holland, Kristin M.; DeGue, Sarah; Matjasko, Jennifer L.; Wolfe, Misty; Reid, Gerald

    2015-01-01

    BACKGROUND AND OBJECTIVES Over the last decade there has been increased attention to the association between bullying involvement (as a victim, perpetrator, or bully-victim) and suicidal ideation/behaviors. We conducted a meta-analysis to estimate the association between bullying involvement and suicidal ideation and behaviors. METHODS We searched multiple online databases and reviewed reference sections of articles derived from searches to identify cross-sectional studies published through July 2013. Using search terms associated with bullying, suicide, and youth, 47 studies (38.3% from the United States, 61.7% in non-US samples) met inclusion criteria. Seven observers independently coded studies and met in pairs to reach consensus. RESULTS Six different meta-analyses were conducted by using 3 predictors (bullying victimization, bullying perpetration, and bully/victim status) and 2 outcomes (suicidal ideation and suicidal behaviors). A total of 280 effect sizes were extracted and multilevel, random effects meta-analyses were performed. Results indicated that each of the predictors were associated with risk for suicidal ideation and behavior (range, 2.12 [95% confidence interval (CI), 1.67–2.69] to 4.02 [95% CI, 2.39–6.76]). Significant heterogeneity remained across each analysis. The bullying perpetration and suicidal behavior effect sizes were moderated by the study’s country of origin; the bully/victim status and suicidal ideation results were moderated by bullying assessment method. CONCLUSIONS Findings demonstrated that involvement in bullying in any capacity is associated with suicidal ideation and behavior. Future research should address mental health implications of bullying involvement to prevent suicidal ideation/behavior. PMID:25560447

  14. Hydropower externalities: a meta analysis

    NARCIS (Netherlands)

    Mattmann, M.; Logar, I.; Brouwer, R.

    2016-01-01

    This paper presents a meta-analysis of existing research related to the economic valuation of the external effects of hydropower. A database consisting of 81 observations derived from 29 studies valuing the non-market impacts of hydropower electricity generation is constructed with the main aim to

  15. Quantitative Trait Locus (QTL meta-analysis and comparative genomics for candidate gene prediction in perennial ryegrass (Lolium perenne L.

    Directory of Open Access Journals (Sweden)

    Shinozuka Hiroshi

    2012-11-01

    Full Text Available Abstract Background In crop species, QTL analysis is commonly used for identification of factors contributing to variation of agronomically important traits. As an important pasture species, a large number of QTLs have been reported for perennial ryegrass based on analysis of biparental mapping populations. Further characterisation of those QTLs is, however, essential for utilisation in varietal improvement programs. Results A bibliographic survey of perennial ryegrass trait-dissection studies identified a total of 560 QTLs from previously published papers, of which 189, 270 and 101 were classified as morphology-, physiology- and resistance/tolerance-related loci, respectively. The collected dataset permitted a subsequent meta-QTL study and implementation of a cross-species candidate gene identification approach. A meta-QTL analysis based on use of the BioMercator software was performed to identify two consensus regions for pathogen resistance traits. Genes that are candidates for causal polymorphism underpinning perennial ryegrass QTLs were identified through in silico comparative mapping using rice databases, and 7 genes were assigned to the p150/112 reference map. Markers linked to the LpDGL1, LpPh1 and LpPIPK1 genes were located close to plant size, leaf extension time and heading date-related QTLs, respectively, suggesting that these genes may be functionally associated with important agronomic traits in perennial ryegrass. Conclusions Functional markers are valuable for QTL meta-analysis and comparative genomics. Enrichment of such genetic markers may permit further detailed characterisation of QTLs. The outcomes of QTL meta-analysis and comparative genomics studies may be useful for accelerated development of novel perennial ryegrass cultivars with desirable traits.

  16. Effects of tibolone on fibrinogen and antithrombin III: A systematic review and meta-analysis of controlled trials.

    Science.gov (United States)

    Bała, Małgorzata; Sahebkar, Amirhossein; Ursoniu, Sorin; Serban, Maria-Corina; Undas, Anetta; Mikhailidis, Dimitri P; Lip, Gregory Y H; Rysz, Jacek; Banach, Maciej

    2017-10-01

    Tibolone is a synthetic steroid with estrogenic, androgenic and progestogenic activity, but the evidence regarding its effects on fibrinogen and antithrombin III (ATIII) has not been conclusive. We assessed the impact of tibolone on fibrinogen and ATIII through a systematic review and meta-analysis of available randomized controlled trials (RCTs). The search included PUBMED, Web of Science, Scopus, and Google Scholar (up to January 31st, 2016) to identify controlled clinical studies investigating the effects of oral tibolone treatment on fibrinogen and ATIII. Overall, the impact of tibolone on plasma fibrinogen concentrations was reported in 10 trials comprising 11 treatment arms. Meta-analysis did not suggest a significant reduction of fibrinogen levels following treatment with tibolone (WMD: -5.38%, 95% CI: -11.92, +1.16, p=0.107). This result was robust in the sensitivity analysis and not influenced after omitting each of the included studies from meta-analysis. When the studies were categorized according to the duration of treatment, there was no effect in the subsets of trials lasting either analysis. There was no differential effect of tibolone on plasma ATIII concentrations in trials with either analysis, meta-regression did not suggest any significant association between the changes in plasma concentrations of fibrinogen (slope: +0.40; 95% CI: -0.39, +1.19; p=0.317) and ATIII (slope: -0.17; 95% CI: -0.54, +0.20; p=0.374) with duration of treatment. In conclusion, meta-analysis did not suggest a significant reduction of fibrinogen and ATIII levels following treatment with tibolone. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Radiofrequency Ablation versus Cryoablation in the Treatment of Paroxysmal Atrial Fibrillation: A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Ali H. Hachem

    2018-01-01

    Full Text Available Background. Pulmonary vein isolation is commonly performed using radiofrequency energy with cryoablation gaining acceptance. We performed a meta-analysis of randomized controlled trials which compared radiofrequency versus cryoablation for patients with atrial fibrillation. Methods. A systematic search strategy identified both published and unpublished articles from inception to November 10, 2016, in multiple databases. The primary outcomes for this meta-analysis were long-term freedom from atrial fibrillation at 12-month follow-up and overall postoperative complication rates. For all included studies, the methodological quality was assessed through the Cochrane Collaboration’s tool for risk of bias. Results. A total of 247 articles were identified with eight being included in this review as they satisfied the prespecified inclusion criteria. Overall, there was no significant difference in freedom from atrial fibrillation at ≥12-month follow-up between those receiving cryoballoon and radiofrequency ablation, respectively (OR = 0.98, CI = 0.67–1.43, I2 = 56%, p=0.90. Additionally, the secondary outcomes of duration of ablation, fluoroscopy time, and ablation time failed to reach significance. Cryoballoon ablation had significantly greater odds of postoperative phrenic nerve injury at 12-month follow-up. Conclusions. Our meta-analysis suggests that cryoballoon ablation provides comparable benefits with regard to freedom from atrial fibrillation at medium-term follow-up, fluoroscopy time, ablation time, operative duration, and overall complication rate in comparison to radiofrequency ablation.

  18. MADAM - An open source meta-analysis toolbox for R and Bioconductor

    Directory of Open Access Journals (Sweden)

    Graber Armin

    2010-03-01

    Full Text Available Abstract Background Meta-analysis is a major theme in biomedical research. In the present paper we introduce a package for R and Bioconductor that provides useful tools for performing this type of work. One idea behind the development of MADAM was that many meta-analysis methods, which are available in R, are not able to use the capacities of parallel computing yet. In this first version, we implemented one meta-analysis method in such a parallel manner. Additionally, we provide tools for combining the results from a set of methods in an ensemble approach. Functionality for visualization of results is also provided. Results The presented package enables the carrying out of meta-analysis either by providing functions directly or by wrapping them to existing implementations. Overall, five different meta-analysis methods are now usable through MADAM, along with another three methods for combining the corresponding results. Visualizing the results is eased by three included functions. For developing and testing meta-analysis methods, a mock up data generator is integrated. Conclusions The use of MADAM enables a user to focus on one package, in turn enabling them to work with the same data types across a set of methods. By making use of the snow package, MADAM can be made compatible with an existing parallel computing infrastructure. MADAM is open source and freely available within CRAN http://cran.r-project.org.

  19. Motor function and incident dementia: a systematic review and meta-analysis.

    Science.gov (United States)

    Kueper, Jacqueline Kathleen; Speechley, Mark; Lingum, Navena Rebecca; Montero-Odasso, Manuel

    2017-09-01

    cognitive and mobility decline are interrelated processes, whereby mobility decline coincides or precedes the onset of cognitive decline. to assess whether there is an association between performance on motor function tests and incident dementia. electronic database, grey literature and hand searching identified studies testing for associations between baseline motor function and incident dementia in older adults. of 2,540 potentially relevant documents, 37 met the final inclusion criteria and were reviewed qualitatively. Three meta-analyses were conducted using data from 10 studies. Three main motor domains-upper limb motor function, parkinsonism and lower limb motor function-emerged as associated with increased risk of incident dementia. Studies including older adults without neurological overt disease found a higher risk of incident dementia associated with poorer performance on composite motor function scores, balance and gait velocity (meta-analysis pooled HR = 1.94, 95% CI: 1.41, 2.65). Mixed results were found across different study samples for upper limb motor function, overall parkinsonism (meta-analysis pooled OR = 3.05, 95% CI: 1.31, 7.08), bradykinesia and rigidity. Studies restricted to older adults with Parkinson's Disease found weak or no association with incident dementia even for motor domains highly associated in less restrictive samples. Tremor was not associated with an increased risk of dementia in any population (meta-analysis pooled HR = 0.80, 95% CI 0.31, 2.03). lower limb motor function was associated with increased risk of developing dementia, while tremor and hand grip strength were not. Our results support future research investigating the inclusion of quantitative motor assessment, specifically gait velocity tests, for clinical dementia risk evaluation. © The Author 2017. Published by Oxford University Press on behalf of the British Geriatrics Society.All rights reserved. For permissions, please email: journals.permissions@oup.com

  20. Body mass index and hand osteoarthritis susceptibility: an updated meta-analysis.

    Science.gov (United States)

    Jiang, Liying; Xie, Xiaohua; Wang, Yidan; Wang, Yingchen; Lu, Yihua; Tian, Tian; Chu, Minjie; Shen, Yi

    2016-12-01

    Numerous epidemiologic studies have evaluated the association between overweight and hand osteoarthritis; However, the existing results are inconsistent. Systematic searches were performed and reference lists from the retrieved trials were searched. This meta-analysis and meta-regression was executed to identify all English-language articles that quantitatively assess the strength of associations between body mass index and hand osteoarthritis risk. Study-specific incremental estimates were standardized to determine the risk associated with a 5 kg/m 2 increase in body mass index. We conducted the study according to the guidelines for the meta-analysis of observational studies in epidemiology. Of the 21 studies included, 13 were cross-sectional studies, three were case control studies and five were cohort studies. The pooled summary estimates were 1.10 (95%CI: 0.98-1.24) with no significant difference (P = 0.09). Subgroup analysis shows that body mass index was positively associated with hand osteoarthritis in cross-sectional studies (1.05 [95%CI: 1.02-1.08] P osteoarthritis risk was found. The summary estimates were 1.06 (95%CI: 1.02-1.10) in studies defined by radiography and 1.25 (95%CI: 1.06-1.49) by radiography and clinically (P osteoarthritis, as defined radiographically and/or radiographically and clinically. The effects vary by study design and osteoarthritis definition. © 2016 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

  1. Association between Hypertension and Epistaxis: Systematic Review and Meta-analysis.

    Science.gov (United States)

    Min, Hyun Jin; Kang, Hyun; Choi, Geun Joo; Kim, Kyung Soo

    2017-12-01

    Objective Whether there is an association or a cause-and-effect relationship between epistaxis and hypertension is a subject of longstanding controversy. The objective of this systematic review and meta-analysis was to determine the association between epistaxis and hypertension and to verify whether hypertension is an independent risk factor of epistaxis. Data Sources A comprehensive search was performed using the MEDLINE, EMBASE, and Cochrane Library databases. Review Methods The review was performed according to the Meta-analysis of Observational Studies in Epidemiology guidelines and reported using the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. Results We screened 2768 unique studies and selected 10 for this meta-analysis. Overall, the risk of epistaxis was significantly increased for patients with hypertension (odds ratio, 1.532 [95% confidence interval (CI), 1.181-1.986]; number needed to treat, 14.9 [95% CI, 12.3-19.0]). Results of the Q test and I 2 statistics suggested considerable heterogeneity ([Formula: see text] = 0.038, I 2 = 49.3%). The sensitivity analysis was performed by excluding 1 study at a time, and it revealed no change in statistical significance. Conclusion Although this meta-analysis had some limitations, our study demonstrated that hypertension was significantly associated with the risk of epistaxis. However, since this association does not support a causal relationship between hypertension and epistaxis, further clinical trials with large patient populations will be required to determine the impact of hypertension on epistaxis.

  2. Tetracycline as local drug delivery in treatment of chronic periodontitis: A systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Prasad Shyamrajan Nadig

    2016-01-01

    Full Text Available Background: The aim of the present meta-analysis is to determine the efficacy of tetracycline group of antibiotics as local drug delivery agents in the treatment of chronic periodontitis. Materials and Methods: MEDLINE, EBSCO, Cochrane database, and Google Scholar were used to identify studies in English published up to January 31, 2017. An additional hand search of relevant journals and of the bibliographies of the paper identified was also performed. Articles retrieved were screened using specific inclusion criteria by two independent reviewers. Randomized control trials investigating the effect of tetracycline group of antibiotics as local drug delivery agents in chronic periodontitis were included in the study. Results: Ten relevant articles were selected for the meta-analysis, of which five articles were retrieved after electronic search, three articles were included after hand search, and two unpublished articles were included. The number of patients in studies ranged from 13 to 140 sites with mean age ranging from 20 to 75. A total of 588 sites were treated using tetracycline group of antibiotics as local drug delivery agents in the treatment of chronic periodontitis. The meta-analysis showed standard difference in mean −1.02 mm (95% confidence interval [CI] 0.28, 1.75 for clinical gain in attachment in favor of tetracycline group. Standard difference in mean for probing depth (PD was 1.20 mm (95% CI 0.57, 1.87 in tetracycline group. Conclusion: The results of this meta-analysis showed a significant improvement in periodontal parameters such as CAL, PD, and sulcular bleeding index in favor of tetracycline as local drug delivery compared to placebo.

  3. Genome-Wide Meta-Analysis of Sciatica in Finnish Population.

    Directory of Open Access Journals (Sweden)

    Susanna Lemmelä

    Full Text Available Sciatica or the sciatic syndrome is a common and often disabling low back disorder in the working-age population. It has a relatively high heritability but poorly understood molecular mechanisms. The Finnish population is a genetic isolate where small founder population and bottleneck events have led to enrichment of certain rare and low frequency variants. We performed here the first genome-wide association (GWAS and meta-analysis of sciatica. The meta-analysis was conducted across two GWAS covering 291 Finnish sciatica cases and 3671 controls genotyped and imputed at 7.7 million autosomal variants. The most promising loci (p<1x10-6 were replicated in 776 Finnish sciatica patients and 18,489 controls. We identified five intragenic variants, with relatively low frequencies, at two novel loci associated with sciatica at genome-wide significance. These included chr9:14344410:I (rs71321981 at 9p22.3 (NFIB gene; p = 1.30x10-8, MAF = 0.08 and four variants at 15q21.2: rs145901849, rs80035109, rs190200374 and rs117458827 (MYO5A; p = 1.34x10-8, MAF = 0.06; p = 2.32x10-8, MAF = 0.07; p = 3.85x10-8, MAF = 0.06; p = 4.78x10-8, MAF = 0.07, respectively. The most significant association in the meta-analysis, a single base insertion rs71321981 within the regulatory region of the transcription factor NFIB, replicated in an independent Finnish population sample (p = 0.04. Despite identifying 15q21.2 as a promising locus, we were not able to replicate it. It was differentiated; the lead variants within 15q21.2 were more frequent in Finland (6-7% than in other European populations (1-2%. Imputation accuracies of the three significantly associated variants (chr9:14344410:I, rs190200374, and rs80035109 were validated by genotyping. In summary, our results suggest a novel locus, 9p22.3 (NFIB, which may be involved in susceptibility to sciatica. In addition, another locus, 15q21.2, emerged as a promising one, but failed to replicate.

  4. Examining the central and peripheral processes of written word production through meta-analysis

    Directory of Open Access Journals (Sweden)

    Jeremy ePurcell

    2011-10-01

    Full Text Available Producing written words requires central cognitive processes (such as orthographic long-term and working memory as well as more peripheral processes responsible for generating the motor actions needed for producing written words in a variety of formats (handwriting, typing, etc.. In recent years, various functional neuroimaging studies have examined the neural substrates underlying the central and peripheral processes of written word production. This study provides the first quantitative meta-analysis of these studies by applying Activation Likelihood Estimation methods (Turkeltaub et al., 2002. For alphabet languages, we identified 11 studies (with a total of 17 experimental contrasts that had been designed to isolate central and/or peripheral processes of word spelling (total number of participants = 146. Three ALE meta-analyses were carried out. One involved the complete set of 17 contrasts; two others were applied to subsets of contrasts to distinguish the neural substrates of central from peripheral processes. These analyses identified a network of brain regions reliably associated with the central and peripheral processes of word spelling. Among the many significant results, is the finding that the regions with the greatest correspondence across studies were in the left inferior temporal/fusiform gyri and left inferior frontal gyrus. Furthermore, although the angular gyrus has traditionally been identified as a key site within the written word production network, none of the meta-analyses found it to be a consistent site of activation, identifying instead a region just superior/medial to the left angular gyrus in the left posterior intraparietal sulcus. In general these meta-analyses and the discussion of results provide a valuable foundation upon which future studies that examine the neural basis of written word production can build.

  5. [Effectiveness of acupuncture in postoperative ileus: a systematic review and Meta-analysis].

    Science.gov (United States)

    Cheong, Kah Bik; Zhang, Jiping; Huang, Yong

    2016-06-01

    To conduct a systematic review and Meta-analysis of the effectiveness of acupuncture and common acupoint selection for postoperative ileus (POI). Randomized controlled trials (RCTs) comparing acupuncture and non-acupuncture treatment were identified from the databases PubMed, Cochrane, EBSCO (Academic Source Premier and MEDLINE), Ovid (including Evidence-Based Medicine Reviews), China National Knowledge Infrastructure, and Wanfang Data. The data from eligible studies were extracted and a Meta-analysis performed using a fixed-effects model. Results were expressed as relative risk (RR) for dichotomous data, and 95% CI (confidence intervals) were calculated. Each trial was evaluated using the CONSORT (Consolidated Standards of Reporting Trials) and STRICTA (STandards for Reporting Interventions in Controlled Trials of Acupuncture) guideline . The quality of the study was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Of the 69 studies screened, eight RCTs were included for review. Among these, four RCTs (with a total of 123 patients in the intervention groups and 124 patients in the control groups) met the criteria for Meta-analysis. The Meta-analysis results indicated that acupuncture combined with usual care showed a significantly higher total effective rate than the control condition (usual care) (RR 1.09, 95% CI 1.01, 1.18; P = 0.02). Zusanli (ST 36) and Shangjuxu (ST 37) were the most common acupoints selected. However, the quality of the studies was generally low, as they did not emphasize the use of blinding. The results suggested that acupuncture might be effective in improving POI; however, a definite conclusion could not be drawn because of the low quality of trials. Further large-scale, high-quality randomized clinical trials are needed to validate these findings and to develop a standardized method of treatment. We hope that the present results will lead to improved research, resulting in better

  6. Individual Participant Data Meta-Analysis of Mechanical Workplace Risk Factors and Low Back Pain

    Science.gov (United States)

    Shannon, Harry S.; Wells, Richard P.; Walter, Stephen D.; Cole, Donald C.; Côté, Pierre; Frank, John; Hogg-Johnson, Sheilah; Langlois, Lacey E.

    2012-01-01

    Objectives. We used individual participant data from multiple studies to conduct a comprehensive meta-analysis of mechanical exposures in the workplace and low back pain. Methods. We conducted a systematic literature search and contacted an author of each study to request their individual participant data. Because outcome definitions and exposure measures were not uniform across studies, we conducted 2 substudies: (1) to identify sets of outcome definitions that could be combined in a meta-analysis and (2) to develop methods to translate mechanical exposure onto a common metric. We used generalized estimating equation regression to analyze the data. Results. The odds ratios (ORs) for posture exposures ranged from 1.1 to 2.0. Force exposure ORs ranged from 1.4 to 2.1. The magnitudes of the ORs differed according to the definition of low back pain, and heterogeneity was associated with both study-level and individual-level characteristics. Conclusions. We found small to moderate ORs for the association of mechanical exposures and low back pain, although the relationships were complex. The presence of individual-level OR modifiers in such an area can be best understood by conducting a meta-analysis of individual participant data. PMID:22390445

  7. Cost-Effectiveness Analysis of Regorafenib for Metastatic Colorectal Cancer.

    Science.gov (United States)

    Goldstein, Daniel A; Ahmad, Bilal B; Chen, Qiushi; Ayer, Turgay; Howard, David H; Lipscomb, Joseph; El-Rayes, Bassel F; Flowers, Christopher R

    2015-11-10

    Regorafenib is a standard-care option for treatment-refractory metastatic colorectal cancer that increases median overall survival by 6 weeks compared with placebo. Given this small incremental clinical benefit, we evaluated the cost-effectiveness of regorafenib in the third-line setting for patients with metastatic colorectal cancer from the US payer perspective. We developed a Markov model to compare the cost and effectiveness of regorafenib with those of placebo in the third-line treatment of metastatic colorectal cancer. Health outcomes were measured in life-years and quality-adjusted life-years (QALYs). Drug costs were based on Medicare reimbursement rates in 2014. Model robustness was addressed in univariable and probabilistic sensitivity analyses. Regorafenib provided an additional 0.04 QALYs (0.13 life-years) at a cost of $40,000, resulting in an incremental cost-effectiveness ratio of $900,000 per QALY. The incremental cost-effectiveness ratio for regorafenib was > $550,000 per QALY in all of our univariable and probabilistic sensitivity analyses. Regorafenib provides minimal incremental benefit at high incremental cost per QALY in the third-line management of metastatic colorectal cancer. The cost-effectiveness of regorafenib could be improved by the use of value-based pricing. © 2015 by American Society of Clinical Oncology.

  8. A meta-analysis of changes in brain activity in clinical depression

    Directory of Open Access Journals (Sweden)

    Susan Mary Palmer

    2015-01-01

    Full Text Available Insights into neurobiological mechanisms of depression are increasingly being sought via brain imaging studies. Our aim was to quantitatively summarize overlap and divergence in regions of altered brain activation associated with depression under emotionally-valenced compared to cognitively-demanding task conditions, with reference to intrinsic functional connectivity. We hypothesized differences reflective of task demands. A coordinate-based meta-analysis technique, Activation Likelihood Estimation (ALE, was used to analyze relevant imaging literature. These studies compared brain activity in depressed adults relative to healthy controls during three conditions: (i emotionally-valenced (cognitively easy tasks (n=29; (ii cognitively-demanding tasks (n=15; and (iii resting conditions (n=21.The meta-analyses identified 5, 8 and 7 significant clusters of altered brain activity under emotion, cognition and resting conditions respectively in depressed individuals compared to healthy controls. Regions of overlap and divergence between pairs of the three separate meta-analyses were quantified. There were no significant regions of overlap between emotion and cognition meta-analyses, but several divergent clusters were found. Cognitively-demanding conditions were associated with greater activation of right medial frontal and insula regions while bilateral amygdala was more significantly altered during emotion (cognitively-undemanding conditions; consistent with task demands.Overlap was present in left amygdala and right subcallosal cingulate between emotion and resting meta-analyses, with no significant divergence.Our meta-analyses highlight alteration of common brain regions, during cognitively-undemanding emotional tasks and resting conditions but divergence of regions between emotional and cognitively-demanding tasks. Regions altered reflect current biological and system-level models of depression and highlight the relationship with task condition and

  9. H Ferritin Gene Silencing in a Human Metastatic Melanoma Cell Line: A Proteomic Analysis

    DEFF Research Database (Denmark)

    Di Sanzo, Maddalena; Gaspari, Marco; Misaggi, Roberta

    2011-01-01

    Ferritin, the major intracellular iron-storage protein, is made of 24 subunits of two types, H and L. Besides regulating intracellular iron homeostasis, it has been found that ferritin, in particular the H subunit (FHC), is involved in different biological events such as cell differentiation...... and pathologic states (i.e., neurodegeneration and cancer). This study is aimed at investigating the whole-cell proteome of FHC-expressing and sh-RNA-silenced human metastatic melanoma cells (MM07(m)) in the attempt to identify and classify the highest number of proteins directly or indirectly controlled...... of H ferritin signaling pathways and lend support to the hypothesis that specific targeting of this gene might be an attractive and potentially effective strategy for the management of metastatic melanoma....

  10. META-ANALYSIS OF GENOME-WIDE STUDIES IDENTIFIES WNT16 AND ESR1 SNPS ASSOCIATED WITH BONE MINERAL DENSITY IN PREMENOPAUSAL WOMEN

    Science.gov (United States)

    Koller, Daniel L.; Zheng, Hou-Feng; Karasik, David; Yerges-Armstrong, Laura; Liu, Ching-Ti; McGuigan, Fiona; Kemp, John P.; Giroux, Sylvie; Lai, Dongbing; Edenberg, Howard J.; Peacock, Munro; Czerwinski, Stefan A.; Choh, Audrey C.; McMahon, George; St Pourcain, Beate; Timpson, Nicholas J.; Lawlor, Debbie A; Evans, David M; Towne, Bradford; Blangero, John; Carless, Melanie A.; Kammerer, Candace; Goltzman, David; Kovacs, Christopher S.; Prior, Jerilynn C.; Spector, Tim D.; Rousseau, Francois; Tobias, Jon H.; Akesson, Kristina; Econs, Michael J.; Mitchell, Braxton D.; Richards, J. Brent; Kiel, Douglas P.; Foroud, Tatiana

    2013-01-01

    Previous genome-wide association studies (GWAS) have identified common variants in genes associated with variation in bone mineral density (BMD), although most have been carried out in combined samples of older women and men. Meta-analyses of these results have identified numerous SNPs of modest effect at genome-wide significance levels in genes involved in both bone formation and resorption, as well as other pathways. We performed a meta-analysis restricted to premenopausal white women from four cohorts (n= 4,061 women, ages 20 to 45) to identify genes influencing peak bone mass at the lumbar spine and femoral neck. Following imputation, age- and weight-adjusted BMD values were tested for association with each SNP. Association of a SNP in the WNT16 gene (rs3801387; p=1.7 × 10−9) and multiple SNPs in the ESR1/C6orf97 (rs4870044; p=1.3 × 10−8) achieved genome-wide significance levels for lumbar spine BMD. These SNPs, along with others demonstrating suggestive evidence of association, were then tested for association in seven Replication cohorts that included premenopausal women of European, Hispanic-American, and African-American descent (combined n=5,597 for femoral neck; 4,744 for lumbar spine). When the data from the Discovery and Replication cohorts were analyzed jointly, the evidence was more significant (WNT16 joint p=1.3 × 10−11; ESR1/C6orf97 joint p= 1.4 × 10−10). Multiple independent association signals were observed with spine BMD at the ESR1 region after conditioning on the primary signal. Analyses of femoral neck BMD also supported association with SNPs in WNT16 and ESR1/C6orf97 (p< 1 × 10−5). Our results confirm that several of the genes contributing to BMD variation across a broad age range in both sexes have effects of similar magnitude on BMD of the spine in premenopausal women. These data support the hypothesis that variants in these genes of known skeletal function also affect BMD during the premenopausal period. PMID:23074152

  11. Individual and Work-Related Factors Influencing Burnout of Mental Health Professionals: A Meta-Analysis

    Science.gov (United States)

    Lim, Nayoung; Kim, Eun Kyoung; Kim, Hyunjung; Yang, Eunjoo; Lee, Sang Min

    2010-01-01

    The current study identifies and assesses individual and work-related factors as correlates of burnout among mental health professionals. Results of a meta-analysis indicate that age and work setting variables are the most significant indicators of emotional exhaustion and depersonalization. In terms of level of personal accomplishment, the age…

  12. Likelihood ratio meta-analysis: New motivation and approach for an old method.

    Science.gov (United States)

    Dormuth, Colin R; Filion, Kristian B; Platt, Robert W

    2016-03-01

    A 95% confidence interval (CI) in an updated meta-analysis may not have the expected 95% coverage. If a meta-analysis is simply updated with additional data, then the resulting 95% CI will be wrong because it will not have accounted for the fact that the earlier meta-analysis failed or succeeded to exclude the null. This situation can be avoided by using the likelihood ratio (LR) as a measure of evidence that does not depend on type-1 error. We show how an LR-based approach, first advanced by Goodman, can be used in a meta-analysis to pool data from separate studies to quantitatively assess where the total evidence points. The method works by estimating the log-likelihood ratio (LogLR) function from each study. Those functions are then summed to obtain a combined function, which is then used to retrieve the total effect estimate, and a corresponding 'intrinsic' confidence interval. Using as illustrations the CAPRIE trial of clopidogrel versus aspirin in the prevention of ischemic events, and our own meta-analysis of higher potency statins and the risk of acute kidney injury, we show that the LR-based method yields the same point estimate as the traditional analysis, but with an intrinsic confidence interval that is appropriately wider than the traditional 95% CI. The LR-based method can be used to conduct both fixed effect and random effects meta-analyses, it can be applied to old and new meta-analyses alike, and results can be presented in a format that is familiar to a meta-analytic audience. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Age, the psychological contract, and job attitudes : a meta-analysis

    NARCIS (Netherlands)

    Bal, P. Matthijs; de Lange, Annet H.; Jansen, Paul G. W.; van der Velde, Mandy E. G.

    Age, the psychological contract, and job attitudes: a meta-analysis P.M. Bal, A H. De Lange, P.G.W Jansen Er M.E G Van der Velde, Gedrag en Organisatie, volume 23, March 2010, nr 1, pp 44-72. The meta-analysis investigated the relations between age and psychological contracts It was expected that

  14. Chronic subdural hematoma: a systematic review and meta-analysis of surgical procedures.

    Science.gov (United States)

    Liu, Weiming; Bakker, Nicolaas A; Groen, Rob J M

    2014-09-01

    In this paper the authors systematically evaluate the results of different surgical procedures for chronic subdural hematoma (CSDH). The MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and other databases were scrutinized according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) statement, after which only randomized controlled trials (RCTs) and quasi-RCTs were included. At least 2 different neurosurgical procedures in the management of chronic subdural hematoma (CSDH) had to be evaluated. Included studies were assessed for the risk of bias. Recurrence rates, complications, and outcome including mortality were taken as outcome measures. Statistical heterogeneity in each meta-analysis was assessed using the T(2) (tau-squared), I(2), and chi-square tests. The DerSimonian-Laird method was used to calculate the summary estimates using the fixed-effect model in meta-analysis. Of the 297 studies identified, 19 RCTs were included. Of them, 7 studies evaluated the use of postoperative drainage, of which the meta-analysis showed a pooled OR of 0.36 (95% CI 0.21-0.60; p < 0.001) in favor of drainage. Four studies compared twist drill and bur hole procedures. No significant differences between the 2 methods were present, but heterogeneity was considered to be significant. Three studies directly compared the use of irrigation before drainage. A fixed-effects meta-analysis showed a pooled OR of 0.49 (95% CI 0.21-1.14; p = 0.10) in favor of irrigation. Two studies evaluated postoperative posture. The available data did not reveal a significant advantage in favor of the postoperative supine posture. Regarding positioning of the catheter used for drainage, it was shown that a frontal catheter led to a better outcome. One study compared duration of drainage, showing that 48 hours of drainage was as effective as 96 hours of drainage. Postoperative drainage has the advantage of reducing recurrence without increasing complications

  15. Genome-wide association analysis of more than 120,000 individuals identifies 15 new susceptibility loci for breast cancer

    NARCIS (Netherlands)

    K. Michailidou (Kyriaki); J. Beesley (Jonathan); S. Lindstrom (Stephen); S. Canisius (Sander); J. Dennis (Joe); M. Lush (Michael); M. Maranian (Melanie); M.K. Bolla (Manjeet); Q. Wang (Qing); M. Shah (Mitul); B. Perkins (Barbara); K. Czene (Kamila); M. Eriksson (Mikael); H. Darabi (Hatef); J.S. Brand (Judith S.); S.E. Bojesen (Stig); B.G. Nordestgaard (Børge); H. Flyger (Henrik); S.F. Nielsen (Sune); N. Rahman (Nazneen); C. Turnbull (Clare); O. Fletcher (Olivia); J. Peto (Julian); L.J. Gibson (Lorna); I. dos Santos Silva (Isabel); J. Chang-Claude (Jenny); D. Flesch-Janys (Dieter); A. Rudolph (Anja); U. Eilber (Ursula); T.W. Behrens (Timothy); H. Nevanlinna (Heli); T.A. Muranen (Taru); K. Aittomäki (Kristiina); C. Blomqvist (Carl); S. Khan (Sofia); K. Aaltonen (Kirsimari); H. Ahsan (Habibul); M.G. Kibriya (Muhammad); A.S. Whittemore (Alice S.); E.M. John (Esther M.); K.E. Malone (Kathleen E.); M.D. Gammon (Marilie); R.M. Santella (Regina M.); G. Ursin (Giske); E. Makalic (Enes); D.F. Schmidt (Daniel); G. Casey (Graham); D.J. Hunter (David J.); S.M. Gapstur (Susan M.); M.M. Gaudet (Mia); W.R. Diver (Ryan); C.A. Haiman (Christopher A.); F.R. Schumacher (Fredrick); B.E. Henderson (Brian); L. Le Marchand (Loic); C.D. Berg (Christine); S.J. Chanock (Stephen); J.D. Figueroa (Jonine); R.N. Hoover (Robert N.); D. Lambrechts (Diether); P. Neven (Patrick); H. Wildiers (Hans); E. van Limbergen (Erik); M.K. Schmidt (Marjanka); A. Broeks (Annegien); S. Verhoef; S. Cornelissen (Sten); F.J. Couch (Fergus); J.E. Olson (Janet); B. Hallberg (Boubou); C. Vachon (Celine); Q. Waisfisz (Quinten); E.J. Meijers-Heijboer (Hanne); M.A. Adank (Muriel); R.B. van der Luijt (Rob); J. Li (Jingmei); J. Liu (Jianjun); M.K. Humphreys (Manjeet); D. Kang (Daehee); J.-Y. Choi (Ji-Yeob); S.K. Park (Sue K.); K.Y. Yoo; K. Matsuo (Keitaro); H. Ito (Hidemi); H. Iwata (Hiroji); K. Tajima (Kazuo); P. Guénel (Pascal); T. Truong (Thérèse); C. Mulot (Claire); M. Sanchez (Marie); B. Burwinkel (Barbara); F. Marme (Federick); H. Surowy (Harald); C. Sohn (Christof); A.H. Wu (Anna H); C.-C. Tseng (Chiu-chen); D. Van Den Berg (David); D.O. Stram (Daniel O.); A. González-Neira (Anna); J. Benítez (Javier); M.P. Zamora (Pilar); J.I.A. Perez (Jose Ignacio Arias); X.-O. Shu (Xiao-Ou); W. Lu (Wei); Y. Gao; H. Cai (Hui); A. Cox (Angela); S.S. Cross (Simon); M.W.R. Reed (Malcolm); I.L. Andrulis (Irene); J.A. Knight (Julia); G. Glendon (Gord); A.-M. Mulligan (Anna-Marie); E.J. Sawyer (Elinor); I.P. Tomlinson (Ian); M. Kerin (Michael); N. Miller (Nicola); A. Lindblom (Annika); S. Margolin (Sara); S.H. Teo (Soo Hwang); C.H. Yip (Cheng Har); N.A.M. Taib (Nur Aishah Mohd); G.-H. Tan (Gie-Hooi); M.J. Hooning (Maartje); A. Hollestelle (Antoinette); J.W.M. Martens (John); J.M. Collée (Margriet); W.J. Blot (William); L.B. Signorello (Lisa B.); Q. Cai (Qiuyin); J. Hopper (John); M.C. Southey (Melissa); H. Tsimiklis (Helen); C. Apicella (Carmel); C-Y. Shen (Chen-Yang); C.-N. Hsiung (Chia-Ni); P.-E. Wu (Pei-Ei); M.-F. Hou (Ming-Feng); V. Kristensen (Vessela); S. Nord (Silje); G.G. Alnæs (Grethe); G.G. Giles (Graham G.); R.L. Milne (Roger); C.A. McLean (Catriona Ann); F. Canzian (Federico); D. Trichopoulos (Dimitrios); P.H.M. Peeters; E. Lund (Eiliv); R. Sund (Reijo); K.T. Khaw; M.J. Gunter (Marc J.); D. Palli (Domenico); L.M. Mortensen (Lotte Maxild); L. Dossus (Laure); J.-M. Huerta (Jose-Maria); A. Meindl (Alfons); R.K. Schmutzler (Rita); C. Sutter (Christian); R. Yang (Rongxi); K. Muir (Kenneth); A. Lophatananon (Artitaya); S. Stewart-Brown (Sarah); P. Siriwanarangsan (Pornthep); J.M. Hartman (Joost); X. Miao; K.S. Chia (Kee Seng); C.W. Chan (Ching Wan); P.A. Fasching (Peter); R. Hein (Rebecca); M.W. Beckmann (Matthias); L. Haeberle (Lothar); H. Brenner (Hermann); A.K. Dieffenbach (Aida Karina); V. Arndt (Volker); C. Stegmaier (Christa); A. Ashworth (Alan); N. Orr (Nick); M. Schoemaker (Minouk); A.J. Swerdlow (Anthony ); L.A. Brinton (Louise); M. García-Closas (Montserrat); W. Zheng (Wei); S.L. Halverson (Sandra L.); M. Shrubsole (Martha); J. Long (Jirong); M.S. Goldberg (Mark); F. Labrèche (France); M. Dumont (Martine); R. Winqvist (Robert); K. Pykäs (Katri); A. Jukkola-Vuorinen (Arja); M. Grip (Mervi); H. Brauch (Hiltrud); U. Hamann (Ute); T. Brüning (Thomas); P. Radice (Paolo); P. Peterlongo (Paolo); S. Manoukian (Siranoush); L. Bernard (Loris); N.V. Bogdanova (Natalia); T. Dörk (Thilo); A. Mannermaa (Arto); V. Kataja (Vesa); V-M. Kosma (Veli-Matti); J.M. Hartikainen (J.); P. Devilee (Peter); R.A.E.M. Tollenaar (Rob); C.M. Seynaeve (Caroline); C.J. van Asperen (Christi); A. Jakubowska (Anna); J. Lubinski (Jan); K. Jaworska (Katarzyna); T. Huzarski (Tomasz); S. Sangrajrang (Suleeporn); V. Gaborieau (Valerie); P. Brennan (Paul); J.D. McKay (James); S. Slager (Susan); A.E. Toland (Amanda); C.B. Ambrosone (Christine); D. Yannoukakos (Drakoulis); M. Kabisch (Maria); D. Torres (Diana); S.L. Neuhausen (Susan); H. Anton-Culver (Hoda); C. Luccarini (Craig); C. Baynes (Caroline); S. Ahmed (Shahana); S. Healey (Sue); D.C. Tessier (Daniel C.); D. Vincent (Daniel); F. Bacot (Francois); G. Pita (Guillermo); M.R. Alonso (Rosario); N. Álvarez (Nuria); D. Herrero (Daniel); J. Simard (Jacques); P.P.D.P. Pharoah (Paul P.D.P.); P. Kraft (Peter); A.M. Dunning (Alison); G. Chenevix-Trench (Georgia); P. Hall (Per); D.F. Easton (Douglas)

    2015-01-01

    textabstractGenome-wide association studies (GWAS) and large-scale replication studies have identified common variants in 79 loci associated with breast cancer, explaining ∼14% of the familial risk of the disease. To identify new susceptibility loci, we performed a meta-analysis of 11 GWAS,

  16. Role of peripheral inflammatory markers in postoperative cognitive dysfunction (POCD: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Linying Peng

    Full Text Available BACKGROUND: Postoperative cognitive dysfunction (POCD is common following cardiac and non-cardiac surgery, but the pathogenic mechanisms remain unknown. Many studies suggest that an inflammatory response is a key contributor to POCD. The current meta-analysis shows that the levels of peripheral inflammatory markers are associated with POCD. METHODS: An online search was performed to identify peer-reviewed studies without language restriction that measured peripheral inflammatory markers of patients with and without POCD, using PubMed, ScienceDirect, SinoMed and the National Knowledge Infrastructure database. Extracted data were analyzed with STATA (version 12.The standardized mean difference (SMD and the 95% confidence interval (95%CI were calculated for each outcome using a random effect model. Tests of heterogeneity assessment of bias, and meta-regression were performed in the meta-analysis. RESULTS: A total of 13 studies that measured the concentrations of peripheral inflammatory markers were included. The current meta-analysis found significantly higher concentrations of S-100β(SMD[95%CI] (1.377 [0.423, 2.331], p-value < 0.001, N [POCD/non-POCD] =178/391, 7 studies, and interleukin(IL-6 (SMD[95%CI] (1.614 [0.603,2.624], p-value < 0.001, N[POCD/non-POCD] = 91/99, 5 studies, but not of neuron specific enolase, interleukin-1β, or tumor necrosis factor-α , in POCD compared with patients without POCD. In meta-regression analyses, a significant positive association was found between the SMD and the preoperative interleukin-6 peripheral blood concentration in patients with POCD (Coef.= 0.0587, p-value=0.038, 5 studies. CONCLUSIONS: This study shows that POCD is indeed correlated with the concentrations of peripheral inflammatory markers, particularly interleukin-6 and S-100β.

  17. Adult weight gain and colorectal adenomas-a systematic review and meta-analysis.

    Science.gov (United States)

    Schlesinger, S; Aleksandrova, K; Abar, L; Vieria, A R; Vingeliene, S; Polemiti, E; Stevens, C A T; Greenwood, D C; Chan, D S M; Aune, D; Norat, T

    2017-06-01

    Colorectal adenomas are known as precursors for the majority of colorectal carcinomas. While weight gain during adulthood has been identified as a risk factor for colorectal cancer, the association is less clear for colorectal adenomas. We conducted a systematic review and meta-analysis to quantify the evidence on this association. We searched Medline up to September 2016 to identify observational (prospective, cross-sectional and retrospective) studies on weight gain during adulthood and colorectal adenoma occurrence and recurrence. We conducted meta-analysis on high weight gain versus stable weight, linear and non-linear dose-response meta-analyses to analyze the association. Summary odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using a random effects model. For colorectal adenoma occurrence, the summary OR was 1.39 (95% CI: 1.17-1.65; I2: 43%, N = 9 studies, cases = 5507) comparing high (midpoint: 17.4 kg) versus stable weight gain during adulthood and with each 5 kg weight gain the odds increased by 7% (2%-11%; I2: 65%, N = 7 studies). Although there was indication of non-linearity (Pnon-linearity firm conclusions. Even a small amount of adult weight gain was related to a higher odds of colorectal adenoma occurrence. Our findings add to the benefits of weight control in adulthood regarding colorectal adenoma occurrence, which might be relevant for early prevention of colorectal cancer. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  18. Working after a metastatic cancer diagnosis: factors affecting employment in the metastatic setting from ECOG’s Symptom Outcomes and Practice Patterns (SOAPP) study

    Science.gov (United States)

    Tevaarwerk, Amye; Lee, Ju-Whei; Terhaar, Abigail; Sesto, Mary; Smith, Mary Lou; Cleeland, Charles; Fisch, Michael

    2015-01-01

    Background Improved survival for individuals with metastatic cancer accentuates the importance of employment for cancer survivors. Better understanding of how metastatic cancer affects employment is a necessary step towards the development of tools to assist survivors in this important realm. Methods We analyzed the Eastern Cooperative Oncology Group’s “Symptom Outcomes and Practice Patterns (SOAPP)” study to investigate what factors were associated with employment of 680 metastatic cancer patients. Univariable and multivariable logistic regression analyses were conducted to compare patients stably working (Group A) to patients no longer working (Group B). Results There were 668 metastatic working-age participants in our analysis; 236 (35%) worked full or part-time while 302 (45%) stopped working due to illness. Overall, 58% reported some change in employment due to illness. Better performance status and non-Hispanic White ethnicity/race were significantly associated with continuing to work despite a metastatic cancer diagnosis on multivariable analysis. Disease type, time since metastatic diagnosis, number of metastatic sites, location of metastatic disease, and treatment status had no significant impact. Among the potentially modifiable factors, receiving hormonal treatment (if a viable option) and decreasing symptom interference were associated with continuing to work. Conclusions A significant percentage of metastatic patients remain employed; symptom burden was associated with change to no longer working. Modifiable factors resulting in work interference should be minimized so that patients with metastatic disease may continue working, if desired. Improvements in symptom control and strategies developed to help address work place difficulties have promise to improve this aspect of survivorship. PMID:26687819

  19. Accuracy of Percutaneous Core Biopsy in the Diagnosis of Small Renal Masses (≤4.0 cm: A Meta-analysis

    Directory of Open Access Journals (Sweden)

    Qiqi He

    2015-02-01

    Full Text Available Objective To use meta-analysis to determine the accuracy of percutaneous core needle biopsy in the diagnosis of small renal masses (SMRs≤4.0 cm. Materials and Methods Studies were identified by searching PubMed, Embase, and the Cochrane Library database up to March 2013. Two of the authors independently assessed the study quality using QUADAS-2 tool and extracted data that met the inclusion criteria. The sensitivity, specificity, likelihood ratios, diagnostic odds ratio (DOR and also summary receiver operating characteristic (SROC curve were investigated and draw. Deek’s funnel plot was used to evaluate the publication bias. Result A total of 9 studies with 788 patients (803 biopsies were included. Failed biopsies without repeated or aborted from follow-up/surgery result were excluded (232 patients and 353 biopsies. For all cases, the pooled sensitivity was 94.0% (95% CI: 91.0%, 95.0%, the pooled positive likelihood was 22.57 (95% CI: 9.20-55.34, the pooled negative likelihood was 0.09 (95% CI: 0.06-0.13, the pooled DOR was 296.52(95% CI: 99. 42-884.38. The area under the curve of SROC analysis was 0.959±0.0254. Conclusion Imaging-guided percutaneous core needle biopsy of small renal masses (SMRs≤4.0 cm is highly accurate to malignant tumor diagnosis with unknown metastatic status and could be offered to some patients after clinic judgment prior to surgical intervention consideration.

  20. The Impact of Uncertainty on Investment. A Meta-Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Koetse, M.J. [Department of Spatial Economics, Vrije Universiteit Amsterdam (Netherlands); De Groot, Henri L.F. [Tinbergen Institute, Amsterdam (Netherlands); Florax, R.J.G.M. [Department of Agricultural Economics, Purdue University, West Lafayette (United States)

    2006-07-01

    In this paper we perform a meta-analysis on empirical estimates of the impact between investment and uncertainty. Since the outcomes of primary studies are largely incomparable with respect to the magnitude of the effect, our analysis focuses on the direction and statistical significance of the relationship. The standard approach in this situation is to estimate an ordered probit model on a categorical estimate, defined in terms of the direction of the effect. The estimates are transformed into marginal effects, in order to represent the changes in the probability of finding a negative significant, insignificant, and positive significant estimate. Although a meta-analysis generally does not allow for inferences on the correctness of model specifications in primary studies, our results give clear directions for model building in empirical investment research. For example, not including factor prices in investment models may seriously affect the model outcomes. Furthermore, we find that Q models produce more negative significant estimates than other models do, ceteris paribus. The outcome of a study is also affected by the type of data used in a primary study. Although it is clear that meta-analysis cannot always give decisive insights into the explanations for the variation in empirical outcomes, our meta-analysis shows that we can explain to a large extent why empirical estimates of the investment uncertainty relationship differ.

  1. Physical Readiness Training: A Meta-Analysis

    National Research Council Canada - National Science Library

    Vickers, Jr, Ross R

    2007-01-01

    .... This meta-analysis of available PRT studies (k = 3) indicated that (a) Fitness gains in the PRT program were equal to the gains in traditional fitness programs, and (b) the injury rate (i.e., hazard ratio...

  2. Hydropower externalities: A meta-analysis

    International Nuclear Information System (INIS)

    Mattmann, Matteo; Logar, Ivana; Brouwer, Roy

    2016-01-01

    This paper presents a meta-analysis of existing research related to the economic valuation of the external effects of hydropower. A database consisting of 81 observations derived from 29 studies valuing the non-market impacts of hydropower electricity generation is constructed with the main aim to quantify and explain the economic values for positive and negative hydropower externalities. Different meta-regression model specifications are used to test the robustness of significant determinants of non-market values, including different types of hydropower impacts. The explanatory and predictive power of the estimated models is relatively high. Whilst controlling for sample and study characteristics, we find significant evidence for public aversion towards deteriorations of landscape, vegetation and wildlife caused by hydropower projects. There is however only weak evidence of willingness to pay for mitigating these effects. The main positive externality of hydropower generation, the avoidance of greenhouse gas emission, positively influences welfare estimates when combined with the share of hydropower in national energy production. Sensitivity to scope is detected, but not linked to specific externalities or non-market valuation methods. - Highlights: • A global meta-analysis of valuation studies of hydropower externalities is presented. • Positive and negative externalities are distinguished. • Welfare losses due to environmental deteriorations outweigh gains of GHG reductions. • There is only weak evidence of public WTP for mitigating negative externalities. • The non-market values of hydropower externalities are sensitive to scope.

  3. Occupational exposure to hexavalent chromium and cancers of the gastrointestinal tract: a meta-analysis.

    Science.gov (United States)

    Gatto, Nicole M; Kelsh, Michael A; Mai, Diem Ha; Suh, Mina; Proctor, Deborah M

    2010-08-01

    We conducted a systematic literature review and meta-analysis of oral cavity, esophageal, stomach, small intestine, colon, and rectal cancers among workers occupationally exposed to Cr(VI). Using PubMed, studies published from 1950 to 2009 evaluating the relationship between Cr(VI) exposure and GI cancers were identified. Measures of effect and variability were extracted from 32 studies meeting specific inclusion criteria, and meta-analysis summary relative risk measures were calculated using random effects models and inverse variance weighting methods. Meta-standardized mortality ratios (SMRs) were, for cancer of the: oral cavity [1.02 (95% CI=0.77-1.34)]; esophagus [1.17 (95% CI=0.90-1.51)]; stomach [1.09 (95% CI=0.93-1.28)]; colon [0.89 (95% CI=0.70-1.12)]; and rectum [1.17 (95% CI=0.98-1.39)]. Analyses of more highly exposed subgroups included in the studies or subgroups based on geographic region or by industry with recognized Cr(VI) exposures (welding, chrome plating, chromate production, and pigment production) did not result in elevated meta-SMRs except for esophageal cancer among US cohorts [meta-SMR=1.49 (95% CI=1.06-2.09)]. However, that finding was based on a subgroup of only four studies, one of which was a PMR study. Potential confounding by socioeconomic status (SES), diet and/or smoking, or limitations due to the healthy-worker effect (HWE) were evaluated, and while smoking, diet and SES may be important factors that may have upwardly biased the meta-SMRs, HWE is not likely to have significantly affected the summary results. None of three studies reporting small intestine cancers observed a statistically significant increased risk. These meta-analyses and literature review indicate that Cr(VI)-exposed workers are not at a greater risk of GI cancers than the general population.

  4. Can chocolate consumption reduce cardio-cerebrovascular risk? A systematic review and meta-analysis.

    Science.gov (United States)

    Gianfredi, Vincenza; Salvatori, Tania; Nucci, Daniele; Villarini, Milena; Moretti, Massimo

    2018-02-01

    A systematic review and meta-analysis of the literature was performed to assess the relationship between chocolate intake and cardio-cerebrovascular risk in the general population. A structured search of the literature was performed in the PubMed database up to September 26, 2016, using predetermined keywords. Epidemiologic studies evaluating the risk for cardiovascular diseases (CVDs; i.e., stroke, acute myocardial infarction [MI], heart failure, coronary heart disease) were included according to different rates of chocolate intake. The software ProMeta 3 was used to perform the meta-analysis. The systematic review identified 16 eligible studies. The majority of the studies showed a protective effect of chocolate intake compared with unexposed individuals. The overall risk ratio (effect size [ES]) of CVD for the highest versus the lowest category of chocolate consumption was 0.77 (95% confidence interval [CI], 0.71-0.84; P = 0.000) with a moderate heterogeneity. The risk related to subgroups of CVD and in particular, the risk for MI was further analyzed: ES = 0.78 (95% CI, 0.64-0.94; P = 0.009) without statistical heterogeneity (I 2  = 46.56%; P = 0.13). Moreover, the analysis performed based on sex found an ES = 0.85 (95% CI, 0.77-0.95; P = 0.003) for women, with a very low grade of heterogeneity (I 2  = 62.21%; P = 0.005). The results of the meta-analysis showed a potential protective effect of moderate consumption of chocolate on cardiovascular risk, especially for women, and against MI for both sexes. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Telemedicine Technologies for Diabetes in Pregnancy: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Ming, Wai-Kit; Mackillop, Lucy H; Farmer, Andrew J; Loerup, Lise; Bartlett, Katy; Levy, Jonathan C; Tarassenko, Lionel; Velardo, Carmelo; Kenworthy, Yvonne; Hirst, Jane E

    2016-11-09

    Diabetes in pregnancy is a global problem. Technological innovations present exciting opportunities for novel approaches to improve clinical care delivery for gestational and other forms of diabetes in pregnancy. To perform an updated and comprehensive systematic review and meta-analysis of the literature to determine whether telemedicine solutions offer any advantages compared with the standard care for women with diabetes in pregnancy. The review was developed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework. Randomized controlled trials (RCT) in women with diabetes in pregnancy that compared telemedicine blood glucose monitoring with the standard care were identified. Searches were performed in SCOPUS and PubMed, limited to English language publications between January 2000 and January 2016. Trials that met the eligibility criteria were scored for risk of bias using the Cochrane Collaborations Risk of Bias Tool. A meta-analysis was performed using Review Manager software version 5.3 (Nordic Cochrane Centre, Cochrane Collaboration). A total of 7 trials were identified. Meta-analysis demonstrated a modest but statistically significant improvement in HbA1c associated with the use of a telemedicine technology. The mean HbA1c of women using telemedicine was 5.33% (SD 0.70) compared with 5.45% (SD 0.58) in the standard care group, representing a mean difference of -0.12% (95% CI -0.23% to -0.02%). When this comparison was limited to women with gestational diabetes mellitus (GDM) only, the mean HbA1c of women using telemedicine was 5.22% (SD 0.70) compared with 5.37% (SD 0.61) in the standard care group, mean difference -0.14% (95% CI -0.25% to -0.04%). There were no differences in other maternal and neonatal outcomes reported. There is currently insufficient evidence that telemedicine technology is superior to standard care for women with diabetes in pregnancy; however, there was no evidence of harm. No trials were

  6. Prevalence of rapid eye movement sleep behavior disorder (RBD) in Parkinson's disease: a meta and meta-regression analysis.

    Science.gov (United States)

    Zhang, Xiaona; Sun, Xiaoxuan; Wang, Junhong; Tang, Liou; Xie, Anmu

    2017-01-01

    Rapid eye movement sleep behavior disorder (RBD) is thought to be one of the most frequent preceding symptoms of Parkinson's disease (PD). However, the prevalence of RBD in PD stated in the published studies is still inconsistent. We conducted a meta and meta-regression analysis in this paper to estimate the pooled prevalence. We searched the electronic databases of PubMed, ScienceDirect, EMBASE and EBSCO up to June 2016 for related articles. STATA 12.0 statistics software was used to calculate the available data from each research. The prevalence of RBD in PD patients in each study was combined to a pooled prevalence with a 95 % confidence interval (CI). Subgroup analysis and meta-regression analysis were performed to search for the causes of the heterogeneity. A total of 28 studies with 6869 PD cases were deemed eligible and included in our meta-analysis based on the inclusion and exclusion criteria. The pooled prevalence of RBD in PD was 42.3 % (95 % CI 37.4-47.1 %). In subgroup analysis and meta-regression analysis, we found that the important causes of heterogeneity were the diagnosis criteria of RBD and age of PD patients (P = 0.016, P = 0.019, respectively). The results indicate that nearly half of the PD patients are suffering from RBD. Older age and longer duration are risk factors for RBD in PD. We can use the minimal diagnosis criteria for RBD according to the International Classification of Sleep Disorders to diagnose RBD patients in our daily work if polysomnography is not necessary.

  7. BMI levels with MS Bone mineral density levels in adults with multiple sclerosis: a meta-analysis.

    Science.gov (United States)

    Huang, Zhongming; Qi, Yiying; Du, Shaohua; Chen, Guangnan; Yan, Weiqi

    2015-01-01

    Multiple sclerosis (MS) and osteoporosis (OP) affect a substantial proportion of the population. Accumulating evidence suggests that MS patients are at high risk for OP. We performed a meta-analysis to identify risk factors for lowered bone mineral density (BMD) in MS patients. We searched for articles within the Medline, Embase and Cochrane Library databases, published up to March 2014, pertaining to associations between MS and BMD. A total of 11 studies was included in the meta-analysis. The analysis indicated that MS patients have reduced lumbar spine, femur neck, and hip BMD compared with healthy controls (lumbar spine, standardized mean difference (SMD) = -0.76, 95% CI: -1.07, -0.45; femur neck, SMD = -0.56, 95% CI: -0.84, -0.29; and hip, SMD = -0.62, 95% CI: -0.96, -0.29). Further subgroup analysis revealed that a disease duration of >7 years, total steroid dose during the disease of >15 g, and an Expanded Disability Status Scale (EDSS) score of > 3, increased the risk of reduced BMD in the lumbar spine and femoral neck, but not in the hip. Meta-regression analysis did not explain the heterogeneity in the clinical characteristics or outcome definitions. Our meta-analysis suggests that MS patients have reduced overall BMD compared with healthy controls. Furthermore, disease duration (>7 years), total steroid dose (>15 g), and EDSS score (>3) are risk factors for reduced BMD in MS patients.

  8. Functionalization of nanotextured substrates for enhanced identification of metastatic breast cancer cells

    Science.gov (United States)

    Mansur, Nuzhat; Raziul Hasan, Mohammad; Kim, Young-tae; Iqbal, Samir M.

    2017-09-01

    Metastasis is the major cause of low survival rates among cancer patients. Once cancer cells metastasize, it is extremely difficult to contain the disease. We report on a nanotextured platform for enhanced detection of metastatic cells. We captured metastatic (MDA-MDB-231) and non-metastatic (MCF-7) breast cancer cells on anti-EGFR aptamer modified plane and nanotextured substrates. Metastatic cells were seen to change their morphology at higher rates when captured on nanotextured substrates than on plane substrates. Analysis showed statistically different morphological behaviors of metastatic cells that were very pronounced on the nanotextured substrates. Several distance matrices were calculated to quantify the dissimilarity of cell shape change. Nanotexturing increased the dissimilarity of the metastatic cells and as a result the contrast between metastatic and non-metastatic cells increased. Jaccard distance measurements found that the shape change ratio of the non-metastatic and metastatic cells was enhanced from 1:1.01 to 1:1.81, going from plane to nanotextured substrates. The shape change ratio of the non-metastatic to metastatic cells improved from 1:1.48 to 1:2.19 for the Hausdorff distance and from 1:1.87 to 1:4.69 for the Mahalanobis distance after introducing nanotexture. Distance matrix analysis showed that nanotexture increased the shape change ratios of non-metastatic and metastatic cells. Hence, the detectability of metastatic cells increased. These calculated matrices provided clear and explicit measures to discriminate single cells for their metastatic state on functional nanotextured substrates.

  9. MANAGEMENT OF ENDOCRINE DISEASE: Recurrence or new tumors after complete resection of pheochromocytomas and paragangliomas: a systematic review and meta-analysis.

    Science.gov (United States)

    Amar, Laurence; Lussey-Lepoutre, Charlotte; Lenders, Jacques W M; Djadi-Prat, Juliette; Plouin, Pierre-Francois; Steichen, Olivier

    2016-10-01

    To systematically review the incidence and factors associated with recurrences or new tumors after apparent complete resection of pheochromocytoma or thoraco-abdomino-pelvic paraganglioma. A systematic review and meta-analysis of published literature was performed. Pubmed and Embase from 1980 to 2012 were searched for studies published in English on patients with non-metastatic pheochromocytoma or thoraco-abdomino-pelvic paraganglioma, complete tumor resection, postoperative follow-up exceeding 1 month, and recurrence or new tumor documented by pathology, hormonal dosages, or imaging tests. Incidence rates of new events after curative surgery were calculated for each study that had sufficient information and pooled using random-effect meta-analysis. In total, 38 studies were selected from 3518 references, of which 36 reported retrospective cohorts from the USA, Europe, and Asia. Patient follow-up was neither standardized nor exhaustive in the included studies. A clear description of patient retrieval methods was available for nine studies and the follow-up protocol and patient flow for four studies. Only two studies used multivariable methods to assess potential predictors of postoperative events.The overall rate of recurrent disease from 34 studies was 0.98 events/100 person-years (95% confidence interval 0.71, 1.25). Syndromic diseases and paragangliomas were consistently associated with a higher risk of a new event in individual studies and in meta-regression analysis. The risk of recurrent disease after complete resection of pheochromocytoma may be lower than that previously estimated, corresponding to five events for 100 patients followed up for 5 years after complete resection. Risk stratification is required to tailor the follow-up protocol after complete resection of a pheochromocytoma or paraganglioma. Large multicenter studies are needed to this end. © 2016 European Society of Endocrinology.

  10. Meta-analysis of Renal Function Following Infrarenal EVAR using Suprarenal or Infrarenal Fixation Devices.

    Science.gov (United States)

    Stather, Philip W; Ferguson, James; Awopetu, Ayoola; Boyle, Jonathan R

    2018-03-03

    The effect of suprarenal (SR) as opposed to infrarenal (IR) fixation on renal outcomes post-endovascular aneurysm repair (EVAR) remains controversial. This meta-analysis aims to update current understanding of this issue. A prior meta-analysis was updated through a Preferred Reporting Items for Systematic reviews and Meta-Analyses search for additional studies published in the last 3 years reporting on renal dysfunction or related outcomes post-EVAR. Random effects meta-analysis was undertaken using SPSS. A total of 25 non-randomised studies comparing SR with IR fixation were included, totalling 54,832 patients. In total, 16,634 underwent SR and 38,198 IR. Baseline characteristics, including age, baseline estimated glomerular filtration rate, diabetes, cardiac disease, and smoking, were similar between the groups. There was a small but significant difference in outcomes for renal dysfunction at the study end point (SR 5.98% vs. IR 4.83%; odds ratio [OR] 1.29, 95% confidence interval [CI] 1.18-1.40 [p analysis. Incidence of renal infarcts (SR 6.6% vs. IR 2.3%; OR 2.78, 95% CI 1.46-5.29 [p = .002]), renal stenosis (SR 2.4% vs. IR 0.8%; OR 2.89, 95% CI 1.00-8.38 [p = .05]), and renal artery occlusion (SR 2.4% vs. IR 1.2%; OR 2.21, 95% CI 1.15-4.25 [p = 0.02]) favoured IR fixation; however, there was no difference in haemodialysis rates. This meta-analysis has identified small but significantly worse renal outcomes in patients having SR fixation devices compared with IR; however, there was no difference in dialysis rates and a small effect on renal dysfunction, which did not stand up to rigorous sensitivity analysis. This should be taken into consideration during graft selection, and further studies must assess renal outcomes in the longer term, and in those with pre-existing renal dysfunction. Copyright © 2018 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.

  11. Diet influenced tooth erosion prevalence in children and adolescents: Results of a meta-analysis and meta-regression

    NARCIS (Netherlands)

    Salas, M.M.; Nascimento, G.G.; Vargas-Ferreira, F.; Tarquinio, S.B.; Huysmans, M.C.D.N.J.M.; Demarco, F.F.

    2015-01-01

    OBJECTIVE: The aim of the present study was to assess the influence of diet in tooth erosion presence in children and adolescents by meta-analysis and meta-regression. DATA: Two reviewers independently performed the selection process and the quality of studies was assessed. SOURCES: Studies

  12. Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci

    NARCIS (Netherlands)

    Franke, Andre; McGovern, Dermot P. B.; Barrett, Jeffrey C.; Wang, Kai; Radford-Smith, Graham L.; Ahmad, Tariq; Lees, Charlie W.; Balschun, Tobias; Lee, James; Roberts, Rebecca; Anderson, Carl A.; Bis, Joshua C.; Bumpstead, Suzanne; Ellinghaus, David; Festen, Eleonora M.; Georges, Michel; Green, Todd; Haritunians, Talin; Jostins, Luke; Latiano, Anna; Mathew, Christopher G.; Montgomery, Grant W.; Prescott, Natalie J.; Raychaudhuri, Soumya; Rotter, Jerome I.; Schumm, Philip; Sharma, Yashoda; Simms, Lisa A.; Taylor, Kent D.; Whiteman, David; Wijmenga, Cisca; Baldassano, Robert N.; Barclay, Murray; Bayless, Theodore M.; Brand, Stephan; Buening, Carsten; Cohen, Albert; Colombel, Jean-Frederick; Cottone, Mario; Stronati, Laura; Denson, Ted; De Vos, Martine; D'Inca, Renata; Dubinsky, Marla; Edwards, Cathryn; Florin, Tim; Franchimont, Denis; Gearry, Richard; Glas, Juergen; Van Gossum, Andre; Guthery, Stephen L.; Halfvarson, Jonas; Verspaget, Hein W.; Hugot, Jean-Pierre; Karban, Amir; Laukens, Debby; Lawrance, Ian; Lemann, Marc; Levine, Arie; Libioulle, Cecile; Louis, Edouard; Mowat, Craig; Newman, William; Panes, Julian; Phillips, Anne; Proctor, Deborah D.; Regueiro, Miguel; Russell, Richard; Rutgeerts, Paul; Sanderson, Jeremy; Sans, Miquel; Seibold, Frank; Steinhart, A. Hillary; Stokkers, Pieter C. F.; Torkvist, Leif; Kullak-Ublick, Gerd; Wilson, David; Walters, Thomas; Targan, Stephan R.; Brant, Steven R.; Rioux, John D.; D'Amato, Mauro; Weersma, Rinse K.; Kugathasan, Subra; Griffiths, Anne M.; Mansfield, John C.; Vermeire, Severine; Duerr, Richard H.; Silverberg, Mark S.; Satsangi, Jack; Schreiber, Stefan; Cho, Judy H.; Annese, Vito; Hakonarson, Hakon; Daly, Mark J.; Parkes, Miles

    2010-01-01

    We undertook a meta-analysis of six Crohn's disease genome-wide association studies (GWAS) comprising 6,333 affected individuals (cases) and 15,056 controls and followed up the top association signals in 15,694 cases, 14,026 controls and 414 parent-offspring trios. We identified 30 new

  13. Neurological Soft Signs in Schizophrenia: A Meta-analysis

    Science.gov (United States)

    Chan, Raymond C. K.; Xu, Ting; Heinrichs, R. Walter; Yu, Yue; Wang, Ya

    2010-01-01

    Background: Neurological soft signs (NSS) are hypothesized as candidate endophenotypes for schizophrenia, but their prevalence and relations with clinical and demographic data are unknown. The authors undertook a quantification (meta-analysis) of the published literature on NSS in patients with schizophrenia and healthy controls. A systematic search was conducted for published articles reporting NSS and related data using standard measures in schizophrenia and healthy comparison groups. Method: A systematic search was conducted for published articles reporting data on the prevalence of NSS in schizophrenia using standard clinical rating scales and healthy comparison groups. Meta-analyses were performed using the Comprehensive Meta-analysis software package. Effect sizes (Cohen d) indexing the difference between schizophrenic patients and the healthy controls were calculated on the basis of reported statistics. Potential moderator variables evaluated included age of patient samples, level of education, sample sex proportions, medication doses, and negative and positive symptoms. Results: A total of 33 articles met inclusion criteria for the meta-analysis. A large and reliable group difference (Cohen d) indicated that, on average, a majority of patients (73%) perform outside the range of healthy subjects on aggregate NSS measures. Cognitive performance and positive and negative symptoms share 2%–10% of their variance with NSS. Conclusions: NSS occur in a majority of the schizophrenia patient population and are largely distinct from symptomatic and cognitive features of the illness. PMID:19377058

  14. Feedback for Simulation-Based Procedural Skills Training: A Meta-Analysis and Critical Narrative Synthesis

    Science.gov (United States)

    Hatala, Rose; Cook, David A.; Zendejas, Benjamin; Hamstra, Stanley J.; Brydges, Ryan

    2014-01-01

    Although feedback has been identified as a key instructional feature in simulation based medical education (SBME), we remain uncertain as to the magnitude of its effectiveness and the mechanisms by which it may be effective. We employed a meta-analysis and critical narrative synthesis to examine the effectiveness of feedback for SBME procedural…

  15. GetReal in network meta-analysis : a review of the methodology

    NARCIS (Netherlands)

    Efthimiou, Orestis; Debray, Thomas P A; van Valkenhoef, Gert; Trelle, Sven; Panayidou, Klea; Moons, Karel G M; Reitsma, Johannes B.; Shang, Aijing; Salanti, Georgia

    2016-01-01

    Pairwise meta-analysis is an established statistical tool for synthesizing evidence from multiple trials, but it is informative only about the relative efficacy of two specific interventions. The usefulness of pairwise meta-analysis is thus limited in real-life medical practice, where many competing

  16. Network meta-analysis-highly attractive but more methodological research is needed

    NARCIS (Netherlands)

    Li, Tianjing; Puhan, Milo A.; Vedula, Swaroop S.; Singh, Sonal; Dickersin, Kay; Cameron, Chris; Goodman, Steven N.; Mills, Edward; Musch, David; ter Riet, Gerben; Robinson, Karen; Schmid, Christopher; Song, Fujian; Thorlund, Kristian; Trikalinos, Thomas

    2011-01-01

    Network meta-analysis, in the context of a systematic review, is a meta-analysis in which multiple treatments (that is, three or more) are being compared using both direct comparisons of interventions within randomized controlled trials and indirect comparisons across trials based on a common

  17. Updated Meta-Analysis of Learner Control within Educational Technology

    Science.gov (United States)

    Karich, Abbey C.; Burns, Matthew K.; Maki, Kathrin E.

    2014-01-01

    Giving a student control over their learning has theoretical and intuitive appeal, but its effects are neither powerful nor consistent in the empirical literature base. This meta-analysis updated previous meta-analytic research by Niemiec, Sikorski, and Walberg by studying the overall effectiveness of providing learner control within educational…

  18. Insulin glargine and cancer risk in patients with diabetes: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Xulei Tang

    Full Text Available AIM: The role of insulin glargine as a risk factor for cancer is controversial in human studies. The aim of this meta-analysis was to evaluate the relationship between insulin glargine and cancer incidence. METHODS: All observational studies and randomized controlled trials evaluating the relationship of insulin glargine and cancer risk were identified in PubMed, Embase, Web of Science, Cochrane Library and the Chinese Biomedical Medical Literature Database, through March 2012. Odds ratios (ORs with corresponding 95% confidence interval (CI were calculated with a random-effects model. Confidence in the estimates of the obtained effects (quality of evidence was assessed by using the Grading of Recommendations Assessment, Development, and Evaluation approach. RESULTS: A total of 11 studies including 448,928 study subjects and 19,128 cancer patients were finally identified for the meta-analysis. Insulin glargine use was associated with a lower odds of cancer compared with non-glargine insulin use (OR 0.81, 95% CI 0.68 to 0.98, P = 0.03; very low-quality evidence. Glargine did not increase the odds of breast cancer (OR 0.99, 95% CI 0.68 to 1.46, P = 0.966; very low-quality evidence. Compared with non-glargine insulin, no significant association was found between insulin glargine and prostate cancer, pancreatic cancer and respiratory tract cancer. Insulin glargine use was associated with lower odds of other site-specific cancer. CONCLUSIONS: Results from the meta-analysis don't support the link between insulin glargine and an increased risk of cancer and the confidence in the estimates of the effects is very low. Further studies are needed to examine the relation between insulin glargine and cancer risk, especially breast cancer.

  19. Genome-wide association analysis of more than 120,000 individuals identifies 15 new susceptibility loci for breast cancer

    NARCIS (Netherlands)

    Michailidou, Kyriaki; Beesley, Jonathan; Lindstrom, Sara; Canisius, Sander; Dennis, Joe; Lush, Michael J.; Maranian, Mel J.; Bolla, Manjeet K.; Wang, Qin; Shah, Mitul; Perkins, Barbara J.; Czene, Kamila; Eriksson, Mikael; Darabi, Hatef; Brand, Judith S.; Bojesen, Stig E.; Nordestgaard, Borge G.; Flyger, Henrik; Nielsen, Sune F.; Rahman, Nazneen; Turnbull, Clare; Fletcher, Olivia; Peto, Julian; Gibson, Lorna; dos-Santos-Silva, Isabel; Chang-Claude, Jenny; Flesch-Janys, Dieter; Rudolph, Anja; Eilber, Ursula; Behrens, Sabine; Nevanlinna, Heli; Muranen, Taru A.; Aittomaki, Kristiina; Blomqvist, Carl; Khan, Sofia; Aaltonen, Kirsimari; Ahsan, Habibul; Kibriya, Muhammad G.; Whittemore, Alice S.; John, Esther M.; Malone, Kathleen E.; Gammon, Marilie D.; Santella, Regina M.; Ursin, Giske; Makalic, Enes; Schmidt, Daniel F.; Casey, Graham; Hunter, David J.; Gapstur, Susan M.; Gaudet, Mia M.; Diver, W. Ryan; Haiman, Christopher A.; Schumacher, Fredrick; Henderson, Brian E.; Le Marchand, Loic; Berg, Christine D.; Chanock, Stephen J.; Figueroa, Jonine; Hoover, Robert N.; Lambrechts, Diether; Neven, Patrick; Wildiers, Hans; van Limbergen, Erik; Schmidt, Marjanka K.; Broeks, Annegien; Verhoef, Senno; Cornelissen, Sten; Couch, Fergus J.; Olson, Janet E.; Hallberg, Emily; Vachon, Celine; Waisfisz, Quinten; Meijers-Heijboer, Hanne; Adank, Muriel A.; van der Luijt, Rob B.; Li, Jingmei; Liu, Jianjun; Humphreys, Keith; Kang, Daehee; Choi, Ji-Yeob; Park, Sue K.; Yoo, Keun-Young; Matsuo, Keitaro; Ito, Hidemi; Iwata, Hiroji; Tajima, Kazuo; Guenel, Pascal; Truong, Therese; Mulot, Claire; Sanchez, Marie; Burwinkel, Barbara; Marme, Frederik; Surowy, Harald; Sohn, Christof; Wu, Anna H.; Tseng, Chiu-chen; Van den Berg, David; Stram, Daniel O.; Gonzalez-Neira, Anna; Benitez, Javier; Zamora, M. Pilar; Arias Perez, Jose Ignacio; Shu, Xiao-Ou; Lu, Wei; Gao, Yu-Tang; Cai, Hui; Cox, Angela; Cross, Simon S.; Reed, Malcolm W. R.; Andrulis, Irene L.; Knight, Julia A.; Glendon, Gord; Mulligan, Anna Marie; Sawyer, Elinor J.; Tomlinson, Ian; Kerin, Michael J.; Miller, Nicola; Lindblom, Annika; Margolin, Sara; Teo, Soo Hwang; Yip, Cheng Har; Taib, Nur Aishah Mohd; Tan, Gie-Hooi; Hooning, Maartje J.; Hollestelle, Antoinette; Martens, John W. M.; Collee, J. Margriet; Blot, William; Signorello, Lisa B.; Cai, Qiuyin; Hopper, John L.; Southey, Melissa C.; Tsimiklis, Helen; Apicella, Carmel; Shen, Chen-Yang; Hsiung, Chia-Ni; Wu, Pei-Ei; Hou, Ming-Feng; Kristensen, Vessela N.; Nord, Silje; Alnaes, Grethe I. Grenaker; Giles, Graham G.; Milne, Roger L.; McLean, Catriona; Canzian, Federico; Trichopoulos, Dimitrios; Peeters, Petra; Lund, Eiliv; Sund, Malin; Khaw, Kay-Tee; Gunter, Marc J.; Palli, Domenico; Mortensen, Lotte Maxild; Dossus, Laure; Huerta, Jose-Maria; Meindl, Alfons; Schmutzler, Rita K.; Sutter, Christian; Yang, Rongxi; Muir, Kenneth; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Hartman, Mikael; Miao, Hui; Chia, Kee Seng; Chan, Ching Wan; Fasching, Peter A.; Hein, Alexander; Beckmann, Matthias W.; Haeberle, Lothar; Brenner, Hermann; Dieffenbach, Aida Karina; Arndt, Volker; Stegmaier, Christa; Ashworth, Alan; Orr, Nick; Schoemaker, Minouk J.; Swerdlow, Anthony J.; Brinton, Louise; Garcia-Closas, Montserrat; Zheng, Wei; Halverson, Sandra L.; Shrubsole, Martha; Long, Jirong; Goldberg, Mark S.; Labreche, France; Dumont, Martine; Winqvist, Robert; Pylkas, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Brauch, Hiltrud; Hamann, Ute; Bruening, Thomas; Radice, Paolo; Peterlongo, Paolo; Manoukian, Siranoush; Bernard, Loris; Bogdanova, Natalia V.; Doerk, Thilo; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M.; Devilee, Peter; Tollenaar, Robert A. E. M.; Seynaeve, Caroline; Van Asperen, Christi J.; Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Huzarski, Tomasz; Sangrajrang, Suleeporn; Gaborieau, Valerie; Brennan, Paul; Mckay, James; Slager, Susan; Toland, Amanda E.; Ambrosone, Christine B.; Yannoukakos, Drakoulis; Kabisch, Maria; Torres, Diana; Neuhausen, Susan L.; Anton-Culver, Hoda; Luccarini, Craig; Baynes, Caroline; Ahmed, Shahana; Healey, Catherine S.; Tessier, Daniel C.; Vincent, Daniel; Bacot, Francois; Pita, Guillermo; Rosario Alonso, M.; Alvarez, Nuria; Herrero, Daniel; Simard, Jacques; Pharoah, Paul P. D. P.; Kraft, Peter; Dunning, Alison M.; Chenevix-Trench, Georgia; Hall, Per; Easton, Douglas F.

    Genome-wide association studies (GWAS) and large-scale replication studies have identified common variants in 79 loci associated with breast cancer, explaining similar to 14% of the familial risk of the disease. To identify new susceptibility loci, we performed a meta-analysis of 11 GWAS, comprising

  20. Genome-wide association analysis of more than 120,000 individuals identifies 15 new susceptibility loci for breast cancer

    DEFF Research Database (Denmark)

    Michailidou, Kyriaki; Beesley, Jonathan; Lindstrom, Sara

    2015-01-01

    Genome-wide association studies (GWAS) and large-scale replication studies have identified common variants in 79 loci associated with breast cancer, explaining ∼14% of the familial risk of the disease. To identify new susceptibility loci, we performed a meta-analysis of 11 GWAS, comprising 15,748...

  1. A systematic review and meta-analysis of the circulatory, erythrocellular and CSF selenium levels in Alzheimer's disease: A metal meta-analysis (AMMA study-I).

    Science.gov (United States)

    Reddy, Varikasuvu Seshadri; Bukke, Suman; Dutt, Naveen; Rana, Puneet; Pandey, Arun Kumar

    2017-07-01

    Available studies in the literature on the selenium levels in Alzheimer's disease (AD) are inconsistent with some studies reporting its decrease in the circulation, while others reported an increase or no change as compared to controls. The objective of this study was to perform a meta-analysis of circulatory (plasma/serum and blood), erythrocyte and cerebrospinal fluid (CSF) selenium levels in AD compared controls. We also performed a meta-analysis of the correlation coefficients (r) to demonstrate the associations between selenium and glutathione peroxidase (GPx) in AD patients. All major databases were searched for eligible studies. We included 12 case-control/observational studies reporting selenium concentrations in AD and controls. Pooled-overall effect size as standardized mean difference (SMD) and pooled r-values were generated using Review Manager 5.3 and MedCalc 15.8 software. Random-effects meta-analysis indicated a decrease in circulatory (SMD=-0.44), erythrocellular (SMD=-0.52) and CSF (SMD=-0.14) selenium levels in AD patients compared to controls. Stratified meta-analysis demonstrated that the selenium levels were decreased in both the subgroups with (SMD=-0.55) and without (SMD=-0.37) age matching between AD and controls. Our results also demonstrated a direct association between decreased selenium levels and GPx in AD. This meta-analysis suggests that circulatory selenium concentration is significantly lower in AD patients compared to controls and this decrease in selenium is directly correlated with an important antioxidant enzyme, the GPx, in AD. Copyright © 2017 Elsevier GmbH. All rights reserved.

  2. Real-time polymerase chain reaction for diagnosing infectious mononucleosis in pediatric patients: A systematic review and meta-analysis.

    Science.gov (United States)

    Jiang, Sha-Yi; Yang, Jing-Wei; Shao, Jing-Bo; Liao, Xue-Lian; Lu, Zheng-Hua; Jiang, Hui

    2016-05-01

    In this meta-analysis, we evaluated the diagnostic role of Epstein-Barr virus deoxyribonucleic acid detection and quantitation in the serum of pediatric and young adult patients with infectious mononucleosis. The primary outcome of this meta-analysis was the sensitivity and specificity of Epstein-Barr virus (EBV) deoxyribonucleic acid (DNA) detection and quantitation using polymerase chain reaction (PCR). A systematic review and meta-analysis was performed by searching for articles that were published through September 24, 2014 in the following databases: Medline, Cochrane, EMBASE, and Google Scholar. The following keywords were used for the search: "Epstein-Barr virus," "infectious mononucleosis," "children/young adults/infant/pediatric," and "polymerase chain reaction or PCR." Three were included in this analysis. We found that for detection by PCR, the pooled sensitivity for detecting EBV DNA was 77% (95%CI, 66-86%) and the pooled specificity for was 98% (95%CI, 93-100%). Our findings indicate that this PCR-based assay has high specificity and good sensitivity for detecting of EBV DNA, indicating it may useful for identifying patients with infectious mononucleosis. This assay may also be helpful to identify young athletic patients or highly physically active pediatric patients who are at risk for a splenic rupture due to acute infectious mononucleosis. © 2015 Wiley Periodicals, Inc.

  3. A meta-frontier approach for causal inference in productivity analysis

    DEFF Research Database (Denmark)

    Henningsen, Arne; Mpeta, Daniel F.; Adem, Anwar S.

    (2012) and create a meta-frontier in order to estimate the effects of participation on the farms’ meta-technology ratio, their group technical efficiency, and their meta-technology technical efficiency. The empirical analysis uses a cross-sectional data set from sunflower farmers in Tanzania, where some...... by the contractor’s provision of (additional) extension service and seeds of high-yielding varieties to the contract farmers....

  4. Clinical Significance of Resistin Expression in Osteoarthritis: A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Xiao-Chuan Li

    2014-01-01

    Full Text Available Background. The objective of this study was to conduct a systematic review of literature evaluating human resistin expression as a diagnostic factor in osteoarthritis development and to quantify the overall diagnostic effect. Method. Relevant studies were identified and evaluated for quality through multiple search strategies. Studies analyzing resistin expression in the development of OA were eligible for inclusion. Data from eligible studies were extracted and included into the meta-analysis using a random-effects model. Results. Four case-control studies consisting of a total of 375 OA patients and 214 controls as well as three sex-stratified analyses composed of 53 males and 104 females were incorporated into our meta-analysis. Our results revealed that resistin levels were significantly higher in male OA subjects and OA patients overall. Country-stratified analysis yielded significantly different estimates in resistin levels between male OA subjects and female OA subjects in the Canadian subgroup but not among the French and USA subgroups. Based on the resistin levels in OA cases and controls, resistin levels were heightened in OA patients in the Dutch population. Conclusion. These results support the hypothesis that high expression of resistin represents a significant and reproducible marker of poor progression in OA patients, especially in males.

  5. Meta-analysis of randomized controlled trials on risk of myocardial infarction from the use of oral direct thrombin inhibitors

    DEFF Research Database (Denmark)

    Artang, Ramin; Rome, Eric; Nielsen, Jørn Dalsgaard

    2013-01-01

    . To address these questions, we systematically searched MEDLINE and performed a meta-analysis on randomized trials that compared oral DTIs with warfarin for any indication with end point of MIs after randomization. We furthermore performed a secondary meta-analysis on atrial fibrillation stroke prevention...... to experience an MI than their counterparts treated with warfarin (285 of 23,333 vs 133 of 16,024, odds ratio 1.35, 95% confidence interval 1.10 to 1.66, p = 0.005). For secondary analysis, 8 studies (69,615 patients) were identified that compared warfarin with alternative anticoagulant including factor Xa...

  6. Neural Correlates of Psychotherapy in Anxiety and Depression: A Meta-Analysis

    Science.gov (United States)

    Messina, Irene; Sambin, Marco; Palmieri, Arianna; Viviani, Roberto

    2013-01-01

    Several studies have used neuroimaging methods to identify neural change in brain networks associated to emotion regulation after psychotherapy of depression and anxiety. In the present work we adopted a meta-analytic technique specific to neuroimaging data to evaluate the consistence of empirical findings and assess models of therapy that have been proposed in the literature. Meta-analyses were conducted with the Activation Likelihood Estimation technique, which evaluates the overlap between foci of activation across studies. The analysis included 16 studies found in Pubmed (200 foci of activation and 193 patients). Separate meta-analyses were conducted on studies of 1) depression, post-traumatic stress disorder and panic disorder investigated with rest state metabolism (6 studies, 70 patients); 2) depression, post-traumatic stress disorder and panic disorder investigated with task-related activation studies (5 studies, 65 patients); 3) the previous studies considered jointly; and 4) phobias investigated with studies on exposure-related activation (5 studies, 57 patients). Studies on anxiety and depression gave partially consistent results for changes in the dorsomedial prefrontal cortex and in the posterior cingulated gyrus/precuneus. Several areas of change in the temporal lobes were also observed. Studies on the therapy of phobia were consistent with a reduction of activity in medial temporal areas. The cluster of change in the prefrontal cortex may refer to increased recruitment of control processes, as hypothesized by influential models of emotion regulation changes due to psychotherapy. However, not all areas associated with controlled emotion regulation were detected in the meta-analysis, while involvement of midline structures suggested changes in self-related information processing. Changes in phobia were consistent with reduced reactivity to phobic stimuli. PMID:24040309

  7. Neural correlates of psychotherapy in anxiety and depression: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Irene Messina

    Full Text Available Several studies have used neuroimaging methods to identify neural change in brain networks associated to emotion regulation after psychotherapy of depression and anxiety. In the present work we adopted a meta-analytic technique specific to neuroimaging data to evaluate the consistence of empirical findings and assess models of therapy that have been proposed in the literature. Meta-analyses were conducted with the Activation Likelihood Estimation technique, which evaluates the overlap between foci of activation across studies. The analysis included 16 studies found in Pubmed (200 foci of activation and 193 patients. Separate meta-analyses were conducted on studies of 1 depression, post-traumatic stress disorder and panic disorder investigated with rest state metabolism (6 studies, 70 patients; 2 depression, post-traumatic stress disorder and panic disorder investigated with task-related activation studies (5 studies, 65 patients; 3 the previous studies considered jointly; and 4 phobias investigated with studies on exposure-related activation (5 studies, 57 patients. Studies on anxiety and depression gave partially consistent results for changes in the dorsomedial prefrontal cortex and in the posterior cingulated gyrus/precuneus. Several areas of change in the temporal lobes were also observed. Studies on the therapy of phobia were consistent with a reduction of activity in medial temporal areas. The cluster of change in the prefrontal cortex may refer to increased recruitment of control processes, as hypothesized by influential models of emotion regulation changes due to psychotherapy. However, not all areas associated with controlled emotion regulation were detected in the meta-analysis, while involvement of midline structures suggested changes in self-related information processing. Changes in phobia were consistent with reduced reactivity to phobic stimuli.

  8. Cognitive-Based Interventions to Improve Mobility: A Systematic Review and Meta-analysis.

    Science.gov (United States)

    Marusic, Uros; Verghese, Joe; Mahoney, Jeannette R

    2018-06-01

    A strong relation between cognition and mobility has been identified in aging, supporting a role for enhancement mobility through cognitive-based interventions. However, a critical evaluation of the consistency of treatment effects of cognitive-based interventions is currently lacking. The objective of this study was 2-fold: (1) to review the existing literature on cognitive-based interventions aimed at improving mobility in older adults and (2) to assess the clinical effectiveness of cognitive interventions on gait performance. A systematic review of randomized controlled trials (RCT) of cognitive training interventions for improving simple (normal walking) and complex (dual task walking) gait was conducted in February 2018. Older adults without major cognitive, psychiatric, neurologic, and/or sensory impairments were included. Random effect meta-analyses and a subsequent meta-regression were performed to generate overall cognitive intervention effects on single- and dual-task walking conditions. Ten RCTs met inclusion criteria, with a total of 351 participants included in this meta-analysis. Cognitive training interventions revealed a small effect of intervention on complex gait [effect size (ES) = 0.47, 95% confidence interval (CI) 0.13 to 0.81, P = .007, I 2  = 15.85%], but not simple gait (ES = 0.35, 95% CI -0.01 to 0.71, P = .057, I 2  = 57.32%). Moreover, a meta-regression analysis revealed that intervention duration, training frequency, total number of sessions, and total minutes spent in intervention were not significant predictors of improvement in dual-task walking speed, though there was a suggestive trend toward a negative association between dual-task walking speed improvements and individual training session duration (P = .067). This meta-analysis provides support for the fact that cognitive training interventions can improve mobility-related outcomes, especially during challenging walking conditions requiring higher-order executive

  9. Effect of Whey Supplementation on Circulating C-Reactive Protein: A Meta-Analysis of Randomized Controlled Trials

    Science.gov (United States)

    Zhou, Ling-Mei; Xu, Jia-Ying; Rao, Chun-Ping; Han, Shufen; Wan, Zhongxiao; Qin, Li-Qiang

    2015-01-01

    Whey supplementation is beneficial for human health, possibly by reducing the circulating C-reactive protein (CRP) level, a sensitive marker of inflammation. Thus, a meta-analysis of randomized controlled trials was conducted to evaluate their relationship. A systematic literature search was conducted in July, 2014, to identify eligible studies. Either a fixed-effects model or a random-effects model was used to calculate pooled effects. The meta-analysis results of nine trials showed a slight, but no significant, reduction of 0.42 mg/L (95% CI −0.96, 0.13) in CRP level with the supplementation of whey protein and its derivates. Relatively high heterogeneity across studies was observed. Subgroup analyses showed that whey significantly lowered CRP by 0.72 mg/L (95% CI −0.97, −0.47) among trials with a daily whey dose ≥20 g/day and by 0.67 mg/L (95% CI −1.21, −0.14) among trials with baseline CRP ≥3 mg/L. Meta-regression analysis revealed that the baseline CRP level was a potential effect modifier of whey supplementation in reducing CRP. In conclusion, our meta-analysis did not find sufficient evidence that whey and its derivates elicited a beneficial effect in reducing circulating CRP. However, they may significantly reduce CRP among participants with highly supplemental doses or increased baseline CRP levels. PMID:25671415

  10. Disclosure of sensitive behaviors across self-administered survey modes: a meta-analysis.

    Science.gov (United States)

    Gnambs, Timo; Kaspar, Kai

    2015-12-01

    In surveys, individuals tend to misreport behaviors that are in contrast to prevalent social norms or regulations. Several design features of the survey procedure have been suggested to counteract this problem; particularly, computerized surveys are supposed to elicit more truthful responding. This assumption was tested in a meta-analysis of survey experiments reporting 460 effect sizes (total N =125,672). Self-reported prevalence rates of several sensitive behaviors for which motivated misreporting has been frequently observed were compared across self-administered paper-and-pencil versus computerized surveys. The results revealed that computerized surveys led to significantly more reporting of socially undesirable behaviors than comparable surveys administered on paper. This effect was strongest for highly sensitive behaviors and surveys administered individually to respondents. Moderator analyses did not identify interviewer effects or benefits of audio-enhanced computer surveys. The meta-analysis highlighted the advantages of computerized survey modes for the assessment of sensitive topics.

  11. A meta-analysis of serious digital games for healthy lifestyle promotion

    Science.gov (United States)

    Several systematic reviews have described health-promoting effects of serious games, but so far no meta-analysis has been reported. This paper presents a meta-analysis of 54 serious digital game studies for healthy lifestyle promotion, in which we investigated the overall effectiveness of serious di...

  12. Interleukin-8 for diagnosis of neonatal sepsis: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Min Zhou

    Full Text Available Neonatal sepsis (NS is a life-threatening disorder and an important cause of morbidity and mortality in neonates. Previous studies showed that interleukin 8 (IL-8 may effectively and rapidly diagnose NS.We conducted the systematic review and meta-analysis to investigate the diagnostic value of the IL-8 in NS.The literature was searched in PUBMED, EMBASE, Cochrane Library, CNKI, VIP and other Chinese Medical Databases during October 1998 to January 2014 using set search criteria. Each included study was evaluated by quality assessment of diagnostic accuracy studies tool. Two investigators independently extracted the data and study characteristics, and disagreements, if any, were resolved by consensus. Meta-disc software was used to calculate the pooled sensitivity, specificity and summary diagnostic odds ratio (SDOR, I² or Cochrane Q to test heterogeneity, and meta-regression to investigate the source of heterogeneity. Funnel plots were used to test the potential presence of publication bias. False-positive report probability (FPRP was calculated to confirm the significance of the results.Eight studies (548 neonates were included in this meta-analysis. The pooled sensitivity and specificity of IL-8 were 0.78 and 0.84, respectively, which had moderate accuracy in the diagnosis of NS. The pooled diagnostic odds ratio (DOR and area under curve (AUC was 21.64 and 0.8908 (Q*=0.8215, respectively. The diagnostic threshold analysis showed that there was no threshold effect. The meta-regression analysis showed the cut-off, QUADAS and onset time have no effect on the heterogeneity. The funnel plots showed the existence of publication bias.Meta-analysis showed IL-8 had a moderate accuracy (AUC=0.8908 for the diagnosis of NS. IL-8 is a helpful biomarker for early diagnosis of NS. However, we should combine the results with clinical symptoms and signs, laboratory and microbial results.

  13. Multiple urinary bladder masses from metastatic prostate adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Richard Choo

    2010-12-01

    Full Text Available We present an unusual case of metastatic prostate adenocarcinoma that manifested with multiple exophytic intravesical masses, mimicking a multifocal primary bladder tumor. Biopsy with immunohistochemical analysis confirmed metastatic prostate adenocarcinoma. The patient was treated palliatively with external beam radiotherapy to prevent possible symptoms from local tumor progression. This case illustrates that when a patient with known prostate cancer presents with multifocal bladder tumors, the possibility of metastatic prostate cancer should be considered.

  14. Association between the interleukin-1β C-511T polymorphism and periodontitis: a meta-analysis in the Chinese population.

    Science.gov (United States)

    Wang, H F; He, F Q; Xu, C J; Li, D M; Sun, X J; Chi, Y T; Guo, W

    2017-02-23

    The association between the interleukin-1 beta (IL-1β) C-511T (or rs16944) polymorphism and periodontitis remains inconclusive, even though there have been previous studies on this association. To assess the effects of IL-1β C-511T variants on the risk of development of periodontitis, a meta-analysis was performed in a single ethnic population. Studies, published up to December 2015, were selected for the meta-analysis from PubMed and Chinese databases. The associations were assessed with pooled OR and 95%CI. This meta-analysis identified 8 studies, including 1276 periodontitis cases and 1558 controls. Overall, a significant association between the IL-1β C-511T polymorphism and periodontitis was found in the Chinese population (TT vs CC: OR = 1.48, 95%CI = 1.19-1.85; TT + CT vs CC: OR = 1.50, 95%CI = 1.25-1.81; T vs C: OR = 1.33, 95%CI = 1.06-1.68). In the subgroup analyses based on geographical area(s), source of controls, and type of periodontitis, significant results were obtained for the association between IL-1β C-511T variants and periodontitis. Our meta-analysis indicated that the IL-1β C-511T polymorphism may be a genetic susceptibility factor for periodontitis in the Chinese population. This marker could be used to identify Chinese individuals at a high risk for periodontitis.

  15. Fatal flaws in a recent meta-analysis on abortion and mental health.

    Science.gov (United States)

    Steinberg, Julia R; Trussell, James; Hall, Kelli S; Guthrie, Kate

    2012-11-01

    Similar to other reviews within the last 4 years, a thorough review by the Royal College of Psychiatrists, published in December 2011, found that compared to delivery of an unintended pregnancy, abortion does not increase women's risk of mental health problems. In contrast, a meta-analysis published in September 2011 concluded that abortion increases women's risk of mental health problems by 81% and that 10% of mental health problems are attributable to abortions. Like others, we strongly question the quality of this meta-analysis and its conclusions. Here we detail seven errors of this meta-analysis and three significant shortcomings of the included studies because policy, practice and the public have been misinformed. These errors and shortcomings render the meta-analysis' conclusions invalid. Copyright © 2012 Elsevier Inc. All rights reserved.

  16. Interferon alpha adjuvant therapy in patients with high-risk melanoma: a systematic review and meta-analysis.

    Science.gov (United States)

    Mocellin, Simone; Pasquali, Sandro; Rossi, Carlo R; Nitti, Donato

    2010-04-07

    Based on previous meta-analyses of randomized controlled trials (RCTs), the use of interferon alpha (IFN-alpha) in the adjuvant setting improves disease-free survival (DFS) in patients with high-risk cutaneous melanoma. However, RCTs have yielded conflicting data on the effect of IFN-alpha on overall survival (OS). We conducted a systematic review and meta-analysis to examine the effect of IFN-alpha on DFS and OS in patients with high-risk cutaneous melanoma. The systematic review was performed by searching MEDLINE, EMBASE, Cancerlit, Cochrane, ISI Web of Science, and ASCO databases. The meta-analysis was performed using time-to-event data from which hazard ratios (HRs) and 95% confidence intervals (CIs) of DFS and OS were estimated. Subgroup and meta-regression analyses to investigate the effect of dose and treatment duration were also performed. Statistical tests were two-sided. The meta-analysis included 14 RCTs, published between 1990 and 2008, and involved 8122 patients, of which 4362 patients were allocated to the IFN-alpha arm. IFN-alpha alone was compared with observation in 12 of the 14 trials, and 17 comparisons (IFN-alpha vs comparator) were generated in total. IFN-alpha treatment was associated with a statistically significant improvement in DFS in 10 of the 17 comparisons (HR for disease recurrence = 0.82, 95% CI = 0.77 to 0.87; P < .001) and improved OS in four of the 14 comparisons (HR for death = 0.89, 95% CI = 0.83 to 0.96; P = .002). No between-study heterogeneity in either DFS or OS was observed. No optimal IFN-alpha dose and/or treatment duration or a subset of patients more responsive to adjuvant therapy was identified using subgroup analysis and meta-regression. In patients with high-risk cutaneous melanoma, IFN-alpha adjuvant treatment showed statistically significant improvement in both DFS and OS.

  17. The Neural Correlates of Moral Thinking: A Meta-Analysis

    OpenAIRE

    Douglas J. Bryant; Wang F; Kelley Deardeuff; Emily Zoccoli; Chang S. Nam

    2016-01-01

    We conducted a meta-analysis to evaluate current research that aims to map the neural correlates of two typical conditions of moral judgment: right-wrong moral judgments and decision-making in moral dilemmas. Utilizing the activation likelihood estimation (ALE) method, we conducted a meta-analysis using neuroimaging data obtained from twenty-one previous studies that measured responses in one or the other of these conditions. We found that across the studies (n = 400), distinct neural circuit...

  18. Different patterns and development characteristics of processing written logographic characters and alphabetic words: an ALE meta-analysis.

    Science.gov (United States)

    Zhu, Linlin; Nie, Yaoxin; Chang, Chunqi; Gao, Jia-Hong; Niu, Zhendong

    2014-06-01

    The neural systems for phonological processing of written language have been well identified now, while models based on these neural systems are different for different language systems or age groups. Although each of such models is mostly concordant across different experiments, the results are sensitive to the experiment design and intersubject variability. Activation likelihood estimation (ALE) meta-analysis can quantitatively synthesize the data from multiple studies and minimize the interstudy or intersubject differences. In this study, we performed two ALE meta-analysis experiments: one was to examine the neural activation patterns of the phonological processing of two different types of written languages and the other was to examine the development characteristics of such neural activation patterns based on both alphabetic language and logographic language data. The results of our first meta-analysis experiment were consistent with the meta-analysis which was based on the studies published before 2005. And there were new findings in our second meta-analysis experiment, where both adults and children groups showed great activation in the left frontal lobe, the left superior/middle temporal gyrus, and the bilateral middle/superior occipital gyrus. However, the activation of the left middle/inferior frontal gyrus was found increase with the development, and the activation was found decrease in the following areas: the right claustrum and inferior frontal gyrus, the left inferior/medial frontal gyrus, the left middle/superior temporal gyrus, the right cerebellum, and the bilateral fusiform gyrus. It seems that adults involve more phonological areas, whereas children involve more orthographic areas and semantic areas. Copyright © 2013 Wiley Periodicals, Inc.

  19. How Will DSM-5 Affect Autism Diagnosis? A Systematic Literature Review and Meta-Analysis

    Science.gov (United States)

    Kulage, Kristine M.; Smaldone, Arlene M.; Cohn, Elizabeth G.

    2014-01-01

    We conducted a systematic review and meta-analysis to determine the effect of changes to the Diagnostic and Statistical Manual (DSM)-5 on autism spectrum disorder (ASD) and explore policy implications. We identified 418 studies; 14 met inclusion criteria. Studies consistently reported decreases in ASD diagnosis (range 7.3-68.4%) using DSM-5…

  20. Meta-Analysis: Reduced Risk of Anxiety with Psychostimulant Treatment in Children with Attention-Deficit/Hyperactivity Disorder.

    Science.gov (United States)

    Coughlin, Catherine G; Cohen, Stephanie C; Mulqueen, Jilian M; Ferracioli-Oda, Eduardo; Stuckelman, Zachary D; Bloch, Michael H

    2015-10-01

    Anxiety is a commonly reported side-effect of psychostimulant treatment. Our goal was to quantify the risk of anxiety as a side effect of psychostimulant treatment for attention-deficit/hyperactivity disorder (ADHD). We conducted a PubMed search to identify all double-blind, randomized, placebo-controlled trials examining the efficacy of psychostimulant medications in the treatment of children with ADHD. We used a fixed-effects meta-analysis to examine the risk ratio of anxiety reported as a side effect in children treated with psychostimulants compared with those treated with placebo. We used stratified subgroup analysis and meta-regression to examine the effects of stimulant type, dosage, duration of use, and trial design on the measured risk of anxiety. We identified 23 studies involving 2959 children with ADHD for inclusion in our meta-analysis. The risk of anxiety associated with psychostimulant treatment was significantly lower than that experienced with placebo (relative risk [RR] = 0.86 [95% CI: 0.77, 0.95], z = -2.90, p anxiety of psychostimulants when compared with placebo (β = -0.0039 [95% CI: -0.00718, -0.00064], z = -2.34, p = 0.019). Meta-analysis suggests that treatment with psychostimulants significantly reduced the risk of anxiety when compared with placebo. This finding does not rule out the possibility that some children experience increased anxiety when treated with psychostimulants, but suggests that those risks are outweighed by the number of children who experience improvement in anxiety symptoms (possibly as a secondary effect of improved control of ADHD symptoms). Clinicians should consider rechallenging children with ADHD who report new-onset or worsening anxiety with psychostimulants, as these symptoms are much more likely to be coincidental rather than caused by psychostimulants.