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Sample records for subgroup analysis revealed

  1. Is synaesthesia one condition or many? A large-scale analysis reveals subgroups.

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    Novich, Scott; Cheng, Sherry; Eagleman, David M

    2011-09-01

    Synaesthesia is a broadly defined neural phenomenon in which stimulation of a sense or concept triggers a second perception not normally associated with the stimulus. For example, letters or numbers may trigger a colour experience, sounds may trigger a taste sensation, or tastes may trigger a feeling of touch. Dozens of forms of synaesthesia have been reported, but the relationship between the different forms has not been studied: is someone with a particular form of synaesthesia likely to possess other types? If so, which ones? As an inroad to illuminating underlying mechanisms, we here examine which different synaesthesia types tend to co-occur. We analyzed reports of the forms of synaesthesia experienced by 19,133 participants who completed the Synaesthesia Battery (Eagleman, Kagan, Nelson, Sagaram, & Sarma, 2007), using correlation analysis, exploratory factor analysis (EFA), confirmatory factor analysis (CFA), and multidimensional scaling (MDS). Our analyses converged on the finding of five distinct groupings of synaesthesia forms. We label these coloured sequence synaesthesias (CSSs), coloured music synaesthesias, non-visual sequela synaesthesias, spatial sequence synaesthesia (SSS), and coloured sensation synaesthesias. Collectively, our findings reveal that synaesthesia is an umbrella term that encompasses several distinct groups with independent probabilities of expression, and this may in turn suggest distinct underlying mechanisms and the possibility of different genetic bases. ©2011 The British Psychological Society.

  2. Active medulloblastoma enhancers reveal subgroup-specific cellular origins

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    Lin, Charles Y.; Erkek, Serap; Tong, Yiai; Yin, Linlin; Federation, Alexander J.; Zapatka, Marc; Haldipur, Parthiv; Kawauchi, Daisuke; Risch, Thomas; Warnatz, Hans-Jörg; Worst, Barbara C.; Ju, Bensheng; Orr, Brent A.; Zeid, Rhamy; Polaski, Donald R.; Segura-Wang, Maia; Waszak, Sebastian M.; Jones, David T.W.; Kool, Marcel; Hovestadt, Volker; Buchhalter, Ivo; Sieber, Laura; Johann, Pascal; Chavez, Lukas; Gröschel, Stefan; Ryzhova, Marina; Korshunov, Andrey; Chen, Wenbiao; Chizhikov, Victor V.; Millen, Kathleen J.; Amstislavskiy, Vyacheslav; Lehrach, Hans; Yaspo, Marie-Laure; Eils, Roland; Lichter, Peter; Korbel, Jan O.; Pfister, Stefan M.; Bradner, James E.; Northcott, Paul A.

    2016-01-01

    Summary Medulloblastoma is a highly malignant paediatric brain tumour, often inflicting devastating consequences on the developing child. Genomic studies have revealed four distinct molecular subgroups with divergent biology and clinical behaviour. An understanding of the regulatory circuitry governing the transcriptional landscapes of medulloblastoma subgroups, and how this relates to their respective developmental origins, is lacking. Using H3K27ac and BRD4 ChIP-Seq, coupled with tissue-matched DNA methylation and transcriptome data, we describe the active cis-regulatory landscape across 28 primary medulloblastoma specimens. Analysis of differentially regulated enhancers and super-enhancers reinforced inter-subgroup heterogeneity and revealed novel, clinically relevant insights into medulloblastoma biology. Computational reconstruction of core regulatory circuitry identified a master set of transcription factors, validated by ChIP-Seq, that are responsible for subgroup divergence and implicate candidate cells-of-origin for Group 4. Our integrated analysis of enhancer elements in a large series of primary tumour samples reveals insights into cis-regulatory architecture, unrecognized dependencies, and cellular origins. PMID:26814967

  3. Identifying Tinnitus Subgroups With Cluster Analysis

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    Tyler, Richard; Coelho, Claudia; Tao, Pan; Ji, Haihong; Noble, William; Gehringer, Anne; Gogel, Stephanie

    2009-01-01

    Purpose We believe it is important to uncover tinnitus subgroups to identify subsets of patients most likely to benefit from different treatments. We review strategies for subgrouping based on etiology, subjective reports, the audiogram, psychoacoustics, imaging, and cluster analysis. Method Preliminary results of a 2-step cluster analysis based on 246 participants from whom we had 26 categorical and 25 continuous variables were determined. Results A 4-cluster solution suggested the following subgroups: (a) constant distressing tinnitus, (b) varying tinnitus that is worse in noise, (c) tinnitus patients who are copers and whose tinnitus is not influenced by touch (somatic modulation), and (d) tinnitus patients who are copers but whose tinnitus is worse in quiet environments. Conclusions Subgroups of tinnitus patients can be identified by using statistical approaches. The subgroups we identify here represent a preliminary attempt at identifying such patients. One next step would be to explore clinical trials of tinnitus treatments based on subgroup analyses or on using subgroups in the selection criteria. PMID:19056922

  4. Meta-analysis and gene set enrichment relative to er status reveal elevated activity of MYC and E2F in the "basal" breast cancer subgroup.

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    M Chehani Alles

    Full Text Available BACKGROUND: Breast cancers lacking the estrogen receptor (ER can be distinguished from other breast cancers on the basis of poor prognosis, high grade, distinctive histopathology and unique molecular signatures. These features further distinguish estrogen receptor negative (ER- tumor subtypes, but targeted therapy is currently limited to tumors over-expressing the ErbB2 receptor. METHODOLOGY/PRINCIPAL FINDINGS: To uncover the pathways against which future therapies could be developed we undertook a meta-analysis of gene expression from five large microarray datasets relative to ER status. A measure of association with ER status was calculated for every Affymetrix HG-U133A probe set and the pathways that distinguished ER- tumors were defined by testing for enrichment of biologically defined gene sets using Gene Set Enrichment Analysis (GSEA. As expected, the expression of the direct transcriptional targets of the ER was muted in ER- tumors, but the expression of genes indirectly regulated by estrogen was enhanced. We also observed enrichment of independent MYC- and E2F-driven transcriptional programs. We used a cell model of estrogen and MYC action to define the interaction between estrogen and MYC transcriptional activity in breast cancer. We found that the basal subgroup of ER- breast cancer showed a strong MYC transcriptional response that reproduced the indirect estrogen response seen in estrogen receptor positive (ER+ breast cancer cells. CONCLUSIONS/SIGNIFICANCE: Increased transcriptional activity of MYC is a characteristic of basal breast cancers where it mimics a large part of an estrogen response in the absence of the ER, suggesting a mechanism by which these cancers achieve estrogen-independence and providing a potential therapeutic target for this poor prognosis sub group of breast cancer.

  5. Large-scale mitochondrial DNA analysis of native honey bee Apis mellifera populations reveals a new African subgroup private to the South West Indian Ocean islands.

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    Techer, Maéva Angélique; Clémencet, Johanna; Simiand, Christophe; Preeaduth, Sookar; Azali, Hamza Abdou; Reynaud, Bernard; Hélène, Delatte

    2017-06-02

    The South West Indian Ocean (SWIO) archipelagos and Madagascar constitute a hotspot of biodiversity with a high rate of endemism. In this area, the endemic subspecies A. m. unicolor has been described in Madagascar. It belongs to the African lineage, one of the four described evolutionary lineages in honey bees. Despite a long beekeeping tradition and several recorded European introductions, few studies have been carried out on the diversity and proportion of honey bee subspecies. In order to identify and define which evolutionary lineages and potential sub-lineages are present in the SWIO, the COI-COII intergenic region and the ND2 gene of the mtDNA were sequenced in honey bee colonies from three archipelagos. An extensive sampling (n = 1184 colonies) was done in the Mascarene (La Réunion, Mauritius, Rodrigues), Seychelles (Mahé, Praslin, La Digue) and Comoros (Grande Comore, Mohéli, Anjouan, Mayotte) archipelagos. Islands genetic diversity was compared to newly sampled populations from Madagascar, continental African and European populations. African lineage haplotypes were found in all islands (except for Rodrigues). Madagascar, Comoros and Seychelles had 100% of A lineage, 95.5% in La Réunion and 56.1% in Mauritius. Among all African colonies detected in the SWIO, 98.1% (n = 633) of COI-COII haplotypes described the presence of the subspecies A. M. unicolor. Both genetic markers revealed i) a new private A I mitochondrial group shared by the SWIO archipelagos and Madagascar distant from continental populations; ii) the private African haplotypes for each island suggested diversity radiation in the archipelagos; iii) the detection of the Comoros archipelago as a possible contact area between insular and continental African populations. The exotic European C and M lineages were only detected in the Mascarene archipelago, but striking differences of proportion were observed among islands. Merely 4.6% of European colonies were found in La Réunion whereas

  6. Subgroup Analysis in Burnout: Relations Between Fatigue, Anxiety, and Depression

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    van Dam, Arno

    2016-01-01

    Several authors have suggested that burned out patients do not form a homogeneous group and that subgroups should be considered. The identification of these subgroups may contribute to a better understanding of the burnout construct and lead to more specific therapeutic interventions. Subgroup analysis may also help clarify whether burnout is a distinct entity and whether subgroups of burnout overlap with other disorders such as depression and chronic fatigue syndrome. In a group of 113 clinically diagnosed burned out patients, levels of fatigue, depression, and anxiety were assessed. In order to identify possible subgroups, we performed a two-step cluster analysis. The analysis revealed two clusters that differed from one another in terms of symptom severity on the three aforementioned measures. Depression appeared to be the strongest predictor of group membership. These results are considered in the light of the scientific debate on whether burnout can be distinguished from depression and whether burnout subtyping is useful. Finally, implications for clinical practice and future research are discussed. PMID:26869983

  7. Subgroup analysis in burnout: relations between fatigue, anxiety and depression

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    Arno eVan Dam

    2016-02-01

    Full Text Available Several authors have suggested that burned out patients do not form a homogeneous group and that subgroups should be considered. The identification of these subgroups may contribute to a better understanding of the burnout construct and lead to more specific therapeutic interventions. Subgroup analysis may also help clarify whether burnout is a distinct entity and whether subgroups of burnout overlap with other disorders such as depression and chronic fatigue syndrome. In a group of 113 clinically-diagnosed burned out patients, levels of fatigue, depression and anxiety were assessed. In order to identify possible subgroups, we performed a two-step cluster analysis. The analysis revealed two clusters that differed from one another in terms of symptom severity on the three aforementioned measures. Depression appeared to be the strongest predictor of group membership. These results are considered in the light of the scientific debate on whether burnout can be distinguished from depression and whether burnout subtyping is useful. Finally, implications for clinical practice and future research are discussed.

  8. Subgroup Analysis of Trials Is Rarely Easy (SATIRE: a study protocol for a systematic review to characterize the analysis, reporting, and claim of subgroup effects in randomized trials

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    Malaga German

    2009-11-01

    Full Text Available Abstract Background Subgroup analyses in randomized trials examine whether effects of interventions differ between subgroups of study populations according to characteristics of patients or interventions. However, findings from subgroup analyses may be misleading, potentially resulting in suboptimal clinical and health decision making. Few studies have investigated the reporting and conduct of subgroup analyses and a number of important questions remain unanswered. The objectives of this study are: 1 to describe the reporting of subgroup analyses and claims of subgroup effects in randomized controlled trials, 2 to assess study characteristics associated with reporting of subgroup analyses and with claims of subgroup effects, and 3 to examine the analysis, and interpretation of subgroup effects for each study's primary outcome. Methods We will conduct a systematic review of 464 randomized controlled human trials published in 2007 in the 118 Core Clinical Journals defined by the National Library of Medicine. We will randomly select journal articles, stratified in a 1:1 ratio by higher impact versus lower impact journals. According to 2007 ISI total citations, we consider the New England Journal of Medicine, JAMA, Lancet, Annals of Internal Medicine, and BMJ as higher impact journals. Teams of two reviewers will independently screen full texts of reports for eligibility, and abstract data, using standardized, pilot-tested extraction forms. We will conduct univariable and multivariable logistic regression analyses to examine the association of pre-specified study characteristics with reporting of subgroup analyses and with claims of subgroup effects for the primary and any other outcomes. Discussion A clear understanding of subgroup analyses, as currently conducted and reported in published randomized controlled trials, will reveal both strengths and weaknesses of this practice. Our findings will contribute to a set of recommendations to optimize

  9. Identifying subgroups of patients using latent class analysis

    DEFF Research Database (Denmark)

    Nielsen, Anne Mølgaard; Kent, Peter; Hestbæk, Lise

    2017-01-01

    BACKGROUND: Heterogeneity in patients with low back pain (LBP) is well recognised and different approaches to subgrouping have been proposed. Latent Class Analysis (LCA) is a statistical technique that is increasingly being used to identify subgroups based on patient characteristics. However, as ...

  10. A Bayesian subgroup analysis using collections of ANOVA models.

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    Liu, Jinzhong; Sivaganesan, Siva; Laud, Purushottam W; Müller, Peter

    2017-07-01

    We develop a Bayesian approach to subgroup analysis using ANOVA models with multiple covariates, extending an earlier work. We assume a two-arm clinical trial with normally distributed response variable. We also assume that the covariates for subgroup finding are categorical and are a priori specified, and parsimonious easy-to-interpret subgroups are preferable. We represent the subgroups of interest by a collection of models and use a model selection approach to finding subgroups with heterogeneous effects. We develop suitable priors for the model space and use an objective Bayesian approach that yields multiplicity adjusted posterior probabilities for the models. We use a structured algorithm based on the posterior probabilities of the models to determine which subgroup effects to report. Frequentist operating characteristics of the approach are evaluated using simulation. While our approach is applicable in more general cases, we mainly focus on the 2 × 2 case of two covariates each at two levels for ease of presentation. The approach is illustrated using a real data example. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Cluster analysis of clinical data identifies fibromyalgia subgroups.

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    Elisa Docampo

    Full Text Available INTRODUCTION: Fibromyalgia (FM is mainly characterized by widespread pain and multiple accompanying symptoms, which hinder FM assessment and management. In order to reduce FM heterogeneity we classified clinical data into simplified dimensions that were used to define FM subgroups. MATERIAL AND METHODS: 48 variables were evaluated in 1,446 Spanish FM cases fulfilling 1990 ACR FM criteria. A partitioning analysis was performed to find groups of variables similar to each other. Similarities between variables were identified and the variables were grouped into dimensions. This was performed in a subset of 559 patients, and cross-validated in the remaining 887 patients. For each sample and dimension, a composite index was obtained based on the weights of the variables included in the dimension. Finally, a clustering procedure was applied to the indexes, resulting in FM subgroups. RESULTS: VARIABLES CLUSTERED INTO THREE INDEPENDENT DIMENSIONS: "symptomatology", "comorbidities" and "clinical scales". Only the two first dimensions were considered for the construction of FM subgroups. Resulting scores classified FM samples into three subgroups: low symptomatology and comorbidities (Cluster 1, high symptomatology and comorbidities (Cluster 2, and high symptomatology but low comorbidities (Cluster 3, showing differences in measures of disease severity. CONCLUSIONS: We have identified three subgroups of FM samples in a large cohort of FM by clustering clinical data. Our analysis stresses the importance of family and personal history of FM comorbidities. Also, the resulting patient clusters could indicate different forms of the disease, relevant to future research, and might have an impact on clinical assessment.

  12. Cluster Analysis of Clinical Data Identifies Fibromyalgia Subgroups

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    Docampo, Elisa; Collado, Antonio; Escaramís, Geòrgia; Carbonell, Jordi; Rivera, Javier; Vidal, Javier; Alegre, José

    2013-01-01

    Introduction Fibromyalgia (FM) is mainly characterized by widespread pain and multiple accompanying symptoms, which hinder FM assessment and management. In order to reduce FM heterogeneity we classified clinical data into simplified dimensions that were used to define FM subgroups. Material and Methods 48 variables were evaluated in 1,446 Spanish FM cases fulfilling 1990 ACR FM criteria. A partitioning analysis was performed to find groups of variables similar to each other. Similarities between variables were identified and the variables were grouped into dimensions. This was performed in a subset of 559 patients, and cross-validated in the remaining 887 patients. For each sample and dimension, a composite index was obtained based on the weights of the variables included in the dimension. Finally, a clustering procedure was applied to the indexes, resulting in FM subgroups. Results Variables clustered into three independent dimensions: “symptomatology”, “comorbidities” and “clinical scales”. Only the two first dimensions were considered for the construction of FM subgroups. Resulting scores classified FM samples into three subgroups: low symptomatology and comorbidities (Cluster 1), high symptomatology and comorbidities (Cluster 2), and high symptomatology but low comorbidities (Cluster 3), showing differences in measures of disease severity. Conclusions We have identified three subgroups of FM samples in a large cohort of FM by clustering clinical data. Our analysis stresses the importance of family and personal history of FM comorbidities. Also, the resulting patient clusters could indicate different forms of the disease, relevant to future research, and might have an impact on clinical assessment. PMID:24098674

  13. Subgroup analysis in burnout : Relations between fatigue, anxiety, and depression.

    NARCIS (Netherlands)

    van Dam, A.

    2016-01-01

    Several authors have suggested that burned out patients do not form a homogeneous group and that subgroups should be considered. The identification of these subgroups may contribute to a better understanding of the burnout construct and lead to more specific therapeutic interventions. Subgroup

  14. Cumulative subgroup analysis to reduce waste in clinical research for individualised medicine.

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    Song, Fujian; Bachmann, Max O

    2016-12-15

    Although subgroup analyses in clinical trials may provide evidence for individualised medicine, their conduct and interpretation remain controversial. Subgroup effect can be defined as the difference in treatment effect across patient subgroups. Cumulative subgroup analysis refers to a series of repeated pooling of subgroup effects after adding data from each of related trials chronologically, to investigate the accumulating evidence for subgroup effects. We illustrated the clinical relevance of cumulative subgroup analysis in two case studies using data from published individual patient data (IPD) meta-analyses. Computer simulations were also conducted to examine the statistical properties of cumulative subgroup analysis. In case study 1, an IPD meta-analysis of 10 randomised trials (RCTs) on beta blockers for heart failure reported significant interaction of treatment effects with baseline rhythm. Cumulative subgroup analysis could have detected the subgroup effect 15 years earlier, with five fewer trials and 71% less patients, than the IPD meta-analysis which first reported it. Case study 2 involved an IPD meta-analysis of 11 RCTs on treatments for pulmonary arterial hypertension that reported significant subgroup effect by aetiology. Cumulative subgroup analysis could have detected the subgroup effect 6 years earlier, with three fewer trials and 40% less patients than the IPD meta-analysis. Computer simulations have indicated that cumulative subgroup analysis increases the statistical power and is not associated with inflated false positives. To reduce waste of research data, subgroup analyses in clinical trials should be more widely conducted and adequately reported so that cumulative subgroup analyses could be timely performed to inform clinical practice and further research.

  15. Medulloblastoma in China: Clinicopathologic Analyses of SHH, WNT, and Non-SHH/WNT Molecular Subgroups Reveal Different Therapeutic Responses to Adjuvant Chemotherapy

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    Ren, Yong; Yao, Yu; Li, Kay Ka-Wai; Ng, Ho-Keung; Mao, Ying; Zhou, Liang-Fu; Zhong, Ping

    2014-01-01

    Medulloblastoma (MB) is one of the most common primary central nervous system tumors in children. Data is lacking of a large cohort of medulloblastoma patients in China. Also, our knowledge on the sensitivity of different molecular subgroups of MB to adjuvant radiation therapy (RT) or chemotherapy (CHT) is still limited. The authors performed a retrospective study of 173 medulloblastoma patients treated at two institutions from 2002 to 2011. Formalin-fixed paraffin embedded (FFPE) tissues were available in all the cases and sections were stained to classify histological and molecular subgroups. Univariate and multivariate analyses were used to investigate prognostic factors. Of 173 patients, there were 118 children and 55 adults, 112 males and 61 females. Estimated 5-year overall survival (OS) rates for all patients, children and adults were 52%, 48% and 63%, respectively. After multivariate analysis, postoperative primary radiation therapy (RT) and chemotherapy (CHT) were revealed as favorable prognostic factors influencing OS and EFS. Postoperative primary chemotherapy (CHT) was found significantly improving the survival of children (pmedulloblastoma (CMB) (OS pmedulloblastoma (DMB) (OS p = 0.361, EFS p = 0.834) and Non-SHH/WNT subgroup (OS p = 0.127, EFS p = 0.055). Our study showed postoperative primary CHT significantly influence the survival of CMB, SHH subgroup and WNT subgroup but not in DMB and Non-SHH/WNT subgroup of MB. PMID:24932704

  16. Low Back Pain Subgroups using Fear-Avoidance Model Measures: Results of a Cluster Analysis

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    Beneciuk, Jason M.; Robinson, Michael E.; George, Steven Z.

    2012-01-01

    Objectives The purpose of this secondary analysis was to test the hypothesis that an empirically derived psychological subgrouping scheme based on multiple Fear-Avoidance Model (FAM) constructs would provide additional capabilities for clinical outcomes in comparison to a single FAM construct. Methods Patients (n = 108) with acute or sub-acute low back pain (LBP) enrolled in a clinical trial comparing behavioral physical therapy interventions to classification based physical therapy completed baseline questionnaires for pain catastrophizing (PCS), fear-avoidance beliefs (FABQ-PA, FABQ-W), and patient-specific fear (FDAQ). Clinical outcomes were pain intensity and disability measured at baseline, 4-weeks, and 6-months. A hierarchical agglomerative cluster analysis was used to create distinct cluster profiles among FAM measures and discriminant analysis was used to interpret clusters. Changes in clinical outcomes were investigated with repeated measures ANOVA and differences in results based on cluster membership were compared to FABQ-PA subgrouping used in the original trial. Results Three distinct FAM subgroups (Low Risk, High Specific Fear, and High Fear & Catastrophizing) emerged from cluster analysis. Subgroups differed on baseline pain and disability (p’s<.01) with the High Fear & Catastrophizing subgroup associated with greater pain than the Low Risk subgroup (p<.01) and the greatest disability (p’s<.05). Subgroup × time interactions were detected for both pain and disability (p’s<.05) with the High Fear & Catastrophizing subgroup reporting greater changes in pain and disability than other subgroups (p’s<.05). In contrast, FABQ-PA subgroups used in the original trial were not associated with interactions for clinical outcomes. Discussion These data suggest that subgrouping based on multiple FAM measures may provide additional information on clinical outcomes in comparison to determining subgroup status by FABQ-PA alone. Subgrouping methods for

  17. Stratification of randomization is not required for a pre-specified subgroup analysis.

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    Kaiser, Lee D

    2013-01-01

    Published literature and regulatory agency guidance documents provide conflicting recommendations as to whether a pre-specified subgroup analysis also requires for its validity that the study employ randomization that is stratified on subgroup membership. This is an important issue, as subgroup analyses are often required to demonstrate efficacy in the development of drugs with a companion diagnostic. Here, it is shown, for typical randomization methods, that the fraction of patients in the subgroup given experimental treatment matches, on average, the target fraction in the entire study. Also, mean covariate values are balanced, on average, between treatment arms in the subgroup, and it is argued that the variance in covariate imbalance between treatment arms in the subgroup is at worst only slightly increased versus a subgroup-stratified randomization method. Finally, in an analysis of variance setting, a least-squares treatment effect estimator within the subgroup is shown to be unbiased whether or not the randomization is stratified on subgroup membership. Thus, a requirement that a study be stratified on subgroup membership would place an artificial roadblock to innovation and the goals of personalized healthcare. Copyright © 2012 John Wiley & Sons, Ltd.

  18. Exercise challenge in Gulf War Illness reveals two subgroups with altered brain structure and function.

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    Rakib U Rayhan

    Full Text Available Nearly 30% of the approximately 700,000 military personnel who served in Operation Desert Storm (1990-1991 have developed Gulf War Illness, a condition that presents with symptoms such as cognitive impairment, autonomic dysfunction, debilitating fatigue and chronic widespread pain that implicate the central nervous system. A hallmark complaint of subjects with Gulf War Illness is post-exertional malaise; defined as an exacerbation of symptoms following physical and/or mental effort. To study the causal relationship between exercise, the brain, and changes in symptoms, 28 Gulf War veterans and 10 controls completed an fMRI scan before and after two exercise stress tests to investigate serial changes in pain, autonomic function, and working memory. Exercise induced two clinical Gulf War Illness subgroups. One subgroup presented with orthostatic tachycardia (n = 10. This phenotype correlated with brainstem atrophy, baseline working memory compensation in the cerebellar vermis, and subsequent loss of compensation after exercise. The other subgroup developed exercise induced hyperalgesia (n = 18 that was associated with cortical atrophy and baseline working memory compensation in the basal ganglia. Alterations in cognition, brain structure, and symptoms were absent in controls. Our novel findings may provide an understanding of the relationship between the brain and post-exertional malaise in Gulf War Illness.

  19. Latent class analysis derived subgroups of low back pain patients - do they have prognostic capacity?

    DEFF Research Database (Denmark)

    Mølgaard Nielsen, Anne; Hestbaek, Lise; Vach, Werner

    2017-01-01

    BACKGROUND: Heterogeneity in patients with low back pain is well recognised and different approaches to subgrouping have been proposed. One statistical technique that is increasingly being used is Latent Class Analysis as it performs subgrouping based on pattern recognition with high accuracy. Pr...

  20. Subgrouping of Readers Based on Performance Measures: A Latent Profile Analysis

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    Wolff, Ulrika

    2010-01-01

    By using latent profile analysis eight stable and interpretable subgroups of readers were identified. The basis for subgrouping was different performance measures with four aspects of reading in focus: reading of continuous texts, reading of document texts, word reading and reading speed. Participants were 9-year-old Swedish students included in…

  1. Medulloblastoma in China: clinicopathologic analyses of SHH, WNT, and non-SHH/WNT molecular subgroups reveal different therapeutic responses to adjuvant chemotherapy.

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    Zhen-Yu Zhang

    Full Text Available Medulloblastoma (MB is one of the most common primary central nervous system tumors in children. Data is lacking of a large cohort of medulloblastoma patients in China. Also, our knowledge on the sensitivity of different molecular subgroups of MB to adjuvant radiation therapy (RT or chemotherapy (CHT is still limited. The authors performed a retrospective study of 173 medulloblastoma patients treated at two institutions from 2002 to 2011. Formalin-fixed paraffin embedded (FFPE tissues were available in all the cases and sections were stained to classify histological and molecular subgroups. Univariate and multivariate analyses were used to investigate prognostic factors. Of 173 patients, there were 118 children and 55 adults, 112 males and 61 females. Estimated 5-year overall survival (OS rates for all patients, children and adults were 52%, 48% and 63%, respectively. After multivariate analysis, postoperative primary radiation therapy (RT and chemotherapy (CHT were revealed as favorable prognostic factors influencing OS and EFS. Postoperative primary chemotherapy (CHT was found significantly improving the survival of children (p<0.001 while it was not a significant prognostic factor for adult patients. Moreover, patients in WNT subtype had better OS (p = 0.028 than others (SHH and Non-SHH/WNT subtypes given postoperative adjuvant therapies. Postoperative primary RT was found to be a strong prognostic factor influencing the survival in all histological and molecular subgroups (p<0.001. Postoperative primary CHT was found significantly to influence the survival of classic medulloblastoma (CMB (OS p<0.001, EFS p<0.001, SHH subgroup (OS p = 0.020, EFS p = 0.049 and WNT subgroup (OS p = 0.003, EFS p = 0.016 but not in desmoplastic/nodular medulloblastoma (DMB (OS p = 0.361, EFS p = 0.834 and Non-SHH/WNT subgroup (OS p = 0.127, EFS p = 0.055. Our study showed postoperative primary CHT significantly influence the

  2. Discrete subgroups of adolescents diagnosed with borderline personality disorder: a latent class analysis of personality features.

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    Ramos, Vera; Canta, Guilherme; de Castro, Filipa; Leal, Isabel

    2014-08-01

    Research suggests that borderline personality disorder (BPD) can be diagnosed in adolescents and is marked by considerable heterogeneity. This study aimed to identify personality features characterizing adolescents with BPD and possible meaningful patterns of heterogeneity that could lead to personality subgroups. The authors analyzed data on 60 adolescents, ages 15 to 18 years, who met DSM criteria for a BPD diagnosis. The authors used latent class analysis (LCA) to identify subgroups based on the personality pattern scales from the Millon Adolescent Clinical Inventory (MACI). LCA indicated that the best-fitting solution was a two-class model, identifying two discrete subgroups of BPD adolescents that were described as internalizing and externalizing. The subgroups were then compared on clinical and sociodemographic variables, measures of personality dimensions, DSM BPD criteria, and perception of attachment styles. Adolescents with a BPD diagnosis constitute a heterogeneous group and vary meaningfully on personality features that can have clinical implications for treatment.

  3. Pediatric RSV Infection During Two Winter Seasons in British Columbia: A Role for Subgroup Analysis in Young Children?

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    E Wilson

    1990-01-01

    Full Text Available Using a panel of eight monoclonal antibodies directed against the G, F and NP proteins of respiratory syncytial virus, 167 virus isolates from nasopharyngeal washing cultures at British Columbia Children’s Hospital during two consecutive epidemics were subgrouped. Slides made and frozen at the time of virus isolation or prepared from recovered frozen passage material, were assayed by indirect immunofluorescence. Of 85 strains tested in 1987–88, 54 (64% were subgroup A, and 31 (36% subgroup B. By contrast, of 82 strains tested in 1988–89 five (6% were subgroup A and 77 (94% subgroup B. Review of patient charts did not reveal significant differences in clinical course of patients infected with the two subgroups, but the risk of infection with subgroup A was significantly greater than the risk of subgroup B infection in younger patients.

  4. Somatosensory nociceptive characteristics differentiate subgroups in people with chronic low back pain: a cluster analysis.

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    Rabey, Martin; Slater, Helen; OʼSullivan, Peter; Beales, Darren; Smith, Anne

    2015-10-01

    The objectives of this study were to explore the existence of subgroups in a cohort with chronic low back pain (n = 294) based on the results of multimodal sensory testing and profile subgroups on demographic, psychological, lifestyle, and general health factors. Bedside (2-point discrimination, brush, vibration and pinprick perception, temporal summation on repeated monofilament stimulation) and laboratory (mechanical detection threshold, pressure, heat and cold pain thresholds, conditioned pain modulation) sensory testing were examined at wrist and lumbar sites. Data were entered into principal component analysis, and 5 component scores were entered into latent class analysis. Three clusters, with different sensory characteristics, were derived. Cluster 1 (31.9%) was characterised by average to high temperature and pressure pain sensitivity. Cluster 2 (52.0%) was characterised by average to high pressure pain sensitivity. Cluster 3 (16.0%) was characterised by low temperature and pressure pain sensitivity. Temporal summation occurred significantly more frequently in cluster 1. Subgroups were profiled on pain intensity, disability, depression, anxiety, stress, life events, fear avoidance, catastrophizing, perception of the low back region, comorbidities, body mass index, multiple pain sites, sleep, and activity levels. Clusters 1 and 2 had a significantly greater proportion of female participants and higher depression and sleep disturbance scores than cluster 3. The proportion of participants undertaking Low back pain, therefore, does not appear to be homogeneous. Pain mechanisms relating to presentations of each subgroup were postulated. Future research may investigate prognoses and interventions tailored towards these subgroups.

  5. Paternal age related schizophrenia (PARS): Latent subgroups detected by k-means clustering analysis.

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    Lee, Hyejoo; Malaspina, Dolores; Ahn, Hongshik; Perrin, Mary; Opler, Mark G; Kleinhaus, Karine; Harlap, Susan; Goetz, Raymond; Antonius, Daniel

    2011-05-01

    Paternal age related schizophrenia (PARS) has been proposed as a subgroup of schizophrenia with distinct etiology, pathophysiology and symptoms. This study uses a k-means clustering analysis approach to generate hypotheses about differences between PARS and other cases of schizophrenia. We studied PARS (operationally defined as not having any family history of schizophrenia among first and second-degree relatives and fathers' age at birth ≥ 35 years) in a series of schizophrenia cases recruited from a research unit. Data were available on demographic variables, symptoms (Positive and Negative Syndrome Scale; PANSS), cognitive tests (Wechsler Adult Intelligence Scale-Revised; WAIS-R) and olfaction (University of Pennsylvania Smell Identification Test; UPSIT). We conducted a series of k-means clustering analyses to identify clusters of cases containing high concentrations of PARS. Two analyses generated clusters with high concentrations of PARS cases. The first analysis (N=136; PARS=34) revealed a cluster containing 83% PARS cases, in which the patients showed a significant discrepancy between verbal and performance intelligence. The mean paternal and maternal ages were 41 and 33, respectively. The second analysis (N=123; PARS=30) revealed a cluster containing 71% PARS cases, of which 93% were females; the mean age of onset of psychosis, at 17.2, was significantly early. These results strengthen the evidence that PARS cases differ from other patients with schizophrenia. Hypothesis-generating findings suggest that features of PARS may include a discrepancy between verbal and performance intelligence, and in females, an early age of onset. These findings provide a rationale for separating these phenotypes from others in future clinical, genetic and pathophysiologic studies of schizophrenia and in considering responses to treatment. Copyright © 2011 Elsevier B.V. All rights reserved.

  6. [Identification of subgroups with lower level of stroke knowledge using decision-tree analysis].

    Science.gov (United States)

    Kim, Hyun Kyung; Jeong, Seok Hee; Kang, Hyun Cheol

    2014-02-01

    This study was performed to explore levels of stroke knowledge and identify subgroups with lower levels of stroke knowledge among adults in Korea. A cross-sectional survey was used and data were collected in 2012. A national sample of 990 Koreans aged 20 to 74 years participated in this study. Knowledge of risk factors, warning signs, and first action for stroke were surveyed using face-to-face interviews. Descriptive statistics and decision tree analysis were performed using SPSS WIN 20.0 and Answer Tree 3.1. Mean score for stroke risk factor knowledge was 7.7 out of 10. The least recognized risk factor was diabetes and four subgroups with lower levels of knowledge were identified. Score for knowledge of stroke warning signs was 3.6 out of 6. The least recognized warning sign was sudden severe headache and six subgroups with lower levels of knowledge were identified. The first action for stroke was recognized by 65.7 percent of participants and four subgroups with lower levels of knowledge were identified. Multi-faceted education should be designed to improve stroke knowledge among Korean adults, particularly focusing on subgroups with lower levels of knowledge and less recognition of items in this study.

  7. The Importance of Risk and Subgroup Analysis of Nonparticipants in a Geriatric Intervention Study

    DEFF Research Database (Denmark)

    Rosted, E.; Poulsen, Ingrid; Hendriksen, C

    2016-01-01

    Background. A major concern in intervention studies is the generalizability of the findings due to refusal of intended participants to actually take part. In studies including ill older people the number of those declining to participate may be large and the concern is therefore relevant...... randomized study. Conclusion. We recommend that intervention studies among older people or other fragile patient groups include analysis of relevant risk and subgroup analyses of refusers........ Objectives. To compare patients characteristics, rates of acute readmission, and mortality after one and six months among older persons who agreed and those who declined to participate in a randomized controlled trial and to describe subgroups of nonparticipants. Design. Comparative study based...

  8. The Importance of Risk and Subgroup Analysis of Nonparticipants in a Geriatric Intervention Study

    DEFF Research Database (Denmark)

    Rosted, E.; Poulsen, Ingrid; Hendriksen, C

    2016-01-01

    . Objectives. To compare patients characteristics, rates of acute readmission, and mortality after one and six months among older persons who agreed and those who declined to participate in a randomized controlled trial and to describe subgroups of nonparticipants. Design. Comparative study based...... on a randomized controlled trial. Setting. University hospital in the Capital Region of Denmark. Participants. Patients >70 years discharged home after a short Emergency Department stay. 399 were requested to participate; 271 consented, whereas 128 refused. Results. Refusers were more likely to be readmitted (p...... randomized study. Conclusion. We recommend that intervention studies among older people or other fragile patient groups include analysis of relevant risk and subgroup analyses of refusers....

  9. Cluster analysis for identifying sub-groups and selecting potential discriminatory variables in human encephalitis

    Directory of Open Access Journals (Sweden)

    Crowcroft Natasha S

    2010-12-01

    Full Text Available Abstract Background Encephalitis is an acute clinical syndrome of the central nervous system (CNS, often associated with fatal outcome or permanent damage, including cognitive and behavioural impairment, affective disorders and epileptic seizures. Infection of the central nervous system is considered to be a major cause of encephalitis and more than 100 different pathogens have been recognized as causative agents. However, a large proportion of cases have unknown disease etiology. Methods We perform hierarchical cluster analysis on a multicenter England encephalitis data set with the aim of identifying sub-groups in human encephalitis. We use the simple matching similarity measure which is appropriate for binary data sets and performed variable selection using cluster heatmaps. We also use heatmaps to visually assess underlying patterns in the data, identify the main clinical and laboratory features and identify potential risk factors associated with encephalitis. Results Our results identified fever, personality and behavioural change, headache and lethargy as the main characteristics of encephalitis. Diagnostic variables such as brain scan and measurements from cerebrospinal fluids are also identified as main indicators of encephalitis. Our analysis revealed six major clusters in the England encephalitis data set. However, marked within-cluster heterogeneity is observed in some of the big clusters indicating possible sub-groups. Overall, the results show that patients are clustered according to symptom and diagnostic variables rather than causal agents. Exposure variables such as recent infection, sick person contact and animal contact have been identified as potential risk factors. Conclusions It is in general assumed and is a common practice to group encephalitis cases according to disease etiology. However, our results indicate that patients are clustered with respect to mainly symptom and diagnostic variables rather than causal agents

  10. Clinical trials with nested subgroups: Analysis, sample size determination and internal pilot studies.

    Science.gov (United States)

    Placzek, Marius; Friede, Tim

    2017-01-01

    The importance of subgroup analyses has been increasing due to a growing interest in personalized medicine and targeted therapies. Considering designs with multiple nested subgroups and a continuous endpoint, we develop methods for the analysis and sample size determination. First, we consider the joint distribution of standardized test statistics that correspond to each (sub)population. We derive multivariate exact distributions where possible, providing approximations otherwise. Based on these results, we present sample size calculation procedures. Uncertainties about nuisance parameters which are needed for sample size calculations make the study prone to misspecifications. We discuss how a sample size review can be performed in order to make the study more robust. To this end, we implement an internal pilot study design where the variances and prevalences of the subgroups are reestimated in a blinded fashion and the sample size is recalculated accordingly. Simulations show that the procedures presented here do not inflate the type I error significantly and maintain the prespecified power as long as the sample size of the smallest subgroup is not too small. We pay special attention to the case of small sample sizes and attain a lower boundary for the size of the internal pilot study.

  11. Distinctive subgroups derived by cluster analysis based on pain and psychological symptoms in Swedish older adults with chronic pain - a population study (PainS65+).

    Science.gov (United States)

    Larsson, Britt; Gerdle, Björn; Bernfort, Lars; Levin, Lars-Åke; Dragioti, Elena

    2017-09-02

    Improved knowledge based on clinical features of chronic pain in older adults would be valuable in terms of patient-orientated approaches and would provide support for health care systems in optimizing health care resources. This study identifies subgroups based on pain and psychological symptoms among Swedish older adults in the general population and compares derived subgroups with respect to socio-demographics, health aspects, and health care costs. This cross-sectional study uses data collected from four registers and one survey. The total sample comprised 2415 individuals ≥65 years old. A two-step cluster analysis was performed. Data on pain intensity, number of pain sites, anxiety, depression, and pain catastrophizing were used as classification variables. Differences in socio-demographics, quality of life, general health, insomnia, and health care costs among the clusters were investigated. Association of the clusters with the above parameters was further evaluated using multinomial logistic regression. Four major clusters were identified: Subgroup 1 (n = 325; 15%) - moderate pain and high psychological symptoms; Subgroup 2 (n = 516; 22%) - high pain and moderate psychological symptoms; Subgroup 3 (n = 686; 30%) - low pain and moderate psychological symptoms; and Subgroup 4 (n = 767; 33%) - low pain and low psychological symptoms. Significant differences were found between the four clusters with regard to age, sex, educational level, family status, quality of life, general health, insomnia, and health care costs. The multinomial logistic regression analysis revealed that Subgroups 1 and 2, compared to Subgroup 4, were significantly associated with decreased quality of life, decreased general health, and increased insomnia. Subgroup 3, compared to Subgroup 4, was associated with decreased general health and increased insomnia. In addition, compared to Subgroup 4, Subgroups 1 and 2 were significantly associated with higher health care costs. Two

  12. Diagnostic accuracy of digital versus film mammography: exploratory analysis of selected population subgroups in DMIST.

    Science.gov (United States)

    Pisano, Etta D; Hendrick, R Edward; Yaffe, Martin J; Baum, Janet K; Acharyya, Suddhasatta; Cormack, Jean B; Hanna, Lucy A; Conant, Emily F; Fajardo, Laurie L; Bassett, Lawrence W; D'Orsi, Carl J; Jong, Roberta A; Rebner, Murray; Tosteson, Anna N A; Gatsonis, Constantine A

    2008-02-01

    To retrospectively compare the accuracy of digital versus film mammography in population subgroups of the Digital Mammographic Imaging Screening Trial (DMIST) defined by combinations of age, menopausal status, and breast density, by using either biopsy results or follow-up information as the reference standard. DMIST included women who underwent both digital and film screening mammography. Institutional review board approval at all participating sites and informed consent from all participating women in compliance with HIPAA was obtained for DMIST and this retrospective analysis. Areas under the receiver operating characteristic curve (AUCs) for each modality were compared within each subgroup evaluated (age or= 65 years, dense vs nondense breasts at mammography, and pre- or perimenopausal vs postmenopausal status for the two younger age cohorts [10 new subgroups in toto]) while controlling for multiple comparisons (P film vs both vs neither), mammographic lesion type (mass, calcifications, or other), digital machine type, mammographic and pathologic size and diagnosis, existence of prior mammographic study at time of interpretation, months since prior mammographic study, and compressed breast thickness. Thirty-three centers enrolled 49 528 women. Breast cancer status was determined for 42,760 women, the group included in this study. Pre- or perimenopausal women younger than 50 years who had dense breasts at film mammography comprised the only subgroup for which digital mammography was significantly better than film (AUCs, 0.79 vs 0.54; P = .0015). Breast Imaging Reporting and Data System-based sensitivity in this subgroup was 0.59 for digital and 0.27 for film mammography. AUCs were not significantly different in any of the other subgroups. For women aged 65 years or older with fatty breasts, the AUC showed a nonsignificant tendency toward film being better than digital mammography (AUCs, 0.88 vs 0.70; P = .0025). Digital mammography performed significantly better

  13. The Importance of Risk and Subgroup Analysis of Nonparticipants in a Geriatric Intervention Study

    Directory of Open Access Journals (Sweden)

    Elizabeth Rosted

    2016-01-01

    Full Text Available Background. A major concern in intervention studies is the generalizability of the findings due to refusal of intended participants to actually take part. In studies including ill older people the number of those declining to participate may be large and the concern is therefore relevant. Objectives. To compare patients characteristics, rates of acute readmission, and mortality after one and six months among older persons who agreed and those who declined to participate in a randomized controlled trial and to describe subgroups of nonparticipants. Design. Comparative study based on a randomized controlled trial. Setting. University hospital in the Capital Region of Denmark. Participants. Patients ≥70 years discharged home after a short Emergency Department stay. 399 were requested to participate; 271 consented, whereas 128 refused. Results. Refusers were more likely to be readmitted (p<0.001 or die (p=0.006. The largest subgroup of refusers described as “too ill” had the highest risk of readmission (OR = 3.00, 95% CI = 1.61–5.47, p=0.001 and of mortality within six months (OR = 3.50, 95% CI = 1.64–7.49, p=0.002. However, this seems not to have affected the results of our randomized study. Conclusion. We recommend that intervention studies among older people or other fragile patient groups include analysis of relevant risk and subgroup analyses of refusers.

  14. Baseline hospital performance and the impact of medical emergency teams: Modelling vs. conventional subgroup analysis

    Directory of Open Access Journals (Sweden)

    Hillman Ken

    2009-12-01

    Full Text Available Abstract Background To compare two approaches to the statistical analysis of the relationship between the baseline incidence of adverse events and the effect of medical emergency teams (METs. Methods Using data from a cluster randomized controlled trial (the MERIT study, we analysed the relationship between the baseline incidence of adverse events and its change from baseline to the MET activation phase using quadratic modelling techniques. We compared the findings with those obtained with conventional subgroup analysis. Results Using linear and quadratic modelling techniques, we found that each unit increase in the baseline incidence of adverse events in MET hospitals was associated with a 0.59 unit subsequent reduction in adverse events (95%CI: 0.33 to 0.86 after MET implementation and activation. This applied to cardiac arrests (0.74; 95%CI: 0.52 to 0.95, unplanned ICU admissions (0.56; 95%CI: 0.26 to 0.85 and unexpected deaths (0.68; 95%CI: 0.45 to 0.90. Control hospitals showed a similar reduction only for cardiac arrests (0.95; 95%CI: 0.56 to 1.32. Comparison using conventional subgroup analysis, on the other hand, detected no significant difference between MET and control hospitals. Conclusions Our study showed that, in the MERIT study, when there was dependence of treatment effect on baseline performance, an approach based on regression modelling helped illustrate the nature and magnitude of such dependence while sub-group analysis did not. The ability to assess the nature and magnitude of such dependence may have policy implications. Regression technique may thus prove useful in analysing data when there is a conditional treatment effect.

  15. An observation on inappropriate probiotic subgroup classifications in the meta-analysis by Lau and Chamberlain

    Directory of Open Access Journals (Sweden)

    McFarl

    2016-09-01

    Full Text Available Lynne V McFarland Department of Medicinal Chemistry, University of Washington, Seattle, WA, USA I read with great interest the systematic review of meta-analysis assessing probiotics for the prevention of Clostridium difficile-associated diarrhea (CDAD published in the International Journal of General Medicine. These authors pooled 26 randomized controlled trials (RCTs and concluded that Lactobacilli, mixtures, and Saccharomyces probiotics were effective in preventing CDAD. However, the meta-analysis by Lau and Chamberlain is flawed due to improper classification by the types of probiotics. It is important to recognize that the efficacy of probiotics for various diseases has been shown to be strain specific for each probiotic product, and thus the data should only be pooled for probiotics that are of the identical type. In their analysis of probiotic subgroups by various species, the authors have inappropriately merged different types of Lactobacilli into one subgroup “Lactobacilli” and different types of mixtures into one group classified as “Mix”.View the original paper by Lau and Chamberlain. 

  16. Three subgroups of pain profiles identified in 227 women with arthritis: a latent class analysis.

    Science.gov (United States)

    de Luca, Katie; Parkinson, Lynne; Downie, Aron; Blyth, Fiona; Byles, Julie

    2017-03-01

    The objectives were to identify subgroups of women with arthritis based upon the multi-dimensional nature of their pain experience and to compare health and socio-demographic variables between subgroups. A latent class analysis of 227 women with self-reported arthritis was used to identify clusters of women based upon the sensory, affective, and cognitive dimensions of the pain experience. Multivariate multinomial logistic regression analysis was used to determine the relationship between cluster membership and health and sociodemographic characteristics. A three-class cluster model was most parsimonious. 39.5 % of women had a unidimensional pain profile; 38.6 % of women had moderate multidimensional pain profile that included additional pain symptomatology such as sensory qualities and pain catastrophizing; and 21.9 % of women had severe multidimensional pain profile that included prominent pain symptomatology such as sensory and affective qualities of pain, pain catastrophizing, and neuropathic pain. Women with severe multidimensional pain profile have a 30.5 % higher risk of poorer quality of life and a 7.3 % higher risk of suffering depression, and women with moderate multidimensional pain profile have a 6.4 % higher risk of poorer quality of life when compared to women with unidimensional pain. This study identified three distinct subgroups of pain profiles in older women with arthritis. Women had very different experiences of pain, and cluster membership impacted significantly on health-related quality of life. These preliminary findings provide a stronger understanding of profiles of pain and may contribute to the development of tailored treatment options in arthritis.

  17. Cost-Effectiveness of Endovascular Stroke Therapy: A Patient Subgroup Analysis From a US Healthcare Perspective.

    Science.gov (United States)

    Kunz, Wolfgang G; Hunink, M G Myriam; Sommer, Wieland H; Beyer, Sebastian E; Meinel, Felix G; Dorn, Franziska; Wirth, Stefan; Reiser, Maximilian F; Ertl-Wagner, Birgit; Thierfelder, Kolja M

    2016-11-01

    Endovascular therapy in addition to standard care (EVT+SC) has been demonstrated to be more effective than SC in acute ischemic large vessel occlusion stroke. Our aim was to determine the cost-effectiveness of EVT+SC depending on patients' initial National Institutes of Health Stroke Scale (NIHSS) score, time from symptom onset, Alberta Stroke Program Early CT Score (ASPECTS), and occlusion location. A decision model based on Markov simulations estimated lifetime costs and quality-adjusted life years (QALYs) associated with both strategies applied in a US setting. Model input parameters were obtained from the literature, including recently pooled outcome data of 5 randomized controlled trials (ESCAPE [Endovascular Treatment for Small Core and Proximal Occlusion Ischemic Stroke], EXTEND-IA [Extending the Time for Thrombolysis in Emergency Neurological Deficits-Intra-Arterial], MR CLEAN [Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands], REVASCAT [Randomized Trial of Revascularization With Solitaire FR Device Versus Best Medical Therapy in the Treatment of Acute Stroke Due to Anterior Circulation Large Vessel Occlusion Presenting Within 8 Hours of Symptom Onset], and SWIFT PRIME [Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment]). Probabilistic sensitivity analysis was performed to estimate uncertainty of the model results. Net monetary benefits, incremental costs, incremental effectiveness, and incremental cost-effectiveness ratios were derived from the probabilistic sensitivity analysis. The willingness-to-pay was set to $50 000/QALY. Overall, EVT+SC was cost-effective compared with SC (incremental cost: $4938, incremental effectiveness: 1.59 QALYs, and incremental cost-effectiveness ratio: $3110/QALY) in 100% of simulations. In all patient subgroups, EVT+SC led to gained QALYs (range: 0.47-2.12), and mean incremental cost-effectiveness ratios were considered cost

  18. Dysexecutive versus amnestic Alzheimer disease subgroups: analysis of demographic, genetic, and vascular factors.

    Science.gov (United States)

    Mez, Jesse; Cosentino, Stephanie; Brickman, Adam M; Huey, Edward D; Manly, Jennifer J; Mayeux, Richard

    2013-01-01

    The objective of this study was to compare the demographic and vascular characteristics and APOE genotypes of a dysexecutive subgroup of Alzheimer disease (AD) with an amnestic subgroup of AD early in the disease course. A total of 2224 participants from the National Alzheimer's Coordinating Center database who carried a diagnosis of mild cognitive impairment (n=1188) or mild AD (clinical dementia rating ≤1) (n=1036) were included in this study. A subset of the mild cognitive impairment (n=61) and mild AD (n=79) participants underwent an autopsy. A dysexecutive subgroup (n=587) was defined as having executive performance >1 SD worse than memory performance, and an amnestic subgroup (n=549) was defined conversely. Among the autopsy subset, the odds of an AD pathologic diagnosis were compared in the 2 subgroups. The demographics, APOE[Latin Small Letter Open E]4 status, and vascular risk factors were compared in the 2 subgroups. Among the autopsy subset, the odds of having an AD pathologic diagnosis did not differ between the dysexecutive and amnestic subgroups. Under an additive model, participants in the dysexecutive subgroup possessed the APOE[Latin Small Letter Open E]4 allele less frequently compared with those in the amnestic subgroup. The dysexecutive subgroup had a history of hypertension less frequently compared with the amnestic subgroup. These distinct characteristics add to accumulating evidence that a dysexecutive subgroup of AD may have a unique underlying pathophysiology.

  19. Commognitive analysis of undergraduate mathematics students' first encounter with the subgroup test

    Science.gov (United States)

    Ioannou, Marios

    2017-08-01

    This study analyses learning aspects of undergraduate mathematics students' first encounter with the subgroup test, using the commognitive theoretical framework. It focuses on students' difficulties as these are related to the object-level and metalevel mathematical learning in group theory, and, when possible, highlights any commognitive conflicts. In the data analysis, one can identify three types of difficulties, relevant to object-level learning: namely regarding the frequently observed confusion between groups and sets, the object-level rules of visual mediators, and the object-level rules of contextual notions, such as permutations, exponentials, sets and matrices. In addition, data analysis suggests two types of difficulties, relevant to metalevel learning. The first refers to the actual proof that the three conditions of subgroup test hold, and the second is related to syntactic inaccuracies, incomplete argumentation and problematic use of visual mediators. Finally, this study suggests that there are clear links between object-level and metalevel learning, mainly due to the fact that objectification of the various relevant mathematical notions influences the endorsement of the governing metarules.

  20. MORS Workshop - Chem-Bio WMD: Understanding the Problem, Operations Analysis Working Group, Low Spectrum Conflict Subgroup

    National Research Council Canada - National Science Library

    Andreozzi, Gregory

    2001-01-01

    This report documents the insights developed by the Low Spectrum Conflict Subgroup of the Operations Analysis Working Group at the 30 January - 1 February 2001 Military Operations Research Society (MORS...

  1. Functional analysis of the C-II subgroup killer toxin-like chitinases in the filamentous ascomycete Aspergillus nidulans.

    Science.gov (United States)

    Tzelepis, Georgios D; Melin, Petter; Stenlid, Jan; Jensen, Dan Funck; Karlsson, Magnus

    2014-03-01

    Chitinases are hydrolytic enzymes responsible for chitin polymer degradation. Fungal chitinases belong exclusively to glycoside hydrolases family 18 and they are categorized into three phylogenetic groups (A, B and C), which are further divided into subgroups (A-II to A-V, B-I to B-V and C-I to C-II). Subgroup C chitinases display similarity with the α/β-subunit of the zymocin yeast killer toxin produced by Kluyveromyces lactis, suggesting a role of these enzymes in fungal-fungal interactions. In this study, we investigated the regulation and function of 4 Aspergillus nidulans subgroup C-II killer toxin-like chitinases by quantitative PCR and by constructing gene deletion strains. Our results showed that all 4 genes were highly induced during interactions with Botrytis cinerea and Rhizoctonia solani, compared to self-interactions. In addition, chiC2-2 and chiC2-3 were also induced during contact with Fusarium sporotrichoides, while none of these genes were induced during interactions with Phytophthora niederhauserii. In contrast, no difference in expression levels were observed between growth on glucose-rich media compared with media containing colloidal chitin, while all genes were repressed during growth on R. solani cell wall material. Phenotypic analysis of chitinase gene deletion strains revealed that B. cinerea biomass was significantly higher in culture filtrate derived from the ΔchiC2-2 strain compared to biomasses grown in media derived from A. nidulans wild type or the other chitinase gene deletion strains. The analysis also showed that all chitinase gene deletion strains displayed increased biomass production in liquid cultures, and altered response to abiotic stress. In summary, our gene expression data suggest the involvement of A. nidulans subgroup C-II chitinases in fungal-fungal interactions, which is further proven for ChiC2-2. In addition, lacking any of the 4 chitinases influenced the growth of A. nidulans. Copyright © 2013 Elsevier Inc. All

  2. Genetic diversity among phytoplasmas infecting Opuntia species: virtual RFLP analysis identifies new subgroups in the peanut witches'-broom phytoplasma group.

    Science.gov (United States)

    Cai, Hong; Wei, Wei; Davis, Robert E; Chen, Hairu; Zhao, Yan

    2008-06-01

    Phytoplasmas were detected in cactus (Opuntia species) plants exhibiting witches'-broom disease symptoms in Yunnan Province, south-western China. Comparative and phylogenetic analyses of 16S rRNA gene sequences indicated that an overwhelming majority of the cactus-infecting phytoplasmas under study belonged to the peanut witches'-broom phytoplasma group (16SrII). Genotyping through use of computer-simulated restriction fragment length polymorphism (RFLP) analysis of 16S rRNA genes revealed a remarkable genetic diversity among these cactus-infecting phytoplasma strains. Based on calculated coefficients of RFLP pattern similarities, seven new 16SrII subgroups were recognized, bringing the total of described group 16SrII subgroups to 12 worldwide. Geographical areas differed from one another in the extent of genetic diversity among cactus-infecting phytoplasma strains. The findings have implications for relationships between ecosystem distribution and the emergence of group 16SrII subgroup diversity.

  3. Ranibizumab in Myopic Choroidal Neovascularization: A Subgroup Analysis by Ethnicity, Age, and Ocular Characteristics in RADIANCE.

    Science.gov (United States)

    Holz, Frank G; Tufail, Adnan; Leveziel, Nicolas; Lai, Timothy Y Y; Lanzetta, Paolo; Wong, Tien Y; Yu, Hyeong Gon; Chen, You Xin; Heinrichs, Nikol; Pilz, Stefan; Ohno-Matsui, Kyoko

    2016-01-01

    To assess the impact of ethnicity, age, and ocular characteristics on ranibizumab efficacy in myopic choroidal neovascularization (CNV). In this post hoc subgroup analysis from the phase III RADIANCE study, best-corrected visual acuity (BCVA) outcomes and treatment exposure were analyzed in 105 patients treated with ranibizumab 0.5 mg. Baseline categories included ethnicity, age, baseline BCVA, lesion area, CNV lesion area, refraction sphere, axial length, subretinal fluid, and location of CNV. At month 12, the mean change in BCVA was numerically higher in East-Asians than in Caucasians (17.0 vs. 14.1 letters). The median number of injections varied with ethnicity (East-Asians vs. Caucasians: 2 vs. 3), baseline BCVA (highest vs. lowest: 1 vs. 4), CNV lesion area and lesion area (largest vs. smallest: 5 vs. 1 and 5 vs. 2). East-Asians showed numerically higher BCVA gains than Caucasians. The number of injections varied across subgroups, emphasizing the need for individualized treatment. © 2016 S. Karger AG, Basel.

  4. Assessing the relationship between the Driver Behavior Questionnaire and the Driver Skill Inventory: Revealing sub-groups of drivers

    DEFF Research Database (Denmark)

    Martinussen, Laila Marianne; Møller, Mette; Prato, Carlo Giacomo

    2014-01-01

    The Driver Behavior Questionnaire and the Driver Skill Inventory are two of the most frequently used measures of self-reported driving style and driving skill. The motivation behind the present study was to identify sub-groups of drivers that potentially act dangerously in traffic (as measured by...... driving behaviors, and vice versa. The present findings highlight the need to look into driver’s attitudes towards safety, and to devise differential interventions targeting specific problematic groups of the population in the attempt to improve road safety nationwide....

  5. Subgroup analysis of telehealthcare for patients with chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Witt Udsen, Flemming; Lilholt, Pernille H.; Hejlesen, Ole K.

    2017-01-01

    -to-pay threshold values. The purpose of this article was to assess potential sources of variation across subgroups, which could explain overall cost-effectiveness results or be utilized in future economic studies in telehealthcare research. METHODS: First, the cost-structures and cost-effectiveness across COPD...... investigated post hoc. In analyzing cost-effectiveness, two separate linear mixed-effects models with treatment-by-covariate interactions were applied: one for quality-adjusted life-year (QALY) gain and one for total healthcare and social sector costs. Probabilistic sensitivity analysis was used for each......PURPOSE: Results from the Danish cluster-randomized trial of telehealthcare to 1,225 patients with chronic obstructive pulmonary disease (COPD), the Danish Telecare North Trial, concluded that the telehealthcare solution was unlikely to be cost-effective, by applying international willingness...

  6. The effect of active video games by ethnicity, sex and fitness: subgroup analysis from a randomised controlled trial

    OpenAIRE

    Foley, Louise; Jiang, Yannan; Ni Mhurchu, Cliona; Jull, Andrew; Prapavessis, Harry; Rodgers,Anthony; Maddison, Ralph

    2014-01-01

    Background The prevention and treatment of childhood obesity is a key public health challenge. However, certain groups within populations have markedly different risk profiles for obesity and related health behaviours. Well-designed subgroup analysis can identify potential differential effects of obesity interventions, which may be important for reducing health inequalities. The study aim was to evaluate the consistency of the effects of active video games across important subgroups in a rand...

  7. Whole-breast irradiation: a subgroup analysis of criteria to stratify for prone position treatment

    Energy Technology Data Exchange (ETDEWEB)

    Ramella, Sara, E-mail: s.ramella@unicampus.it [Radiation Oncology, Campus Bio-Medico University, Rome (Italy); Trodella, Lucio; Ippolito, Edy; Fiore, Michele; Cellini, Francesco; Stimato, Gerardina; Gaudino, Diego; Greco, Carlo [Radiation Oncology, Campus Bio-Medico University, Rome (Italy); Ramponi, Sara; Cammilluzzi, Eugenio; Cesarini, Claudio [Breast Unit, S. Pertini Hospital, Rome (Italy); Piermattei, Angelo [Department of Physics, Catholic University, Rome (Italy); Cesario, Alfredo [CdC San Raffaele Velletri (Italy); Department of Thoracic Surgery, Catholic University, Rome (Italy); D' Angelillo, Rolando Maria [Radiation Oncology, Campus Bio-Medico University, Rome (Italy)

    2012-07-01

    To select among breast cancer patients and according to breast volume size those who may benefit from 3D conformal radiotherapy after conservative surgery applied with prone-position technique. Thirty-eight patients with early-stage breast cancer were grouped according to the target volume (TV) measured in the supine position: small ({<=}400 mL), medium (400-700 mL), and large ({>=}700 ml). An ad-hoc designed and built device was used for prone set-up to displace the contralateral breast away from the tangential field borders. All patients underwent treatment planning computed tomography in both the supine and prone positions. Dosimetric data to explore dose distribution and volume of normal tissue irradiated were calculated for each patient in both positions. Homogeneity index, hot spot areas, the maximum dose, and the lung constraints were significantly reduced in the prone position (p < 0.05). The maximum heart distance and the V{sub 5Gy} did not vary consistently in the 2 positions (p = 0.06 and p = 0.7, respectively). The number of necessary monitor units was significantly higher in the supine position (312 vs. 232, p < 0.0001). The subgroups analysis pointed out the advantage in lung sparing in all TV groups (small, medium and large) for all the evaluated dosimetric constraints (central lung distance, maximum lung distance, and V{sub 5Gy}, p < 0.0001). In the small TV group, a dose reduction in nontarget areas of 22% in the prone position was detected (p = 0.056); in the medium and high TV groups, the difference was of about -10% (p = NS). The decrease in hot spot areas in nontarget tissues was 73%, 47%, and 80% for small, medium, and large TVs in the prone position, respectively. Although prone breast radiotherapy is normally proposed in patients with breasts of large dimensions, this study gives evidence of dosimetric benefit in all patient subgroups irrespective of breast volume size.

  8. Identification of subgroups of patients with low back pain using Latent Class Analysis

    DEFF Research Database (Denmark)

    Nielsen, Anne Mølgaard

    Low back pain (LBP) is a major global health problem but the evidence base available to inform clinical decision making and to provide prognostic information to patients, is less than ideal. Therefore, there is a need for further knowledge about this largely non‐specific condition. Within...... questionnaire and the clinicians’ findings on a standardised examination of the low back. By using pattern recognition, subgroups of patients were identified within which their responses and scores are similar, and therefore the patients are more alike within the subgroups than across the subgroups. Latent...... in the outcomes, their prognostic capacity was as high or higher than two existing subgrouping tools (STarT Back Tool and Quebec Task Force Classification), and three baseline characteristics (LBP intensity, leg pain intensity and pain‐related disability). In contrast, the novel subgroupings had a lower...

  9. Mixture model analysis identifies irritable bowel syndrome subgroups characterised by specific profiles of gastrointestinal, extraintestinal somatic and psychological symptoms.

    Science.gov (United States)

    Polster, A; Van Oudenhove, L; Jones, M; Öhman, L; Törnblom, H; Simrén, M

    2017-09-01

    Current subgrouping of Irritable Bowel Syndrome (IBS) is exclusively based on stool consistency without considering other relevant gastrointestinal (GI), extraintestinal somatic or psychological features. To identify subgroups based on a comprehensive set of IBS-related parameters. Mixture model analysis was used, with the following input variables: 13 single-item scores from the IBS-specific Gastrointestinal Symptom Rating Scale, average stool consistency and frequency from a 7-day Bristol Stool Form diary, 12 single-item extraintestinal symptom scores from the Patient Health Questionnaire-12, and anxiety and depression subscale scores from the Hospital Anxiety and Depression scale. The resulting latent subgroups were compared regarding symptom profiles using analysis of variance followed by pair-wise comparisons. One hundred and seventy-two IBS patients (Rome III; 69% female; mean age 33.7 [range 18-60] years) were included. The optimal subgrouping showed six latent groups, characterised by: (I) constipation with low comorbidities, (II) constipation with high comorbidities, (III) diarrhoea with low comorbidities, (IV) diarrhoea and pain with high comorbidities, (V) mixed GI symptoms with high comorbidities, (VI) a mix of symptoms with overall mild severity. The subgroups showed differences in the distribution of Rome III-subtypes, IBS severity, presence of anxiety and depression, and gender, but not regarding age, IBS duration or reported post-infectious onset of IBS. This model-based subgrouping of IBS partly supports the distinction of subgroups based on bowel habits, but additionally distinguishes subgroups with or without co-morbid extraintestinal somatic and psychological symptoms. The resulting groups show specific profiles of symptom combinations. © 2017 John Wiley & Sons Ltd.

  10. Genetic Sequencing Analysis of A307 Subgroup of ABO Blood Group.

    Science.gov (United States)

    Huang, Ying; Lin, Jiajin; Zhu, Suiyong

    2015-09-18

    BACKGROUND The aim of this study was to investigate the serology and gene sequence characteristics of the A307 subgroup of the ABO blood group. MATERIAL AND METHODS Monoclonal anti-A and anti-B antibodies were used to detect the ABO antigens of a proband whose positive blood type was not consistent with the negative blood type of the ABO blood group. Standard A-, B-, and O-negative typing cells were used to test for ABO antibodies in the serum. Additionally, polymerase chain reaction with sequence-specific primer (PCR-SSP) was used to confirm the genotype, and subsequently, exons 6 and 7 of the ABO gene were detected by gene sequencing. Samples from the wife and daughters of the proband were also used for serological and genetic testing. RESULTS Red blood cells of the proband showed weak agglutination reaction with anti-A antibody, while anti-B antibody was detected in the serum. Moreover, PCR-SSP detected A307 and O02 alleles, while gene sequencing revealed mutation of c.745C>T in exon 7, which produced a polypeptide chain p.R249W. The A307 gene of the proband was not inherited by his daughters. CONCLUSIONS A mutation (c.745 C>T) in exon 7 of the ABO blood group gene resulted in low activity of a-1,3-N-acetyl-galactosaminyl transferase, producing A3 phenotype.

  11. Subgrouping of risky behaviors among Iranian college students: a latent class analysis

    Directory of Open Access Journals (Sweden)

    Safiri S

    2016-07-01

    Full Text Available Saeid Safiri,1,2 Afarin Rahimi-Movaghar,3 Masud Yunesian,4,5 Homayoun Sadeghi-Bazargani,6 Mansour Shamsipour,5 Mohammad Ali Mansournia,1 Akbar Fotouhi1 1Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, 2Department of Public Health, School of Nursing and Midwifery, Maragheh University of Medical Sciences, Maragheh, 3Iranian National Center for Addiction Studies (INCAS, Iranian Institute for Reduction of High-Risk Behaviors, Tehran University of Medical Sciences, Tehran, 4Department of Environmental Health Engineering, School of Public Health, 5Department of Research Methodology and Data Analysis, Institute for Environmental Research, Tehran University of Medical Sciences, Tehran, 6Road Traffic Injury Research Center, Department of Statistics & Epidemiology, Tabriz University of Medical Sciences, Tabriz, Iran Background: Risky behaviors may interrupt development or cause considerable morbidity or mortality. This study’s purpose was to determine subgroups of students based on risky behaviors and assess the prevalence of risky behaviors in each of the subgroups.Participants and methods: This anonymous cross-sectional study was carried out in October 2015 and November 2015, with 1,777 students from Tabriz University of Medical Sciences, through multistage random sampling method. The data were analyzed by latent class analysis.Results: The prevalence rates of cigarette smoking (more than or equal to ten cigarettes, hookah use (≥1 time/month, and alcohol consumption (≥1 time/month during the last year were 12.4% (95% confidence interval [CI]: 10.9–14.0, 11.6% (95% CI: 10.0–13.1, and 4.9% (95% CI: 3.8–5.9, respectively. The prevalence rates of illicit opioids (1.8%, 95% CI: 1.2–2.5, cannabis (1.2%, 95% CI: 0.7–1.7, methamphetamine (1.1%, 95% CI: 0.6–1.6, methylphenidate (2.5%, 95% CI: 1.7–3.2, and extramarital sex (5.5%, 95% CI: 4.5–6.6 over the last year were

  12. Recovery of motor deficit accompanying sciatica--subgroup analysis of a randomized controlled trial.

    Science.gov (United States)

    Overdevest, Gijsbert M; Vleggeert-Lankamp, Carmen L A M; Jacobs, Wilco C H; Brand, Ronald; Koes, Bart W; Peul, Wilco C

    2014-09-01

    In patients with sciatica due to a lumbar disc herniation, it is generally recommended to reserve surgical treatment for those who suffer from intolerable pain or those who demonstrate persistent symptoms after conservative management. Controversy exists about the necessity of early surgical intervention for those patients that have an additional motor deficit. The aim of this study was to compare the recovery of motor deficit among patients receiving early surgery to those receiving prolonged conservative treatment. Subgroup analysis of a randomized controlled trial. This subgroup analysis focuses on 150 (53%) of 283 patients with sciatica due to a lumbar disc herniation and whose symptoms at baseline (before randomization) were accompanied by a motor deficit. Motor deficit was assessed through manual muscle testing and graded according to the Medical Research Council (MRC) scale. In total, 150 patients with 6 to 12 weeks of sciatica due to a lumbar disc herniation and whose symptoms were accompanied by a moderate (MRC Grade 4) or severe (MRC Grade 3) motor deficit were randomly allocated to early surgery or prolonged conservative treatment. Repeated standardized neurologic examinations were performed at baseline and at 8, 26, and 52 weeks after randomization. This study was supported by a grant from the Netherlands Organization for Health Research and Development (ZonMW) and the Hoelen Foundation The Hague. Sciatica recovered among seven (10%) of the 70 patients assigned to early surgery before surgery could be performed, and of the 80 patients assigned to conservative treatment, 32 patients (40%) were treated surgically because of intolerable pain. Baseline severity of motor deficit was graded moderate in 84% of patients and severe in 16% of patients. Motor deficit recovered significantly faster among patients allocated to early surgery (p=.01), but the difference was no longer significant at 26 (p=.21) or 52 weeks (p=.92). At 1 year, complete recovery of motor

  13. Cluster analysis differentiates high and low community functioning in schizophrenia: Subgroups differ on working memory but not other neurocognitive domains.

    Science.gov (United States)

    Alden, Eva C; Cobia, Derin J; Reilly, James L; Smith, Matthew J

    2015-10-01

    Schizophrenia is characterized by impairment in multiple aspects of community functioning. Available literature suggests that community functioning may be enhanced through cognitive remediation, however, evidence is limited regarding whether specific neurocognitive domains may be treatment targets. We characterized schizophrenia subjects based on their level of community functioning through cluster analysis in an effort to identify whether specific neurocognitive domains were associated with variation in functioning. Schizophrenia (SCZ, n=60) and control (CON, n=45) subjects completed a functional capacity task, social competence role-play, functional attainment interview, and a neuropsychological battery. Multiple cluster analytic techniques were used on the measures of functioning in the schizophrenia subjects to generate functionally-defined subgroups. MANOVA evaluated between-group differences in neurocognition. The cluster analysis revealed two distinct groups, consisting of 36 SCZ characterized by high levels of community functioning (HF-SCZ) and 24 SCZ with low levels of community functioning (LF-SCZ). There was a main group effect for neurocognitive performance (pcluster analysis classified schizophrenia subjects in HF-SCZ and LF-SCZ using a multidimensional assessment of community functioning. Moreover, HF-SCZ demonstrated rather preserved verbal working memory relative to LF-SCZ. The results suggest that verbal working memory may play a critical role in community functioning, and is a potential cognitive treatment target for schizophrenia subjects. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Subgrouping High School Students for Substance Abuse-Related Behaviors: A Latent Class Analysis.

    Science.gov (United States)

    Khayyati, Fariba; Mohammadpoorasl, Asghar; Allahverdipour, Hamid; AsghariJafarabadi, Mohammad; Kouzekanani, Kamiar

    2017-07-01

    The aim of the current study was to characterize the prevalence of latent groups in terms of smoking, hookah, and alcohol in a sample of Iranian high school students. In this cross-sectional study, 4,422 high school students were assessed in East Azerbaijan Province, Iran. Latent class analysis was applied to determine the subgroups and prevalence of each class using the procLCA in SAS 9.2 software. The prevalence of hookah smoking was the highest among the other substances and had the greatest abuse among males than females. Nearly 86%, 9.5%, and 4.6% of the participants were low risk, tobacco experimenter, and high risk, respectively. The odds ratio indices of membership in each class, compared with the first class, associated with the independent variables. A fair number of students, males in particular, were identified as high risk-takers. Considering the simultaneous incidence of multiple high-risk behaviors, interventions must cover multiple aspects of the issue at the same time.

  15. The effect of active video games by ethnicity, sex and fitness: subgroup analysis from a randomised controlled trial.

    Science.gov (United States)

    Foley, Louise; Jiang, Yannan; Ni Mhurchu, Cliona; Jull, Andrew; Prapavessis, Harry; Rodgers, Anthony; Maddison, Ralph

    2014-04-03

    The prevention and treatment of childhood obesity is a key public health challenge. However, certain groups within populations have markedly different risk profiles for obesity and related health behaviours. Well-designed subgroup analysis can identify potential differential effects of obesity interventions, which may be important for reducing health inequalities. The study aim was to evaluate the consistency of the effects of active video games across important subgroups in a randomised controlled trial (RCT). A two-arm, parallel RCT was conducted in overweight or obese children (n=322; aged 10-14 years) to determine the effect of active video games on body composition. Statistically significant overall treatment effects favouring the intervention group were found for body mass index, body mass index z-score and percentage body fat at 24 weeks. For these outcomes, pre-specified subgroup analyses were conducted among important baseline demographic (ethnicity, sex) and prognostic (cardiovascular fitness) groups. No statistically significant interaction effects were found between the treatment and subgroup terms in the main regression model (p=0.36 to 0.93), indicating a consistent treatment effect across these groups. Preliminary evidence suggests an active video games intervention had a consistent positive effect on body composition among important subgroups. This may support the use of these games as a pragmatic public health intervention to displace sedentary behaviour with physical activity in young people.

  16. An overview of statistical and regulatory issues in the planning, analysis, and interpretation of subgroup analyses in confirmatory clinical trials.

    Science.gov (United States)

    Hemmings, Robert

    2014-01-01

    Whether confirmatory or exploratory in nature, the investigation of subgroups poses statistical and interpretational challenges, yet these investigations can have important consequences for product licensing, labeling, reimbursement, and prescribing decisions. This article provides a high-level, nontechnical summary of key statistical issues in the analysis of subgroups, with a focus on the regulatory context in which drug development and licensing decisions are made. References to specific aspects of regulatory processes are based on the system in Europe, though it is hoped that the principles outlined can be generally applied to other regulatory regions. This article challenges the common assumption that a clinical trial population should be assumed to be homogeneous, with homogeneous response to treatment, and asks whether commonly employed strategies for handling and identifying potential heterogeneity are sufficient. Investigations into subgroups are unavoidable, yet subgroup analyses suffer from fundamental complications and limitations of which those planning and interpreting clinical trials must be aware. Some areas for further methodological work and an improved methodological framework for the conduct of exploratory subgroup analyses are discussed. Above all, the need for an integrated scientific approach is highlighted.

  17. Identification of five chronic obstructive pulmonary disease subgroups with different prognoses in the ECLIPSE cohort using cluster analysis.

    Science.gov (United States)

    Rennard, Stephen I; Locantore, Nicholas; Delafont, Bruno; Tal-Singer, Ruth; Silverman, Edwin K; Vestbo, Jørgen; Miller, Bruce E; Bakke, Per; Celli, Bartolomé; Calverley, Peter M A; Coxson, Harvey; Crim, Courtney; Edwards, Lisa D; Lomas, David A; MacNee, William; Wouters, Emiel F M; Yates, Julie C; Coca, Ignacio; Agustí, Alvar

    2015-03-01

    Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease that likely includes clinically relevant subgroups. To identify subgroups of COPD in ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) subjects using cluster analysis and to assess clinically meaningful outcomes of the clusters during 3 years of longitudinal follow-up. Factor analysis was used to reduce 41 variables determined at recruitment in 2,164 patients with COPD to 13 main factors, and the variables with the highest loading were used for cluster analysis. Clusters were evaluated for their relationship with clinically meaningful outcomes during 3 years of follow-up. The relationships among clinical parameters were evaluated within clusters. Five subgroups were distinguished using cross-sectional clinical features. These groups differed regarding outcomes. Cluster A included patients with milder disease and had fewer deaths and hospitalizations. Cluster B had less systemic inflammation at baseline but had notable changes in health status and emphysema extent. Cluster C had many comorbidities, evidence of systemic inflammation, and the highest mortality. Cluster D had low FEV1, severe emphysema, and the highest exacerbation and COPD hospitalization rate. Cluster E was intermediate for most variables and may represent a mixed group that includes further clusters. The relationships among clinical variables within clusters differed from that in the entire COPD population. Cluster analysis using baseline data in ECLIPSE identified five COPD subgroups that differ in outcomes and inflammatory biomarkers and show different relationships between clinical parameters, suggesting the clusters represent clinically and biologically different subtypes of COPD.

  18. Treatment in patients who are not eligible for intravenous alteplase: MR CLEAN subgroup analysis.

    Science.gov (United States)

    Mulder, Maxim Jhl; Berkhemer, Olvert A; Fransen, Puck Ss; Beumer, Debbie; van den Berg, Lucie A; Lingsma, Hester F; Roos, Yvo Bwem; van Oostenbrugge, Robert J; van Zwam, Wim H; Majoie, Charles Blm; van der Lugt, Aad; Dippel, Diederik Wj

    2016-08-01

    Patients with acute ischemic stroke due to intracranial large vessel occlusion benefit from intra-arterial therapy. Uncertainty exists about the effect of intra-arterial therapy in patients with contraindications for treatment with intravenous alteplase treatment. Our aim was to describe the clinical characteristics of this subgroup of patients and whether intra-arterial therapy is as safe and effective as it is after intravenous alteplase treatment. All 500 MR CLEAN patients were included and we distinguished between patients who were and were not treated with intravenous alteplase treatment. We estimated the effect of intra-arterial therapy on the shift on the modified Rankin Scale score with ordinal logistic regression analysis and tested for interaction of intravenous alteplase treatment with intra-arterial therapy on outcome. Furthermore, safety parameters and serious adverse events were analyzed. Fifty-five patients (11%) were not treated with intravenous alteplase treatment, mostly because of prolonged coagulation time tests or recent surgery. These patients were older and more often had atrial fibrillation or other vascular comorbidity. There was no interaction between intravenous alteplase treatment and intervention effect (p = 0.927). Intra-arterial therapy effect size in patients without intravenous alteplase treatment was 2.06 [95% CI: 0.69-6.13] and in patients with intravenous alteplase treatment 1.71 [95% CI: 1.22-2.40]. There were no safety issues. For patients with acute ischemic anterior circulation stroke caused by intracranial large vessel occlusion, who have contraindications for intravenous alteplase, intra-arterial treatment is not less effective or less safe than in patients who receive the treatment after intravenous alteplase. Clinical trial registration-URL: http://www.trialregister.nl. Unique identifier: (NTR)1804.Clinical trial registration-URL: http://www.controlled-trials.com. Unique identifier: ISRCTN10888758. © 2016 World

  19. Subgrouping Automata: automatic sequence subgrouping using phylogenetic tree-based optimum subgrouping algorithm.

    Science.gov (United States)

    Seo, Joo-Hyun; Park, Jihyang; Kim, Eun-Mi; Kim, Juhan; Joo, Keehyoung; Lee, Jooyoung; Kim, Byung-Gee

    2014-02-01

    Sequence subgrouping for a given sequence set can enable various informative tasks such as the functional discrimination of sequence subsets and the functional inference of unknown sequences. Because an identity threshold for sequence subgrouping may vary according to the given sequence set, it is highly desirable to construct a robust subgrouping algorithm which automatically identifies an optimal identity threshold and generates subgroups for a given sequence set. To meet this end, an automatic sequence subgrouping method, named 'Subgrouping Automata' was constructed. Firstly, tree analysis module analyzes the structure of tree and calculates the all possible subgroups in each node. Sequence similarity analysis module calculates average sequence similarity for all subgroups in each node. Representative sequence generation module finds a representative sequence using profile analysis and self-scoring for each subgroup. For all nodes, average sequence similarities are calculated and 'Subgrouping Automata' searches a node showing statistically maximum sequence similarity increase using Student's t-value. A node showing the maximum t-value, which gives the most significant differences in average sequence similarity between two adjacent nodes, is determined as an optimum subgrouping node in the phylogenetic tree. Further analysis showed that the optimum subgrouping node from SA prevents under-subgrouping and over-subgrouping. Copyright © 2013. Published by Elsevier Ltd.

  20. Full-length genome sequence analysis of four subgroup J avian leukosis virus strains isolated from chickens with clinical hemangioma.

    Science.gov (United States)

    Lin, Lulu; Wang, Peikun; Yang, Yongli; Li, Haijuan; Huang, Teng; Wei, Ping

    2017-12-01

    Since 2014, cases of hemangioma associated with avian leukosis virus subgroup J (ALV-J) have been emerging in commercial chickens in Guangxi. In this study, four strains of the subgroup J avian leukosis virus (ALV-J), named GX14HG01, GX14HG04, GX14LT07, and GX14ZS14, were isolated from chickens with clinical hemangioma in 2014 by DF-1 cell culture and then identified with ELISA detection of ALV group specific antigen p27, the detection of subtype specific PCR and indirect immunofluorescence assay (IFA) with ALV-J specific monoclonal antibody. The complete genomes of the isolates were sequenced and it was found that the gag and pol were relatively conservative, while env was variable especially the gp85 gene. Homology analysis of the env gene sequences showed that the env gene of all the four isolates had higher similarities with the hemangioma (HE)-type reference strains than that of the myeloid leukosis (ML)-type strains, and moreover, the HE-type strains' specific deletion of 205-bp sequence covering the rTM and DR1 in 3'UTR fragment was also found in the four isolates. Further analysis on the sequences of subunits of env gene revealed an interesting finding: the gp85 of isolates GX14ZS14 and GX14HG04 had a higher similarity with HPRS-103 and much lower similarity with the HE-type reference strains resulting in GX14ZS14, GX14HG04, and HPRS-103 being clustered in the same branch, while gp37 had higher similarities with the HE-type reference strains when compared to that of HPRS-103, resulted in GX14ZS14, GX14HG04, and HE-type reference strains being clustered in the same branch. The results suggested that isolates GX14ZS14 and GX14HG04 may be the recombinant strains of the foreign strain HPRS-103 with the local epidemic HE-type strains of ALV-J.

  1. Using Social Network Analysis to Identify Sub-Groups in the Operating Room

    NARCIS (Netherlands)

    Listyowardojo, Tita A.; Steglich, Christian; Peuchen, Stephen; Johnson, Addie; de Waard, D.; Godthelp, J.; Kooi, F.L.; Brookhuis, K.A.

    2009-01-01

    The frequency with which operating room (OR) staff work together can impact patient safety because staff who often work together share a set of experiences which may enable them to anticipate each other’s actions and reactions in the future. Identifying sub-groups of staff who frequently work

  2. Multimodality Management of Spetzler-Martin Grade 3 Brain Arteriovenous Malformations with Subgroup Analysis.

    Science.gov (United States)

    Abecassis, Isaac Josh; Nerva, John D; Feroze, Abdullah; Barber, Jason; Ghodke, Basavaraj V; Kim, Louis J; Sekhar, Laligam N

    2017-06-01

    Spetzler-Martin grade 3 (SM3) lesions entail 4 distinct subtypes described based on size, eloquence, and deep venous drainage (3A-3D). The ideal management of each is contentious, and the results of A Randomized Trial of Unruptured Brain AVMs (ARUBA) introduced additional controversy and attention toward management strategies of unruptured brain arteriovenous malformations (bAVMs). We retrospectively reviewed 114 patients with treated SM3 bAVMs, including both ruptured and unruptured lesions. Primary outcomes included modified Rankin score at most recent follow-up, angiographic cure, and permanent treatment-related complications (morbidity). Other outcomes included mortality, bAVM recurrence or rebleed, and transient treatment-related complications. We used univariate and multivariate modeling to determine whether any specific features were predictive of outcomes. For unruptured bAVMs, an "ARUBA eligible" subgroup analysis was performed. We also reviewed the literature on management of ruptured and unruptured SM3 bAVMs. Of the 114 identified SM3 bAVMs, 40% were unruptured. Most (43.5%) lesions in the unruptured group were type 3C, whereas most ruptured bAVMs (66.2%) were type 3A. Unruptured lesions were mostly managed with radiosurgery (47.8%) and ruptured ones with preoperative embolization and surgery (36.7%). Surgical intervention was predictive of angiographic cure in multivariate modeling, even after controlling for ≥2 years of follow-up, although associated with a slightly higher rate of morbidity. Focal neurological deficit was the only predictor of a worse (modified Rankin score ≥2) functional outcome in follow-up for unruptured bAVMs. For ruptured bAVMs, superficial and cerebellar locations were predictive of better outcomes in multivariate models, in the absence of a focal neurological deficit at presentation and new after surgery deficit. ARUBA SM3 bAVMs specifically underwent more embolization as a monotherapy and less microsurgical resection than

  3. Subgroup analysis of large trials can guide further research: a case study of vitamin E and pneumonia

    Directory of Open Access Journals (Sweden)

    Harri Hemilä

    2011-02-01

    Full Text Available Harri Hemilä, Jaakko KaprioDepartment of Public Health, University of Helsinki, Helsinki, FinlandBackground: Biology is complex and the effects of many interventions may vary between population groups. Subgroup analysis can give estimates for specific populations, but trials are usually too small for such analyses.Purpose: To test whether the effect of vitamin E on pneumonia risk is uniform over subgroups defined by smoking and exercise.Methods: The Alpha-Tocopherol Beta-Carotene Cancer Prevention Study examined the effects of vitamin E (50 mg per day and β-carotene (20 mg per day on lung cancer in 29,133 male smokers aged 50–69 years using a 2 × 2 factorial design. The trial was conducted among the general community in Finland during 1985–1993; the intervention lasted for 6.0 years (median. In the present study, we tested the uniformity of vitamin E effect on the risk of hospital-treated pneumonia (898 cases by adding a dummy variable to allow each subgroup its own vitamin E effect in a Cox model covering all participants.Results: Vitamin E effect was not uniform over eight subgroups defined by baseline smoking (5–19 vs ≥20 cigarettes per day, age of smoking initiation (≤20 vs ≥21 years, and exercise during leisure time (yes vs no. Vitamin E decreased pneumonia risk by 69% (95% CI: 43% to 83% among participants who had the least exposure to smoking and exercised during leisure time. Vitamin E increased pneumonia risk by 79% (95% CI: 27% to 150% among those who had the highest exposure to smoking and did not exercise.Limitations: Although the evidence of heterogeneity is strong, it is not evident to what extent the estimates of effect or the limits between the subgroups can be extrapolated to other populations.Conclusion: Subgroup analysis of large trials should be encouraged, though caution is needed in the interpretation of findings. The role of vitamin E in susceptibility to pneumonia in physically active nonsmokers warrants

  4. Subgroup analysis of Asian patients in the INPULSIS® trials of nintedanib in idiopathic pulmonary fibrosis.

    Science.gov (United States)

    Taniguchi, Hiroyuki; Xu, Zuojun; Azuma, Arata; Inoue, Yoshikazu; Li, Huiping; Fujimoto, Tsuyoshi; Bailes, Zelie; Schlenker-Herceg, Rozsa; Kim, Dong S

    2016-11-01

    In the two-replicate randomized Phase III INPULSIS® trials in patients with idiopathic pulmonary fibrosis (IPF), nintedanib 150 mg bd significantly reduced the annual rate of decline in forced vital capacity (FVC) compared with placebo. The key secondary endpoints were time to first investigator-reported acute exacerbation and change from baseline in St George's Respiratory Questionnaire total score, both over 52 weeks. Here, we assessed the effect of nintedanib in Asian patients. Pre-specified subgroup analyses of the effect of nintedanib on the primary and key secondary endpoints in Asian versus White patients were undertaken based on pooled data from the two INPULSIS® trials. Safety data were analyzed descriptively. Of the treated patients, 322 were Asian (nintedanib n = 194; placebo n = 128) and 608 were White (nintedanib n = 360; placebo n = 248). In Asian patients, the nintedanib versus placebo difference in the adjusted annual rate of decline in FVC was 94.1 mL/year (95% CI: 33.7, 154.6). The treatment effect of nintedanib on the annual rate of decline in FVC in Asian and White patients was similar (treatment-by-subgroup interaction P = 0.72) and consistent with the overall population. No significant treatment-by-subgroup interaction was observed for the key secondary endpoints between Asian and White patients. In Asian patients, the most common adverse event in the nintedanib group was diarrhoea (56.2% of patients vs 15.6% for placebo). In pre-specified subgroup analyses of Asian versus White patients with IPF in the INPULSIS® trials, race did not influence the effect of nintedanib on disease progression. © 2016 Asian Pacific Society of Respirology.

  5. Mindfulness and Emotional Outcomes: Identifying Subgroups of College Students using Latent Profile Analysis

    OpenAIRE

    Pearson, Matthew R.; Lawless, Adrienne K.; Brown, David B.; Bravo, Adrian J.

    2015-01-01

    In non-meditating samples, distinct facets of mindfulness are found to be negatively correlated, preventing the meaningful creation of a total mindfulness score. The present study used person-centered analyses to distinguish subgroups of college students based on their mindfulness scores, which allows the examination of individuals who are high (or low) on all facets of mindfulness. Using the Lo-Mendell-Rubin Adjusted LRT test, we settled on a 4-class solution that included a high mindfulness...

  6. Identification of Responders to Amiodarone: Subgroup Analysis of the EMIAT Study

    OpenAIRE

    Kehl, Victoria; Ulm, Kurt; Schmidt, G; Barthel, P.; Malik, Marek

    2003-01-01

    Clinical trials often judge the efficacy of a new treatment by comparing the survival patterns of patients who are randomly assigned to undergo the new or a standard/placebo treatment. Usually, the entire groups are analyzed, although certain subgroups of patients may react differently to the new treatment than others. Some patients taking the new treatment might benefit from it (the positive responders) while others may be harmed by it (the negative responders). We applied a newly developed ...

  7. Kuwaiti population subgroup of nomadic Bedouin ancestry—Whole genome sequence and analysis

    Directory of Open Access Journals (Sweden)

    Sumi Elsa John

    2015-03-01

    Full Text Available Kuwaiti native population comprises three distinct genetic subgroups of Persian, “city-dwelling” Saudi Arabian tribe, and nomadic “tent-dwelling” Bedouin ancestry. Bedouin subgroup is characterized by presence of 17% African ancestry; it owes it origin to nomadic tribes of the deserts of Arabian Peninsula and North Africa. By sequencing whole genome of a Kuwaiti male from this subgroup at 41X coverage, we report 3,752,878 SNPs, 411,839 indels, and 8451 structural variations. Neighbor-joining tree, based on shared variant positions carrying disease-risk alleles between the Bedouin and other continental genomes, places Bedouin genome at the nexus of African, Asian, and European genomes in concordance with geographical location of Kuwait and Peninsula. In congruence with participant's medical history for morbid obesity and bronchial asthma, risk alleles are seen at deleterious SNPs associated with obesity and asthma. Many of the observed deleterious ‘novel’ variants lie in genes associated with autosomal recessive disorders characteristic of the region.

  8. Kuwaiti population subgroup of nomadic Bedouin ancestry-Whole genome sequence and analysis.

    Science.gov (United States)

    John, Sumi Elsa; Thareja, Gaurav; Hebbar, Prashantha; Behbehani, Kazem; Thanaraj, Thangavel Alphonse; Alsmadi, Osama

    2015-03-01

    Kuwaiti native population comprises three distinct genetic subgroups of Persian, "city-dwelling" Saudi Arabian tribe, and nomadic "tent-dwelling" Bedouin ancestry. Bedouin subgroup is characterized by presence of 17% African ancestry; it owes it origin to nomadic tribes of the deserts of Arabian Peninsula and North Africa. By sequencing whole genome of a Kuwaiti male from this subgroup at 41X coverage, we report 3,752,878 SNPs, 411,839 indels, and 8451 structural variations. Neighbor-joining tree, based on shared variant positions carrying disease-risk alleles between the Bedouin and other continental genomes, places Bedouin genome at the nexus of African, Asian, and European genomes in concordance with geographical location of Kuwait and Peninsula. In congruence with participant's medical history for morbid obesity and bronchial asthma, risk alleles are seen at deleterious SNPs associated with obesity and asthma. Many of the observed deleterious 'novel' variants lie in genes associated with autosomal recessive disorders characteristic of the region.

  9. Analysis of efficacy and safety of treatment with collagenase Clostridium histolyticum among subgroups of patients with Dupuytren contracture.

    Science.gov (United States)

    Raven, Raymond B; Kushner, Harvey; Nguyen, Dat; Naam, Nash; Curtin, Catherine

    2014-09-01

    Collagenase Clostridium histolyticum (CCH) injection is a nonoperative treatment of hand contractures from Dupuytren disease. This study assessed the efficacy and safety of CCH in several subgroups of patients with increased surgical risk.Data were pooled from 3 randomized, placebo-controlled, double-blind trials. This analysis included 271 patients with metacarpophalangeal (n = 167) or proximal interphalangeal (n = 104) joint contractures greater than or equal to 20 degrees treated with CCH (0.58 mg collagenase per injection). Subgroups included age, sex, and diabetes status. End points included rate of clinical success (reduction in contracture to 0-5 degrees of normal) and percentage of adverse events.There was no significant difference in clinical success by age, diabetes status, or sex with 63% reaching the end point. There was no difference in adverse events among the subgroups, with peripheral edema, contusion, and injection-site hemorrhage being most common.High-risk subgroups do not demonstrate differences in efficacy or safety with CCH treatment of Dupuytren-related contractures.

  10. Analysis of Species, Subgroups, and Endosymbionts of Bemisia tabaci (Hemiptera: Aleyrodidae) From Southwestern Cotton Fields in Turkey.

    Science.gov (United States)

    Karut, Kamil; Mete Karaca, M; Döker, Ismail; Kazak, Cengiz

    2017-08-01

    Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae) is one of the most important insect pests worldwide including Turkey. Although there are substantial data regarding species composition of Turkish B. tabaci populations, the situation is still not clear and further investigations are needed. Therefore, in this study, species and subgroups of B. tabaci collected from cotton fields in southwestern part of Turkey (Antalya, Aydın, Denizli, and Muğla) were determined using microsatellite analysis, AluI-based mtCOI polymerase chain reaction-random length polymorphism, and sequencing. Secondary endosymbionts were also determined using diagnostic species-specific PCR. Middle East Asia Minor 1 (MEAM1), Mediterranean (MED) Q1, and MED Q2 were the species and subgroups found in this study. The MED species (85.3%) were found to be more dominant than MEAM1. Species status of B. tabaci varied depending on the location. Although all samples collected from Aydın were found to be Q1, three species and subgroups were found in Muğla. Secondary endosymbionts varied according to species and subgroups. Arsenophonus was found only from Q2, while Hamiltonella was detected in MEAM1 and Q1. In addition, high Rickettsia and low Wolbachia infections were detected in MEAM1 and Q1 populations, respectively. In conclusion, for the first time, we report the presence and symbiotic communities of Q1 from Turkey. We also found that the symbiont complement of the Q1 is more congruent with Q1 from Greece than other regions of the world, which may have some interesting implications for movement of this invasive subgroup. © The Authors 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  11. Validation and Analysis of a Multi-site MIS Prospective Registry Through Sub-analysis of an MIS TLIF Subgroup

    Science.gov (United States)

    Raiszadeh, Kamshad; Raiszadeh, Ramin; Kim, Paul; Doerr, Todd; Siddiqi, Farhan; LaMotta, Ivan; Park, Paul; Templin, Cary; Gill, Sandeep; Liang, Kevin; Kim, Choll W.

    2014-01-01

    Study Design Retrospective analysis of multi-site, prospectively collected database. Objective To assess the validity and utility of a prospective spine registry by sub-analysis of patients treated with MIS TLIF. Background The MIS registry is a large-scale, multi-center series of prospectively collected clinical information on outcomes, complications, and adverse events for minimally invasive spine procedures for the treatment of degenerative lumbar conditions. Methods Analysis was performed on the MIS Prospective Registry database. A subgroup of patients treated by MIS TLIF technique was identified. Statistical analyses were performed on pre and post-operative data collected using validated health related quality of life outcome tools. Missing 1-year patient follow-up data was obtained through progressive correspondence modalities. Results Data analysis was performed on 98 MIS TLIF patients (56 female, 42 male) with a median age of 64.5 years (range 25-91 years) which were extracted from a total registry population of 478 patients. The one year follow-up rate was 87%. A total of 64 single-level, 23 two-level, 3 three-level, and 3 combined TLIFs staged with an MIS lateral procedure were included. The primary surgical indications were spondylolisthesis (27%), central stenosis (25%), foraminal stenosis (14%), post-laminectomy syndrome (14%) and degenerative scoliosis (6%). The peri-operative blood transfusion rate was 3%. Complications included intraoperative dural tear (n = 3), deep wound infection (n = 2), superficial dehiscence/cellulitis (n = 2). There was a 4% re-operation rate at the 1 year post-operative time point. Half of patients were discharged within 2 days (range 1-11 days, mean 2.97 days, median 2 days). All patients that were discharged on the first post-operative day (n = 14) underwent a single-level MIS TLIF procedure and had significantly lower pre-op disability index score than those discharged on POD 3-5 (43.7 ± 15.5 vs. 56.0 ± 18.3, p = 0

  12. Association Between Endometrial/Subendometrial Vasculature and Embryo Transfer Outcome: A Meta-analysis and Subgroup Analysis.

    Science.gov (United States)

    Wang, Jianing; Xia, Fei; Zhou, Ying; Wei, Xuedong; Zhuang, Yanyan; Huang, Yingxue

    2018-01-01

    To examine the association between endometrial/subendometrial vasculature and in vitro fertilization-embryo transfer (IVF-ET) and frozen embryo transfer (FET) outcomes. A meta-analysis of studies using endometrial/subendometrial 3-dimensional ultrasound and power Doppler angiography was performed to examine the vascularization index (VI), flow index (FI), and vascularization-flow index (VFI) in pregnant and nonpregnant women. Ten articles were analyzed, including 895 pregnant women and 882 nonpregnant women. A subgroup analysis of the measuring time showed that the endometrial VI (standardized mean difference [SMD], 0.57; 95% confidence interval [CI], 0.40, 0.74; P endometrial VI (SMD, 0.52; 95% CI, 0.30, 0.74; P endometrial VI, FI, and VFI on the ET day are potentially associated with pregnancy occurrence during IVF-ET. The endometrial VI, FI, and VFI could help identify appropriate timing for FET. However, the accuracy of these indices in predicting pregnancy occurrence must be further evaluated in additional large-scale studies. © 2017 by the American Institute of Ultrasound in Medicine.

  13. Sequence and analysis of a whole genome from Kuwaiti population subgroup of Persian ancestry.

    Science.gov (United States)

    Thareja, Gaurav; John, Sumi Elsa; Hebbar, Prashantha; Behbehani, Kazem; Thanaraj, Thangavel Alphonse; Alsmadi, Osama

    2015-02-18

    The 1000 Genome project paved the way for sequencing diverse human populations. New genome projects are being established to sequence underrepresented populations helping in understanding human genetic diversity. The Kuwait Genome Project an initiative to sequence individual genomes from the three subgroups of Kuwaiti population namely, Saudi Arabian tribe; "tent-dwelling" Bedouin; and Persian, attributing their ancestry to different regions in Arabian Peninsula and to modern-day Iran (West Asia). These subgroups were in line with settlement history and are confirmed by genetic studies. In this work, we report whole genome sequence of a Kuwaiti native from Persian subgroup at >37X coverage. We document 3,573,824 SNPs, 404,090 insertions/deletions, and 11,138 structural variations. Out of the reported SNPs and indels, 85,939 are novel. We identify 295 'loss-of-function' and 2,314 'deleterious' coding variants, some of which carry homozygous genotypes in the sequenced genome; the associated phenotypes include pharmacogenomic traits such as greater triglyceride lowering ability with fenofibrate treatment, and requirement of high warfarin dosage to elicit anticoagulation response. 6,328 non-coding SNPs associate with 811 phenotype traits: in congruence with medical history of the participant for Type 2 diabetes and β-Thalassemia, and of participant's family for migraine, 72 (of 159 known) Type 2 diabetes, 3 (of 4) β-Thalassemia, and 76 (of 169) migraine variants are seen in the genome. Intergenome comparisons based on shared disease-causing variants, positions the sequenced genome between Asian and European genomes in congruence with geographical location of the region. On comparison, bead arrays perform better than sequencing platforms in correctly calling genotypes in low-coverage sequenced genome regions however in the event of novel SNP or indel near genotype calling position can lead to false calls using bead arrays. We report, for the first time, reference

  14. Tissue microarrays compared with whole sections and biochemical analyses. A subgroup analysis of DBCG82 b

    DEFF Research Database (Denmark)

    Kyndi, M.; Sorensen, F.B.; Overgaard, M.

    2008-01-01

    b&c trials, were IHC stained for ER, PgR and HER2. In addition, ER and PgR were measured in the DBCG82 b&c trials by a biochemical analysis. Statistical analyses included Kappa statistics, Kaplan-Meier survival curves, Log-rank tests, and Cox regression hazards analyses. Results and conclusion. IHC...... cores and biochemical analyses. Patients and methods. A central and a peripheral 1mm core and a whole section from each of 54 paraffin blocks from 27 breast cancers included in a one-institution cohort, and a single 1 min central TMA core, from each breast tumor from 1000 patients included in the DBCG82...... IHC stainings of TMA cores and biochemical analyses. Divergence between IHC and biochemical analyses was predominantly due to the chosen thresholds. IHC staining of one 1mm core from each tumor revealed a significant independent prognostic value of PgR and HER2 on overall survival. In conclusion, IHC...

  15. Tissue microarrays compared with whole sections and biochemical analyses. A subgroup analysis of DBCG 82 b

    DEFF Research Database (Denmark)

    Kyndi, Marianne; Sørensen, Flemming Brandt; Knudsen, H

    2008-01-01

    &c trials, were IHC stained for ER, PgR and HER2. In addition, ER and PgR were measured in the DBCG82 b&c trials by a biochemical analysis. Statistical analyses included Kappa statistics, Kaplan-Meier survival curves, Log-rank tests, and Cox regression hazards analyses. RESULTS AND CONCLUSION: IHC stainings...... cores and biochemical analyses. PATIENTS AND METHODS: A central and a peripheral 1mm core and a whole section from each of 54 paraffin blocks from 27 breast cancers included in a one-institution cohort, and a single 1mm central TMA core, from each breast tumor from 1000 patients included in the DBCG82 b...... stainings of TMA cores and biochemical analyses. Divergence between IHC and biochemical analyses was predominantly due to the chosen thresholds. IHC staining of one 1mm core from each tumor revealed a significant independent prognostic value of PgR and HER2 on overall survival. In conclusion, IHC stainings...

  16. Is there evidence for aetiologically distinct subgroups of idiopathic congenital talipes equinovarus? A case-only study and pedigree analysis.

    Directory of Open Access Journals (Sweden)

    Amanda H Cardy

    Full Text Available BACKGROUND: Idiopathic congenital talipes equinovarus (CTEV is a common developmental foot disorder, the aetiology of which remains largely unknown. Some aspects of the epidemiology suggest the possibility of aetiologically distinct subgroups. Previous studies consider CTEV as a homogenous entity which may conceal risk factors in particular subgroups. We investigate evidence for aetiologically distinct subgroups of CTEV. METHODS: Parents of 785 probands completed a postal questionnaire. Family pedigrees were compiled by telephone. Case-only analysis was used to investigate interactions between risk factors and sex of the proband, CTEV laterality and CTEV family history. RESULTS: The male:female ratio was 2.3:1, 58% of probands were affected bilaterally and 11% had a first-second degree family history. There were modest interactions between family history and twin births (multivariate case - only odds ratio [ORca] = 3.87, 95%CI 1.19-12.62 and family history and maternal use of folic acid supplements in early pregnancy (ORca = 0.62, 95%CI 0.38-1.01; and between sex of the proband and maternal alcohol consumption during pregnancy (female, positive history and alcohol consumed: ORca = 0.33, 95%CI 0.12-0.89. Previous reports of an interaction between maternal smoking and family history were not confirmed. Relatives of female probands were affected more often than relatives of male probands. CONCLUSIONS: These results provide tentative evidence for aetiologically distinct CTEV subgroups. They support the 'Carter effect', suggesting CTEV develops though a multifactorial threshold model with females requiring a higher risk factor 'load', and suggest areas where future aetiological investigation might focus. Large multi-centre studies are needed to further advance understanding of this common condition.

  17. Is there evidence for aetiologically distinct subgroups of idiopathic congenital talipes equinovarus? A case-only study and pedigree analysis.

    Science.gov (United States)

    Cardy, Amanda H; Sharp, Linda; Torrance, Nicola; Hennekam, Raoul C; Miedzybrodzka, Zosia

    2011-04-20

    Idiopathic congenital talipes equinovarus (CTEV) is a common developmental foot disorder, the aetiology of which remains largely unknown. Some aspects of the epidemiology suggest the possibility of aetiologically distinct subgroups. Previous studies consider CTEV as a homogenous entity which may conceal risk factors in particular subgroups. We investigate evidence for aetiologically distinct subgroups of CTEV. Parents of 785 probands completed a postal questionnaire. Family pedigrees were compiled by telephone. Case-only analysis was used to investigate interactions between risk factors and sex of the proband, CTEV laterality and CTEV family history. The male:female ratio was 2.3:1, 58% of probands were affected bilaterally and 11% had a first-second degree family history. There were modest interactions between family history and twin births (multivariate case - only odds ratio [ORca] = 3.87, 95%CI 1.19-12.62) and family history and maternal use of folic acid supplements in early pregnancy (ORca = 0.62, 95%CI 0.38-1.01); and between sex of the proband and maternal alcohol consumption during pregnancy (female, positive history and alcohol consumed: ORca = 0.33, 95%CI 0.12-0.89). Previous reports of an interaction between maternal smoking and family history were not confirmed. Relatives of female probands were affected more often than relatives of male probands. These results provide tentative evidence for aetiologically distinct CTEV subgroups. They support the 'Carter effect', suggesting CTEV develops though a multifactorial threshold model with females requiring a higher risk factor 'load', and suggest areas where future aetiological investigation might focus. Large multi-centre studies are needed to further advance understanding of this common condition.

  18. Predictive factors for bleeding during treatment with rivaroxaban and warfarin in Japanese patients with atrial fibrillation - Subgroup analysis of J-ROCKET AF.

    Science.gov (United States)

    Hori, Masatsugu; Matsumoto, Masayasu; Tanahashi, Norio; Momomura, Shin-Ichi; Uchiyama, Shinichiro; Goto, Shinya; Izumi, Tohru; Koretsune, Yukihiro; Kajikawa, Mariko; Kato, Masaharu; Cavaliere, Mary; Iekushi, Kazuma; Yamanaka, Satoshi

    2016-12-01

    Results from the J-ROCKET AF study revealed that rivaroxaban was non-inferior to warfarin with respect to the principal safety outcomes in patients with non-valvular atrial fibrillation. This subgroup analysis evaluated whether non-major clinically relevant bleeding (NMCRB) could be a predictive factor for major bleeding (MB). Other predictive factors for MB were also obtained in both rivaroxaban and warfarin treatment groups. The temporal incidence of MB was compared between the rivaroxaban and warfarin treatment groups. Assessment was made whether MB events were often preceded by NMCRB. Univariate and multivariate analyses were carried out to identify any independent predictive factors for MB in both treatment groups. The incidences of MB and NMCRB were 18.04% (138/639 patients) in the rivaroxaban arm, and 16.42% in the warfarin arm (124/639 patients). NMCRB preceded MB in only four patients in each treatment group (rivaroxaban: 4/117 and warfarin: 4/98). Multivariate analysis identified predictive factors for bleeding events: anemia with warfarin treatment and concomitant use of antiplatelet agents with rivaroxaban treatment. Results from this subgroup analysis, particularly the fact that there was no repeated or sequential pattern between NMCRB and MB occurrences in both treatment groups, suggests that NMCRB might not be a predictive factor for MB. On the contrary, anemia and concomitant use of antiplatelet therapy were likely predictive factors for bleeding with warfarin and rivaroxaban treatment, respectively. Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

  19. “Real-life” inhaled corticosteroid withdrawal in COPD: a subgroup analysis of DACCORD

    Directory of Open Access Journals (Sweden)

    Vogelmeier C

    2017-02-01

    Full Text Available Claus Vogelmeier,1 Heinrich Worth,2 Roland Buhl,3 Carl-Peter Criée,4 Nadine S Lossi,5 Claudia Mailänder,5 Peter Kardos6 1Department of Medicine, Pulmonary and Critical Care Medicine, University Medical Center Giessen and Marburg, Philipps-University Marburg, Member of the German Center for Lung Research (DZL, Marburg, 2Facharzt Forum Fürth, Fürth, 3Pulmonary Department, Mainz University Hospital, Mainz, 4Department of Sleep and Respiratory Medicine, Evangelical Hospital Göttingen-Weende, Bovenden, 5Clinical Research, Respiratory, Novartis Pharma GmbH, Nürnberg, 6Group Practice and Centre for Allergy, Respiratory and Sleep Medicine, Red Cross Maingau Hospital, Frankfurt am Main, Germany Abstract: Many patients with chronic obstructive pulmonary disease (COPD receive inhaled corticosteroids (ICSs without a clear indication, and thus, the impact of ICS withdrawal on disease control is of great interest. DACCORD is a prospective, noninterventional 2-year study in the primary and secondary care throughout Germany. A subgroup of patients were taking ICS prior to entry – 1,022 patients continued to receive ICS for 2 years; physicians withdrew ICS on entry in 236 patients. Data from these two subgroups were analyzed to evaluate the impact of ICS withdrawal. Patients aged ≥40 years with COPD, initiating or changing COPD maintenance medication were recruited, excluding patients with asthma. Demographic and disease characteristics, prescribed COPD medication, COPD Assessment Test, exacerbations, and lung function were recorded. There were few differences in baseline characteristics; ICS withdrawn patients had shorter disease duration and better lung function, with 74.2% of ICS withdrawn patients not exacerbating, compared with 70.7% ICS-continued patients. During Year 1, exacerbation rates were 0.414 in the withdrawn group and 0.433 in the continued group. COPD Assessment Test total score improved from baseline in both groups. These data suggest

  20. Mindfulness and Emotional Outcomes: Identifying Subgroups of College Students using Latent Profile Analysis.

    Science.gov (United States)

    Pearson, Matthew R; Lawless, Adrienne K; Brown, David B; Bravo, Adrian J

    2015-04-01

    In non-meditating samples, distinct facets of mindfulness are found to be negatively correlated, preventing the meaningful creation of a total mindfulness score. The present study used person-centered analyses to distinguish subgroups of college students based on their mindfulness scores, which allows the examination of individuals who are high (or low) on all facets of mindfulness. Using the Lo-Mendell-Rubin Adjusted LRT test, we settled on a 4-class solution that included a high mindfulness group (high on all 5 facets, N = 245), low mindfulness group (moderately low on all 5 facets, N = 563), judgmentally observing group (high on observing, but low on non-judging and acting with awareness, N =63), and non-judgmentally aware group (low on observing, but high on non-judging and acting with awareness, N =70). Consistent across all emotional outcomes including depressive symptoms, anxiety symptoms (i.e., worry), affective instability, and distress intolerance, we found that the judgmentally observing group had the most maladaptive emotional outcomes followed by the low mindfulness group. Both the high mindfulness group and the non-judgmentally aware group had the most adaptive emotional outcomes. We discuss the implications of person-centered analyses to exploring mindfulness as it relates to important psychological health outcomes.

  1. Nintedanib in Japanese patients with idiopathic pulmonary fibrosis: A subgroup analysis of the INPULSIS® randomized trials.

    Science.gov (United States)

    Azuma, Arata; Taniguchi, Hiroyuki; Inoue, Yoshikazu; Kondoh, Yasuhiro; Ogura, Takashi; Homma, Sakae; Fujimoto, Tsuyoshi; Sakamoto, Wataru; Sugiyama, Yukihiko; Nukiwa, Toshihiro

    2017-05-01

    Idiopathic pulmonary fibrosis (IPF) is a specific form of chronic, progressive fibrosing interstitial pneumonia. Nintedanib significantly reduced the annual rate of decline in forced vital capacity (FVC) compared with placebo in patients with IPF in two replicate trials (INPULSIS®). We examined the efficacy and safety of nintedanib in Japanese patients. We conducted pre-specified subgroup analyses of the annual rate of decline in FVC, time to first acute exacerbation (AE), change from baseline in St George's Respiratory Questionnaire (SGRQ) total score and safety using pooled data from the INPULSIS® trials for Japanese patients. In the overall population, 76 of 638 and 50 of 423 patients in the nintedanib and placebo groups, respectively, were Japanese. Results in Japanese patients were consistent with those in the overall population. In Japanese patients, the adjusted annual rate of decline in FVC was -135.9 mL/year in the nintedanib group and -267.7 mL/year in the placebo group (difference (95% CI): 131.9 (50.7, 213.1) mL/year); the hazard ratio for the time to first AE was 0.25 (0.06, 1.02); and the adjusted mean change from baseline in SGRQ total score at week 52 was 5.81 in the nintedanib group and 9.68 in the placebo group (difference: -3.87 (-8.51, 0.76)). Diarrhoea and liver-related adverse events were the most common events in the nintedanib group, but were reversible following dose reduction, drug interruption or symptomatic therapy. The present results indicate that the efficacy and safety of nintedanib in Japanese patients are comparable with those in the overall population. © 2016 The Authors. Respirology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Respirology.

  2. Novel subgroups of attention-deficit/hyperactivity disorder identified by topological data analysis and their functional network modular organizations.

    Science.gov (United States)

    Kyeong, Sunghyon; Kim, Jae-Jin; Kim, Eunjoo

    2017-01-01

    Attention-deficit/hyperactivity disorder (ADHD) is a clinically heterogeneous condition and identification of clinically meaningful subgroups would open up a new window for personalized medicine. Thus, we aimed to identify new clinical phenotypes in children and adolescents with ADHD and to investigate whether neuroimaging findings validate the identified phenotypes. Neuroimaging and clinical data from 67 children with ADHD and 62 typically developing controls (TDCs) from the ADHD-200 database were selected. Clinical measures of ADHD symptoms and intelligence quotient (IQ) were used as input features into a topological data analysis (TDA) to identify ADHD subgroups within our sample. As external validators, graph theoretical measures obtained from the functional connectome were compared to address the biological meaningfulness of the identified subtypes. The TDA identified two unique subgroups of ADHD, labelled as mild symptom ADHD (mADHD) and severe symptom ADHD (sADHD). The output topology shape was repeatedly observed in the independent validation dataset. The graph theoretical analysis showed a decrease in the degree centrality and PageRank in the bilateral posterior cingulate cortex in the sADHD group compared with the TDC group. The mADHD group showed similar patterns of intra- and inter-module connectivity to the sADHD group. Relative to the TDC group, the inter-module connectivity between the default mode network and executive control network were significantly increased in the sADHD group but not in the mADHD group. Taken together, our results show that the data-driven TDA is potentially useful in identifying objective and biologically relevant disease phenotypes in children and adolescents with ADHD.

  3. Classification tree analysis of race-specific subgroups at risk for a central venous catheter-related bloodstream infection.

    Science.gov (United States)

    Studnicki, James; Ekezue, Bola F; Tsulukidze, Maka; Honoré, Peggy; Moonesinghe, Ramal; Fisher, John

    2014-03-01

    Studies of racial disparities in patient safety events often do not use race-specific risk adjustment and do not account for reciprocal covariate interactions. These limitations were addressed by using classification tree analysis separately for black patients and white patients to identify characteristics that segment patients who have increased risks for a venous catheter-related bloodstream infection. A retrospective, cross-sectional analysis of 5,236,045 discharges from 103 Florida acute hospitals in 2005-2009 was conducted. Hospitals were rank ordered on the basis of the black/white Patient Safety Indicator (PSI) 7 rate ratio as follows: Group 1 (white rate higher), Group 2, (equivalent rates), Group 3, (black rate higher), and Group 4, (black rate highest). Predictor variables included 26 comorbidities (Elixhauser Comorbidity Index) and demographic characteristics. Four separate classification tree analyses were completed for each race/hospital group. Individual characteristics and groups of characteristics associated with increased PSI 7 risk differed for black and white patients. The average age for both races was different across the hospital groups (p < .01). Weight loss was the strongest single delineator and common to both races. The black subgroups with the highest PSI 7 risk were Medicare beneficiaries who were either < or = 25.5 years without hypertension or < or = 39.5 years without hypertension but with an emergency or trauma admission. The white subgroup with the highest PSI 7 risk consisted of patients < or = 45.5 years who had congestive heart failure but did not have either hypertension or weight loss. Identifying subgroups of patients at risk for a rare safety event such as PSI 7 should aid effective clinical decisions and efficient use of resources and help to guide patient safety interventions.

  4. Novel subgroups of attention-deficit/hyperactivity disorder identified by topological data analysis and their functional network modular organizations.

    Directory of Open Access Journals (Sweden)

    Sunghyon Kyeong

    Full Text Available Attention-deficit/hyperactivity disorder (ADHD is a clinically heterogeneous condition and identification of clinically meaningful subgroups would open up a new window for personalized medicine. Thus, we aimed to identify new clinical phenotypes in children and adolescents with ADHD and to investigate whether neuroimaging findings validate the identified phenotypes. Neuroimaging and clinical data from 67 children with ADHD and 62 typically developing controls (TDCs from the ADHD-200 database were selected. Clinical measures of ADHD symptoms and intelligence quotient (IQ were used as input features into a topological data analysis (TDA to identify ADHD subgroups within our sample. As external validators, graph theoretical measures obtained from the functional connectome were compared to address the biological meaningfulness of the identified subtypes. The TDA identified two unique subgroups of ADHD, labelled as mild symptom ADHD (mADHD and severe symptom ADHD (sADHD. The output topology shape was repeatedly observed in the independent validation dataset. The graph theoretical analysis showed a decrease in the degree centrality and PageRank in the bilateral posterior cingulate cortex in the sADHD group compared with the TDC group. The mADHD group showed similar patterns of intra- and inter-module connectivity to the sADHD group. Relative to the TDC group, the inter-module connectivity between the default mode network and executive control network were significantly increased in the sADHD group but not in the mADHD group. Taken together, our results show that the data-driven TDA is potentially useful in identifying objective and biologically relevant disease phenotypes in children and adolescents with ADHD.

  5. Four Distinct Subgroups of Self-Injurious Behavior among Chinese Adolescents: Findings from a Latent Class Analysis.

    Directory of Open Access Journals (Sweden)

    Xiuhong Xin

    Full Text Available Self-injurious behavior (SIB among adolescents is an important public health issue worldwide. It is still uncertain whether homogeneous subgroups of SIB can be identified and whether constellations of SIBs can co-occur due to the high heterogeneity of these behaviors. In this study, a cross-sectional study was conducted on a large school-based sample and latent class analysis was performed (n = 10,069, mean age = 15 years to identify SIB classes based on 11 indicators falling under direct SIB (DSIB, indirect SIB (ISIB, and suicide attempts (SAs. Social and psychological characteristics of each subgroup were examined after controlling for age and gender. Results showed that a four-class model best fit the data and each class had a distinct pattern of co-occurrence of SIBs and external measures. Class 4 (the baseline/normative group, 65.3% had a low probability of SIB. Class 3 (severe SIB group, 3.9% had a high probability of SIB and the poorest social and psychological status. Class 1 (DSIB+SA group, 14.2% had similar scores for external variables compared to class 3, and included a majority of girls [odds ratio (OR = 1.94]. Class 2 (ISIB group, 16.6% displayed moderate endorsement of ISIB items, and had a majority of boys and older adolescents (OR = 1.51. These findings suggest that SIB is a heterogeneous entity, but it may be best explained by four homogenous subgroups that display quantitative and qualitative differences. Findings in this study will improve our understanding on SIB and may facilitate the prevention and treatment of SIB.

  6. Prognostic value of medulloblastoma extent of resection after accounting for molecular subgroup: a retrospective integrated clinical and molecular analysis.

    Science.gov (United States)

    Thompson, Eric M; Hielscher, Thomas; Bouffet, Eric; Remke, Marc; Luu, Betty; Gururangan, Sridharan; McLendon, Roger E; Bigner, Darell D; Lipp, Eric S; Perreault, Sebastien; Cho, Yoon-Jae; Grant, Gerald; Kim, Seung-Ki; Lee, Ji Yeoun; Rao, Amulya A Nageswara; Giannini, Caterina; Li, Kay Ka Wai; Ng, Ho-Keung; Yao, Yu; Kumabe, Toshihiro; Tominaga, Teiji; Grajkowska, Wieslawa A; Perek-Polnik, Marta; Low, David C Y; Seow, Wan Tew; Chang, Kenneth T E; Mora, Jaume; Pollack, Ian F; Hamilton, Ronald L; Leary, Sarah; Moore, Andrew S; Ingram, Wendy J; Hallahan, Andrew R; Jouvet, Anne; Fèvre-Montange, Michelle; Vasiljevic, Alexandre; Faure-Conter, Cecile; Shofuda, Tomoko; Kagawa, Naoki; Hashimoto, Naoya; Jabado, Nada; Weil, Alexander G; Gayden, Tenzin; Wataya, Takafumi; Shalaby, Tarek; Grotzer, Michael; Zitterbart, Karel; Sterba, Jaroslav; Kren, Leos; Hortobágyi, Tibor; Klekner, Almos; László, Bognár; Pócza, Tímea; Hauser, Peter; Schüller, Ulrich; Jung, Shin; Jang, Woo-Youl; French, Pim J; Kros, Johan M; van Veelen, Marie-Lise C; Massimi, Luca; Leonard, Jeffrey R; Rubin, Joshua B; Vibhakar, Rajeev; Chambless, Lola B; Cooper, Michael K; Thompson, Reid C; Faria, Claudia C; Carvalho, Alice; Nunes, Sofia; Pimentel, José; Fan, Xing; Muraszko, Karin M; López-Aguilar, Enrique; Lyden, David; Garzia, Livia; Shih, David J H; Kijima, Noriyuki; Schneider, Christian; Adamski, Jennifer; Northcott, Paul A; Kool, Marcel; Jones, David T W; Chan, Jennifer A; Nikolic, Ana; Garre, Maria Luisa; Van Meir, Erwin G; Osuka, Satoru; Olson, Jeffrey J; Jahangiri, Arman; Castro, Brandyn A; Gupta, Nalin; Weiss, William A; Moxon-Emre, Iska; Mabbott, Donald J; Lassaletta, Alvaro; Hawkins, Cynthia E; Tabori, Uri; Drake, James; Kulkarni, Abhaya; Dirks, Peter; Rutka, James T; Korshunov, Andrey; Pfister, Stefan M; Packer, Roger J; Ramaswamy, Vijay; Taylor, Michael D

    2016-04-01

    Patients with incomplete surgical resection of medulloblastoma are controversially regarded as having a marker of high-risk disease, which leads to patients undergoing aggressive surgical resections, so-called second-look surgeries, and intensified chemoradiotherapy. All previous studies assessing the clinical importance of extent of resection have not accounted for molecular subgroup. We analysed the prognostic value of extent of resection in a subgroup-specific manner. We retrospectively identified patients who had a histological diagnosis of medulloblastoma and complete data about extent of resection and survival from centres participating in the Medulloblastoma Advanced Genomics International Consortium. We collected from resections done between April, 1997, and February, 2013, at 35 international institutions. We established medulloblastoma subgroup affiliation by gene expression profiling on frozen or formalin-fixed paraffin-embedded tissues. We classified extent of resection on the basis of postoperative imaging as gross total resection (no residual tumour), near-total resection (30 Gy vs no craniospinal irradiation). The primary analysis outcome was the effect of extent of resection by molecular subgroup and the effects of other clinical variables on overall and progression-free survival. We included 787 patients with medulloblastoma (86 with WNT tumours, 242 with SHH tumours, 163 with group 3 tumours, and 296 with group 4 tumours) in our multivariable Cox models of progression-free and overall survival. We found that the prognostic benefit of increased extent of resection for patients with medulloblastoma is attenuated after molecular subgroup affiliation is taken into account. We identified a progression-free survival benefit for gross total resection over sub-total resection (hazard ratio [HR] 1·45, 95% CI 1·07-1·96, p=0·16) but no overall survival benefit (HR 1·23, 0·87-1·72, p=0·24). We saw no progression-free survival or overall survival

  7. Subgroup analysis of telehealthcare for patients with chronic obstructive pulmonary disease: the cluster-randomized Danish Telecare North Trial

    Directory of Open Access Journals (Sweden)

    Witt Udsen F

    2017-07-01

    Full Text Available Flemming Witt Udsen,1 Pernille H Lilholt,2 Ole K Hejlesen,2 Lars H Ehlers1 1Danish Centre for Healthcare Improvements, Aalborg University, Aalborg, Denmark; 2Department of Health Science and Technology, Aalborg University, Aalborg, Denmark Purpose: Results from the Danish cluster-randomized trial of telehealthcare to 1,225 patients with chronic obstructive pulmonary disease (COPD, the Danish Telecare North Trial, concluded that the telehealthcare solution was unlikely to be cost-effective, by applying international willingness-to-pay threshold values. The purpose of this article was to assess potential sources of variation across subgroups, which could explain overall cost-effectiveness results or be utilized in future economic studies in telehealthcare research. Methods: First, the cost-structures and cost-effectiveness across COPD severities were analyzed. Second, five additional subgroup analyses were conducted, focusing on differences in cost-effectiveness across a set of comorbidities, age-groups, genders, resource patterns (resource use in the social care sector prior to randomization, and delivery sites. All subgroups were ­investigated post hoc. In analyzing cost-effectiveness, two separate linear mixed-effects models with treatment-by-covariate interactions were applied: one for quality-adjusted life-year (QALY gain and one for total healthcare and social sector costs. Probabilistic sensitivity analysis was used for each subgroup result in order to quantify the uncertainty around the cost-effectiveness results. Results: The study concludes that, across the COPD severities, patients with severe COPD (GOLD 3 classification are likely to be the most cost-effective group. This is primarily due to lower hospital-admission and primary-care costs. Telehealthcare for patients younger than 60 years is also more likely to be cost-effective than for older COPD patients. Overall, results indicate that existing resource patterns of patients and

  8. No Higher Risk of CRPS After External Fixation of Distal Radial Fractures - Subgroup Analysis Under Randomised Vitamin C Prophylaxis.

    Science.gov (United States)

    Zollinger, Paul E; Kreis, Robert W; van der Meulen, Hub G; van der Elst, Maarten; Breederveld, Roelf S; Tuinebreijer, Wim E

    2010-02-17

    Operative and conservative treatment of wrist fractures might lead to complex regional pain syndrome (CRPS) type I.In our multicenter dose response study in which patients with distal radial fractures were randomly allocated to placebo or vitamin C in a daily dose of 200mg, 500mg or 1500mg during 50 days, an operated subgroup was analyzed.48 (of 427) fractures) were operated (11.2%). Twenty-nine patients (60%) were treated with external fixation, 14 patients (29%) with K-wiring according to Kapandji and five patients (10%) with internal plate fixation. The 379 remaining patients were treated with a plaster.In the operated group of patients who received vitamin C no CRPS (0/37) was seen in comparison with one case of CRPS (Kapandji technique) in the operated group who received placebo (1/11 = 9%, p=.23). There was no CRPS after external fixation.In the conservatively treated group 17 cases of CRPS (17/379 = 4.5%) occurred in comparison with one in case of CRPS in the operated group (1/48 = 2.1%, p=.71).External fixation doesn't necessarily lead to a higher incidence of CRPS in distal radial fractures. Vitamin C may also play a role in this. This subgroup analysis in operated distal radial fractures showed no CRPS occurrence with vitamin C prophylaxis.

  9. Combined olmesartan, amlodipine, and hydrochlorothiazide therapy in randomized patients with hypertension: a subgroup analysis of the TRINITY study by age.

    Science.gov (United States)

    Lewin, Andrew J; Izzo, Joseph L; Melino, Michael; Lee, James; Fernandez, Victor; Heyrman, Reinilde

    2013-07-01

    Hypertension is often inadequately controlled in older people. This prespecified subgroup analysis assessed the efficacy and safety of an olmesartan medoxomil (OM) 40 mg/amlodipine besylate (AML) 10 mg/hydrochlorothiazide (HCTZ) 25 mg triple-combination treatment compared with the 3 components as dual-combination treatments in participants with hypertension who were 9 %). Participants were randomized, stratified by age, diabetes status, and race to one of four treatment assignments: OM 40/AML 10/HCTZ 25 mg, OM 40/AML 10 mg, OM 40/HCTZ 25 mg, or AML 10/HCTZ 25 mg. Least squares (LS) mean change from baseline in seated diastolic blood pressure (SeDBP) at week 12 (last observation carried forward) in each age subgroup (prespecified analysis). Of the 2492 randomized participants in the study (total cohort), 2021 (81.1 %) were <65 and 471 (18.9 %) were ≥ 65 years of age, including 79 (3.2 %) who were ≥ 75 years of age. OM 40/AML 10/HCTZ 25 mg triple-combination treatment resulted in a significantly greater reduction in LS mean SeDBP at week 12 than dual-combination component treatments in participants in both cohorts: <65 years (21.0 vs. 14.2-17.2 mmHg; p < 0.0001) and ≥ 65 years (23.7 vs. 17.3-20.0 mmHg; p ≤ 0.002). Similarly, triple-combination treatment resulted in a greater reduction in LS mean seated systolic blood pressure (SeSBP) at week 12 than dual-combination component treatments: <65 years (38.2 vs. 28.3-31.4 mmHg; p < 0.0001) and ≥ 65 years (39.2 vs. 29.3-31.1 mmHg; p < 0.0001). Triple-combination treatment was more effective than dual-combination treatments in enabling participants to reach SeBP goal (<140/90 mmHg [<130/80 mmHg in participants with diabetes, chronic kidney disease, or chronic cardiovascular disease]) in both age subgroups (<65 years: 65 vs. 34-50 %, respectively, p < 0.0001 and ≥ 65 years: 63 vs. 32-39 %; p ≤ 0.0004). All 4 treatments were safe and well tolerated with low discontinuation rates in both age subgroups. There were

  10. Exploring Treatment by Covariate Interactions Using Subgroup Analysis and Meta-Regression in Cochrane Reviews: A Review of Recent Practice

    Science.gov (United States)

    Donegan, Sarah; Williams, Lisa; Tudur-Smith, Catrin

    2015-01-01

    Background Treatment by covariate interactions can be explored in reviews using interaction analyses (e.g., subgroup analysis). Such analyses can provide information on how the covariate modifies the treatment effect and is an important methodological approach for personalising medicine. Guidance exists regarding how to apply such analyses but little is known about whether authors follow the guidance. Methods Using published recommendations, we developed criteria to assess how well interaction analyses were designed, applied, interpreted, and reported. The Cochrane Database of Systematic Reviews was searched (8th August 2013). We applied the criteria to the most recently published review, with an accessible protocol, for each Cochrane Review Group. We excluded review updates, diagnostic test accuracy reviews, withdrawn reviews, and overviews of reviews. Data were summarised regarding reviews, covariates, and analyses. Results Each of the 52 included reviews planned or did interaction analyses; 51 reviews (98%) planned analyses and 33 reviews (63%) applied analyses. The type of analysis planned and the type subsequently applied (e.g., sensitivity or subgroup analysis) was discrepant in 24 reviews (46%). No review reported how or why each covariate had been chosen; 22 reviews (42%) did state each covariate a priori in the protocol but no review identified each post-hoc covariate as such. Eleven reviews (21%) mentioned five covariates or less. One review reported planning to use a method to detect interactions (i.e., interaction test) for each covariate; another review reported applying the method for each covariate. Regarding interpretation, only one review reported whether an interaction was detected for each covariate and no review discussed the importance, or plausibility, of the results, or the possibility of confounding for each covariate. Conclusions Interaction analyses in Cochrane Reviews can be substantially improved. The proposed criteria can be used to

  11. Generalized efficacy of t-PA for acute stroke. Subgroup analysis of the NINDS t-PA Stroke Trial.

    Science.gov (United States)

    1997-11-01

    We sought to identify subgroups of stroke patients in whom thrombolytic therapy is particularly hazardous or efficacious. We conducted a post hoc subgroup analysis of a randomized, double-blind, placebo-controlled clinical trial of intravenous tissue plasminogen activator (t-PA) for stroke patients presenting within 3 hours after symptom onset. Before treatment, historical, physical, and laboratory findings were summarized. We identified variables that might predict outcome and/or differential response to t-PA therapy. Outcome was measured with four stroke rating scales administered 3 months after treatment. Statistical significance was assessed with a global outcome procedure that considers the results of all four scales simultaneously. Using regression analysis, we compared the information collected before treatment with the global outcome. Multivariable procedures were used to find information that could guide selection of patients for t-PA therapy. No pretreatment information significantly affected patients response to t-PA. The power of the model to detect a treatment interaction was greater than 90%, and therefore the probability of a type II error is very low. Apart from t-PA therapy, outcome was related to age-by-deficit severity interaction, diabetes, age-by-blood pressure interaction, and early CT findings. These variables and interactions altered long-term patient outcome irrespective of t-PA treatment but did not alter the likelihood of responding favorably to t-PA therapy. Patients should be selected for t-PA thrombolysis according to the guidelines published in the report of the NINDS t-PA Stroke Trial. Further subselection of patients, such as by age or stroke severity, is not supported by our post hoc analysis.

  12. Exploring treatment by covariate interactions using subgroup analysis and meta-regression in cochrane reviews: a review of recent practice.

    Directory of Open Access Journals (Sweden)

    Sarah Donegan

    Full Text Available Treatment by covariate interactions can be explored in reviews using interaction analyses (e.g., subgroup analysis. Such analyses can provide information on how the covariate modifies the treatment effect and is an important methodological approach for personalising medicine. Guidance exists regarding how to apply such analyses but little is known about whether authors follow the guidance.Using published recommendations, we developed criteria to assess how well interaction analyses were designed, applied, interpreted, and reported. The Cochrane Database of Systematic Reviews was searched (8th August 2013. We applied the criteria to the most recently published review, with an accessible protocol, for each Cochrane Review Group. We excluded review updates, diagnostic test accuracy reviews, withdrawn reviews, and overviews of reviews. Data were summarised regarding reviews, covariates, and analyses.Each of the 52 included reviews planned or did interaction analyses; 51 reviews (98% planned analyses and 33 reviews (63% applied analyses. The type of analysis planned and the type subsequently applied (e.g., sensitivity or subgroup analysis was discrepant in 24 reviews (46%. No review reported how or why each covariate had been chosen; 22 reviews (42% did state each covariate a priori in the protocol but no review identified each post-hoc covariate as such. Eleven reviews (21% mentioned five covariates or less. One review reported planning to use a method to detect interactions (i.e., interaction test for each covariate; another review reported applying the method for each covariate. Regarding interpretation, only one review reported whether an interaction was detected for each covariate and no review discussed the importance, or plausibility, of the results, or the possibility of confounding for each covariate.Interaction analyses in Cochrane Reviews can be substantially improved. The proposed criteria can be used to help guide the reporting and

  13. Identifying Subgroups of Tinnitus Using Novel Resting State fMRI Biomarkers and Cluster Analysis

    Science.gov (United States)

    2016-10-01

    humanities . The following activities were undertaken o disseminate preliminary research data to communities of interest and to obtain feedback. One...processing, which are important to the underlying neural mechanisms of tinnitus. This study uses functional magnetic resonance imaging (fMRI) and is...analysis, active duty service members, resting-state fMRI, UIUC, WHASC 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES

  14. Soil Acidobacterial 16S rRNA Gene Sequences Reveal Subgroup Level Differences between Savanna-Like Cerrado and Atlantic Forest Brazilian Biomes

    Directory of Open Access Journals (Sweden)

    Elisa C. P. Catão

    2014-01-01

    Full Text Available 16S rRNA sequences from the phylum Acidobacteria have been commonly reported from soil microbial communities, including those from the Brazilian Savanna (Cerrado and the Atlantic Forest biomes, two biomes that present contrasting characteristics of soil and vegetation. Using 16S rRNA sequences, the present work aimed to study acidobacterial diversity and distribution in soils of Cerrado savanna and two Atlantic forest sites. PCA and phylogenetic reconstruction showed that the acidobacterial communities found in “Mata de galeria” forest soil samples from the Cerrado biome have a tendency to separate from the other Cerrado vegetation microbial communities in the direction of those found in the Atlantic Forest, which is correlated with a high abundance of Acidobacteria subgroup 2 (GP2. Environmental conditions seem to promote a negative correlation between GP2 and subgroup 1 (GP1 abundance. Also GP2 is negatively correlated to pH, but positively correlated to high Al3+ concentrations. The Cerrado soil showed the lowest Acidobacteria richness and diversity indexes of OTUs at the species and subgroups levels when compared to Atlantic Forest soils. These results suggest specificity of acidobacterial subgroups to soils of different biomes and are a starting point to understand their ecological roles, a topic that needs to be further explored.

  15. Diversity in Older Adults' Use of the Internet: Identifying Subgroups Through Latent Class Analysis.

    Science.gov (United States)

    van Boekel, Leonieke C; Peek, Sebastiaan Tm; Luijkx, Katrien G

    2017-05-24

    As for all individuals, the Internet is important in the everyday life of older adults. Research on older adults' use of the Internet has merely focused on users versus nonusers and consequences of Internet use and nonuse. Older adults are a heterogeneous group, which may implicate that their use of the Internet is diverse as well. Older adults can use the Internet for different activities, and this usage can be of influence on benefits the Internet can have for them. The aim of this paper was to describe the diversity or heterogeneity in the activities for which older adults use the Internet and determine whether diversity is related to social or health-related variables. We used data of a national representative Internet panel in the Netherlands. Panel members aged 65 years and older and who have access to and use the Internet were selected (N=1418). We conducted a latent class analysis based on the Internet activities that panel members reported to spend time on. Second, we described the identified clusters with descriptive statistics and compared the clusters using analysis of variance (ANOVA) and chi-square tests. Four clusters were distinguished. Cluster 1 was labeled as the "practical users" (36.88%, n=523). These respondents mainly used the Internet for practical and financial purposes such as searching for information, comparing products, and banking. Respondents in Cluster 2, the "minimizers" (32.23%, n=457), reported lowest frequency on most Internet activities, are older (mean age 73 years), and spent the smallest time on the Internet. Cluster 3 was labeled as the "maximizers" (17.77%, n=252); these respondents used the Internet for various activities, spent most time on the Internet, and were relatively younger (mean age below 70 years). Respondents in Cluster 4, the "social users," mainly used the Internet for social and leisure-related activities such as gaming and social network sites. The identified clusters significantly differed in age (PInternet

  16. Exclusion of deep vein thrombosis using the Wells rule in clinically important subgroups: individual patient data meta-analysis.

    Science.gov (United States)

    Geersing, G J; Zuithoff, N P A; Kearon, C; Anderson, D R; Ten Cate-Hoek, A J; Elf, J L; Bates, S M; Hoes, A W; Kraaijenhagen, R A; Oudega, R; Schutgens, R E G; Stevens, S M; Woller, S C; Wells, P S; Moons, K G M

    2014-03-10

    To assess the accuracy of the Wells rule for excluding deep vein thrombosis and whether this accuracy applies to different subgroups of patients. Meta-analysis of individual patient data. Authors of 13 studies (n = 10,002) provided their datasets, and these individual patient data were merged into one dataset. Studies were eligible if they enrolled consecutive outpatients with suspected deep vein thrombosis, scored all variables of the Wells rule, and performed an appropriate reference standard. Multilevel logistic regression models, including an interaction term for each subgroup, were used to estimate differences in predicted probabilities of deep vein thrombosis by the Wells rule. In addition, D-dimer testing was added to assess differences in the ability to exclude deep vein thrombosis using an unlikely score on the Wells rule combined with a negative D-dimer test result. Overall, increasing scores on the Wells rule were associated with an increasing probability of having deep vein thrombosis. Estimated probabilities were almost twofold higher in patients with cancer, in patients with suspected recurrent events, and (to a lesser extent) in males. An unlikely score on the Wells rule (≤ 1) combined with a negative D-dimer test result was associated with an extremely low probability of deep vein thrombosis (1.2%, 95% confidence interval 0.7% to 1.8%). This combination occurred in 29% (95% confidence interval 20% to 40%) of patients. These findings were consistent in subgroups defined by type of D-dimer assay (quantitative or qualitative), sex, and care setting (primary or hospital care). For patients with cancer, the combination of an unlikely score on the Wells rule and a negative D-dimer test result occurred in only 9% of patients and was associated with a 2.2% probability of deep vein thrombosis being present. In patients with suspected recurrent events, only the modified Wells rule (adding one point for the previous event) is safe. Combined with a negative D

  17. Timing of surgery for sciatica: subgroup analysis alongside a randomized trial

    Science.gov (United States)

    Arts, Mark P.; Brand, Ronald; Koes, Bart W.

    2009-01-01

    Surgery speeds up recovery for sciatica. Prolonged conservative care with surgery for those patients with persistent sciatica however, yields similar results at 1 year. To investigate whether baseline variables modify the difference in recovery rates between these treatment strategies, baseline data of 283 patients enrolled in a randomized trial, comparing early surgery with prolonged conservative care, were used to analyse effect modification of the allotted treatment strategy. For predictors shown to modify the effect of the treatment strategy, repeated measurement analyses with the Roland Disability Questionnaire and visual analogue scale pain as continuous outcomes were performed for every level of that predictor. Presumed predictive variables did not have any interaction with treatment, while “sciatica provoked by sitting” showed to be a significant effect modifier (P = 0.07). In a Cox model we estimated a hazard ratio (HR, surgery versus conservative) of 2.2 (95% CI 1.7–3.0) in favour of surgery when sciatica was provoked by sitting, while the HR was 1.3 (95% CI 0.8–2.2) when this sign was absent. The interaction effect is marginally significant (interactions are usually tested at the 10% level) but the patterns generated by the repeated measurement analyses of all primary outcomes are completely consistent with the inferred pattern from the survival analysis. Classical signs did not show any contribution as decision support tools in deciding when to operate for sciatica, whereas treatment effects of early surgery are emphasized when sciatica is provoked by sitting and negligible when this symptom is absent. PMID:19132412

  18. Identifying Differences in Early Literacy Skills Across Subgroups of Language-Minority Children: A Latent Profile Analysis.

    Science.gov (United States)

    Lonigan, Christopher J; Goodrich, J Marc; Farver, JoAnn M

    2017-12-18

    Despite acknowledgment that language-minority children come from a wide variety of home language backgrounds and have a wide range of proficiency in their first (L1) and second (L2) languages, it is unknown whether differences across language-minority children in relative and absolute levels of proficiency in L1 and L2 predict subsequent development of literacy-related skills. The purpose of this study was to identify subgroups of language-minority children and evaluate whether differences in level and rate of growth of early literacy skills differed across subgroups. Five-hundred and twenty-six children completed measures of Spanish and English language and early literacy skills at the beginning, middle, and end of the preschool year. Latent growth models indicated that children's early literacy skills were increasing over the course of the preschool year. Latent profile analysis indicated that language-minority children could be classified into nine distinct groups, each with unique patterns of absolute and relative levels of proficiency in L1 and L2. Results of three-step mixture models indicated that profiles were closely associated with level of early literacy skills at the beginning of the preschool year. Initial level of early literacy skills was positively associated with growth in code-related skills (i.e., print knowledge, phonological awareness) and inversely associated with growth in language skills. These findings suggest that language-minority children are a diverse group with regard to their L1 and L2 proficiencies and that growth in early literacy skills is most associated with level of proficiency in the same language. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  19. A comparison of three clustering methods for finding subgroups in MRI, SMS or clinical data: SPSS TwoStep Cluster analysis, Latent Gold and SNOB.

    Science.gov (United States)

    Kent, Peter; Jensen, Rikke K; Kongsted, Alice

    2014-10-02

    There are various methodological approaches to identifying clinically important subgroups and one method is to identify clusters of characteristics that differentiate people in cross-sectional and/or longitudinal data using Cluster Analysis (CA) or Latent Class Analysis (LCA). There is a scarcity of head-to-head comparisons that can inform the choice of which clustering method might be suitable for particular clinical datasets and research questions. Therefore, the aim of this study was to perform a head-to-head comparison of three commonly available methods (SPSS TwoStep CA, Latent Gold LCA and SNOB LCA). The performance of these three methods was compared: (i) quantitatively using the number of subgroups detected, the classification probability of individuals into subgroups, the reproducibility of results, and (ii) qualitatively using subjective judgments about each program's ease of use and interpretability of the presentation of results.We analysed five real datasets of varying complexity in a secondary analysis of data from other research projects. Three datasets contained only MRI findings (n = 2,060 to 20,810 vertebral disc levels), one dataset contained only pain intensity data collected for 52 weeks by text (SMS) messaging (n = 1,121 people), and the last dataset contained a range of clinical variables measured in low back pain patients (n = 543 people). Four artificial datasets (n = 1,000 each) containing subgroups of varying complexity were also analysed testing the ability of these clustering methods to detect subgroups and correctly classify individuals when subgroup membership was known. The results from the real clinical datasets indicated that the number of subgroups detected varied, the certainty of classifying individuals into those subgroups varied, the findings had perfect reproducibility, some programs were easier to use and the interpretability of the presentation of their findings also varied. The results from the artificial datasets

  20. Outcome After Sentinel Lymph Node Dissection in Vulvar Cancer: A Subgroup Analysis of the AGO-CaRE-1 Study.

    Science.gov (United States)

    Klapdor, Rüdiger; Hillemanns, Peter; Wölber, Linn; Jückstock, Julia; Hilpert, Felix; de Gregorio, Nikolaus; Iborra, Severine; Sehouli, Jalid; Habermann, Anika; Fürst, Sophie Teresa; Strauß, Hans Georg; Baumann, Klaus; Thiel, Falk; Mustea, Alexander; Meier, Werner; Harter, Philipp; Wimberger, Pauline; Hanker, Lars; Schmalfeldt, Barbara; Canzler, Ulrich; Fehm, Tanja; Luyten, Alexander; Hellriegel, Martin; Kosse, Jens; Heiss, Christoph; Hantschmann, Peer; Mallmann, Peter; Tanner, Berno; Pfisterer, Jacobus; Richter, Barbara; Jäger, Martin; Mahner, Sven

    2017-05-01

    Analyzing the large patient cohort of the multicenter AGO-CaRE-1 study, we compared isolated sentinel lymph node dissection (SLND) with radical lymph node dissection (LND) of the groin in relation to recurrence rates and survival. The AGO-CaRE-1 study retrospectively collected data on treatment patterns and follow-up of vulvar cancer patients [International Federation of Gynecology and Obstetrics (FIGO) stage ≥1B] treated at 29 gynecologic cancer centers between 1998 and 2008. This subgroup analysis evaluated the influence of SLND alone on progression-free survival (PFS) and overall survival (OS). In 487 (63.1%) of 772 included patients with tumors smaller than 4 cm, an LND was performed and no metastatic lymph nodes were detected (LN0). Another 69/772 (8.9%) women underwent SLND alone, showing a negative SLN (SLN0). Tumors in the LN0 group were larger and showed a deeper invasion (LN0 vs. SLN0 tumor diameter: 20.0 vs. 13.0 mm, p < 0.001; depth of invasion: 4.0 vs. 3.0 mm, p = 0.002). After a median follow-up of 33 months (0-156), no significant differences in relation to isolated groin recurrence rates (SLN0 3.0% vs. LN0 3.4%, p = 0.845) were detected. Similarly, univariate 3-year PFS analysis showed no significant differences between both groups (SLN0 82.7% vs. LN0 77.6%, p = 0.230). A multivariate Cox regression analysis, including tumor diameter, depth of invasion, age, grading, and lymphovascular space invasion was performed: PFS [hazard ratio (HR) 0.970, 95% confidence interval (CI) 0.517-1.821] and OS (HR 0.695, 95% CI 0.261-1.849) did not differ significantly between both cohorts. This subgroup analysis of the large AGO-CaRE-1 study showed similar results for groin LND and SLND alone with regard to recurrence rates and survival in node-negative patients with tumors <4 cm.

  1. Racial/ethnic disparities in magnesium sulfate neuroprotection: a subgroup analysis of a multicenter randomized controlled trial.

    Science.gov (United States)

    Vilchez, Gustavo; Dai, Jing; Kumar, Komal; Mundy, David; Kontopoulos, Eftichia; Sokol, Robert J

    2017-10-04

    Despite known racial disparities in obstetrics, as well as differences in magnesium pharmacodynamics according to race, the effect of race/ethnicity in magnesium sulfate (MgSO4) use during pregnancy has not been studied. Whether some mothers are at increased risk of side effects, or infants at decreased neuroprotective effects is unknown. We analyze the effect of race/ethnicity in maternal/infant outcomes after MgSO4 neuroprotection. Subgroup analysis of a multicenter clinical trial (BEAM trial) where pregnant women at risk of preterm birth were randomized to either MgSO4 or placebo. For this study, nonanomalous singleton pregnancies were studied. The effect of race in maternal/neonatal outcomes after MgSO4 was analyzed with Breslow-Day and multifactorial ANOVA. Logistic regression was used to calculate odds ratios (OR) of complications according to race. 922 MgSO4 and 972 placebo cases were included (45.0% African-American, 36.2% Caucasian, 17.8% Hispanics, and 1.0% Asians). Interaction analysis showed a significant effect of race/ethnicity (p = .043). Hispanics presented the highest frequency (88.3%, p effects [OR(95%CI) = 6.6 (1.3-33.8)]. Hispanics present increased risk of magnesium toxicity compared to other racial/ethnic groups. Whether specific racial/ethnic groups require closer surveillance for early signs of magnesium toxicity needs to be further explored.

  2. Patterns of cervical and masticatory impairment in subgroups of people with temporomandibular disorders-an explorative approach based on factor analysis.

    Science.gov (United States)

    Ballenberger, Nikolaus; von Piekartz, Harry; Danzeisen, Mira; Hall, Toby

    2017-03-20

    To identify clinical patterns of impairment affecting the cervical spine and masticatory systems in different subcategories of temporomandibular disorder (TMD) by an explorative data-driven approach. For this observational study, 144 subjects were subdivided according to Research Diagnostic Criteria for TMDs into: Healthy controls, temporomandibular joint (TMJ) signs without symptoms, TMJ affected, temporomandibular muscles affected, or TMJ and muscles affected. Factor analysis and linear regression were applied to cervical spine and masticatory data to identify and characterize clinical patterns in subgroups. Factor analysis identified five clinical dimensions, which explained 59% of all variance: Mechanosensitivity, cervical movement, cervical and masticatory dysfunction, jaw movement, and upper cervical movement. Regression analysis identified different clinical dimensions in each TMD subgroup. Distinct clinical patterns of cervical spine and masticatory function were found among subgroups of TMD, which has clinical implications for therapeutic management.

  3. Topology based data analysis identifies a subgroup of breast cancers with a unique mutational profile and excellent survival.

    Science.gov (United States)

    Nicolau, Monica; Levine, Arnold J; Carlsson, Gunnar

    2011-04-26

    High-throughput biological data, whether generated as sequencing, transcriptional microarrays, proteomic, or other means, continues to require analytic methods that address its high dimensional aspects. Because the computational part of data analysis ultimately identifies shape characteristics in the organization of data sets, the mathematics of shape recognition in high dimensions continues to be a crucial part of data analysis. This article introduces a method that extracts information from high-throughput microarray data and, by using topology, provides greater depth of information than current analytic techniques. The method, termed Progression Analysis of Disease (PAD), first identifies robust aspects of cluster analysis, then goes deeper to find a multitude of biologically meaningful shape characteristics in these data. Additionally, because PAD incorporates a visualization tool, it provides a simple picture or graph that can be used to further explore these data. Although PAD can be applied to a wide range of high-throughput data types, it is used here as an example to analyze breast cancer transcriptional data. This identified a unique subgroup of Estrogen Receptor-positive (ER(+)) breast cancers that express high levels of c-MYB and low levels of innate inflammatory genes. These patients exhibit 100% survival and no metastasis. No supervised step beyond distinction between tumor and healthy patients was used to identify this subtype. The group has a clear and distinct, statistically significant molecular signature, it highlights coherent biology but is invisible to cluster methods, and does not fit into the accepted classification of Luminal A/B, Normal-like subtypes of ER(+) breast cancers. We denote the group as c-MYB(+) breast cancer.

  4. Vitamin A supplementation in extremely low-birth-weight infants: subgroup analysis in small-for-gestational-age infants.

    Science.gov (United States)

    Londhe, Vedang A; Nolen, Tracy L; Das, Abhik; Higgins, Rosemary D; Tyson, Jon E; Oh, William; Devaskar, Sherin U

    2013-10-01

    Preterm infants with intrauterine growth restriction are at increased risk of respiratory distress syndrome and bronchopulmonary dysplasia (BPD). A randomized clinical trial by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Neonatal Research Network demonstrated that vitamin A supplementation in extremely low-birth-weight (ELBW) preterm infants requiring early respiratory support decreased the risk of developing BPD. A subgroup analysis of small-for-gestational-age (SGA) infants from the original NICHD trial was performed to test the hypothesis that in infants requiring early respiratory support, vitamin A supplementation decreases the relative risk of BPD or death in premature SGA infants to a greater extent than in gestational age-equivalent vitamin A-treated appropriate-for-gestational-age (AGA) infants. Although vitamin A supplementation significantly increased serum retinol concentrations in AGA ELBW infants (median [5th percentile, 95th percentile]: 16.3 [-7.0, 68.8] versus 2.4 [-13.9, 55.1]; p supplementation in preterm SGA infants requiring early respiratory support decreases the relative risk of BPD or death as compared with preterm AGA infants. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  5. The stable subgroup graph

    Directory of Open Access Journals (Sweden)

    Behnaz Tolue

    2018-07-01

    Full Text Available In this paper we introduce stable subgroup graph associated to the group $G$. It is a graph with vertex set all subgroups of $G$ and two distinct subgroups $H_1$ and $H_2$ are adjacent if $St_{G}(H_1\\cap H_2\

  6. Nutritional intervention in acute heart failure patients with undernutrition and normalbuminemia: A subgroup analysis of PICNIC study.

    Science.gov (United States)

    Ramiro-Ortega, Esmeralda; Bonilla-Palomas, Juan L; Gámez-López, Antonio L; Moreno-Conde, Mirian; López-Ibáñez, María C; Alhambra-Expósito, Rosa; Anguita Sánchez, Manuel

    2017-07-14

    Hypoalbuminemia is common in acute heart failure (HF) patients and has been associated with increased hospital mortality and long-term mortality. Undernutrition is a factor causing hypoalbuminemia. The PICNIC study results show that a nutritional intervention in undernourished acute HF patients reduces the risks of all-cause death and of readmission for HF. We aimed to investigate whether the efficacy of a nutritional intervention is consistent among the subgroups of patients with and without hypoalbuminemia. In PICNIC study, a total of 120 malnourished hospitalized patients due to acute HF were randomized to conventional HF treatment or conventional HF treatment combined with an individualized nutritional intervention. The primary endpoint was a composite of all-cause death or readmission for worsening of HF, with a maximum follow-up of 12 months. In this post-hoc sub-analysis we assessed the interaction of the effects of a nutritional intervention among patients with and without hypoalbuminemia. Analysis was by intention to treat. 59 (49,2%) patients demonstrated hypoalbuminemia and 61 (50,8%) had normalbuminemia. At 12 months, the number of events for the primary endpoint in the intervention group compared with the control group was consistent among patients with hypoalbuminemia (28.6% intervention vs 61.3% control, HR 0,35, 95% CI 0,15-0,81) and those without (25.8% intervention vs 60% control, HR 0,35, 95% CI 0,15-0,79; interaction p = 0,86). There was no evidence that the relative efficacy of a nutritional intervention in undernourished acute HF patients was different between patients with normalbuminemia and those with hypoalbuminemia. Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  7. Haemodynamic response to crystalloids or colloids in shock: an exploratory subgroup analysis of a randomised controlled trial.

    Science.gov (United States)

    Heming, Nicholas; Elatrous, Souheil; Jaber, Samir; Dumenil, Anne Sylvie; Cousson, Joël; Forceville, Xavier; Kimmoun, Antoine; Trouillet, Jean Louis; Fichet, Jérôme; Anguel, Nadia; Darmon, Michael; Martin, Claude; Chevret, Sylvie; Annane, Djillali

    2017-10-06

    To compare the haemodynamic effect of crystalloids and colloids during acute severe hypovolaemic shock. Exploratory subgroup analysis of a multicentre randomised controlled trial (Colloids Versus Crystalloids for the Resuscitation of the Critically Ill, CRISTAL, ClinicalTrials.gov NCT00318942). CRISTAL was conducted in intensive care units in Europe, North Africa and Canada. Current analysis included all patients who had a pulmonary artery catheter in place at randomisation. 220 patients (117 received crystalloids vs 103 colloids) underwent pulmonary artery catheterisation. Crystalloids versus colloids for fluid resuscitation in hypovolaemic shock. Haemodynamic data were collected at the time of randomisation and subsequently on days 1, 2, 3, 4, 5, 6 and 7. Median cumulative volume of fluid administered during the first 7 days was higher in the crystalloids group than in the colloids group (3500 (2000-6000) vs 2500 (1000-4000) mL, p=0.01). Patients in the colloids arm exhibited a lower heart rate over time compared with those allocated to the crystalloids arm (p=0.014). There was no significant difference in Cardiac Index (p=0.053), mean blood pressure (p=0.4), arterial lactates (p=0.9) or global Sequential Organ Failure Assessment score (p=0.3) over time between arms. During acute severe hypovolaemic shock, patients monitored by a pulmonary artery catheter achieved broadly similar haemodynamic outcomes, using lower volumes of colloids than crystalloids. The heart rate was lower in the colloids arm. © 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.

  8. [The Efficacy of Near-Infrared Devices in Facilitating Peripheral Intravenous Access in Children: A Systematic Review and Subgroup Meta-Analysis].

    Science.gov (United States)

    Kuo, Chia-Chi; Feng, I-Jung; Lee, Wei-Jing

    2017-10-01

    Peripheral intravenous access is a common and invasive procedure that is performed in pediatric clinical settings. Children often have difficult intravenous-access problems that may not only increase staff stress but also affect the timeliness of immediate treatments. To determine the efficacy of near-infrared devices in facilitating peripheral intravenous access in children, using a systematic review and meta-analysis. Six databases, namely the Index to Taiwan Periodical Literature System, Airiti Library, CINAHL, Cochrane Library, PubMed/MEDLINE, and ProQuest were searched for related articles that were published between the earliest year available and February 2017. The search was limited to studies on populations of children that used either a randomized controlled trial or controlled clinical trial approach and used the key words "near-infrared devices" AND "peripheral intravenous access." The 12 articles that met these criteria were included in the analysis. The Cochrane Collaboration bias assessment tool was used to assess the methodological quality. In addition, RevMan 5.3.5 software was used to conduct the meta-analysis. The near-infrared devices did not significantly improve the first-attempt success rate, number of attempts, or the procedural time of peripheral intravenous access in children. However, the subgroup analysis of difficult intravenous-access factors revealed a significant improvement in the first-attempt success rate of children with difficult intravenous access scores (OR = 1.83, p = .03). Near-infrared devices may improve the first-attempt success rate in children with difficult intravenous access by allowing healthcare professionals to visualize the peripheral veins. Therefore, we suggest that the difficult intravenous-access score be used as a screening tool to suggest when to apply near-infrared devices to children with difficult peripheral intravenous access in order to maximize efficacy of treatment.

  9. Identification of Patient Benefit From Proton Therapy for Advanced Head and Neck Cancer Patients Based on Individual and Subgroup Normal Tissue Complication Probability Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Jakobi, Annika, E-mail: Annika.Jakobi@OncoRay.de [OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Dresden (Germany); Bandurska-Luque, Anna [OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Dresden (Germany); Department of Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden (Germany); Stützer, Kristin; Haase, Robert; Löck, Steffen [OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Dresden (Germany); Wack, Linda-Jacqueline [Section for Biomedical Physics, University Hospital for Radiation Oncology, Eberhard Karls Universät Tübingen (Germany); Mönnich, David [Section for Biomedical Physics, University Hospital for Radiation Oncology, Eberhard Karls Universät Tübingen (Germany); German Cancer Research Center, Heidelberg (Germany); German Cancer Consortium, Tübingen (Germany); Thorwarth, Daniela [Section for Biomedical Physics, University Hospital for Radiation Oncology, Eberhard Karls Universät Tübingen (Germany); and others

    2015-08-01

    Purpose: The purpose of this study was to determine, by treatment plan comparison along with normal tissue complication probability (NTCP) modeling, whether a subpopulation of patients with head and neck squamous cell carcinoma (HNSCC) could be identified that would gain substantial benefit from proton therapy in terms of NTCP. Methods and Materials: For 45 HNSCC patients, intensity modulated radiation therapy (IMRT) was compared to intensity modulated proton therapy (IMPT). Physical dose distributions were evaluated as well as the resulting NTCP values, using modern models for acute mucositis, xerostomia, aspiration, dysphagia, laryngeal edema, and trismus. Patient subgroups were defined based on primary tumor location. Results: Generally, IMPT reduced the NTCP values while keeping similar target coverage for all patients. Subgroup analyses revealed a higher individual reduction of swallowing-related side effects by IMPT for patients with tumors in the upper head and neck area, whereas the risk reduction of acute mucositis was more pronounced in patients with tumors in the larynx region. More patients with tumors in the upper head and neck area had a reduction in NTCP of more than 10%. Conclusions: Subgrouping can help to identify patients who may benefit more than others from the use of IMPT and, thus, can be a useful tool for a preselection of patients in the clinic where there are limited PT resources. Because the individual benefit differs within a subgroup, the relative merits should additionally be evaluated by individual treatment plan comparisons.

  10. Perioperative and continence outcomes of robotic radical prostatectomy in elderly Indian men (≥70 years: A sub-group analysis

    Directory of Open Access Journals (Sweden)

    Rajiv Yadav

    2015-01-01

    Full Text Available Introduction: Many healthy elderly Indian men seek surgical treatment for localized prostate cancer. Quite often, radical surgery is not offered to the patients over 70 years of age due to the perception of increased side-effects and complications. We have previously reported our results of robotic radical prostatectomy in a study comprising 150 Indian patients, where almost a quarter of patients were elderly. This subgroup analysis was therefore focused on evaluating perioperative and continence outcomes in elderly men (≥70 years with localized prostate cancer. Materials and Methods: Between April 2010 and August 2013, 153 men had robot-assisted radical prostatectomy performed by two surgeons. Of the 150 men analyzed, 39 (26% were aged ≥70 years. All patients underwent robotic prostatectomy using a 4 arm da Vinci surgical system. Pre-operative, intraoperative and post-operative parameters were studied. Check cystogram was performed in all patients prior to catheter removal. Complications were categorized using the Clavien-Dindo classification system. Continence was defined as use of "no pad" or security liner only. All data were recorded prospectively and analyzed using SPSS version 20. Results: There were no significant intraoperative or perioperative complications in this group. Median blood loss during surgery was 150 mL. None of the patient required blood transfusion. There were two minor complications (5.1% within the first 30 days of surgery: Minimal anastomotic site leak (one patient requiring replacement and prolongation of Foley′s drainage by 1 week and ileus (one patient. No patient had any cardiopulmonary or vascular complications in the post-operative period. The median duration of hospital stay was 3 days. The median duration of catheterization was 7 days. No patient had problem of bladder neck stenosis in the follow-up period. At 1 month, 3 months, 6 months and 1 year of follow-up, 66.7% (n = 26, 74.3% (n = 29, 87.9% (n = 34

  11. Is the performance of MRI in preoperative staging of breast cancer independent of clinical and histological factors? A subgroup analysis.

    Science.gov (United States)

    Carreira Gómez, C; Zamora Romero, J; Gil de Miguel, A; Chiva de Agustín, M; Plana Farrás, M N; Martínez González, J

    2015-01-01

    To determine whether preoperative breast MRI is more useful in patients according to their breast density, age, menopausal status, and biopsy findings of carcinoma in situ. We retrospectively studied 264 patients treated for breast cancer who had undergone mammography, ultrasonography, and MRI. We compared the size of the tumor on the three techniques and the sensitivity of the techniques for detecting additional lesions both in the overall group and in subgroups of patients classified according to their breast density, age, menopausal status, and histological findings of intraductal carcinoma. The definitive histological diagnosis was used as the gold standard. MRI was the technique that was most concordant with the histological findings for the size of the lesion, and it was also the technique that detected the most additional lesions. With MRI, we observed no differences in lesion size between the overall group and the subgroups in which MRI provided added value. Likewise, we observed no differences in the number of additional lesions detected in the overall group except for multicentric lesions, which was larger in older patients (P=.02). In the subgroup of patients in which MRI provided added value, the sensitivity for bilateral lesions was higher in patients with fatty breasts (P=.04). Multifocal lesions were detected significantly better in premenopausal patients (P=.03). MRI is better than mammography and better than ultrasonography for establishing the size of the tumor and for detecting additional lesions. Our results did not identify any subgroups in which the technique was more useful. Copyright © 2013 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

  12. A comprehensive analysis of the mortality experience of hispanic subgroups in the United States: Variation by age, country of origin, and nativity

    Directory of Open Access Journals (Sweden)

    Andrew Fenelon

    2017-12-01

    Full Text Available Although those identifying as “Hispanic or Latino” experience lower adult mortality than the more socioeconomically advantaged non-Hispanic white population, the ethnic category Hispanic conceals variation by country of origin, nativity, age, and immigration experience. The current analysis examines adult mortality differentials among 12 Hispanic subgroups by region of origin and nativity, and non-Hispanic whites, adjusting for socioeconomic and demographic characteristics. We use the National Health Interview Survey Linked Mortality Files pooled 1990–2009 to obtain sufficient sample of each subgroup to calculate mortality estimates by sex and age group (25–64, 65+. Among adults aged 65 and over, all foreign born subgroups have an advantage over non-Hispanic whites, and many USB subgroups exhibit an advantage in the adjusted model. Foreign-born Dominicans, Central/South Americans, and other Hispanics exhibit consistent advantages across models for both men and women, aged 25–64 and 65 and over, and both unadjusted and adjusted for socioeconomic covariates. Both US-born and foreign-born Mexicans between ages 25 and 64 have mortality disadvantaged relative to non-Hispanic whites, while older Mexicans exhibit clear advantages. Our results complicate the traditional formulation of the Hispanic Paradox and cast doubt on the singularity of the mortality experience of those of Hispanic origin.

  13. A Randomised, Double-Blind, Placebo-Controlled Trial with Vitamin D3 in MS: Subgroup Analysis of Patients with Baseline Disease Activity Despite Interferon Treatment

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    J. Åivo

    2012-01-01

    Full Text Available We present a subgroup analysis of the first double-blind, placebo-controlled, randomised trial with vitamin D3 in MS. In the overall study population, there were 34 patients in the vitamin D arm and 32 patients in the placebo arm. All the patients were using interferon-β-1b (IFNB therapy. The subgroup consisted of 15 patients in the vitamin D arm and 15 patients in the placebo arm, who had either at least one relapse during the year preceding the study or enhancing T1 lesions at the baseline MRI scan. We measured the total number of MRI T1 enhancing lesions, the number of new/enlarging T2 lesions and T2 lesion volume (BOD (mm3, EDSS (Expanded Disability Status Scale, annual relapse Rate (ARR, timed 25-foot walk (T25FW, and timed 10-foot tandem walk (TT10W at baseline and at 12 months in the vitamin D-treated and in the placebo-treated patients. There was a statistically significant reduction in the number of T1 enhancing lesions, a smaller T2 lesion volume growth and less new/enlarging T2 brain MRI lesions in the vitamin D3-treated than in the placebo-treated subgroup patients. The MRI results were slightly more pronounced in the subgroup than in the overall study population.

  14. Efficacy and safety of liraglutide 3.0 mg for weight management are similar across races: subgroup analysis across the SCALE and phase II randomized trials.

    Science.gov (United States)

    Ard, J; Cannon, A; Lewis, C E; Lofton, H; Vang Skjøth, T; Stevenin, B; Pi-Sunyer, X

    2016-04-01

    The efficacy and safety of liraglutide 3.0 mg versus placebo, as adjunct to diet and exercise, was evaluated in racial subgroups. This post hoc analysis of pooled data from five double-blind randomized, placebo-controlled trials was conducted in 5325 adults with either a body mass index (BMI) ≥27 kg/m(2) plus ≥1 comorbidity or a BMI ≥30 kg/m(2). Statistical interaction tests evaluated possible treatment effect differences between racial subgroups: white (4496, 84.4%), black/African-American (550, 10.3%), Asian (168, 3.2%) and other (111, 2.1%). Effects of liraglutide 3.0 mg on weight loss, associated metabolic effects and safety profile were generally consistent across racial subgroups. All achieved statistically significant mean weight loss at end-of-treatment with liraglutide 3.0 mg versus placebo: white 7.7% versus 2.3%, black/African-American 6.3% versus 1.4%, Asian 6.3% versus 2.5%, other 7.3% versus 0.49%. Treatment effects on weight and cardiovascular risk markers generally showed no dependence on race (interaction test p > 0.05). Adverse events were similar across racial subgroups. © 2016 John Wiley & Sons Ltd.

  15. Integrated genotypic analysis of hedgehog-related genes identifies subgroups of keratocystic odontogenic tumor with distinct clinicopathological features.

    Directory of Open Access Journals (Sweden)

    Yasuyuki Shimada

    Full Text Available Keratocystic odontogenic tumor (KCOT arises as part of Gorlin syndrome (GS or as a sporadic lesion. Gene mutations and loss of heterozygosity (LOH of the hedgehog receptor PTCH1 plays an essential role in the pathogenesis of KCOT. However, some KCOT cases lack evidence for gene alteration of PTCH1, suggesting that other genes in the hedgehog pathway may be affected. PTCH2 and SUFU participate in the occurrence of GS-associated tumors, but their roles in KCOT development are unknown. To elucidate the roles of these genes, we enrolled 36 KCOT patients in a study to sequence their entire coding regions of PTCH1, PTCH2 and SUFU. LOH and immunohistochemical expression of these genes, as well as the downstream targets of hedgehog signaling, were examined using surgically-excised KCOT tissues. PTCH1 mutations, including four novel ones, were found in 9 hereditary KCOT patients, but not in sporadic KCOT patients. A pathogenic mutation of PTCH2 or SUFU was not found in any patients. LOH at PTCH1 and SUFU loci correlated with the presence of epithelial budding. KCOT harboring a germline mutation (Type 1 showed nuclear localization of GLI2 and frequent histological findings such as budding and epithelial islands, as well as the highest recurrence rate. KCOT with LOH but without a germline mutation (Type 2 less frequently showed these histological features, and the recurrence rate was lower. KCOT with neither germline mutation nor LOH (Type 3 consisted of two subgroups, Type 3A and 3B, which were characterized by nuclear and cytoplasmic GLI2 localization, respectively. Type 3B rarely exhibited budding and recurrence, behaving as the most amicable entity. The expression patterns of CCND1 and BCL2 tended to correlate with these subgroups. Our data indicates a significant role of PTCH1 and SUFU in the pathogenesis of KCOT, and the genotype-oriented subgroups constitute entities with different potential aggressiveness.

  16. Phylogenomic analysis of proteins that are distinctive of Archaea and its main subgroups and the origin of methanogenesis

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    Gupta Radhey S

    2007-03-01

    Full Text Available Abstract Background The Archaea are highly diverse in terms of their physiology, metabolism and ecology. Presently, very few molecular characteristics are known that are uniquely shared by either all archaea or the different main groups within archaea. The evolutionary relationships among different groups within the Euryarchaeota branch are also not clearly understood. Results We have carried out comprehensive analyses on each open reading frame (ORFs in the genomes of 11 archaea (3 Crenarchaeota – Aeropyrum pernix, Pyrobaculum aerophilum and Sulfolobus acidocaldarius; 8 Euryarchaeota – Pyrococcus abyssi, Methanococcus maripaludis, Methanopyrus kandleri, Methanococcoides burtonii, Halobacterium sp. NCR-1, Haloquadratum walsbyi, Thermoplasma acidophilum and Picrophilus torridus to search for proteins that are unique to either all Archaea or for its main subgroups. These studies have identified 1448 proteins or ORFs that are distinctive characteristics of Archaea and its various subgroups and whose homologues are not found in other organisms. Six of these proteins are unique to all Archaea, 10 others are only missing in Nanoarchaeum equitans and a large number of other proteins are specific for various main groups within the Archaea (e.g. Crenarchaeota, Euryarchaeota, Sulfolobales and Desulfurococcales, Halobacteriales, Thermococci, Thermoplasmata, all methanogenic archaea or particular groups of methanogens. Of particular importance is the observation that 31 proteins are uniquely present in virtually all methanogens (including M. kandleri and 10 additional proteins are only found in different methanogens as well as A. fulgidus. In contrast, no protein was exclusively shared by various methanogen and any of the Halobacteriales or Thermoplasmatales. These results strongly indicate that all methanogenic archaea form a monophyletic group exclusive of other archaea and that this lineage likely evolved from Archaeoglobus. In addition, 15 proteins

  17. Rivaroxaban versus warfarin in Japanese patients with nonvalvular atrial fibrillation for the secondary prevention of stroke: a subgroup analysis of J-ROCKET AF.

    Science.gov (United States)

    Tanahashi, Norio; Hori, Masatsugu; Matsumoto, Masayasu; Momomura, Shin-ichi; Uchiyama, Shinichiro; Goto, Shinya; Izumi, Tohru; Koretsune, Yukihiro; Kajikawa, Mariko; Kato, Masaharu; Ueda, Hitoshi; Iwamoto, Kazuya; Tajiri, Masahiro

    2013-11-01

    The overall analysis of the rivaroxaban versus warfarin in Japanese patients with atrial fibrillation (J-ROCKET AF) trial revealed that rivaroxaban was not inferior to warfarin with respect to the primary safety outcome. In addition, there was a strong trend for a reduction in the rate of stroke/systemic embolism with rivaroxaban compared with warfarin. In this subanalysis of the J-ROCKET AF trial, we investigated the consistency of safety and efficacy profile of rivaroxaban versus warfarin among the subgroups of patients with previous stroke, transient ischemic attack, or non-central nervous system systemic embolism (secondary prevention group) and those without (primary prevention group). Patients in the secondary prevention group were 63.6% of the overall population of J-ROCKET AF. In the secondary prevention group, the rate of the principal safety outcome (% per year) was 17.02 in rivaroxaban-treated patients and 18.26 in warfarin-treated patients (hazard ratio [HR] 0.95; 95% confidence interval [CI] 0.70-1.29), while the rate of the primary efficacy endpoint was 1.66 in rivaroxaban-treated patients and 3.25 in warfarin-treated patients (HR 0.51; 95% CI 0.23-1.14). There were no significant interactions in the principal safety and the primary efficacy endpoints of rivaroxaban compared to warfarin between the primary and secondary prevention groups (P=.090 and .776 for both interactions, respectively). The safety and efficacy profile of rivaroxaban compared with warfarin was consistent among patients in the primary prevention group and those in the secondary prevention group. Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  18. A post-hoc subgroup analysis of outcomes in the first phase III clinical study of edaravone (MCI-186) in amyotrophic lateral sclerosis.

    Science.gov (United States)

    2017-10-01

    Our first phase III study failed to demonstrate efficacy of edaravone for amyotrophic lateral sclerosis (ALS) compared to placebo. Here, we performed post-hoc subgroup analysis to identify a subgroup in which edaravone might be expected to show efficacy. We focussed on two newly defined subgroups, EESP and dpEESP2y. The EESP was defined as the efficacy-expected subpopulation with % forced vital capacity of ≥80%, and ≥2 points for all item scores in the revised ALS functional rating scale (ALSFRS-R) score before treatment. The dpEESP2y was defined as the greater-efficacy-expected subpopulation within EESP having a diagnosis of 'definite' or 'probable' ALS according to the El Escorial revised Airlie House diagnostic criteria and onset of disease within two years. The primary endpoint of the post-hoc analysis was the change in the ALSFRS-R score during the 24-week treatment period. The intergroup differences of the least-squares mean change in the ALSFRS-R score ± standard error during treatment were 0.65 ± 0.78 (p = 0.4108) in the full analysis set, 2.20 ± 1.03 (p = 0.0360) in the EESP, and 3.01 ± 1.33 (p = 0.0270) in the dpEESP2y. Edaravone exhibited efficacy in the dpEESP2y subgroup. A further clinical study in patients meeting dpEESP2y criteria is warranted.

  19. Subgrouping For Patients With Low Back Pain: A Multidimensional Approach Incorporating Cluster Analysis & The STarT Back Screening Tool

    Science.gov (United States)

    Beneciuk, Jason M.; Robinson, Michael E.; George, Steven Z.

    2014-01-01

    Early screening for psychological distress has been suggested to improve patient management for individuals experiencing low back pain. This study compared two approaches to psychological screening (i.e., multidimensional and unidimensional) so that preliminary recommendations on which approach may be appropriate for use in clinical settings other than primary care could be provided. Specifically, this study investigated STarT Back Screening Tool (SBT): 1) discriminant validity by evaluating its relationship with unidimensional psychological measures and 2) construct validity by evaluating how SBT risk categories compared to empirically derived subgroups using unidimensional psychological and disability measures. Patients (n = 146) receiving physical therapy for LBP were administered the SBT and a battery of unidimensional psychological measures at initial evaluation. Clinical measures consisted of pain intensity and self-reported disability. Several SBT risk dependent relationships (i.e., SBT low psychological measure scores with depressive symptom scores associated with the strongest influence on SBT risk categorization. Empirically derived subgroups indicated that there was no evidence of distinctive patterns amongst psychological or disability measures other than high or low profiles, therefore two groups may provide a more clear representation of the level of pain associated psychological distress, maladaptive coping and disability in this setting, as compared to three groups which have been suggested when using the SBT in primary care settings. PMID:25451622

  20. Breakthrough Pain Management with Sublingual Fentanyl Tablets in Patients with Cancer: Age Subgroup Analysis of a Multicenter Prospective Study.

    Science.gov (United States)

    Guitart, Jordi; Vargas, María Isabel; De Sanctis, Vicente; Folch, Jordi; Salazar, Rafael; Fuentes, José; Coma, Joan; Ferreras, Julia; Moya, Jordi; Tomás, Albert; Estivill, Pere; Rodelas, Francisco; Jiménez, Antonio Javier; Sanz, Almudena

    2017-09-01

    Breakthrough pain (BTP) management in patients with cancer is challenging, especially in the elderly. However, no studies examining the influence of age on BTP medication have been conducted. The aim of this work was to investigate the effect of sublingual fentanyl tablets (SFTs) in terms of efficacy, safety, and quality of life in two age categories. We performed age subgroup analyses (Pain intensity (PI), onset of pain relief, frequency and duration of BTP episodes, and adverse events (AEs) were assessed at 3, 7, 15, and 30 days. Health-status instruments used were the Short Form 12, version 2 (SF-12v2) questionnaire, and the Hospital Anxiety and Depression Scale (HADS-A and HADS-D). Twenty-six patients were aged 65 years. Most patients experienced one to five daily episodes after 30 days, and <5% needed a treatment change. AEs were less frequently reported in older individuals (20.5 vs. 36.4%). Age subgroup analyses suggest that SFTs are an effective and safe treatment for the management of BTP in cancer patients of all ages. SFTs may offer a well-tolerated and efficient option to control cancer BTP in the elderly.

  1. Genomic analysis of diffuse intrinsic pontine gliomas identifies three molecular subgroups and recurrent activating ACVR1 mutations.

    Science.gov (United States)

    Buczkowicz, Pawel; Hoeman, Christine; Rakopoulos, Patricia; Pajovic, Sanja; Letourneau, Louis; Dzamba, Misko; Morrison, Andrew; Lewis, Peter; Bouffet, Eric; Bartels, Ute; Zuccaro, Jennifer; Agnihotri, Sameer; Ryall, Scott; Barszczyk, Mark; Chornenkyy, Yevgen; Bourgey, Mathieu; Bourque, Guillaume; Montpetit, Alexandre; Cordero, Francisco; Castelo-Branco, Pedro; Mangerel, Joshua; Tabori, Uri; Ho, King Ching; Huang, Annie; Taylor, Kathryn R; Mackay, Alan; Bendel, Anne E; Nazarian, Javad; Fangusaro, Jason R; Karajannis, Matthias A; Zagzag, David; Foreman, Nicholas K; Donson, Andrew; Hegert, Julia V; Smith, Amy; Chan, Jennifer; Lafay-Cousin, Lucy; Dunn, Sandra; Hukin, Juliette; Dunham, Chris; Scheinemann, Katrin; Michaud, Jean; Zelcer, Shayna; Ramsay, David; Cain, Jason; Brennan, Cameron; Souweidane, Mark M; Jones, Chris; Allis, C David; Brudno, Michael; Becher, Oren; Hawkins, Cynthia

    2014-05-01

    Diffuse intrinsic pontine glioma (DIPG) is a fatal brain cancer that arises in the brainstem of children, with no effective treatment and near 100% fatality. The failure of most therapies can be attributed to the delicate location of these tumors and to the selection of therapies on the basis of assumptions that DIPGs are molecularly similar to adult disease. Recent studies have unraveled the unique genetic makeup of this brain cancer, with nearly 80% found to harbor a p.Lys27Met histone H3.3 or p.Lys27Met histone H3.1 alteration. However, DIPGs are still thought of as one disease, with limited understanding of the genetic drivers of these tumors. To understand what drives DIPGs, we integrated whole-genome sequencing with methylation, expression and copy number profiling, discovering that DIPGs comprise three molecularly distinct subgroups (H3-K27M, silent and MYCN) and uncovering a new recurrent activating mutation affecting the activin receptor gene ACVR1 in 20% of DIPGs. Mutations in ACVR1 were constitutively activating, leading to SMAD phosphorylation and increased expression of the downstream activin signaling targets ID1 and ID2. Our results highlight distinct molecular subgroups and novel therapeutic targets for this incurable pediatric cancer.

  2. [Subgroup analysis results of platelet inhibition trial in acute coronary syndrome patients (PLATO) who underwent intervention or medical treatment].

    Science.gov (United States)

    Aksakal, Enbiya

    2013-04-01

    Antiplatelet agents are among the most important drug classes in reducing mortality in patients with acute coronary syndromes (ACS). Ticagrelor is the first reversible and direct acting P2Y(12) receptor inhibitor with an earlier onset of action compared to clopidogrel. The PLATO study (Platelet Inhibition and Patient Outcomes) with ticagrelor was conducted with a design providing consistency with the current clinical practice, including all forms of ACS and a wide spectrum of treatment options in 18624 patients from 862 centers in 43 countries. Of these patients, 13408 underwent interventional procedures (ticagrelor/clopidogrel; 6732/6676) (PLATO-INVASIVE). As reported by the investigator, non-invasive treatment strategy was planned for 5216 patients (ticagrelor/clopidogrel; 2601/2615). However, 2040 patients in this group received interventional treatment during the follow-up (PLATO-NON-INVASIVE/MEDICAL TREATMENT). 1261 patients requiring surgical treatment underwent coronary artery bypass grafting (CABG) within 7 days after the discontinuation of study treatment (ticagrelor/clopidogrel; 632/629) (PLATO-CABG). The results of these three subgroups were consistent with the main PLATO study results, demonstrating that ticagrelor reduced the primary (cardiovascular death, myocardial Infarction and stroke) and secondary composite endpoints without increasing bleeding compared with clopidogrel. Ticagrelor fulfills an important unmet need regarding antiplatelet effectiveness in patients with ACS. This review evaluates the INVASIVE and MEDICAL subgroup studies of the PLATO study.

  3. Therapy-Emergent Drug Resistance to Integrase Strand Transfer Inhibitors in HIV-1 Patients: A Subgroup Meta-Analysis of Clinical Trials.

    Directory of Open Access Journals (Sweden)

    Jiangzhou You

    Full Text Available Integrase strand transfer inhibitors (INSTIs are a novel class of anti-HIV agents that show high activity in inhibiting HIV-1 replication. Currently, licensed INSTIs include raltegravir (RAL, elvitegravir (EVG and dolutegravir (DTG; these drugs have played a critical role in AIDS therapy, serving as additional weapons in the arsenal for treating patients infected with HIV-1. To date, long-term data regarding clinical experience with INSTI use and the emergence of resistance remain scarce. However, the literature is likely now sufficiently comprehensive to warrant a meta-analysis of resistance to INSTIs.Our team implemented a manuscript retrieval protocol using Medical Subject Headings (MeSH via the Web of Science, MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases. We screened the literature based on inclusion and exclusion criteria and then performed a quality analysis and evaluation using RevMan software, Stata software, and the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE. We also performed a subgroup analysis. Finally, we calculated resistance rates and risk ratios (RRs for the three types of drugs.We identified 26 references via the database search. A meta-analysis of the RAL data revealed that the resistance rate was 3.9% (95% CI = 2.9%-4.9% for the selected randomized controlled trials (RCTs. However, the RAL resistance rate reached 40.9% (95% CI = 8.8%-72.9% for the selected observational studies (OBSs. The rates of resistance to RAL that were associated with HIV subtypes A, B, and C as well as with more complex subtypes were 0.1% (95% CI = -0.7%-0.9%, 2.5% (95% CI = 0.5%-4.5%, 4.6% (95% CI = 2.7%-6.6% and 2.2% (95% CI = 0.7%-3.7%, respectively. The rates of resistance to EVG and DTG were 1.2% (95% CI = 0.2%-2.2% and 0.1% (95% CI = -0.2%-0.5%, respectively. Furthermore, we found that the RRs for antiviral resistance were 0.414 (95% CI = 0.210-0.816 between DTG and RAL and 0

  4. A randomized clinical trial of manual therapy and physiotherapy for persistent back and neck complaints: subgroup analysis and relationship between outcome measures.

    Science.gov (United States)

    Koes, B W; Bouter, L M; van Mameren, H; Essers, A H; Verstegen, G J; Hofhuizen, D M; Houben, J P; Knipschild, P G

    1993-05-01

    To study the efficacy of manual therapy and physiotherapy in subgroups of patients with persistent back and neck complaints. The second objective was to determine the correlation between three important outcome measures used in this trial. Randomized clinical trial (subgroup analysis). Primary health care in the Netherlands. Two hundred fifty-six patients with nonspecific back and neck complaints of at least 6 wk duration who had not received physiotherapy or manual therapy in the past 2 yr. At the discretion of the manual therapists, physiotherapists and general practitioners. Physiotherapy consisted of exercises, massage and physical therapy (heat, electrotherapy, ultrasound, shortwave diathermy). Manual therapy consisted of manipulation and mobilization of the spine. Treatment by the general practitioner consisted of drugs (e.g., analgesics), advice about posture, home exercises and (bed)rest. Placebo treatment consisted of detuned shortwave diathermy (10 min) and detuned ultrasound (10 min). Changes in severity of the main complaint and limitation of physical functioning measured on 10-point scales by a blinded research assistant and global perceived effect measured on a 6-point scale by the patients. Improvement in the main complaint was larger with manual therapy (4.3) than with physiotherapy (2.5) for patients with chronic conditions (duration complaint of 1 yr or longer). Also, improvement in the main complaint was larger with manual therapy (5.5) than with physiotherapy (4.0) for patients younger than 40 yr (both were measured after 12-mo follow-up). Labeling of patients by the treating manual therapists as "suitable" or "not suitable" for treatment with manual therapy did not predict differences in outcomes. Generally, there was a moderate to strong correlation between the three outcome measures, although a considerable number of patients gave a relatively low score for perceived benefit, while the research assistant gave a high improvement score for the

  5. Molecular subgroups of medulloblastoma

    Science.gov (United States)

    Northcott, Paul A; Dubuc, Adrian M; Pfister, Stefan; Taylor, Michael D

    2014-01-01

    Recent efforts at stratifying medulloblastomas based on their molecular features have revolutionized our understanding of this morbidity. Collective efforts by multiple independent groups have subdivided medulloblastoma from a single disease into four distinct molecular subgroups characterized by disparate transcriptional signatures, mutational spectra, copy number profiles and, most importantly, clinical features. We present a summary of recent studies that have contributed to our understanding of the core medulloblastoma subgroups, focusing largely on clinically relevant discoveries that have already, and will continue to, shape research. PMID:22853794

  6. Does Kinesiophobia Modify the Effects of Physical Therapy on Outcomes in Patients With Sciatica in Primary Care? Subgroup Analysis From a Randomized Controlled Trial.

    Science.gov (United States)

    Verwoerd, Annemieke J H; Luijsterburg, Pim A J; Koes, Bart W; el Barzouhi, Abdelilah; Verhagen, Arianne P

    2015-09-01

    A higher level of kinesiophobia appears to be associated with poor recovery in patients with sciatica. The aim of this study was to investigate whether kinesiophobia modifies the effect of physical therapy on outcomes in patients with sciatica. This was a subgroup analysis from a randomized controlled trial. The study was conducted in a primary care setting. A total of 135 patients with acute sciatica participated. Patients were randomly assigned to groups that received (1) physical therapy plus general practitioners' care (intervention group) or (2) general practitioners' care alone (control group). Kinesiophobia at baseline was measured with the Tampa Scale for Kinesiophobia (TSK) and a single substitute question for kinesiophobia (SQK). Pain and recovery were assessed at 3- and 12-month follow-ups. Regression analysis was used to test for interaction between the level of kinesiophobia at baseline and treatment allocation. Subgroup results were calculated for patients classified with high fear of movement and for those classified with low fear of movement. Kinesiophobia at baseline interacted with physical therapy in the analysis with leg pain intensity at 12-month follow-up. Kinesiophobia at baseline did not interact with physical therapy regarding any outcome at 3-month follow-up or recovery at 12-month follow-up. When comparing both treatment groups in the subgroup of patients with high fear of movement (n=73), the only significant result was found for leg pain intensity difference from baseline at 12-month follow-up (intervention group: X̅=-5.0, SD=2.6; control group: X̅=-3.6, SD=2.7). The post hoc study design and relatively small sample size were limitations of the study. In 135 patients with sciatica, evidence shows that patients with a higher level of kinesiophobia at baseline may particularly benefit from physical therapy with regard to decreasing leg pain intensity at 12-month follow-up. © 2015 American Physical Therapy Association.

  7. The Franco-Canadian multicolumn spinal cord stimulation prospective study: a subgroup analysis focusing on the decisive role of lead positioning.

    Science.gov (United States)

    Delmotte, A; Jacques, L; Kumar, K; Poon, K; Monlezun, O; Roulaud, M; Prevost, A; Munson, R; Guetarni, F; Bataille, B; Rigoard, P

    2015-03-01

    Multicolumn spinal cord stimulation (SCS) is now considered to be effective for the treatment of the radicular and back component in refractory Failed Back Surgery Syndrome (FBSS) patients. The relationship between the paresthesia coverage of the back and clinical outcomes has recently been confirmed by an international prospective study. However, significant disparities in outcomes were identified and could result from the heterogeneity of lead implantation parameters which are dependant on local practices and experience. We therefore sought to analyse the impact of lead implantation level and its lateralization on the ability to address back pain with multicolumn SCS leads. The present study was a retrospective subgroup analysis from an observational, prospective non-randomized trial that included 76 patients with refractory FBSS, implanted with multicolumn SCS between 2008 to 2011 in three neurosurgical pain centres (Poitiers, France, Montreal, Canada and Regina, Canada). A subgroup of 21 patients with "optimized lead positioning" (OLP) was identified, distinguished from the rest of the main study population (NON OLP subgroup; n=51) and submitted to specific data analysis. Baseline characteristics of both groups were strictly comparable. Our primary objective was to analyse the impact of lead positioning (vertebral level and lateralization) on the back paresthesia coverage. The secondary objectives were to compare the analgesic and functional efficacy of multicolumn stimulation in these OLP and NON OLP subgroups and to determine if a paresthesia coverage improvement leads to better clinical outcomes in these difficult-to-treat patients. In this subgroup analysis, unilateral coverage of the low back area was achieved in 85.0% of OLP patients vs. 76.5% in the NON OLP group. Bilateral and complete coverage of the low back area was achieved in 60% of OLP patients vs. 51% in the NON OLP group but these differences were not statistically significant. At 6months, 81

  8. Spatial analysis of air pollution and childhood asthma in Hamilton, Canada: comparing exposure methods in sensitive subgroups

    Directory of Open Access Journals (Sweden)

    Arain Altaf

    2009-04-01

    Full Text Available Abstract Background Variations in air pollution exposure within a community may be associated with asthma prevalence. However, studies conducted to date have produced inconsistent results, possibly due to errors in measurement of the exposures. Methods A standardized asthma survey was administered to children in grades one and eight in Hamilton, Canada, in 1994–95 (N ~1467. Exposure to air pollution was estimated in four ways: (1 distance from roadways; (2 interpolated surfaces for ozone, sulfur dioxide, particulate matter and nitrous oxides from seven to nine governmental monitoring stations; (3 a kriged nitrogen dioxide (NO2 surface based on a network of 100 passive NO2 monitors; and (4 a land use regression (LUR model derived from the same monitoring network. Logistic regressions were used to test associations between asthma and air pollution, controlling for variables including neighbourhood income, dwelling value, state of housing, a deprivation index and smoking. Results There were no significant associations between any of the exposure estimates and asthma in the whole population, but large effects were detected the subgroup of children without hayfever (predominately in girls. The most robust effects were observed for the association of asthma without hayfever and NO2LUR OR = 1.86 (95%CI, 1.59–2.16 in all girls and OR = 2.98 (95%CI, 0.98–9.06 for older girls, over an interquartile range increase and controlling for confounders. Conclusion Our findings indicate that traffic-related pollutants, such as NO2, are associated with asthma without overt evidence of other atopic disorders among female children living in a medium-sized Canadian city. The effects were sensitive to the method of exposure estimation. More refined exposure models produced the most robust associations.

  9. The congruence subgroup problem

    Indian Academy of Sciences (India)

    Home; Journals; Proceedings – Mathematical Sciences; Volume 114; Issue 4. The Congruence Subgroup Problem. M S Raghunathan. Invited Articles Volume 114 ... Author Affiliations. M S Raghunathan1. School of Mathematics, Tata Institute of Fundamental Research, Homi Bhabha Road, Colaba, Mumbai 400 005, India ...

  10. Subgroups Among Opiate Addicts

    Science.gov (United States)

    Berzins, Juris I.; And Others

    1974-01-01

    The principal objective of the present investigation was to delineate homogeneous MMPI profile subgroups (types) through multivariate clustering procedures and to compare the derived (replicable) types on measures of the components of "sociopathy" as well as on other psychometric devices. (Author)

  11. Tissue-specific transcriptomics, chromosomal localization, and phylogeny of chemosensory and odorant binding proteins from the red flour beetle Tribolium castaneum reveal subgroup specificities for olfaction or more general functions.

    Science.gov (United States)

    Dippel, Stefan; Oberhofer, Georg; Kahnt, Jörg; Gerischer, Lizzy; Opitz, Lennart; Schachtner, Joachim; Stanke, Mario; Schütz, Stefan; Wimmer, Ernst A; Angeli, Sergio

    2014-12-18

    Chemoreception is based on the senses of smell and taste that are crucial for animals to find new food sources, shelter, and mates. The initial step in olfaction involves the translocation of odorants from the periphery through the aqueous lymph of the olfactory sensilla to the odorant receptors most likely by chemosensory proteins (CSPs) or odorant binding proteins (OBPs). To better understand the roles of CSPs and OBPs in a coleopteran pest species, the red flour beetle Tribolium castaneum (Coleoptera, Tenebrionidae), we performed transcriptome analyses of male and female antennae, heads, mouthparts, legs, and bodies, which revealed that all 20 CSPs and 49 of the 50 previously annotated OBPs are transcribed. Only six of the 20 CSP are significantly transcriptionally enriched in the main chemosensory tissues (antenna and/or mouthparts), whereas of the OBPs all eight members of the antenna binding proteins II (ABPII) subgroup, 18 of the 20 classic OBP subgroup, the C + OBP, and only five of the 21 C-OBPs show increased chemosensory tissue expression. By MALDI-TOF-TOF MS protein fingerprinting, we confirmed three CSPs, four ABPIIs, three classic OBPs, and four C-OBPs in the antennae. Most of the classic OBPs and all ABPIIs are likely involved in chemoreception. A few are also present in other tissues such as odoriferous glands and testes and may be involved in release or transfer of chemical signals. The majority of the CSPs as well as the C-OBPs are not enriched in antennae or mouthparts, suggesting a more general role in the transport of hydrophobic molecules.

  12. Revealed preference analysis of noncooperative household consumption

    NARCIS (Netherlands)

    Cherchye, L.J.H.; Demuynck, T.; de Rock, B.

    2011-01-01

    We develop a revealed preference approach to analyse non-unitary household consumption behaviour that is not cooperative (or Pareto efficient). We derive global necessary and sufficient conditions for data consistency with the model. We show that the conditions can be verified by means of relatively

  13. Identification of subgroups of inflammatory and degenerative MRI findings in the spine and sacroiliac joints: a latent class analysis of 1037 patients with persistent low back pain

    DEFF Research Database (Denmark)

    Arnbak, Bodil; Jensen, Rikke Krüger; Manniche, Claus

    2016-01-01

    findings' (n = 84). The two SIJ subgroups (Subgroups 4 and 5) had a higher median activity limitation score (Roland Morris Disability Questionnaire calculated as a proportional score: 65 (IQR 48-78)/65 (48-78)) compared with Subgroups 1-3 (48 (35-74)/57 (39-74)/57 (39-74)), a higher prevalence of women (68...

  14. Perioperative outcomes of revisional laparoscopic gastric bypass after failed adjustable gastric banding and after vertical banded gastroplasty: experience with 107 cases and subgroup analysis.

    Science.gov (United States)

    Apers, J A; Wens, C; van Vlodrop, V; Michiels, M; Ceulemans, R; van Daele, G; Jacobs, I

    2013-02-01

    A growing number of revision procedures are to be expected in bariatric surgery after failed restrictive procedures such as failed adjustable gastric banding (AGB) or vertical banded gastroplasty (VBG). Conversion to revisional laparoscopic Roux-en-Y gastric bypass (ReLRYGBP) has been advocated as the procedure of choice. The results of ReLRYGBP were reviewed in a retrospective chart review. A subgroup analysis compared perioperative results after VBG and after AGB. A second subgroup analysis compared perioperative results of ReLRYGBP immediately after AGB removal and after a delay as a two-step procedure. Between 2003 and 2009, ReLRYGBP was performed for 107 patients. Of these 107 operations, 21 were performed after failed VBG and 86 after failed AGB. The mean body mass index (BMI) was 42 kg/m(2). The causes of failure were mainly insufficient weight loss or reflux disease-related symptoms. During a median follow-up period of 44 months, there was no mortality, and morbidity was 34 %, including late complications. Major early complications occurred in 11 % of the cases (n = 12). Conversions and major early complications occurred significantly more frequently after VBG than after AGB (p 0.5). The perioperative outcomes of ReLRYGBP are worse after VBG than after AGB. The ReLRYGBP operation can be performed safely as a one-step procedure after AGB removal.

  15. Intertumoral Heterogeneity within Medulloblastoma Subgroups.

    Science.gov (United States)

    Cavalli, Florence M G; Remke, Marc; Rampasek, Ladislav; Peacock, John; Shih, David J H; Luu, Betty; Garzia, Livia; Torchia, Jonathon; Nor, Carolina; Morrissy, A Sorana; Agnihotri, Sameer; Thompson, Yuan Yao; Kuzan-Fischer, Claudia M; Farooq, Hamza; Isaev, Keren; Daniels, Craig; Cho, Byung-Kyu; Kim, Seung-Ki; Wang, Kyu-Chang; Lee, Ji Yeoun; Grajkowska, Wieslawa A; Perek-Polnik, Marta; Vasiljevic, Alexandre; Faure-Conter, Cecile; Jouvet, Anne; Giannini, Caterina; Nageswara Rao, Amulya A; Li, Kay Ka Wai; Ng, Ho-Keung; Eberhart, Charles G; Pollack, Ian F; Hamilton, Ronald L; Gillespie, G Yancey; Olson, James M; Leary, Sarah; Weiss, William A; Lach, Boleslaw; Chambless, Lola B; Thompson, Reid C; Cooper, Michael K; Vibhakar, Rajeev; Hauser, Peter; van Veelen, Marie-Lise C; Kros, Johan M; French, Pim J; Ra, Young Shin; Kumabe, Toshihiro; López-Aguilar, Enrique; Zitterbart, Karel; Sterba, Jaroslav; Finocchiaro, Gaetano; Massimino, Maura; Van Meir, Erwin G; Osuka, Satoru; Shofuda, Tomoko; Klekner, Almos; Zollo, Massimo; Leonard, Jeffrey R; Rubin, Joshua B; Jabado, Nada; Albrecht, Steffen; Mora, Jaume; Van Meter, Timothy E; Jung, Shin; Moore, Andrew S; Hallahan, Andrew R; Chan, Jennifer A; Tirapelli, Daniela P C; Carlotti, Carlos G; Fouladi, Maryam; Pimentel, José; Faria, Claudia C; Saad, Ali G; Massimi, Luca; Liau, Linda M; Wheeler, Helen; Nakamura, Hideo; Elbabaa, Samer K; Perezpeña-Diazconti, Mario; Chico Ponce de León, Fernando; Robinson, Shenandoah; Zapotocky, Michal; Lassaletta, Alvaro; Huang, Annie; Hawkins, Cynthia E; Tabori, Uri; Bouffet, Eric; Bartels, Ute; Dirks, Peter B; Rutka, James T; Bader, Gary D; Reimand, Jüri; Goldenberg, Anna; Ramaswamy, Vijay; Taylor, Michael D

    2017-06-12

    While molecular subgrouping has revolutionized medulloblastoma classification, the extent of heterogeneity within subgroups is unknown. Similarity network fusion (SNF) applied to genome-wide DNA methylation and gene expression data across 763 primary samples identifies very homogeneous clusters of patients, supporting the presence of medulloblastoma subtypes. After integration of somatic copy-number alterations, and clinical features specific to each cluster, we identify 12 different subtypes of medulloblastoma. Integrative analysis using SNF further delineates group 3 from group 4 medulloblastoma, which is not as readily apparent through analyses of individual data types. Two clear subtypes of infants with Sonic Hedgehog medulloblastoma with disparate outcomes and biology are identified. Medulloblastoma subtypes identified through integrative clustering have important implications for stratification of future clinical trials. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. TruSeq-Based Gene Expression Analysis of Formalin-Fixed Paraffin-Embedded (FFPE Cutaneous T-Cell Lymphoma Samples: Subgroup Analysis Results and Elucidation of Biases from FFPE Sample Processing on the TruSeq Platform

    Directory of Open Access Journals (Sweden)

    Philippe Lefrançois

    2017-09-01

    Full Text Available Cutaneous T-cell lymphomas (CTCLs are a heterogeneous group of malignancies with courses ranging from indolent to potentially lethal. We recently studied in a 157 patient cohort gene expression profiles generated by the TruSeq targeted RNA gene expression sequencing. We observed that the sequencing library quality and depth from formalin-fixed paraffin-embedded (FFPE skin samples were significantly lower when biopsies were obtained prior to 2009. We also observed that the fresh CTCL samples clustered together, even though they included stage I–IV disease. In this study, we compared TruSeq gene expression patterns in older (≤2008 vs. more recent (≥2009 FFPE samples to determine whether these clustering analyses and earlier described differentially expressed gene findings are robust when analyzed based on the year of biopsy. We also explored biases found in FFPE samples when subjected to the TruSeq analysis of gene expression. Our results showed that ≤2008 and ≥2009 samples clustered equally well to the full data set and, importantly, both analyses produced nearly identical trends and findings. Specifically, both analyses enriched nearly identical DEGs when comparing benign vs. (1 stage I–IV and (2 stage IV (alone CTCL samples. Results obtained using either ≤2008 or ≥2009 samples were strongly correlated. Furthermore, by using subgroup analyses, we were able to identify additional novel differentially expressed genes (DEGs, which did not reach statistical significance in the prior full data set analysis. Those included CTCL-upregulated BCL11A, SELL, IRF1, SMAD1, CASP1, BIRC5, and MAX and CTCL-downregulated MDM4, SERPINB3, and THBS4 genes. With respect to sample biases, no matter if we performed subgroup analyses or full data set analysis, fresh samples tightly clustered together. While principal component analysis revealed that fresh samples were spatially closer together, indicating some preprocessing batch effect, they remained

  17. Principal component analysis of ensemble recordings reveals cell assemblies at high temporal resolution

    NARCIS (Netherlands)

    Peyrache, A.; Benchenane, K.; Khamassi, M.; Wiener, S.I.; Battaglia, F.P.

    2010-01-01

    Simultaneous recordings of many single neurons reveals unique insights into network processing spanning the timescale from single spikes to global oscillations. Neurons dynamically self-organize in subgroups of coactivated elements referred to as cell assemblies. Furthermore, these cell assemblies

  18. Monosomic analysis reveals duplicated chromosomal segments in ...

    Indian Academy of Sciences (India)

    Monosomics for chromosome 2 expressed liguleless leaf phenotype due to hemizygous condition of recessive gene lg. Two monosomic-4 plants were identified after test crossing with monosomic tester (see table 2 in electronic supplemen- tary material). Monosomic-6 plants were identified by the cytological analysis (figure ...

  19. Quantitative interactome analysis reveals a chemoresistant edgotype.

    Science.gov (United States)

    Chavez, Juan D; Schweppe, Devin K; Eng, Jimmy K; Zheng, Chunxiang; Taipale, Alex; Zhang, Yiyi; Takara, Kohji; Bruce, James E

    2015-08-03

    Chemoresistance is a common mode of therapy failure for many cancers. Tumours develop resistance to chemotherapeutics through a variety of mechanisms, with proteins serving pivotal roles. Changes in protein conformations and interactions affect the cellular response to environmental conditions contributing to the development of new phenotypes. The ability to understand how protein interaction networks adapt to yield new function or alter phenotype is limited by the inability to determine structural and protein interaction changes on a proteomic scale. Here, chemical crosslinking and mass spectrometry were employed to quantify changes in protein structures and interactions in multidrug-resistant human carcinoma cells. Quantitative analysis of the largest crosslinking-derived, protein interaction network comprising 1,391 crosslinked peptides allows for 'edgotype' analysis in a cell model of chemoresistance. We detect consistent changes to protein interactions and structures, including those involving cytokeratins, topoisomerase-2-alpha, and post-translationally modified histones, which correlate with a chemoresistant phenotype.

  20. Whether the Autism Spectrum Quotient Consists of Two Different Subgroups? Cluster Analysis of the Autism Spectrum Quotient in General Population

    Science.gov (United States)

    Kitazoe, Noriko; Fujita, Naofumi; Izumoto, Yuji; Terada, Shin-ichi; Hatakenaka, Yuhei

    2017-01-01

    The purpose of this study was to investigate whether the individuals in the general population with high scores on the Autism Spectrum Quotient constituted a single homogeneous group or not. A cohort of university students (n = 4901) was investigated by cluster analysis based on the original five subscales of the Autism Spectrum Quotient. Based on…

  1. Cluster Analysis of an International Pressure Pain Threshold Database Identifies 4 Meaningful Subgroups of Adults With Mechanical Neck Pain

    DEFF Research Database (Denmark)

    Walton, David M; Kwok, Timothy S H; Mehta, Swati

    2017-01-01

    OBJECTIVE: To determine pressure pain detection threshold (PPDT) related phenotypes of individuals with mechanical neck pain that may be identifiable in clinical practice. METHODS: This report describes a secondary analysis of 5 independent, international mechanical neck pain databases of PPDT...... below the mean. DISCUSSION: The results suggest that there are a large proportion of people with neck pain that present with signs indicating dysfunction beyond the local tissues. Ongoing exploration of these presentations may lead to more informed management and improved outcomes....

  2. Predictive and prognostic factors associated with soft tissue sarcoma response to chemotherapy: a subgroup analysis of the European Organisation for Research and Treatment of Cancer 62012 study.

    Science.gov (United States)

    Young, Robin J; Litière, Saskia; Lia, Michela; Hogendoorn, Pancras C W; Fisher, Cyril; Mechtersheimer, Gunhild; Daugaard, Søren; Sciot, Raf; Collin, Françoise; Messiou, Christina; Grünwald, Viktor; Gronchi, Alessandro; van der Graaf, Winette; Wardelmann, Eva; Judson, Ian

    2017-07-01

    The European Organization for Research and Treatment of Cancer (EORTC) 62012 study was a Phase III trial of doxorubicin versus doxorubicin-ifosfamide chemotherapy in 455 patients with advanced soft tissue sarcoma (STS). Analysis of the main study showed that combination chemotherapy improved tumor response and progression-free survival, but differences in overall survival (OS) were not statistically significant. We analyzed factors prognostic for tumor response and OS, and assessed histological subgroup and tumor grade as predictive factors to identify patients more likely to benefit from combination chemotherapy. Central pathology review was performed by six reference pathologists. Gender, age, performance status, time from first presentation with sarcoma to starting palliative chemotherapy, tumor grade, histological subgroup, primary tumor site involvement, and sites of metastases were assessed as prognostic factors. Three hundred and ten patients were included in this study. Discordance between local and central pathology opinion of tumor histology and tumor grade was observed in 98 (32%) and 122 (39%) cases, respectively. In multivariate analysis, liposarcoma patients had improved tumor response compared to other histological subgroups, whilst patients with metastases other than lung, liver or bone had a poorer response [odds ratio (OR) 0.42, 95% confidence interval (CI) 0.23-0.78; p = 0.006]. Patients with bone metastases had reduced OS [hazard ratio (HR) 1.56, 95% CI 1.16-2.09; p = 0.003]. By central pathology review, patients with undifferentiated pleomorphic sarcoma (UPS) had improved tumor response and OS with doxorubicin-ifosfamide compared to single-agent doxorubicin (OR 9.90, 95% CI 1.93-50.7 and HR 0.44, 95% CI 0.26-0.79, respectively). Grade III tumors had improved response with combination chemotherapy but there was no interaction between chemotherapy and grade on OS. Prospective central pathology review of tumor histology should be

  3. Karyotype analysis of the acute fibrosarcoma from chickens infected with subgroup J avian leukosis virus associated with v-src oncogene.

    Science.gov (United States)

    Dong, Xuan; Ju, Sidi; Chen, Junxia; Meng, Fanfeng; Sun, Peng; Li, Yang; Wang, Xin; Wang, Yixin; Liu, Juan; Chang, Shuang; Zhao, Peng; Cui, Zhizhong

    2016-01-01

    To understand the cytogenetic characteristics of acute fibrosarcoma in chickens infected with the subgroup J avian leukosis virus associated with the v-src oncogene, we performed a karyotype analysis of fibrosarcoma cell cultures. Twenty-nine of 50 qualified cell culture spreads demonstrated polyploidy of some macrochromosomes, 21 of which were trisomic for chromosome 7, and others were trisomic for chromosomes 3, 4, 5 (sex chromosome w), and 10. In addition, one of them was trisomic for both chromosome 7 and the sex chromosome 5 (w). In contrast, no aneuploidy was found for 10 macrochromosomes of 12 spreads of normal chicken embryo fibroblast cells, although aneuploidy for some microchromosomes was demonstrated in five of the 12 spreads. The cytogenetic mosaicism or polymorphism of the aneuploidy in the acute fibrosarcoma described in this study suggests that the analysed cells are polyclonal.

  4. Efficacy and tolerability of triple-combination therapy with olmesartan, amlodipine, and hydrochlorothiazide: a subgroup analysis of patients stratified by hypertension severity, age, sex, and obesity.

    Science.gov (United States)

    Kreutz, Reinhold; Ammentorp, Bettina; Laeis, Petra; de la Sierra, Alejandro

    2014-10-01

    This prespecified subgroup analysis of a phase III study examined the effect of adding hydrochlorothiazide (HCTZ) to olmesartan (OLM)/amlodipine (AML) in patients with moderate to severe hypertension stratified by age, sex, body mass index, and hypertension severity. A total of 2690 patients, aged 18 years and older, with seated blood pressure (SeBP) ≥160/100 mm Hg received placebo or OLM/AML 20/5 mg, 40/5 mg, or 40/10 mg during a 2-week, double-blind, run-in period, after which they were allocated to one of eight treatment groups with the same OLM/AML dose or with HCTZ 12.5 mg or 25 mg added for 8 weeks. By week 10, greater reductions in SeBP were observed in each OLM/AML/HCTZ group (Page, sex, and obesity. ©2014 Wiley Periodicals, Inc.

  5. Analysis of recombinant Plum pox virus (PPV) isolates from Serbia confirms genetic homogeneity and supports a regional origin for the PPV-Rec subgroup.

    Science.gov (United States)

    Glasa, M; Paunovic, S; Jevremovic, D; Myrta, A; Pittnerová, S; Candresse, T

    2005-10-01

    The recent observation of the frequent occurrence of natural recombinant Plum pox virus (PPV) isolates has led to the identification of a distinct PPV subgroup, named PPV-Rec. The diversity, origin and geographical spread of the recombinant PPV isolates belonging to this subgroup remain, however, relatively poorly known. In an effort to further our understanding of these isolates, eight PPV isolates from Serbia, the country from which the first such recombinant (PPV-o6) originated, were characterized. Depending on the genomic region targeted by different typing assays, seven of the eight isolates tested presented discrepancies in their typing behavior. Sequence analysis of the (Cter)NIb-(Nter)CP region confirmed the recombinant nature of these seven isolates which all presented an identical recombination breakpoint identical to previously characterized PPV-Rec isolates. Biological indexing and immunoblot analysis provided indications that asymptomatic infection of the GF305 peach indicator and migration of the coat protein as a double-band in immunoblots may represent conserved and discriminating properties of PPV-Rec isolates. The genetic diversity of PPV-Rec isolates from former Yugoslavia (Serbia, Bosnia and Herzegovina) was estimated to be twice as large as that of the PPV-Rec isolates obtained from all other countries to date (Albania, Bulgaria, Czech republic, Germany, Hungary and Slovakia). These last results are consistent with the hypothesis that former Yugoslavia is the center of dispersion of PPV-Rec. Taken together, the results presented here provide further evidence for the wide distribution and temporal genetic stability of these natural PPV recombinant isolates and provide for the first time a possible scenario for their dispersion throughout central and eastern Europe.

  6. Escitalopram in the treatment of social anxiety disorder: analysis of efficacy for different clinical subgroups and symptom dimensions

    DEFF Research Database (Denmark)

    Stein, Dan J; Kasper, Siegfried; Andersen, Elisabeth Anne Wreford

    2004-01-01

    Escitalopram has demonstrated efficacy for the acute treatment of social anxiety disorder (SAD) in two placebo-controlled trials and for long-term treatment in a relapse-prevention study. Social anxiety disorder is a heterogeneous disorder. This study questions whether this new selective serotonin...... of the primary efficacy scale, the Liebowitz Social Anxiety Scale (LSAS), was undertaken, and a determination made of whether treatment effects were similar for the different symptom dimensions. Escitalopram was effective in both younger and older patients, in male and female patients, and in patients with more...... and less severe social anxiety symptoms. The LSAS factor analysis showed six factors, which were differentially associated with different areas of disability. Escitalopram was significantly superior to placebo for all six symptom dimensions. The treatment effects of escitalopram were independent of gender...

  7. Mitochondrial DNA analysis reveals a low nucleotide diversity of ...

    African Journals Online (AJOL)

    Mitochondrial DNA analysis reveals a low nucleotide diversity of Caligula japonica in China. ... Mitochondrial DNA analysis reveals a low nucleotide diversity of Caligula japonica in China. Y Li, B Yang, H Wang, R Xia, L Wang, Z Zhang, L Qin, Y Liu ...

  8. Gene-expression Analysis Identifies Specific Patterns of Dysregulated Molecular Pathways and Genetic Subgroups of Human Hepatocellular Carcinoma.

    Science.gov (United States)

    Hass, Holger G; Vogel, Ulrich; Scheurlen, Michael; Jobst, Jürgen

    2016-10-01

    Hepatocellular carcinoma comprises of a group of heterogeneous tumors of different etiologies. The multistep process of liver carcinogenesis involves various genetic and phenotypic alterations. The molecular pathways and driver mutations involved are still under investigation. DNA micorarray technology was used to identify differentially expressed genes between human hepatocarcinoma and non-tumorous liver tissues to establish a unique specific gene-expression profile independent of the underlying liver disease. The validity of this global gene-expression profile was tested for its robustness against biopsies from other liver entities (cirrhotic and non-cirrhotic liver) by diagnosing HCC in blinded samples. Most of the consistently and strongly overexpressed genes were related to cell-cycle regulation and DNA replication [27 genes, e.g. cyclin B1, karyopherin alpha 2 (KPNA2), cyclin-dependent kinase 2 (CDC2)], G-protein depending signaling [e.g. Rac GTPase activating protein 1 (RACGAP1), Rab GTPase YPT1 homolog (RAB1), and ADP-ribosylation factor-like 2 (ARL2)] and extracellular matrix re-modelling or cytoskeleton structure [22 genes, e.g. serine proteinase inhibitor 1 kazal-type (SPINK1), osteopontin (OPN), secreted protein acidic and rich in cysteine (SPARC), collagen type 1 alpha2 (COL1A2), integrin alpha6 (ITGA6), and metalloproteinase 12 (MMP12)]. Furthermore, significantly differentially expressed genes (e.g. calcium-binding proteins, G-proteins, oncofetal proteins) in relation to tumor differentiation were detected using gene-expression analysis. It is suggested that these significantly dysregulated genes are highly specific and potentially utilizable as prognostic markers and may lead to a better understanding of human hepatocarcinogenesis. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  9. Identification of subgroups among fibromyalgia patients

    Directory of Open Access Journals (Sweden)

    D. Chaleil

    2012-09-01

    Full Text Available This paper presents some hypotheses concerning the identification of homogeneous subgroups among fibromyalgia (FM patients in order to improve the management of the disease. It also reviews the available literature about this subject. Three methods for subgrouping are discussed according to clinical features, biomarkers, and gait analysis. Clinical subgrouping based on cluster analysis has been used for the identification of homogeneous subgroups of patients and, more recently, homogeneous clinical features. So far, longitudinal studies using clinical subgroups to direct treatment and predict outcome are still required. Biomarkers in FM, which is a neurobiological disease, are of promising interest, nevertheless currently, none of them can be used to subgroup FM patients. Due to the fact that cortical and subcortical mechanisms of gait control share some cognitive functions which are involved in FM, gait markers have been proposed to evaluate and to subgroup FM patients, in clinical settings. Three out of 4 core FM symptoms are linked to gait markers. Kinesia measured by means of cranio-caudal power is correlated to pain, and could be proposed to assess pain behavior (kinesiophobia. Stride frequency, which is linked to physical component, allows the identification of a hyperkinetic subgroup. Moreover, SF has been correlated to fatigue during the 6 minute walking test. Stride regularity, which expresses the unsteadiness of gait, is correlated to cognitive dysfunction in FM. Decreased stride regularity allows the recognition of a homogeneous subgroup characterized by an increased anxiety and depression, and decreased cognitive functions. These results need further studies to be validated and so used in the daily clinical practice.

  10. Nilotinib vs imatinib as first-line therapy for patients with unresectable or metastatic gastrointestinal stromal tumours: randomised phase 3 trial results and subgroup analysis of molecular subtypes

    Science.gov (United States)

    Blay, Jean-Yves; Shen, Lin; Kang, Yoon-Koo; Rutkowski, Piotr; Qin, Shukui; Nosov, Dmitry; Wan, Desen; Trent, Jonathan; Srimuninnimit, Vichien; Pápai, Zsuzsanna; Le Cesne, Axel; Novick, Steven; Taningco, Lilia; Mo, Shuyuan; Green, Steven; Reichardt, Peter; Demetri, George D

    2015-01-01

    Background Nilotinib inhibits the tyrosine kinase activity of ABL1/BCR-ABL1, as well as KIT, platelet-derived growth factor receptors (PDGFRs), and the discoidin domain receptor. Gain-of-function mutations in KIT or PDGFRα are key drivers in most gastrointestinal stromal tumours (GISTs). This trial was designed to test the efficacy and safety of nilotinib vs imatinib as first-line therapy for patients with advanced GISTs. Methods This randomised, open-label, multicentre phase 3 trial included 647 adult patients with previously untreated, histologically confirmed, metastatic and/or unresectable GISTs. Patients were stratified by prior adjuvant therapy and randomised in a 1:1 ratio to receive oral imatinib 400 mg once daily or oral nilotinib 400 mg twice daily. Centrally reviewed progression-free survival (PFS) was the primary endpoint. Response rates, toxicity, and overall survival were also analysed for the overall population and for mutation-defined subsets. Efficacy endpoints used the intention to treat principle. Here, the final results are reported. This trial is registered with ClinicalTrials.gov, number NCT00785785. Findings Because the futility boundary was crossed at a preplanned interim analysis, trial accrual terminated in April 2011. At final analysis of the core study (data cutoff, October 2012), PFS was higher with imatinib overall (hazard ratio [HR] 1.47) and in the KIT exon 9 subgroup (HR 32.46) but roughly similar between arms in the KIT exon 11 subgroup (HR 1.12). Sensitivity analyses suggested that informative censoring may have contributed, because of the high proportion of premature nilotinib progressions declared by local investigators and the design changes implemented following the interim analysis, potentially biasing PFS data in favour of the nilotinib arm. The most common adverse events were nausea, diarrhoea, and peripheral oedema in the imatinib arm and rash, nausea, and abdominal pain in the nilotinib arm. The most common serious

  11. The effectiveness and safety of amisulpride in Chinese patients with schizophrenia who switch from risperidone or olanzapine: a subgroup analysis of the ESCAPE study

    Directory of Open Access Journals (Sweden)

    Liang Y

    2017-04-01

    Full Text Available Ying Liang, Xin Yu On behalf of the ESCAPE Study Group Peking University Sixth Hospital, Peking University Institute of Mental Health, Key Laboratory of Mental Health, Ministry of Health (Peking University, National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital, Beijing, People’s Republic of China Introduction: Second-generation antipsychotics show significant interpatient variability in treatment response and side-effect profiles, and the majority of patients with schizophrenia require multiple treatment changes. This subgroup analysis of the ESCAPE study evaluated the efficacy and safety of amisulpride in Chinese patients with schizophrenia who switched from risperidone or olanzapine.Methods: ESCAPE was a prospective, open-label, multicenter, single-arm Phase IV study in which Chinese patients with an ICD-10 diagnosis of schizophrenia received amisulpride for 8 weeks. This analysis included 109 patients who switched to amisulpride from risperidone (n=68 or olanzapine (n=41 and 59 treatment-naïve patients for reference. The primary effectiveness outcome was a ≥50% decrease in Positive and Negative Syndrome Scale (PANSS Total score from Baseline to Week 8. The study was registered at ClinicalTrials.gov (NCT01795183.Results: Of the patients who switched from risperidone and olanzapine, 77.9% and 56.1% achieved ≥50% reduction in PANSS Total score from Baseline to Week 8 and 57.4% and 46.3% achieved ≥20% reduction in PANSS score from Baseline to Week 2, respectively; these end points were achieved by 66.1% and 61.0% of treatment-naïve patients, respectively. No unexpected adverse events (AEs were reported. Of the most common AEs, extrapyramidal side effects occurred in 32.4% and 14.6%, blood prolactin increase in 32.4% and 39.0%, and ≥7% increase in body weight in 4.4% and 12% of patients switching from risperidone and olanzapine, respectively.Conclusion: The results of this subgroup analysis suggest

  12. The effectiveness of community-based coordinating interventions in dementia care: a meta-analysis and subgroup analysis of intervention components.

    Science.gov (United States)

    Backhouse, Amy; Ukoumunne, Obioha C; Richards, David A; McCabe, Rose; Watkins, Ross; Dickens, Chris

    2017-11-13

    Interventions aiming to coordinate services for the community-based dementia population vary in components, organisation and implementation. In this review we aimed to evaluate the effectiveness of community-based care coordinating interventions on health outcomes and investigate whether specific components of interventions influence their effects. We searched four databases from inception to April 2017: Medline, The Cochrane Library, EMBASE and PsycINFO. This was aided by a search of four grey literature databases, and backward and forward citation tracking of included papers. Title and abstract screening was followed by a full text screen by two independent reviewers, and quality was assessed using the CASP appraisal tool. We then conducted meta-analyses and subgroup analyses. A total of 14 randomised controlled trials (RCTs) involving 10,372 participants were included in the review. Altogether we carried out 12 meta-analyses and 19 subgroup analyses. Meta-analyses found coordinating interventions showed a statistically significant improvement in both patient behaviour measured using the Neuropsychiatric Inventory (NPI) (mean difference (MD) = -9.5; 95% confidence interval (CI): -18.1 to -1.0; p = 0.03; number of studies (n) = 4; I 2  = 88%) and caregiver burden (standardised mean difference (SMD) = -0.54; 95% CI: -1.01 to -0.07; p = 0.02; n = 5, I 2  = 92%) compared to the control group. Subgroup analyses found interventions using a case manager with a nursing background showed a greater positive effect on caregiver quality of life than those that used case managers from other professional backgrounds (SMD = 0.94 versus 0.03, respectively; p managers showed greater effectiveness for reducing the percentage of patients that are institutionalised compared to those that provided supervision (odds ratio (OR) = 0.27 versus 0.96 respectively; p = 0.02). There was little evidence of effects on other outcomes, or that other intervention components

  13. Photodynamic therapy vs. topical imiquimod for treatment of superficial basal cell carcinoma: a subgroup analysis within a noninferiority randomized controlled trial.

    Science.gov (United States)

    Roozeboom, M H; Nelemans, P J; Mosterd, K; Steijlen, P M; Arits, A H M M; Kelleners-Smeets, N W J

    2015-03-01

    A recent noninferiority randomized controlled trial (RCT) indicated that imiquimod can be considered as superior to methylaminolevulinate photodynamic therapy (MAL-PDT) in the treatment of superficial basal cell carcinoma (sBCC). Knowledge of treatment effectiveness in subgroups of patients is of great value in clinical practice to select the most effective treatment for an individual patient with sBCC. To explore whether the relative treatment effect of MAL-PDT and imiquimod is consistent across subgroups defined by patient and tumour characteristics. Data were derived from a single-blinded, noninferiority, multicentre RCT comparing MAL-PDT, topical imiquimod and fluorouracil (ISRCTN79701845). Treatment success was defined as free of tumour recurrence at 12-month follow-up. Subgroup analyses were performed for subgroups defined by sex, age, tumour location and tumour size. Two hundred and two patients received MAL-PDT and 198 received imiquimod. The superiority of imiquimod vs. MAL-PDT was observed in subgroups of females, sBCC on the trunk and large tumours with risk differences in favour of imiquimod of 18·4% [95% confidence interval (CI) 7·8-29·0%], 21·0% (95% CI 10·9-31·1%) and 18·9% (95% CI 7·1-30·7%), respectively. Higher probability of treatment success for imiquimod vs. MAL-PDT was consistently found in all other subgroups with the exception of sBCC localized on the lower extremities in older patients. In the latter subgroup, the risk difference at the expense of imiquimod was -57·3% (95% CI -81·7% to -32·9%). Imiquimod remains the first-choice treatment for sBCC in terms of effectiveness. In older patients with sBCC on the lower extremities MAL-PDT might be preferred. Results should be interpreted carefully as subgroup analyses were exploratory and not driven by prior hypotheses. © 2014 British Association of Dermatologists.

  14. Finite groups all of whose minimal subgroups are NE-subgroups

    Indian Academy of Sciences (India)

    subgroup of . In this article, we investigate the structure of under the assumption that subgroups of prime order are *-subgroups of . The finite groups, all of whose minimal subgroups of the generalized Fitting subgroup are *-subgroups ...

  15. Vorapaxar for secondary prevention of thrombotic events for patients with previous myocardial infarction: a prespecified subgroup analysis of the TRA 2°P-TIMI 50 trial.

    Science.gov (United States)

    Scirica, Benjamin M; Bonaca, Marc P; Braunwald, Eugene; De Ferrari, Gaetano M; Isaza, Daniel; Lewis, Basil S; Mehrhof, Felix; Merlini, Piera A; Murphy, Sabina A; Sabatine, Marc S; Tendera, Michal; Van de Werf, Frans; Wilcox, Robert; Morrow, David A

    2012-10-13

    Vorapaxar inhibits platelet activation by antagonising thrombin-mediated activation of the protease-activated receptor 1 on human platelets. The effect of adding other antiplatelet drugs to aspirin for long-term secondary prevention of thrombotic events in stable patients with previous myocardial infarction is uncertain. We tested this effect in a subgroup of patients from the Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events (TRA 2°P)-TIMI 50 trial. In TRA 2°P-TIMI 50--a randomised, placebo-controlled, parallel trial--we randomly assigned patients with a history of atherothrombosis to receive vorapaxar (2·5 mg daily) or matching placebo in a 1:1 ratio. Patients, and those giving treatment, assessing outcomes, and analysing results were masked to treatment allocation. Patients with a qualifying myocardial infarction within the previous 2 weeks to 12 months were analysed as a pre-defined subgroup. The primary efficacy endpoint was cardiovascular death, myocardial infarction, or stroke, analysed by intention to treat. We analysed events by Kaplan-Meier analysis and compared groups with a Cox proportional hazard model. TRA 2°P-TIMI 50 is registered at ClinicalTrials.gov (NCT00526474). 17,779 of 26,449 patients had a qualifying myocardial infarction and were assigned treatment (8898 to vorapaxar and 8881 to placebo). Median follow-up was 2·5 years (IQR 2·0-2·9). Cardiovascular death, myocardial infarction, or stroke occurred in 610 of 8898 patients in the vorapaxar group and 750 of 8881 in the placebo group (3-year Kaplan-Meier estimates 8·1%vs 9·7%, HR 0·80, 95% CI 0·72-0·89; p<0·0001). Moderate or severe bleeding was more common in the vorapaxar group versus the placebo group (241/8880 [3·4%, 3-year Kaplan-Meier estimate] vs 151/8849 [2·1%, 3-year Kaplan-Meier estimate], HR 1·61, 95% CI 1·31-1·97; p<0·0001). Intracranial haemorrhage occurred in 43 of 8880 patients (0·6%, 3-year Kaplan-Meier estimate) with

  16. Size is the Most Important Predictor of Aneurysm Rupture Among Multiple Cerebral Aneurysms: Post Hoc Subgroup Analysis of Unruptured Cerebral Aneurysm Study Japan.

    Science.gov (United States)

    Shojima, Masaaki; Morita, Akio; Nakatomi, Hirofumi; Tominari, Shinjiro

    2017-06-20

    Multiple cerebral aneurysms are encountered in approximately 15% to 35% of patients harboring unruptured cerebral aneurysms. It would be of clinical value to determine which of them is most likely to rupture. To characterize features of the ruptured aneurysm relative to other concomitant fellow aneurysms in patients with multiple cerebral aneurysms. From a total of 5720 patients who were prospectively registered in the Unruptured Cerebral Aneurysm Study in Japan, a subgroup of patients with multiple cerebral aneurysms who developed subarachnoid hemorrhage was extracted for this post hoc analysis. Intrapatient comparisons of each aneurysm were carried out using aneurysm-specific factors such as size, location, and shape to identify predictors of rupture among the fellow aneurysms in a patient with multiple cerebral aneurysms. Twenty-five patients with 62 aneurysms were identified from the total cohort of 5720 patients. With the distinctiveness in size, which means the aneurysm was the single largest among the multiple aneurysms, the ruptured aneurysm in each case was discriminated from the other coexisting aneurysms with a sensitivity of 0.76 and specificity of 0.86. Our results suggest that the largest aneurysm is likely to rupture among coexisting aneurysms in a patient with multiple cerebral aneurysms.

  17. Dietary Patterns Derived Using Exploratory and Confirmatory Factor Analysis are Stable and Generalizable Across Race, Region, and Gender Subgroups in the REGARDS Study

    Science.gov (United States)

    Judd, Suzanne E.; Letter, Abraham J.; Shikany, James M.; Roth, David L.; Newby, P. K.

    2015-01-01

    Background: Examining diet as a whole using dietary patterns as exposures is a complementary method to using single food or nutrients in studies of diet and disease, but the generalizability of intake patterns across race, region, and gender in the United States has not been established. Objective: To employ rigorous statistical analysis to empirically derive dietary patterns in a large bi-racial, geographically diverse population and examine whether results are stable across population subgroups. Design: The present analysis utilized data from 21,636 participants in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study who completed the Block 98 food frequency questionnaire. We employed exploratory factor analysis and confirmatory factor analyses on 56 different food groups iteratively and examined differences by race, region, and sex to determine the optimal factor solution in our sample. Results: Five dietary patterns emerged: the “Convenience” pattern was characterized by mixed dishes; the “Plant-based” pattern by fruits, vegetables, and fish; the “Sweets/Fats” pattern by sweet snacks, desserts, and fats and oils; the “Southern” pattern by fried foods, organ meat, and sweetened beverages; and the “Alcohol/Salads” pattern by beer, wine, liquor, and salads. Differences were most pronounced in the Southern pattern with black participants, those residing in the Southeast, and participants not completing high school having the highest scores. Conclusion: Five meaningful dietary patterns emerged in the REGARDS study and showed strong congruence across race, sex, and region. Future research will examine associations between these patterns and health outcomes to better understand racial disparities in disease and inform prevention efforts. PMID:25988129

  18. Dietary Patterns Derived Using Exploratory and Confirmatory Factor Analysis are Stable and Generalizable Across Race, Region, and Gender Subgroups in the REGARDS Study.

    Science.gov (United States)

    Judd, Suzanne E; Letter, Abraham J; Shikany, James M; Roth, David L; Newby, P K

    2014-01-01

    Examining diet as a whole using dietary patterns as exposures is a complementary method to using single food or nutrients in studies of diet and disease, but the generalizability of intake patterns across race, region, and gender in the United States has not been established. To employ rigorous statistical analysis to empirically derive dietary patterns in a large bi-racial, geographically diverse population and examine whether results are stable across population subgroups. The present analysis utilized data from 21,636 participants in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study who completed the Block 98 food frequency questionnaire. We employed exploratory factor analysis and confirmatory factor analyses on 56 different food groups iteratively and examined differences by race, region, and sex to determine the optimal factor solution in our sample. Five dietary patterns emerged: the "Convenience" pattern was characterized by mixed dishes; the "Plant-based" pattern by fruits, vegetables, and fish; the "Sweets/Fats" pattern by sweet snacks, desserts, and fats and oils; the "Southern" pattern by fried foods, organ meat, and sweetened beverages; and the "Alcohol/Salads" pattern by beer, wine, liquor, and salads. Differences were most pronounced in the Southern pattern with black participants, those residing in the Southeast, and participants not completing high school having the highest scores. Five meaningful dietary patterns emerged in the REGARDS study and showed strong congruence across race, sex, and region. Future research will examine associations between these patterns and health outcomes to better understand racial disparities in disease and inform prevention efforts.

  19. Dietary patterns derived using exploratory and confirmatory factor analysis are stable and generalizable across race, region, and gender subgroups in the REGARDS study

    Directory of Open Access Journals (Sweden)

    Suzanne E Judd

    2015-01-01

    Full Text Available Background: Examining diet as a whole using dietary patterns as exposures is a complementary method to using single food or nutrients in studies of diet and disease, but the generalizability of patterns across race, region, and gender in the United States has not been established. Objective: To employ rigorous statistical analysis to empirically derive dietary patterns in a large bi-racial, geographically diverse population and examine whether results are stable across population subgroups.Design: The present analysis utilized data from 21,636 participants in the Reasons for Geographic and Racial Differences in Stroke (REGARDS study who completed the Block98 food frequency questionnaire. We employed exploratory factor analysis and confirmatory factor analyses on 56 different food groups iteratively and examined differences by race, region, sex to determine the optimal factor solution in our sample. Results: Five dietary patterns emerged: the Convenience pattern was characterized by mixed dishes; the Plant-based pattern by fruits, vegetables, and fish; the Sweets/Fats pattern by sweet snacks, desserts, and fats and oils; the Southern pattern by fried foods, organ meat, and sweetened beverages; and the Alcohol/Salads pattern by beer, wine, liquor, and salads. Differences were most pronounced in the Southern pattern with black participants, those residing in the Southeast, and participants not completing high school having the highest scores. Conclusions: Five meaningful dietary patterns emerged in the REGARDS study and showed strong congruence across race, sex and region. Future research will examine associations between these patterns and health outcomes to better understand racial disparities in disease and inform prevention efforts.

  20. Molecular Subgroup Analysis of Clinical Outcomes in a Phase 3 Study of Gemcitabine and Oxaliplatin with or without Erlotinib in Advanced Biliary Tract Cancer

    Directory of Open Access Journals (Sweden)

    Seung Tae Kim

    2015-02-01

    Full Text Available BACKGROUND: We previously reported that the addition of erlotinib to gemcitabine and oxaliplatin (GEMOX resulted in greater antitumor activity and might be a treatment option for patients with biliary tract cancers (BTCs. Molecular subgroup analysis of treatment outcomes in patients who had specimens available for analysis was undertaken. METHODS: Epidermal growth factor receptor (EGFR, KRAS, and PIK3CA mutations were evaluated using peptide nucleic acid–locked nucleic acid polymerase chain reaction clamp reactions. Survival and response rates (RRs were analyzed according to the mutational status. Sixty-four patients (48.1% were available for mutational analysis in the chemotherapy alone group and 61 (45.1% in the chemotherapy plus erlotinib group. RESULTS: 1.6% (2/116 harbored an EGFR mutation (2 patients; exon 20, 9.6% (12/121 harbored a KRAS mutation (12 patients; exon 2, and 9.6% (12/118 harbored a PIK3CA mutation (10 patients, exon 9 and 2 patients, exon 20. The addition of erlotinib to GEMOX in patients with KRAS wild-type disease (n = 109 resulted in significant improvements in overall response compared with GEMOX alone (30.2% vs 12.5%, P = .024. In 95 patients with both wild-type KRAS and PIK3CA, there was evidence of a benefit associated with the addition of erlotinib to GEMOX with respect to RR as compared with GEMOX alone (P = .04. CONCLUSION: This study demonstrates that KRAS mutational status might be considered a predictive biomarker for the response to erlotinib in BTCs. Additionally, the mutation status of PIK3CA may be a determinant for adding erlotinib to chemotherapy in KRAS wild-type BTCs.

  1. Internalin profiling and multilocus sequence typing suggest four Listeria innocua subgroups with different evolutionary distances from Listeria monocytogenes

    Directory of Open Access Journals (Sweden)

    Wang Jun

    2010-03-01

    Full Text Available Abstract Background Ecological, biochemical and genetic resemblance as well as clear differences of virulence between L. monocytogenes and L. innocua make this bacterial clade attractive as a model to examine evolution of pathogenicity. This study was attempted to examine the population structure of L. innocua and the microevolution in the L. innocua-L. monocytogenes clade via profiling of 37 internalin genes and multilocus sequence typing based on the sequences of 9 unlinked genes gyrB, sigB, dapE, hisJ, ribC, purM, gap, tuf and betL. Results L. innocua was genetically monophyletic compared to L. monocytogenes, and comprised four subgroups. Subgroups A and B correlated with internalin types 1 and 3 (except the strain 0063 belonging to subgroup C and internalin types 2 and 4 respectively. The majority of L. innocua strains belonged to these two subgroups. Subgroup A harbored a whole set of L. monocytogenes-L. innocua common and L. innocua-specific internalin genes, and displayed higher recombination rates than those of subgroup B, including the relative frequency of occurrence of recombination versus mutation (ρ/θ and the relative effect of recombination versus point mutation (r/m. Subgroup A also exhibited a significantly smaller exterior/interior branch length ratio than expected under the coalescent model, suggesting a recent expansion of its population size. The phylogram based on the analysis with correction for recombination revealed that the time to the most recent common ancestor (TMRCA of L. innocua subgroups A and B were similar. Additionally, subgroup D, which correlated with internalin type 5, branched off from the other three subgroups. All L. innocua strains lacked seventeen virulence genes found in L. monocytogenes (except for the subgroup D strain L43 harboring inlJ and two subgroup B strains bearing bsh and were nonpathogenic to mice. Conclusions L. innocua represents a young species descending from L. monocytogenes and

  2. Internalin profiling and multilocus sequence typing suggest four Listeria innocua subgroups with different evolutionary distances from Listeria monocytogenes.

    Science.gov (United States)

    Chen, Jianshun; Chen, Qiaomiao; Jiang, Lingli; Cheng, Changyong; Bai, Fan; Wang, Jun; Mo, Fan; Fang, Weihuan

    2010-03-31

    Ecological, biochemical and genetic resemblance as well as clear differences of virulence between L. monocytogenes and L. innocua make this bacterial clade attractive as a model to examine evolution of pathogenicity. This study was attempted to examine the population structure of L. innocua and the microevolution in the L. innocua-L. monocytogenes clade via profiling of 37 internalin genes and multilocus sequence typing based on the sequences of 9 unlinked genes gyrB, sigB, dapE, hisJ, ribC, purM, gap, tuf and betL. L. innocua was genetically monophyletic compared to L. monocytogenes, and comprised four subgroups. Subgroups A and B correlated with internalin types 1 and 3 (except the strain 0063 belonging to subgroup C) and internalin types 2 and 4 respectively. The majority of L. innocua strains belonged to these two subgroups. Subgroup A harbored a whole set of L. monocytogenes-L. innocua common and L. innocua-specific internalin genes, and displayed higher recombination rates than those of subgroup B, including the relative frequency of occurrence of recombination versus mutation (rho/theta) and the relative effect of recombination versus point mutation (r/m). Subgroup A also exhibited a significantly smaller exterior/interior branch length ratio than expected under the coalescent model, suggesting a recent expansion of its population size. The phylogram based on the analysis with correction for recombination revealed that the time to the most recent common ancestor (TMRCA) of L. innocua subgroups A and B were similar. Additionally, subgroup D, which correlated with internalin type 5, branched off from the other three subgroups. All L. innocua strains lacked seventeen virulence genes found in L. monocytogenes (except for the subgroup D strain L43 harboring inlJ and two subgroup B strains bearing bsh) and were nonpathogenic to mice. L. innocua represents a young species descending from L. monocytogenes and comprises four subgroups: two major subgroups A and B

  3. Genetic and molecular alterations across medulloblastoma subgroups.

    Science.gov (United States)

    Skowron, Patryk; Ramaswamy, Vijay; Taylor, Michael D

    2015-10-01

    Medulloblastoma is the most common malignant brain tumour diagnosed in children. Over the last few decades, advances in radiation and chemotherapy have significantly improved the odds of survival. Nevertheless, one third of all patients still succumb to their disease, and many long-term survivors are afflicted with neurocognitive sequelae. Large-scale multi-institutional efforts have provided insight into the transcriptional and genetic landscape of medulloblastoma. Four distinct subgroups of medulloblastoma have been identified, defined by distinct transcriptomes, genetics, demographics and outcomes. Integrated genomic profiling of each of these subgroups has revealed distinct genetic alterations, driving pathways and in some instances cells of origin. In this review, we highlight, in a subgroup-specific manner, our current knowledge of the genetic and molecular alterations in medulloblastoma and underscore the possible avenues for future therapeutic intervention.

  4. Net clinical benefit of rivaroxaban versus warfarin in Japanese patients with nonvalvular atrial fibrillation: a subgroup analysis of J-ROCKET AF.

    Science.gov (United States)

    Uchiyama, Shinichiro; Hori, Masatsugu; Matsumoto, Masayasu; Tanahashi, Norio; Momomura, Shin-Ichi; Goto, Shinya; Izumi, Tohru; Koretsune, Yukihiro; Kajikawa, Mariko; Kato, Masaharu; Ueda, Hitoshi; Iekushi, Kazuma; Yamanaka, Satoshi; Tajiri, Masahiro

    2014-01-01

    The risk factors that have been identified for bleeding events with rivaroxaban are predominantly the same as those predicting thromboembolic ones in patients with atrial fibrillation (AF). Our aim was to determine the net clinical benefit (NCB) from the results of the J-ROCKET AF trial, in which rivaroxaban was compared with warfarin in Japanese patients with AF. Two strategies were adopted to quantify the NCB. First, the NCB was calculated as the number of ischemic strokes avoided with anticoagulation minus the number of excess intracranial hemorrhage (ICH) with a weight of 1.5. Second, the composite end point of major bleeding events and secondary efficacy end points (stroke, noncentral nervous system systemic embolism, myocardial infarction and death) to ascertain the NCB were established. Subgroup analysis by CHADS2 score or creatinine clearance was also performed. The adjusted NCB, which was given a weight of 1.5 for ICH, was nominally significant in favor of rivaroxaban therapy (difference in incidence rate -2.13; 95% confidence interval [CI]: -.26 to -3.99). Furthermore, the event rate of the composite end point tended to be lower in patients treated with rivaroxaban than in those treated with warfarin (rivaroxaban: 4.97% per year, warfarin: 6.11% per year; difference in incidence rate: -1.14; 95% CI: -3.40 to 1.12). The event rate of the composite end point tended to be consistently low in patients treated with rivaroxaban in the subanalysis by CHADS2 score and renal function. Analysis of the NCB supports that rivaroxaban therapy provides clinical benefit for Japanese patients with AF. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  5. What works best for whom? An exploratory, subgroup analysis in a randomized, controlled trial on the effectiveness of a workplace intervention in low back pain patients on return to work

    NARCIS (Netherlands)

    Steenstra, I.A.; Knol, D.L.; Bongers, P.M.; Anema, J.R.; Mechelen, W. van; Vet, H.C.W. de

    2009-01-01

    STUDY DESIGN. Exploratory subgroup analysis in a randomized controlled trial (RCT). OBJECTIVE. To detect possible moderators in the effectiveness of a workplace intervention in a population of workers with sick leave due to sub acute nonspecific low back pain. SUMMARY OF BACKGROUND DATA. In a

  6. Rivaroxaban for the treatment of symptomatic deep-vein thrombosis and pulmonary embolism in Chinese patients: a subgroup analysis of the EINSTEIN DVT and PE studies.

    Science.gov (United States)

    Wang, Yuqi; Wang, Chen; Chen, Zhong; Zhang, Jiwei; Liu, Zhihong; Jin, Bi; Ying, Kejing; Liu, Changwei; Shao, Yuxia; Jing, Zhicheng; Meng, Isabelle Ling; Prins, Martin H; Pap, Akos F; Müller, Katharina; Lensing, Anthonie Wa

    2013-12-16

    The worldwide EINSTEIN DVT and EINSTEIN PE studies randomized 8282 patients with acute symptomatic deep-vein thrombosis (DVT) and/or pulmonary embolism (PE) and, for the first time in trials in this setting, included patients in China. This analysis evaluates the results of these studies in this subgroup of patients. A total of 439 Chinese patients who had acute symptomatic DVT (n=211), or PE with or without DVT (n=228), were randomized to receive rivaroxaban (15 mg twice daily for 21 days, followed by 20 mg once daily) or standard therapy of enoxaparin overlapping with and followed by an adjusted-dose vitamin K antagonist, for 3, 6, or 12 months. The primary efficacy outcome was symptomatic recurrent venous thromboembolism. The principal safety outcome was major or non-major clinically relevant bleeding. The primary efficacy outcome occurred in seven (3.2%) of the 220 patients in the rivaroxaban group and in seven (3.2%) of the 219 patients in the standard-therapy group (hazard ratio, 1.04; 95% confidence interval 0.36-3.0; p=0.94). The principal safety outcome occurred in 13 (5.9%) patients in the rivaroxaban group and in 20 (9.2%) patients in the standard-therapy group (hazard ratio, 0.63; 95% confidence interval 0.31-1.26; p=0.19). Major bleeding was observed in no patients in the rivaroxaban group and in five (2.3%) patients in the standard-therapy group. In fragile patients (defined as age >75 years, creatinine clearance EINSTEIN PE, ClinicalTrials.gov NCT00439777; EINSTEIN DVT, ClinicalTrials.gov NCT00440193.

  7. Rivaroxaban versus warfarin in Japanese patients with non-valvular atrial fibrillation in relation to hypertension: a subgroup analysis of the J-ROCKET AF trial.

    Science.gov (United States)

    Matsumoto, Masayasu; Hori, Masatsugu; Tanahashi, Norio; Momomura, Shin-Ichi; Uchiyama, Shinichiro; Goto, Shinya; Izumi, Tohru; Koretsune, Yukihiro; Kajikawa, Mariko; Kato, Masaharu; Ueda, Hitoshi; Iekushi, Kazuma; Yamanaka, Satoshi; Tajiri, Masahiro

    2014-05-01

    The majority of the patients enrolled in the rivaroxaban vs. warfarin in Japanese patients with atrial fibrillation (J-ROCKET AF) trial had hypertension. In this subgroup analysis, we investigated differences in the safety and efficacy of rivaroxaban and warfarin in subjects with and without hypertension. The baseline blood pressure (BP) measurements of patients with hypertension in the rivaroxaban and warfarin groups were 130/77 mm Hg and 131/77 mm Hg, respectively, whereas those of patients without hypertension were 123/74 mm Hg and 124/73 mm Hg, respectively. The incidence rates of the principal safety outcomes in the rivaroxaban and warfarin groups were 18.39% per year and 16.81% per year, respectively, among patients with baseline hypertension (hazard ratio (HR): 1.10; 95% confidence interval (CI): 0.84-1.45) and 16.71% per year and 15.00% per year, respectively, among patients without hypertension at baseline (HR: 1.14; 95% CI: 0.66-1.97), indicating no significant interaction (P=0.933). The incidence rates of the primary efficacy endpoints in the rivaroxaban group and the warfarin group were 0.54% per year and 2.24% per year, respectively, in patients without baseline hypertension (HR: 0.25; 95% CI: 0.03-2.25), and 1.45% per year and 2.71% per year, respectively, in patients with baseline hypertension (HR: 0.54; 95% CI: 0.25-1.16), indicating no significant interaction (P=0.509). In conclusion, the safety and efficacy profile of rivaroxaban was similar to that of warfarin, independent of baseline hypertensive status.

  8. Crenobalneotherapy (spa therapy) in patients with knee and generalized osteoarthritis: a post-hoc subgroup analysis of a large multicentre randomized trial.

    Science.gov (United States)

    Forestier, R; Genty, C; Waller, B; Françon, A; Desfour, H; Rolland, C; Roques, C-F; Bosson, J-L

    2014-06-01

    To determine whether the addition of spa therapy to home exercises provides any benefit over exercises and the usual treatment alone in the management of generalised osteoarthritis associated with knee osteoarthritis. This study was a post-hoc subgroup analysis of our randomised multicentre trial (www.clinicaltrial.gov: NCT00348777). Participants who met the inclusion criteria of generalized osteoarthritis (Kellgren, American College of Rheumatology, or Dougados criteria) were extracted from the original randomised controlled trial. They had been randomised using Zelen randomisation. The treatment group received 18days of spa treatment in addition to a home exercise programme. Main outcome was number of patients achieving minimal clinically important improvement at six months (MCII) (≥-19.9mm on the VAS pain scale and/or ≥-9.1 points in a WOMAC function subscale), and no knee surgery. Secondary outcomes included the "patient acceptable symptom state" (PASS) defined as VAS pain ≤32.3mm and/or WOMAC function subscale ≤31 points. From the original 462 participants, 214 patients could be categorized as having generalised osteoarthritis. At sixth month, 182 (88 in control and 94 in SA group) patients, were analysed for the main criteria. MCII was observed more often in the spa group (n=52/94 vs. 38/88, P=0.010). There was no difference for the PASS (n=19/88 vs. 26/94, P=0.343). This study indicates that spa therapy with home exercises may be superior to home exercise alone in the management of patients with GOA associated with knee OA. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  9. The effect of tolvaptan on autosomal dominant polycystic kidney disease patients: a subgroup analysis of the Japanese patient subset from TEMPO 3:4 trial.

    Science.gov (United States)

    Muto, Satoru; Kawano, Haruna; Higashihara, Eiji; Narita, Ichiei; Ubara, Yoshifumi; Matsuzaki, Takayuki; Ouyang, John; Torres, Vicente E; Horie, Shigeo

    2015-10-01

    Japan is the first country in the world to approve tolvaptan for the treatment of autosomal dominant polycystic kidney disease (ADPKD), which was based on the results of Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes (TEMPO) 3:4 trial. To evaluate the safety and efficacy of tolvaptan, we performed a subgroup analysis in the participating Japanese ADPKD patient population. The primary outcome was the annual rate of percentage change in the total kidney volume (TKV). The secondary endpoint was the rate of kidney function change. The tolvaptan and placebo groups included 118 and 59 patients, respectively. The annual rate of percentage changes in TKV were 1.3 % [95 % confidence interval (CI) 0.4-2.1] in the tolvaptan group, and 5.0 % (95 % CI 3.9-6.2) in the placebo group (P tolvaptan group and -5.05 mL in the placebo group for a treatment effect of +1.22 mL/min/1.73 m(2) (95 % CI 0.41-2.02: P = 0.003). Hepatic function abnormal as a serious adverse event was observed in 3 patients (2.5 %) in the tolvaptan group. Administration of tolvaptan in the Japanese sub-population reduced the annual rate of TKV growth and slowed the rate of kidney function decline over 36 months compared to patients on placebo, thus providing a novel and effective therapy for the treatment of ADPKD. (TEMPO 3:4 ClinicalTrials.gov number, NCT00428948).

  10. Discovery of miRNAs and Their Corresponding miRNA Genes in Atlantic Cod (Gadus morhua): Use of Stable miRNAs as Reference Genes Reveals Subgroups of miRNAs That Are Highly Expressed in Particular Organs.

    Science.gov (United States)

    Andreassen, Rune; Rangnes, Fredrik; Sivertsen, Maria; Chiang, Michelle; Tran, Michelle; Worren, Merete Molton

    2016-01-01

    Atlantic cod (Gadus morhua) is among the economically most important species in the northern Atlantic Ocean and a model species for studying development of the immune system in vertebrates. MicroRNAs (miRNAs) are an abundant class of small RNA molecules that regulate fundamental biological processes at the post-transcriptional level. Detailed knowledge about a species miRNA repertoire is necessary to study how the miRNA transcriptome modulate gene expression. We have therefore discovered and characterized mature miRNAs and their corresponding miRNA genes in Atlantic cod. We have also performed a validation study to identify suitable reference genes for RT-qPCR analysis of miRNA expression in Atlantic cod. Finally, we utilized the newly characterized miRNA repertoire and the dedicated RT-qPCR method to reveal miRNAs that are highly expressed in certain organs. The discovery analysis revealed 490 mature miRNAs (401 unique sequences) along with precursor sequences and genomic location of the miRNA genes. Twenty six of these were novel miRNA genes. Validation studies ranked gmo-miR-17-1-5p or the two-gene combination gmo-miR25-3p and gmo-miR210-5p as most suitable qPCR reference genes. Analysis by RT-qPCR revealed 45 miRNAs with significantly higher expression in tissues from one or a few organs. Comparisons to other vertebrates indicate that some of these miRNAs may regulate processes like growth, lipid metabolism, immune response to microbial infections and scar damage repair. Three teleost-specific and three novel Atlantic cod miRNAs were among the differentially expressed miRNAs. The number of known mature miRNAs was considerably increased by our identification of miRNAs and miRNA genes in Atlantic cod. This will benefit further functional studies of miRNA expression using deep sequencing methods. The validation study showed that stable miRNAs are suitable reference genes for RT-qPCR analysis of miRNA expression. Applying RT-qPCR we have identified several mi

  11. Discovery of miRNAs and Their Corresponding miRNA Genes in Atlantic Cod (Gadus morhua: Use of Stable miRNAs as Reference Genes Reveals Subgroups of miRNAs That Are Highly Expressed in Particular Organs.

    Directory of Open Access Journals (Sweden)

    Rune Andreassen

    Full Text Available Atlantic cod (Gadus morhua is among the economically most important species in the northern Atlantic Ocean and a model species for studying development of the immune system in vertebrates. MicroRNAs (miRNAs are an abundant class of small RNA molecules that regulate fundamental biological processes at the post-transcriptional level. Detailed knowledge about a species miRNA repertoire is necessary to study how the miRNA transcriptome modulate gene expression. We have therefore discovered and characterized mature miRNAs and their corresponding miRNA genes in Atlantic cod. We have also performed a validation study to identify suitable reference genes for RT-qPCR analysis of miRNA expression in Atlantic cod. Finally, we utilized the newly characterized miRNA repertoire and the dedicated RT-qPCR method to reveal miRNAs that are highly expressed in certain organs.The discovery analysis revealed 490 mature miRNAs (401 unique sequences along with precursor sequences and genomic location of the miRNA genes. Twenty six of these were novel miRNA genes. Validation studies ranked gmo-miR-17-1-5p or the two-gene combination gmo-miR25-3p and gmo-miR210-5p as most suitable qPCR reference genes. Analysis by RT-qPCR revealed 45 miRNAs with significantly higher expression in tissues from one or a few organs. Comparisons to other vertebrates indicate that some of these miRNAs may regulate processes like growth, lipid metabolism, immune response to microbial infections and scar damage repair. Three teleost-specific and three novel Atlantic cod miRNAs were among the differentially expressed miRNAs.The number of known mature miRNAs was considerably increased by our identification of miRNAs and miRNA genes in Atlantic cod. This will benefit further functional studies of miRNA expression using deep sequencing methods. The validation study showed that stable miRNAs are suitable reference genes for RT-qPCR analysis of miRNA expression. Applying RT-qPCR we have identified

  12. Switch to Stribild versus continuation of NVP or RPV with FTC and TDF in virologically suppressed HIV adults: a STRATEGY-NNRTI subgroup analysis

    Directory of Open Access Journals (Sweden)

    Hans-Juergen Stellbrink

    2014-11-01

    Full Text Available Introduction: Switch to Stribild (STB was non-inferior to continuation of a non-nucleoside reverse transcriptase inhibitor (NNRTI with emtricitabine and tenofovir DF (FTC/TDF at week 48 in virologically suppressed HIV adults (1. We report the Week 48 efficacy and safety of STB versus nevirapine (NVP or rilpivirine (RPV with FTC/TDF in suppressed subjects. Materials and Methods: Virologically suppressed subjects on an NNRTI with FTC/TDF regimens for ≥6 months were randomized (2:1 to switch to STB versus continue their NNRTI regimen. Eligibility criteria included no documented resistance to FTC and TDF, no history of virologic failure and eGFR ≥70 mL/min. The primary endpoint was the proportion of subjects in the modified ITT population who maintained HIV-1 RNA <50 copies(c/mL at Week 48 by FDA snapshot algorithm (12% non-inferiority margin. Subgroup analysis by non-EFV NNRTI use (NVP [74]; RPV [19]; etravirine [3] at screening was pre-specified. Results: The mITT population included 433 subjects who were randomized and treated. In the non-EFV NNRTI subgroup, 59 switched to STB; 37 continued a non-EFV NNRTI (27 NVP, 10 RPV with FTC/TDF. At week 48, 97% STB versus 95% non-EFV NNRTI maintained HIV-1 RNA <50 c/mL. No emergent resistance was detected in either group. No difference in median increases from baseline in CD4 count at week 48 (cells/µL: 25 STB versus 55 non-EFV NNRTI (p=0.78. No discontinuation due to adverse events; no cases of proximal renal tubulopathy. As expected, there were no significant changes in the frequency of neuropsychiatric symptoms (i.e. anxiety, insomnia, dizziness, vivid dreams, weird/intense dreams, and nightmares reported on the HIV Symptom Index at week 48 compared to baseline after switching to STB. There was a greater but non-progressive decrease from baseline in eGFR in the STB versus non-EFV NNRTI group; median changes (mL/min at week 48: −9.1 versus −1.4. Switch to STB was associated with a higher

  13. Obesogenic Dietary Practices of Latino and Asian Subgroups of Children in California: An Analysis of the California Health Interview Survey, 2007-2012.

    Science.gov (United States)

    Guerrero, Alma D; Ponce, Ninez A; Chung, Paul J

    2015-08-01

    We examined obesogenic dietary practices among Latino and Asian subgroups of children living in California. We analyzed 2007, 2009, and 2011-2012 California Health Interview Survey data to examine the differences in dietary practices among Mexican and non-Mexican Latino children and 7 ethnic subgroups of Asian children. We used multivariable regression to examine the sociodemographic factors associated with specific dietary practices. Latino subgroups of children had few differences in obesogenic dietary practices, whereas Asian subgroups of children exhibited significant differences in several obesogenic dietary practices. Korean and Filipino children were more likely than Chinese children to consume fast food and have low vegetable intake. Filipino children, followed by Japanese children, had the most obesogenic dietary practices compared with Chinese children, who along with South Asian children appeared to have the least obesogenic dietary practices. In general, income, education, and acculturation did not explain the dietary differences among Asian groups. Our findings suggest the need to disaggregate dietary profiles of Asian and Latino children and to consider nontraditional sociodemographic factors for messaging and counseling on healthy dietary practices among Asian populations.

  14. Proteomic and transcriptomic analysis reveals evidence for the basis ...

    African Journals Online (AJOL)

    Proteomic and transcriptomic analysis reveals evidence for the basis of salt sensitivity in Thai jasmine rice ( Oryza sativa L. cv. ... African Journal of Biotechnology ... the posttranscriptional mechanisms controlling protein expression levels were not as efficient as in Pokkali, indicating targets for future genetic improvement.

  15. Efficacy and safety of omalizumab for the treatment of refractory chronic spontaneous urticaria in Japanese patients: Subgroup analysis of the phase 3 POLARIS study.

    Science.gov (United States)

    Hide, Michihiro; Igarashi, Atsuyuki; Yagami, Akiko; Chinuki, Yuko; Inomata, Naoko; Fukunaga, Atsushi; Kaiser, Guenther; Wang, Junyi; Matsushima, Soichiro; Greenberg, Steven; Khalil, Sam

    2017-11-01

    Omalizumab, a humanized anti-IgE monoclonal antibody, proved efficacious and well tolerated in patients with chronic spontaneous urticaria (CSU) refractory to H1 antihistamines (H1AH) in the POLARIS study (NCT02329223), a randomized, double-blind, placebo-controlled trial in East Asian patients. However, data in Japanese patients, who have specific baseline characteristics (e.g., low angioedema incidence, different background medications) that may impact clinical outcomes, are lacking. This pre-specified analysis presents additional patient-level data over time, pharmacokinetic and pharmacodynamics data for omalizumab and IgE, and efficacy and safety data for omalizumab in Japanese patients. Japanese patients (N = 105) were randomized 1:1:1 to omalizumab 300 mg, 150 mg, or placebo by subcutaneous injection every 4 weeks. Efficacy and safety were assessed primarily based on changes from baseline to Week 12 in weekly itch-severity scores (ISS7) and weekly urticaria activity scores (UAS7), and incidence of adverse events (AEs), respectively. Patient-level UAS7 data over time were also reviewed. At Week 12, least squares mean (LSM) changes from baseline in ISS7 were greater with omalizumab vs. placebo (-9.54 and -7.29 for omalizumab 300 mg and 150 mg, respectively, vs. placebo [-5.17]). Corresponding LSM changes from baseline in UAS7 were -21.61 and -15.59 (vs. placebo [-10.88]). Most responders in the omalizumab 300 mg group displayed improvement of disease activity within 2-4 weeks and had well-controlled symptoms during the treatment period. Overall AE incidence was similar across treatment arms. This subgroup analysis demonstrated that omalizumab is a well-tolerated, beneficial option for treatment of CSU in H1AH-refractory Japanese patients. Copyright © 2017 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

  16. Genome at juncture of early human migration: a systematic analysis of two whole genomes and thirteen exomes from Kuwaiti population subgroup of inferred Saudi Arabian tribe ancestry.

    Science.gov (United States)

    Alsmadi, Osama; John, Sumi E; Thareja, Gaurav; Hebbar, Prashantha; Antony, Dinu; Behbehani, Kazem; Thanaraj, Thangavel Alphonse

    2014-01-01

    Population of the State of Kuwait is composed of three genetic subgroups of inferred Persian, Saudi Arabian tribe and Bedouin ancestry. The Saudi Arabian tribe subgroup traces its origin to the Najd region of Saudi Arabia. By sequencing two whole genomes and thirteen exomes from this subgroup at high coverage (>40X), we identify 4,950,724 Single Nucleotide Polymorphisms (SNPs), 515,802 indels and 39,762 structural variations. Of the identified variants, 10,098 (8.3%) exomic SNPs, 139,923 (2.9%) non-exomic SNPs, 5,256 (54.3%) exomic indels, and 374,959 (74.08%) non-exomic indels are 'novel'. Up to 8,070 (79.9%) of the reported novel biallelic exomic SNPs are seen in low frequency (minor allele frequency high frequencies in this subgroup are: a nonsynonymous deleterious SNP (rs2108622 [19:g.15990431C>T] from CYP4F2 gene [MIM:*604426]) associated with warfarin dosage levels [MIM:#122700] required to elicit normal anticoagulant response; and a 3' UTR SNP (rs6151429 [22:g.51063477T>C]) from ARSA gene [MIM:*607574]) associated with Metachromatic Leukodystrophy [MIM:#250100]. Hemoglobin Riyadh variant (identified for the first time in a Saudi Arabian woman) is observed in the exome data. The mitochondrial haplogroup profiles of the 15 individuals are consistent with the haplogroup diversity seen in Saudi Arabian natives, who are believed to have received substantial gene flow from Africa and eastern provenance. We present the first genome resource imperative for designing future genetic studies in Saudi Arabian tribe subgroup. The full-length genome sequences and the identified variants are available at ftp://dgr.dasmaninstitute.org and http://dgr.dasmaninstitute.org/DGR/gb.html.

  17. Aspirin for primary prevention of cardiovascular events: meta-analysis of randomized controlled trials and subgroup analysis by sex and diabetes status.

    Directory of Open Access Journals (Sweden)

    Manling Xie

    Full Text Available To evaluate the benefits and harms of aspirin for the primary prevention of CVD and determine whether the effects vary by sex and diabetes status.We searched Medline, Embase, and Cochrane databases for randomized controlled trials comparing the effects of aspirin with placebo or control in people with no pre-existing CVD. Two investigators independently extracted data and assessed the study quality. Analyses were performed using Stata version 12.Fourteen trials (107,686 participants were eligible. Aspirin was associated with reductions in major cardiovascular events (risk ratio, 0.90; 95% confidence interval, 0.85-0.95, myocardial infarction (0.86; 0.75-0.93, ischemic stroke (0.86; 0.75-0.98 and all-cause mortality (0.94; 0.89-0.99. There were also increases in hemorrhagic stroke (1.34; 1.01-1.79 and major bleeding (1.55; 1.35-1.78 with aspirin. The number needed to treat to prevent 1 major cardiovascular event over a mean follow-up of 6.8 years was 284. By comparison, the numbers needed to harm to cause 1 major bleeding is 299. In subgroup analyses, pooled results demonstrated a reduction in myocardial infarction among men (0.71; 0.59-0.85 and ischemic stroke among women (0.77; 0.63-0.93. Aspirin use was associated with a reduction (0.65; 0.51-0.82 in myocardial infarction among diabetic men. In meta-regression analyses, the results suggested that aspirin therapy might be associated with a decrease in stroke among diabetic women and a decrease in MI among diabetic men and risk reductions achieved with low doses (75 mg/day were as large as those obtained with higher doses (650 mg/day.The use of low-dose aspirin was beneficial for primary prevention of CVD and the decision regarding an aspirin regimen should be made on an individual patient basis. The effects of aspirin therapy varied by sex and diabetes status. A clear benefit of aspirin in the primary prevention of CVD in people with diabetes needs more trials.

  18. Aspirin for Primary Prevention of Cardiovascular Events: Meta-Analysis of Randomized Controlled Trials and Subgroup Analysis by Sex and Diabetes Status

    Science.gov (United States)

    Zhang, Yan; Chen, Sijing; Yang, Wei; Bao, Wei; Rong, Ying; Yu, Xuefeng; Hu, Frank B.; Liu, Liegang

    2014-01-01

    Objective To evaluate the benefits and harms of aspirin for the primary prevention of CVD and determine whether the effects vary by sex and diabetes status. Methods We searched Medline, Embase, and Cochrane databases for randomized controlled trials comparing the effects of aspirin with placebo or control in people with no pre-existing CVD. Two investigators independently extracted data and assessed the study quality. Analyses were performed using Stata version 12. Results Fourteen trials (107,686 participants) were eligible. Aspirin was associated with reductions in major cardiovascular events (risk ratio, 0.90; 95% confidence interval, 0.85–0.95), myocardial infarction (0.86; 0.75–0.93), ischemic stroke (0.86; 0.75–0.98) and all-cause mortality (0.94; 0.89–0.99). There were also increases in hemorrhagic stroke (1.34; 1.01–1.79) and major bleeding (1.55; 1.35–1.78) with aspirin. The number needed to treat to prevent 1 major cardiovascular event over a mean follow-up of 6.8 years was 284. By comparison, the numbers needed to harm to cause 1 major bleeding is 299. In subgroup analyses, pooled results demonstrated a reduction in myocardial infarction among men (0.71; 0.59–0.85) and ischemic stroke among women (0.77; 0.63–0.93). Aspirin use was associated with a reduction (0.65; 0.51–0.82) in myocardial infarction among diabetic men. In meta-regression analyses, the results suggested that aspirin therapy might be associated with a decrease in stroke among diabetic women and a decrease in MI among diabetic men and risk reductions achieved with low doses (75 mg/day) were as large as those obtained with higher doses (650 mg/day). Conclusions The use of low-dose aspirin was beneficial for primary prevention of CVD and the decision regarding an aspirin regimen should be made on an individual patient basis. The effects of aspirin therapy varied by sex and diabetes status. A clear benefit of aspirin in the primary prevention of CVD in people with diabetes

  19. Methoxyflurane Analgesia in Adult Patients in the Emergency Department: A Subgroup Analysis of a Randomized, Double-blind, Placebo-controlled Study (STOP!).

    Science.gov (United States)

    Coffey, Frank; Dissmann, Patrick; Mirza, Kazim; Lomax, Mark

    2016-11-01

    Acute pain remains highly prevalent in the Emergency Department (ED) setting. This double-blind, randomized, placebo-controlled UK study investigated the efficacy and safety of low-dose methoxyflurane analgesia for the treatment of acute pain in the ED in the adult population of the STOP! trial. Patients presenting to the ED requiring analgesia for acute pain (pain score of 4-7 on the Numerical Rating Scale) due to minor trauma were randomized in a 1:1 ratio to receive methoxyflurane (up to 6 mL) or placebo (normal saline), both via a Penthrox(®) (Medical Developments International Limited, Scoresby, Australia) inhaler. Rescue medication (paracetamol/opioids) was available immediately upon request. Change from baseline in visual analog scale (VAS) pain intensity was the primary endpoint. 300 adult and adolescent patients were randomized; data are presented for the adult subgroup (N = 204). Mean baseline VAS pain score was ~66 mm in both groups. The mean change from baseline to 5, 10, 15 and 20 min was greater for methoxyflurane (-20.7, -27.4, -33.3 and -34.8 mm, respectively) than placebo (-8.0, -11.1, -12.3 and -15.2 mm, respectively). The primary analysis showed a highly significant treatment effect overall across all four time points (-17.4 mm; 95% confidence interval: -22.3 to -12.5 mm; p methoxyflurane [versus 20 min with placebo; (hazard ratio: 2.32; 95% CI: 1.63, 3.30; p methoxyflurane-treated patients experienced pain relief within 1-10 inhalations. 22.8% of placebo-treated patients requested rescue medication within 20 min compared with 2.0% of methoxyflurane-treated patients (p = 0.0003). Methoxyflurane treatment was rated 'Excellent', 'Very Good' or 'Good' by 77.6% of patients, 74.5% of physicians and 72.5% of nurses. Treatment-related adverse events (mostly dizziness/headache) were reported by 42.2% of patients receiving methoxyflurane and 14.9% of patients receiving placebo; none caused withdrawal and the majority were mild and

  20. Elevated Fasting Blood Glucose Is Predictive of Poor Outcome in Non-Diabetic Stroke Patients: A Sub-Group Analysis of SMART.

    Directory of Open Access Journals (Sweden)

    Ming Yao

    Full Text Available Although increasing evidence suggests that hyperglycemia following acute stroke adversely affects clinical outcome, whether the association between glycaemia and functional outcome varies between stroke patients with\\without pre-diagnosed diabetes remains controversial. We aimed to investigate the relationship between the fasting blood glucose (FBG and the 6-month functional outcome in a subgroup of SMART cohort and further to assess whether this association varied based on the status of pre-diagnosed diabetes.Data of 2862 patients with acute ischemic stroke (629 with pre-diagnosed diabetics enrolled from SMART cohort were analyzed. Functional outcome at 6-month post-stroke was measured by modified Rankin Scale (mRS and categorized as favorable (mRS:0-2 or poor (mRS:3-5. Binary logistic regression model, adjusting for age, gender, educational level, history of hypertension and stroke, baseline NIHSS and treatment group, was used in the whole cohort to evaluate the association between admission FBG and functional outcome. Stratified logistic regression analyses were further performed based on the presence/absence of pre-diabetes history.In the whole cohort, multivariable logistical regression showed that poor functional outcome was associated with elevated FBG (OR1.21 (95%CI 1.07-1.37, p = 0.002, older age (OR1.64 (95% CI1.38-1.94, p<0.001, higher NIHSS (OR2.90 (95%CI 2.52-3.33, p<0.001 and hypertension (OR1.42 (95%CI 1.13-1.98, p = 0.04. Stratified logistical regression analysis showed that the association between FBG and functional outcome remained significant only in patients without pre-diagnosed diabetes (OR1.26 (95%CI 1.03-1.55, p = 0.023, but not in those with premorbid diagnosis of diabetes (p = 0.885.The present results demonstrate a significant association between elevated FBG after stroke and poor functional outcome in patients without pre-diagnosed diabetes, but not in diabetics. This finding confirms the importance of glycemic

  1. Individualized functional restoration as an adjunct to advice for lumbar disc herniation with associated radiculopathy. A preplanned subgroup analysis of a randomized controlled trial.

    Science.gov (United States)

    Hahne, Andrew J; Ford, Jon J; Hinman, Rana S; Richards, Matthew C; Surkitt, Luke D; Chan, Alexander Y P; Slater, Sarah L; Taylor, Nicholas F

    2017-03-01

    Physical therapy is commonly sought by people with lumbar disc herniation and associated radiculopathy. It is unclear whether physical therapy is effective for this population. To determine the effectiveness of physical therapist-delivered individualized functional restoration as an adjunct to guideline-based advice in people with lumbar disc herniation and associated radiculopathy. This is a preplanned subgroup analysis of a multicenter parallel group randomized controlled trial. The study included 54 participants with clinical features of radiculopathy (6-week to 6-month duration) and imaging showing a lumbar disc herniation. Primary outcomes were activity limitation (Oswestry Disability Index) and separate 0-10 numerical pain rating scales for leg pain and back pain. Measures were taken at baseline and at 5, 10, 26, and 52 weeks. The participants were randomly allocated to receive either individualized functional restoration incorporating advice (10 sessions) or guideline-based advice alone (2 sessions) over a 10-week period. Treatment was administered by 11 physical therapists at private clinics in Melbourne, Australia. Between-group differences for activity limitation favored the addition of individualized functional restoration to advice alone at 10 weeks (7.7, 95% confidence interval [CI] 0.3-15.1) and 52 weeks (8.2, 95% CI 0.7-15.6), as well as back pain at 10 weeks (1.4, 95% CI 0.2-2.7). There were no significant differences between groups for leg pain at any follow-up. Several secondary outcomes also favored individualized functional restoration over advice. In participants with lumbar disc herniation and associated radiculopathy, an individualized functional restoration program incorporating advice led to greater reduction in activity limitation at 10- and 52-week follow-ups compared with guideline-based advice alone. Although back pain was significantly reduced at 10 weeks with individualized functional restoration, this effect was not maintained at

  2. Longitudinal analysis of cardiovascular disease risk profile in neighbourhood poverty subgroups: 5-year results from an afterschool fitness programme in the USA.

    Science.gov (United States)

    D'Agostino, Emily M; Patel, Hersila H; Hansen, Eric; Mathew, M Sunil; Nardi, Maria; Messiah, Sarah E

    2017-11-24

    The WHO calls for affordable population-based prevention strategies for reducing the global burden of cardiovascular disease (CVD) on morbidity and mortality; however, effective, sustainable and accessible community-based approaches for CVD prevention in at-risk youth have yet to be identified. We examined the effects of implementing a daily park-based afterschool fitness programme on youth CVD risk profiles over 5 years and across area poverty subgroups. The study included 2264 youth (mean age 9.4 years, 54% male, 50% Hispanic, 47% non-Hispanic black, 70% high/very high area poverty) in Miami, Florida, USA. We used three-level repeated measures mixed models to determine the longitudinal effects of programme participation on modifiable CVD outcomes (2010-2016). Duration of programme participation was significantly associated with CVD risk profile improvements, including body mass index (BMI) z-score, diastolic/systolic blood pressure, skinfold thicknesses, waist-hip ratio, sit-ups, push-ups, Progressive Aerobic Cardiovascular Endurance Run (PACER) score, 400 m run time, probability of developing systolic/diastolic hypertension and overweight/obesity in high/very high poverty neighbourhoods (P<0.001). Diastolic blood pressure decreased 3.4 percentile points (95% CI -5.85 to -0.85), 8.1 percentile points (95% CI -11.98 to -4.26), 6.1 percentile points (95% CI -11.49 to -0.66), 7.6 percentile points (95% CI -15.33 to -0.15) and 11.4 percentile points (95% CI -25.32 to 2.61) for 1-5 years, respectively, in high/very high poverty areas. In contrast, significant improvements were found only for PACER score and waist-hip ratio in low/mid poverty areas. This analysis presents compelling evidence demonstrating that park-based afterschool programmes can successfully maintain or improve at-risk youth CVD profiles over multiple years. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No

  3. Genome at juncture of early human migration: a systematic analysis of two whole genomes and thirteen exomes from Kuwaiti population subgroup of inferred Saudi Arabian tribe ancestry.

    Directory of Open Access Journals (Sweden)

    Osama Alsmadi

    Full Text Available Population of the State of Kuwait is composed of three genetic subgroups of inferred Persian, Saudi Arabian tribe and Bedouin ancestry. The Saudi Arabian tribe subgroup traces its origin to the Najd region of Saudi Arabia. By sequencing two whole genomes and thirteen exomes from this subgroup at high coverage (>40X, we identify 4,950,724 Single Nucleotide Polymorphisms (SNPs, 515,802 indels and 39,762 structural variations. Of the identified variants, 10,098 (8.3% exomic SNPs, 139,923 (2.9% non-exomic SNPs, 5,256 (54.3% exomic indels, and 374,959 (74.08% non-exomic indels are 'novel'. Up to 8,070 (79.9% of the reported novel biallelic exomic SNPs are seen in low frequency (minor allele frequency T] from CYP4F2 gene [MIM:*604426] associated with warfarin dosage levels [MIM:#122700] required to elicit normal anticoagulant response; and a 3' UTR SNP (rs6151429 [22:g.51063477T>C] from ARSA gene [MIM:*607574] associated with Metachromatic Leukodystrophy [MIM:#250100]. Hemoglobin Riyadh variant (identified for the first time in a Saudi Arabian woman is observed in the exome data. The mitochondrial haplogroup profiles of the 15 individuals are consistent with the haplogroup diversity seen in Saudi Arabian natives, who are believed to have received substantial gene flow from Africa and eastern provenance. We present the first genome resource imperative for designing future genetic studies in Saudi Arabian tribe subgroup. The full-length genome sequences and the identified variants are available at ftp://dgr.dasmaninstitute.org and http://dgr.dasmaninstitute.org/DGR/gb.html.

  4. Perceived discrimination and chronic health in adults from nine ethnic subgroups in the USA.

    Science.gov (United States)

    Carlisle, Shauna K

    2015-01-01

    This comparative analysis examines the association between chronic cardiovascular, respiratory and pain conditions, race, ethnicity, nativity, length of residency, and perceived discrimination among three racial and nine ethnic subgroups of Asian Americans (Vietnamese, Filipino, and Chinese), Latino-American (Cuban, Portuguese, and Mexican), and Afro-Caribbean American (Haitian, Jamaican, and Trinidadian/Tobagonian) respondents. Analysis used weighted Collaborative Psychiatric Epidemiology Surveys-merged data from the National Latino and Asian American Study and the National Survey of American Life. Logistic regression analysis was conducted to determine which groups within the model were more likely to report perceived discrimination effects. Afro-Caribbean subgroups were more likely to report perceived discrimination than Asian American and Latino-American subgroups were. Logistic regression revealed a significant positive association with perceived discrimination and chronic pain only for Latino-American respondents. Significant differences in reports of perceived discrimination emerged by race and ethnicity. Caribbean respondents were more likely to report high levels of perceived discrimination; however, they showed fewer significant associations related to chronic health conditions compared to Asian Americans and Latino-Americans. Examination of perceived discrimination across ethnic subgroups reveals large variations in the relationship between chronic health and discrimination by race and ethnicity. Examining perceived discrimination by ethnicity may reveal more complex chronic health patterns masked by broader racial groupings.

  5. Cytogenetic Prognostication Within Medulloblastoma Subgroups

    Science.gov (United States)

    Shih, David J.H.; Northcott, Paul A.; Remke, Marc; Korshunov, Andrey; Ramaswamy, Vijay; Kool, Marcel; Luu, Betty; Yao, Yuan; Wang, Xin; Dubuc, Adrian M.; Garzia, Livia; Peacock, John; Mack, Stephen C.; Wu, Xiaochong; Rolider, Adi; Morrissy, A. Sorana; Cavalli, Florence M.G.; Jones, David T.W.; Zitterbart, Karel; Faria, Claudia C.; Schüller, Ulrich; Kren, Leos; Kumabe, Toshihiro; Tominaga, Teiji; Shin Ra, Young; Garami, Miklós; Hauser, Peter; Chan, Jennifer A.; Robinson, Shenandoah; Bognár, László; Klekner, Almos; Saad, Ali G.; Liau, Linda M.; Albrecht, Steffen; Fontebasso, Adam; Cinalli, Giuseppe; De Antonellis, Pasqualino; Zollo, Massimo; Cooper, Michael K.; Thompson, Reid C.; Bailey, Simon; Lindsey, Janet C.; Di Rocco, Concezio; Massimi, Luca; Michiels, Erna M.C.; Scherer, Stephen W.; Phillips, Joanna J.; Gupta, Nalin; Fan, Xing; Muraszko, Karin M.; Vibhakar, Rajeev; Eberhart, Charles G.; Fouladi, Maryam; Lach, Boleslaw; Jung, Shin; Wechsler-Reya, Robert J.; Fèvre-Montange, Michelle; Jouvet, Anne; Jabado, Nada; Pollack, Ian F.; Weiss, William A.; Lee, Ji-Yeoun; Cho, Byung-Kyu; Kim, Seung-Ki; Wang, Kyu-Chang; Leonard, Jeffrey R.; Rubin, Joshua B.; de Torres, Carmen; Lavarino, Cinzia; Mora, Jaume; Cho, Yoon-Jae; Tabori, Uri; Olson, James M.; Gajjar, Amar; Packer, Roger J.; Rutkowski, Stefan; Pomeroy, Scott L.; French, Pim J.; Kloosterhof, Nanne K.; Kros, Johan M.; Van Meir, Erwin G.; Clifford, Steven C.; Bourdeaut, Franck; Delattre, Olivier; Doz, François F.; Hawkins, Cynthia E.; Malkin, David; Grajkowska, Wieslawa A.; Perek-Polnik, Marta; Bouffet, Eric; Rutka, James T.; Pfister, Stefan M.; Taylor, Michael D.

    2014-01-01

    Purpose Medulloblastoma comprises four distinct molecular subgroups: WNT, SHH, Group 3, and Group 4. Current medulloblastoma protocols stratify patients based on clinical features: patient age, metastatic stage, extent of resection, and histologic variant. Stark prognostic and genetic differences among the four subgroups suggest that subgroup-specific molecular biomarkers could improve patient prognostication. Patients and Methods Molecular biomarkers were identified from a discovery set of 673 medulloblastomas from 43 cities around the world. Combined risk stratification models were designed based on clinical and cytogenetic biomarkers identified by multivariable Cox proportional hazards analyses. Identified biomarkers were tested using fluorescent in situ hybridization (FISH) on a nonoverlapping medulloblastoma tissue microarray (n = 453), with subsequent validation of the risk stratification models. Results Subgroup information improves the predictive accuracy of a multivariable survival model compared with clinical biomarkers alone. Most previously published cytogenetic biomarkers are only prognostic within a single medulloblastoma subgroup. Profiling six FISH biomarkers (GLI2, MYC, chromosome 11 [chr11], chr14, 17p, and 17q) on formalin-fixed paraffin-embedded tissues, we can reliably and reproducibly identify very low-risk and very high-risk patients within SHH, Group 3, and Group 4 medulloblastomas. Conclusion Combining subgroup and cytogenetic biomarkers with established clinical biomarkers substantially improves patient prognostication, even in the context of heterogeneous clinical therapies. The prognostic significance of most molecular biomarkers is restricted to a specific subgroup. We have identified a small panel of cytogenetic biomarkers that reliably identifies very high-risk and very low-risk groups of patients, making it an excellent tool for selecting patients for therapy intensification and therapy de-escalation in future clinical trials. PMID

  6. Linear stability analysis reveals exclusion zone for sliding bed transport

    Directory of Open Access Journals (Sweden)

    Talmon Arnold M.

    2015-06-01

    Full Text Available A bend or any another pipe component disturbs solids transport in pipes. Longitudinal pressure profiles downstream of such a component may show a stationary transient harmonic wave, as revealed by a recent settling slurry laboratory experiment. Therefore the fundamental transient response of the two-layer model for fully stratified flow is investigated as a first approach. A linear stability analysis of the sliding bed configuration is conducted. No stationary transient harmonic waves are found in this analysis, but adaptation lengths for exponential recovery are quantified. An example calculation is given for a 0.1 m diameter pipeline.

  7. Microbiota analysis to reveal temperature abuse of fresh pork

    DEFF Research Database (Denmark)

    Buschhardt, Tasja; Bahl, Martin Iain; Hansen, Tina Beck

    Violations of temperature regulations in the meat chain may affect meat safety. Methods are lacking to estimate whether meat has been subjected to temperature abuse. Exposure to too high temperatures may lead to systematic changes in the diverse bacterial communities of fresh meat. We investigated...... whether temperature induced changes in the community composition on fresh meat surfaces can reflect the temperature-history (combination of time and temperature). Sterile pieces of pork were inoculated with a carcass swab homogenate, to which Salmonella was added. Changes in the meat microbiota were...... was dominated by Pseudomonas only. We also showed that the initial community affects subsequent changes during storage. The results suggest that principal coordinate analysis of beta diversity could be a useful tool to reveal temperature abused meat. Sequence data and culturing data revealed a strong positive...

  8. Joint genetic analysis using variant sets reveals polygenic gene-context interactions.

    Directory of Open Access Journals (Sweden)

    Francesco Paolo Casale

    2017-04-01

    Full Text Available Joint genetic models for multiple traits have helped to enhance association analyses. Most existing multi-trait models have been designed to increase power for detecting associations, whereas the analysis of interactions has received considerably less attention. Here, we propose iSet, a method based on linear mixed models to test for interactions between sets of variants and environmental states or other contexts. Our model generalizes previous interaction tests and in particular provides a test for local differences in the genetic architecture between contexts. We first use simulations to validate iSet before applying the model to the analysis of genotype-environment interactions in an eQTL study. Our model retrieves a larger number of interactions than alternative methods and reveals that up to 20% of cases show context-specific configurations of causal variants. Finally, we apply iSet to test for sub-group specific genetic effects in human lipid levels in a large human cohort, where we identify a gene-sex interaction for C-reactive protein that is missed by alternative methods.

  9. Soft n-Ary Subgroups

    Directory of Open Access Journals (Sweden)

    D.R. Prince Williams

    2015-09-01

    Full Text Available Soft set theory plays a vital role in solving many complicated problems with inherited uncertainty. An n-ary algebraic systems is a generalization of algebraic structures and it is the most natural way for the further development, deeper understanding of their properties. In this paper, we apply soft set theory to an n-ary algebraic systems and introduce the notions of soft n-ary groups and soft n-ary subgroups. Further, some operations on soft sets are extended to the former. Finally, we provide the characterization of soft n-ary subgroups over an n-ary group (G,f and study their related properties.

  10. On Cosets and Normal Subgroups

    OpenAIRE

    B. O. ONASANYA; S.A.Ilori

    2014-01-01

    The paper [5] has worked on fuzzy cosets and fuzzy normal subgroups of a group, [8] has extended the idea to fuzzy middle coset. In addition to what has been done, we make a link between fuzzy coset and fuzzy middle coset and investigate some more properties of the fuzzy middle coset. [7] made attempt with some results needing adjustment. [2], [8] and [9] have shown that if f 2 F(Sn), the set of all fuzzy subgroups of Sn, is such that Imf has the highest order and f is constant on the conjuga...

  11. Phylogenetic analysis of ferlin genes reveals ancient eukaryotic origins

    Directory of Open Access Journals (Sweden)

    Lek Monkol

    2010-07-01

    Full Text Available Abstract Background The ferlin gene family possesses a rare and identifying feature consisting of multiple tandem C2 domains and a C-terminal transmembrane domain. Much currently remains unknown about the fundamental function of this gene family, however, mutations in its two most well-characterised members, dysferlin and otoferlin, have been implicated in human disease. The availability of genome sequences from a wide range of species makes it possible to explore the evolution of the ferlin family, providing contextual insight into characteristic features that define the ferlin gene family in its present form in humans. Results Ferlin genes were detected from all species of representative phyla, with two ferlin subgroups partitioned within the ferlin phylogenetic tree based on the presence or absence of a DysF domain. Invertebrates generally possessed two ferlin genes (one with DysF and one without, with six ferlin genes in most vertebrates (three DysF, three non-DysF. Expansion of the ferlin gene family is evident between the divergence of lamprey (jawless vertebrates and shark (cartilaginous fish. Common to almost all ferlins is an N-terminal C2-FerI-C2 sandwich, a FerB motif, and two C-terminal C2 domains (C2E and C2F adjacent to the transmembrane domain. Preservation of these structural elements throughout eukaryotic evolution suggests a fundamental role of these motifs for ferlin function. In contrast, DysF, C2DE, and FerA are optional, giving rise to subtle differences in domain topologies of ferlin genes. Despite conservation of multiple C2 domains in all ferlins, the C-terminal C2 domains (C2E and C2F displayed higher sequence conservation and greater conservation of putative calcium binding residues across paralogs and orthologs. Interestingly, the two most studied non-mammalian ferlins (Fer-1 and Misfire in model organisms C. elegans and D. melanogaster, present as outgroups in the phylogenetic analysis, with results suggesting

  12. The features of Drosophila core promoters revealed by statistical analysis

    Directory of Open Access Journals (Sweden)

    Trifonov Edward N

    2006-06-01

    Full Text Available Abstract Background Experimental investigation of transcription is still a very labor- and time-consuming process. Only a few transcription initiation scenarios have been studied in detail. The mechanism of interaction between basal machinery and promoter, in particular core promoter elements, is not known for the majority of identified promoters. In this study, we reveal various transcription initiation mechanisms by statistical analysis of 3393 nonredundant Drosophila promoters. Results Using Drosophila-specific position-weight matrices, we identified promoters containing TATA box, Initiator, Downstream Promoter Element (DPE, and Motif Ten Element (MTE, as well as core elements discovered in Human (TFIIB Recognition Element (BRE and Downstream Core Element (DCE. Promoters utilizing known synergetic combinations of two core elements (TATA_Inr, Inr_MTE, Inr_DPE, and DPE_MTE were identified. We also establish the existence of promoters with potentially novel synergetic combinations: TATA_DPE and TATA_MTE. Our analysis revealed several motifs with the features of promoter elements, including possible novel core promoter element(s. Comparison of Human and Drosophila showed consistent percentages of promoters with TATA, Inr, DPE, and synergetic combinations thereof, as well as most of the same functional and mutual positions of the core elements. No statistical evidence of MTE utilization in Human was found. Distinct nucleosome positioning in particular promoter classes was revealed. Conclusion We present lists of promoters that potentially utilize the aforementioned elements/combinations. The number of these promoters is two orders of magnitude larger than the number of promoters in which transcription initiation was experimentally studied. The sequences are ready to be experimentally tested or used for further statistical analysis. The developed approach may be utilized for other species.

  13. Eating disorder behavior and early maladaptive schemas in subgroups of eating disorders.

    Science.gov (United States)

    Unoka, Zsolt; Tölgyes, Tamás; Czobor, Pál; Simon, Lajos

    2010-06-01

    To examine relationship between Eating Disorder Behaviors (EDB) and Early Maladaptive Schemas (EMS) across eating disorder (ED) subgroups. EMS and ED behaviors were measured by Young Schema Questionnaire and Eating Behavior Severity Scale, respectively, among patients diagnosed with Restrictive or Binge/purging Anorexia, or bulimia nervosa. Canonical component analysis showed significant association between ED behaviors and EMSs. Canonical factor-pairs (EDB and EMS) revealed specific associations between certain patterns of EDBs, including binge-purging and physical exercise, and certain patterns of maladaptive cognitive schema, including Emotional deprivation, Abandonment, Enmeshments, Subjugation, and Emotional inhibition. ED subgroups significantly differred between the EMS and EDB canonical factors, respectively. Our findings indicate that EMS and EDB are associated, and that the factors that potentially mediate the association differ significantly among ED subgroups. These results are consistent with the notion that EMSs play a specific role in the development and maintenance of ED behaviors.

  14. Hopf algebras and congruence subgroups

    CERN Document Server

    Sommerhauser, Yorck

    2007-01-01

    We prove that the kernel of the natural action of the modular group on the center of the Drinfel'd double of a semisimple Hopf algebra is a congruence subgroup. To do this, we introduce a class of generalized Frobenius-Schur indicators and endow it with an action of the modular group that is compatible with the original one.

  15. Erratum The congruence subgroup problem

    Indian Academy of Sciences (India)

    R. Narasimhan (Krishtel eMaging) 1461 1996 Oct 15 13:05:22

    . 299–308). The congruence subgroup problem. M S RAGHUNATHAN. There is unfortunately an error in the paper cited above in the very first page. We correct this error (which does not materially affect the rest of the paper in any way) below.

  16. Mathematical Analysis of Biomolecular Network Reveals Connections Between Diseases

    Science.gov (United States)

    Wang, Guanyu

    2012-02-01

    Connections between cancer and metabolic diseases may consist in the complex network of interactions among a common set of biomolecules. By applying singularity and bifurcation analysis, the phenotypes constrained by the AKT signaling pathway are identified and mapped onto the parameter space, which include cancer and certain metabolic diseases. By considering physiologic properties (sensitivity, robustness and adaptivity) the AKT pathway must possess in order to efficiently sense growth factors and nutrients, the region of normal responses is located. The analysis illuminates the parameter space and reveals system-level mechanisms in regulating biological functions (cell growth, survival, proliferation and metabolism) and how their deregulation may lead to the development of diseases. The analytical expressions summarize the synergistic interactions among many molecules, which provides valuable insights into therapeutic interventions.

  17. Finite groups all of whose minimal subgroups are NE∗ -subgroups

    Indian Academy of Sciences (India)

    We prove the following theorem which is an improvement of a recent result due to Asaad and Ramadan (see Theorem 1.1 of [2]). Hence, Q8 will denote the quaternion group of order 8 and a group G is called Q8-free if no quotient group of any subgroup of G is isomorphic to Q8. Throughout this paper, L will denote the class.

  18. High local recurrence risk is not associated with large survival reduction after postmastectomy radiotherapy in high-risk breast cancer: a subgroup analysis of DBCG 82 b

    DEFF Research Database (Denmark)

    Kyndi, Marianne; Overgaard, Marie; Nielsen, Hanne M

    2009-01-01

    randomly assigned to not receive radiotherapy, three prognostic subgroups of LR risk were found. "The good" defined by at least four out of five favorable criteria (3 positive nodes, tumor size 2cm, Grade 1 malignancy, estrogen or progesterone receptor positive, HER2 negative), "the Poor" defined...... radiotherapy in the DBCG82 b&c trials. Tissue microarrays had been constructed and sections stained for estrogen, progesterone and HER2 receptors. Median potential follow-up time was 17 years. Endpoints were LR as isolated first event, breast cancer mortality and overall mortality. RESULTS: Among patients...... by at least two out of three un-favorable criteria (>3 positive nodes, tumor size >5cm, Grade 3 malignancy) and finally "the Intermediate" the group in between. The smallest absolute reduction in 5-year LR probability (11%) after radiotherapy was seen for the good prognosis group. A similar absolute reduction...

  19. Subgrouping for patients with low back pain: a multidimensional approach incorporating cluster analysis and the STarT Back Screening Tool.

    Science.gov (United States)

    Beneciuk, Jason M; Robinson, Michael E; George, Steven Z

    2015-01-01

    Early screening for psychological distress has been suggested to improve patient management for individuals experiencing low back pain. This study compared 2 approaches to psychological screening (ie, multidimensional and unidimensional) so that preliminary recommendations on which approach may be appropriate for use in clinical settings other than primary care could be provided. Specifically, this study investigated aspects of the STarT Back Screening Tool (SBT): 1) discriminant validity by evaluating its relationship with unidimensional psychological measures and 2) construct validity by evaluating how SBT risk categories compared to empirically derived subgroups using unidimensional psychological and disability measures. Patients (N = 146) receiving physical therapy for LBP were administered the SBT and a battery of unidimensional psychological measures at initial evaluation. Clinical measures consisted of pain intensity and self-reported disability. Several SBT risk-dependent relationships (ie, SBT low low profiles; therefore, 2 groups may provide a clearer representation of the level of pain-associated psychological distress, maladaptive coping, and disability in this setting compared with 3 groups as suggested when using the SBT in primary care settings. This study suggests that the SBT can replace administering several unidimensional psychological measures as a first-line screening measure for psychological distress. However, clinicians need to be aware of the potential for misclassification with SBT results when compared to unidimensional measures. This study also suggests that a modified SBT risk stratification scheme based on empirically derived subgroups could potentially assist in identifying elevated levels of pain-associated psychological distress, maladaptive coping, and disability in practice settings outside of primary care. Patients identified with elevated levels of pain-associated distress and maladaptive coping may be indicated for

  20. Subgroup analysis of the non-interventional study VIVALDI: agomelatine in treatment-naïve patients, in combination therapy and after treatment switch.

    Science.gov (United States)

    Laux, Gerd; Huttner, Nadja A

    2014-06-01

    Agomelatine has demonstrated antidepressant efficacy in randomized, controlled trials. This non-interventional study VIVALDI evaluated agomelatine treatment under practice conditions. Psychiatrists documented the treatment of 3,317 patients over 12 weeks. According to the treatment condition three subgroups were selected: Agomelatine in treatment-naïve patients as mono-therapy (A), in pretreated patients as add-on-therapy (B), and in pretreated patients switched to agomelatine (C). Effect on depressive symptoms was evaluated via svMADRS and CGI. Daytime functioning and sleep-wake rhythm were assessed by a patient-questionnaire. The svMADRS decreased from values > 30 at baseline to 12.8 (total population), 10.3 (A), 15.1 (B), and 13.5 (C). 76.1%, 55.7%, and 62.5% of patients were responders in subgroups A, B, and C, respectively, 65.8% in the total population. Remission was achieved in 66.5% (A), 44.7% (B), and 50.9% (C) of patients. After 12 weeks, subjective sleep quality and daytime functioning improved in the majority of patients. Adverse drug reactions (ADR/serious ADR) were reported for 6.0%/0% (A), 11.0%/0.2% (B), and 12.6%/0.3% (C) of patients. Overall, 25.8% of patients discontinued treatment prematurely, 5.2% due to ADR. Agomelatine improved depressive symptoms, daytime functioning, and sleep-wake rhythm, and demonstrated good tolerability also in pretreated patients and combination therapy under routine practice.

  1. Principal component analysis of ensemble recordings reveals cell assemblies at high temporal resolution.

    Science.gov (United States)

    Peyrache, Adrien; Benchenane, Karim; Khamassi, Mehdi; Wiener, Sidney I; Battaglia, Francesco P

    2010-08-01

    Simultaneous recordings of many single neurons reveals unique insights into network processing spanning the timescale from single spikes to global oscillations. Neurons dynamically self-organize in subgroups of coactivated elements referred to as cell assemblies. Furthermore, these cell assemblies are reactivated, or replayed, preferentially during subsequent rest or sleep episodes, a proposed mechanism for memory trace consolidation. Here we employ Principal Component Analysis to isolate such patterns of neural activity. In addition, a measure is developed to quantify the similarity of instantaneous activity with a template pattern, and we derive theoretical distributions for the null hypothesis of no correlation between spike trains, allowing one to evaluate the statistical significance of instantaneous coactivations. Hence, when applied in an epoch different from the one where the patterns were identified, (e.g. subsequent sleep) this measure allows to identify times and intensities of reactivation. The distribution of this measure provides information on the dynamics of reactivation events: in sleep these occur as transients rather than as a continuous process.

  2. Functional dyspepsia: relationship between clinical subgroups and Helicobacter pylori status in Western Turkey

    Directory of Open Access Journals (Sweden)

    M. Saruc

    2003-06-01

    Full Text Available The etiology of functional dyspepsia is not known. The objective of the present study was to determine the characteristics of functional dyspepsia in Western Turkey. We divided 900 patients with functional dyspepsia into three subgroups according to symptoms: ulcer-like (UL, 321 (35.6%, motility disorder-like (ML, 281 (31.2%, and the combination (C of these symptoms, 298 (33.1%. All patients were submitted to endoscopic evaluation, with two biopsies taken from the cardia and corpus, and four from the antrum of the stomach. All biopsy samples were studied for Helicobacter pylori (Hp density, chronic inflammation, activity, intestinal metaplasia, atrophy, and the presence of lymphoid aggregates by histological examination. One antral biopsy was used for the rapid urease test. Tissue cagA status was determined by PCR from an antral biopsy specimen by a random sampling method. We also determined the serum levels of tumor necrosis factor-alpha (TNF-alpha and gastrin by the same method. Data were analyzed statistically by the Kolmogorov-Smirnov test and by analysis of variance. Hp and cagA positivity was significantly higher in the UL subgroup than in the others. The patients in the ML subgroup had the lowest Hp and cagA positivity and Hp density. The ML subgroup also showed the lowest level of Hp-induced inflammation among all subgroups. The serum levels of TNF-alpha and gastrin did not reveal any difference between groups. Our findings show a poor association of Hp with the ML subgroup of functional dyspepsia, but a stronger association with the UL and C subgroups.

  3. Comparisons of the Clinical Outcomes and Urodynamic Effects of Mirabegron versus Tolterodine Treatment for Female Overactive Bladder Syndrome: A Subgroup Analysis of a Controlled, Randomised, Prospective Study.

    Science.gov (United States)

    Hsiao, Sheng-Mou; Chang, Ting-Chen; Chen, Chi-Hau; Wu, Wen-Yih; Lin, Ho-Hsiung

    2017-04-23

    The impact of mirabegron on clinical outcome and urodynamic parameters may be important for clinical practice. Thus, the aim of this study was to compare the clinical outcomes and urodynamic effects of mirabegron (Betmiga 50 mg) versus tolterodine (Detrusitol ER 4 mg) treatment for women with overactive bladder syndrome (OAB). Women with OAB were randomized to receive 12 weeks of mirabegron 50 mg, tolterodine extended-release 4 mg or placebo treatment. The clinical outcomes and urodynamic effects were compared between the subgroups. Thirty-three women completed 12 weeks of mirabegron (n = 12), tolterodine (n = 12) or placebo (n = 9) treatment. A significant increase in the volumes at strong desire to void and a decrease in the daytime frequency episodes were identified in the mirabegron and tolterodine groups (all P < 0.05). Nonetheless, a decrease in the total voided volume was identified following mirabegron treatment but not tolterodine (P = 0.02). Mirabegron and tolterodine exhibit similar changes in the urodynamics and bladder diary parameters. However, mirabegron may decrease the total voided volume. These findings may serve as an initial guide or assist in consultations regarding the treatment of OAB patients with mirabegron. © 2017 John Wiley & Sons Australia, Ltd.

  4. Work demands and health consequences of organizational and technological measures introduced to enhance the quality of home care services--A subgroup analysis.

    Science.gov (United States)

    Andersen, Gunn Robstad; Bendal, Synne; Westgaard, Rolf H

    2015-11-01

    This study of home care workers in a Norwegian municipality aimed to examine the effect of two measures involving organizational (job checklists) and technological (personal digital assistants) job aids on perceived work demands and musculoskeletal health. Questionnaire data was collected in 2009 (n = 138, response rate 76.2%) and 2011 (n = 80, response rate 54%). Forty-six home care workers responded at both waves. Respondents were assigned into 'high', 'moderate' and 'low' strain groups based on their responses to open and closed survey questions regarding impact of the two measures. One-way ANOVA with post-hoc t-tests and regression analyses investigated group differences and examined development in variables. Perceived work demands and health effects over the two-year study period were unchanged overall, yet significant differences between subgroups were highlighted. Work demands and shoulder-neck pain remained high for high-strain workers, but were reduced for low and moderate strain workers. Management should be aware of diversity in worker responses to rationalizations and give priority to supplementary, targeted measures to counteract adverse effects. Copyright © 2015 Elsevier Ltd and The Ergonomics Society. All rights reserved.

  5. Rescue of avian leukosis subgroup-J-associated acutely transforming viruses carrying different lengths of the v-fps oncogene and analysis of their tumorigenicity.

    Science.gov (United States)

    Wang, Yixin; Fang, Lichun; Li, Jianliang; Li, Yang; Cui, Shuai; Sun, Xiaolong; Chang, Shuang; Zhao, Peng; Cui, Zhizhong

    2016-12-01

    In our previous study, six subgroup J strains of avian leukosis virus (ALV-J)-associated acutely transforming viruses carrying different lengths of the v-fps oncogene, designated as Fu-J and Fu-J1-5, were isolated and characterized from fibrosarcomas in ALV-J-infected chickens. In the present study, the oncogenic potential of Fu-J and Fu-J1-5 was investigated using a reverse genetics technique. Six replication-defective viruses, named rFu-J and rFu-J1-5, were rescued with the replication-competent rescued ALV-J strain rSDAU1005 as a helper virus by co-transfection of chicken embryo fibroblast monolayers with infectious clone plasmids. Experimental bird studies were performed, demonstrating that only the rescued rFu-J virus carrying the complete v-fps oncogene with rSDAU1005 as the helper virus could induce acute fibrosarcoma after inoculation in specific-pathogen-free (SPF) chickens. These results provide direct evidence that the replication-defective acutely transforming Fu-J virus, with the complete v-fps oncogene, was associated with acute fibrosarcoma in chickens infected with ALV-J in the field, as reported previously.

  6. Sub-grouping of Plasmodium falciparum 3D7 var genes based on sequence analysis of coding and non-coding regions

    DEFF Research Database (Denmark)

    Lavstsen, Thomas; Salanti, Ali; Jensen, Anja T R

    2003-01-01

    -grouped into three major groups (group A, B and C) and two intermediate groups B/A and B/C representing transitions between the three major groups. The best defined var group, group A, comprises telomeric genes transcribed towards the telomere encoding PfEMP1s with complex domain structures different from the 4...... and organization of the 3D7 PfEMP1 repertoire was investigated on the basis of the complete genome sequence. METHODS: Using two tree-building methods we analysed the coding and non-coding sequences of 3D7 var and rif genes as well as var genes of other parasite strains. RESULTS: var genes can be sub......-domain type dominant of groups B and C. Two sequences belonging to the var1 and var2 subfamilies formed independent groups. A rif subgroup transcribed towards the centromere was found neighbouring var genes of group A such that the rif and var 5' regions merged. This organization appeared to be unique...

  7. Efficacy of aripiprazole augmentation in Japanese patients with major depressive disorder: a subgroup analysis and Montgomery-Åsberg Depression Rating Scale and Hamilton Rating Scale for Depression item analyses of the Aripiprazole Depression Multicenter Efficacy study.

    Science.gov (United States)

    Ozaki, Norio; Otsubo, Tempei; Kato, Masaki; Higuchi, Teruhiko; Ono, Hiroaki; Kamijima, Kunitoshi

    2015-01-01

    Results from this randomized, placebo-controlled study of aripiprazole augmentation to antidepressant therapy (ADT) in Japanese patients with major depressive disorder (MDD) (the Aripiprazole Depression Multicenter Efficacy [ADMIRE] study) revealed that aripiprazole augmentation was superior to ADT alone and was well tolerated. In subgroup analyses, we investigated the influence of demographic- and disease-related factors on the observed responses. We also examined how individual symptom improvement was related to overall improvement in MDD. Data from the ADMIRE study were analyzed. Subgroup analyses were performed on the primary outcome measures: the mean change in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score from the end of selective serotonin reuptake inhibitor (SSRI)/serotonin norepinephrine reuptake inhibitor (SNRI) treatment to the end of the randomized treatment. Changes in the MADRS total scores were consistently greater with aripiprazole than placebo in each of the subgroups. Efficacy was not related to sex, age, number of adequate ADT trials in the current episode, MDD diagnosis, number of depressive episodes, duration of the current episode, age at first depressive episode, time since the first depressive episode, type of SSRI/SNRI, or severity at the end of SSRI/SNRI treatment phase. Compared to placebo, aripiprazole resulted in significant and rapid improvement on seven of the 10 MADRS items, including sadness. These post-hoc analyses indicated that aripiprazole was effective for a variety of Japanese patients with MDD who had exhibited inadequate responses to ADT. Additionally, we suggest that aripiprazole significantly and rapidly improved the core depressive symptoms. © 2014 The Authors. Psychiatry and Clinical Neurosciences © 2014 Japanese Society of Psychiatry and Neurology.

  8. Dynamic transcriptome analysis reveals AP2/ERF transcription factors responsible for cold stress in rapeseed (Brassica napus L.).

    Science.gov (United States)

    Du, Chunfang; Hu, Kaining; Xian, Shuanshi; Liu, Chunqing; Fan, Jianchun; Tu, Jinxing; Fu, Tingdong

    2016-06-01

    The APETALA2/ethylene response factor (AP2/ERF) transcription factor (TF) superfamily plays an important regulatory role in signal transduction of the plant responses to various stresses including low temperature. Significant progress has been made in understanding the mechanism of cold resistance in Brassica napus, an important oilseed crop. However, comprehensive studies on the induction and activity of these TFs under low temperature have been lacking. In this study, 132 AP2/ERF genes were identified by transcriptome sequencing of rapeseed leaves exposed to 0, 2, 6, 12, and 24 h of low (4 °C) temperature stress. The genes were classified into 4 subfamilies (AP2, DREB, ERF, and RAV) and 13 subgroups, among which the DREB subfamily and ERF subfamily contained 114 genes, no genes were assigned to soloist or DREB A3 subgroups. One hundred and eighteen genes were located on chromosomes A1 to C9. GO functional analysis and promoter sequence analysis revealed that these genes are involved in many molecular pathways that may enhance cold resistance in plants, such as the low-temperature responsiveness, methyl jasmonate, abscisic acid, and ethylene-responsiveness pathways. Their expression patterns revealed dynamic control at different times following initiation of cold stress; the RAV and DREB subfamilies were expressed at the early stage of cold stress, whereas the AP2 subfamily was expressed later. Quantitative PCR analyses of 13 cold-induced AP2/ERF TFs confirmed the accuracy of above results. This study is the first dynamic analysis of the AP2/ERF TFs responsible for cold stress in rapeseed. These findings will serve as a reference for future functional research on transcription in rapeseed.

  9. Demonstration of Microbial Subgroups among Normal Vaginal Microbiota Data

    OpenAIRE

    Lee, M.-L. T.

    2011-01-01

    In this study we identified subgroups of observations relating to the healthy vaginal microbiota. This microbiota resides in a dynamic environment that undergoes cyclic change during the menstrual cycle. Cluster analysis procedures were applied to divide a set of 226 normal microbiota observations into groups. Three subgroups containing 100, 65, and 61 observations were identified. Plots of principal components determined by canonical analysis were obtained to demonstrate graphically the clus...

  10. Diversity of Pseudomonas Genomes, Including Populus-Associated Isolates, as Revealed by Comparative Genome Analysis

    Science.gov (United States)

    Jun, Se-Ran; Wassenaar, Trudy M.; Nookaew, Intawat; Hauser, Loren; Wanchai, Visanu; Land, Miriam; Timm, Collin M.; Lu, Tse-Yuan S.; Schadt, Christopher W.; Doktycz, Mitchel J.; Pelletier, Dale A.

    2015-01-01

    The Pseudomonas genus contains a metabolically versatile group of organisms that are known to occupy numerous ecological niches, including the rhizosphere and endosphere of many plants. Their diversity influences the phylogenetic diversity and heterogeneity of these communities. On the basis of average amino acid identity, comparative genome analysis of >1,000 Pseudomonas genomes, including 21 Pseudomonas strains isolated from the roots of native Populus deltoides (eastern cottonwood) trees resulted in consistent and robust genomic clusters with phylogenetic homogeneity. All Pseudomonas aeruginosa genomes clustered together, and these were clearly distinct from other Pseudomonas species groups on the basis of pangenome and core genome analyses. In contrast, the genomes of Pseudomonas fluorescens were organized into 20 distinct genomic clusters, representing enormous diversity and heterogeneity. Most of our 21 Populus-associated isolates formed three distinct subgroups within the major P. fluorescens group, supported by pathway profile analysis, while two isolates were more closely related to Pseudomonas chlororaphis and Pseudomonas putida. Genes specific to Populus-associated subgroups were identified. Genes specific to subgroup 1 include several sensory systems that act in two-component signal transduction, a TonB-dependent receptor, and a phosphorelay sensor. Genes specific to subgroup 2 contain hypothetical genes, and genes specific to subgroup 3 were annotated with hydrolase activity. This study justifies the need to sequence multiple isolates, especially from P. fluorescens, which displays the most genetic variation, in order to study functional capabilities from a pangenomic perspective. This information will prove useful when choosing Pseudomonas strains for use to promote growth and increase disease resistance in plants. PMID:26519390

  11. Elevated Fasting Blood Glucose Is Predictive of Poor Outcome in Non-Diabetic Stroke Patients: A Sub-Group Analysis of SMART.

    Science.gov (United States)

    Yao, Ming; Ni, Jun; Zhou, Lixin; Peng, Bin; Zhu, Yicheng; Cui, Liying

    2016-01-01

    Although increasing evidence suggests that hyperglycemia following acute stroke adversely affects clinical outcome, whether the association between glycaemia and functional outcome varies between stroke patients with\\without pre-diagnosed diabetes remains controversial. We aimed to investigate the relationship between the fasting blood glucose (FBG) and the 6-month functional outcome in a subgroup of SMART cohort and further to assess whether this association varied based on the status of pre-diagnosed diabetes. Data of 2862 patients with acute ischemic stroke (629 with pre-diagnosed diabetics) enrolled from SMART cohort were analyzed. Functional outcome at 6-month post-stroke was measured by modified Rankin Scale (mRS) and categorized as favorable (mRS:0-2) or poor (mRS:3-5). Binary logistic regression model, adjusting for age, gender, educational level, history of hypertension and stroke, baseline NIHSS and treatment group, was used in the whole cohort to evaluate the association between admission FBG and functional outcome. Stratified logistic regression analyses were further performed based on the presence/absence of pre-diabetes history. In the whole cohort, multivariable logistical regression showed that poor functional outcome was associated with elevated FBG (OR1.21 (95%CI 1.07-1.37), p = 0.002), older age (OR1.64 (95% CI1.38-1.94), pimportance of glycemic control during acute phase of ischemic stroke especially in patients without pre-diagnosed diabetes. Further investigation for developing optimal strategies to control blood glucose level in hyperglycemic setting is therefore of great importance. ClinicalTrials.gov NCT00664846.

  12. Cardiovascular and renal protective role of angiotensin blockade in hypertension with advanced CKD: a subgroup analysis of ATTEMPT-CVD randomized trial.

    Science.gov (United States)

    Kim-Mitsuyama, Shokei; Soejima, Hirofumi; Yasuda, Osamu; Node, Koichi; Jinnouchi, Hideaki; Yamamoto, Eiichiro; Sekigami, Taiji; Ogawa, Hisao; Matsui, Kunihiko

    2018-02-16

    The ATTEMPT-CVD study was prospective randomized active-controlled trial and the main findings had been reported. According to baseline GFR and albuminuria categories, we divided the patients of the ATTEMPT-CVD study into 2 subgroups: (Group 1) the patients with at least one of eGFR of <45 ml/min per 1.73 m 2 and UACR of ≥300 mg/g creatinine, defined as G3b and/or A3; (Group 2) the patients except for Group 1, defined as the other patients. In patients with G3b and/or A3, the incidence of cardiovascular events was significantly less in ARB group than in non-ARB group (11 vs 22, respectively) (HR = 0.465: 95%CI = 0.224-0.965; P = 0.040). UACR was significantly less in ARB group than in non-ARB group during follow-up period in patients with G3b and/or A3 (P = 0.0003), while eGFR, plasma BNP levels, and blood pressure were comparable between ARB and non-ARB groups. Allocation to ARB therapy was a significant independent prognostic factor for cardiovascular events in patients with G3b and/or A3 (P = 0.0268). On the other hand, in the other patients, the occurrence of cardiovascular events was comparable between ARB and non-ARB groups. In patients with advanced CKD, ARB-based therapy may confer greater benefit in prevention of cardiovascular events than non-ARB therapy.

  13. Discovery-based protein expression profiling identifies distinct subgroups and pathways in leiomyosarcomas

    DEFF Research Database (Denmark)

    Kirik, Ufuk; Hansson, Karin; Krogh, Morten

    2014-01-01

    subgroups within the leiomyosarcomas with distinct protein expression patterns. Pathways analysis indicates that key biologic nodes like apoptosis, cytoskeleton remodeling, and telomere regulation are differentially regulated among these subgroups. Finally, investigating the similarities between protein...

  14. Sequence analysis reveals mosaic genome of Aichi virus

    Directory of Open Access Journals (Sweden)

    Han Xiaohong

    2011-08-01

    Full Text Available Abstract Aichi virus is a positive-sense and single-stranded RNA virus, which demonstrated to be related to diarrhea of Children. In the present study, phylogenetic and recombination analysis based on the Aichi virus complete genomes available in GenBank reveal a mosaic genome sequence [GenBank: FJ890523], of which the nt 261-852 region (the nt position was based on the aligned sequence file shows close relationship with AB010145/Japan with 97.9% sequence identity, while the other genomic regions show close relationship with AY747174/German with 90.1% sequence identity. Our results will provide valuable hints for future research on Aichi virus diversity. Aichi virus is a member of the Kobuvirus genus of the Picornaviridae family 12 and belongs to a positive-sense and single-stranded RNA virus. Its presence in fecal specimens of children suffering from diarrhea has been demonstrated in several Asian countries 3456, in Brazil and German 7, in France 8 and in Tunisia 9. Some reports showed the high level of seroprevalence in adults 710, suggesting the widespread exposure to Aichi virus during childhood. The genome of Aichi virus contains 8,280 nucleotides and a poly(A tail. The single large open reading frame (nt 713-8014 according to the strain AB010145 encodes a polyprotein of 2,432 amino acids that is cleaved into the typical picornavirus structural proteins VP0, VP3, VP1, and nonstructural proteins 2A, 2B, 2C, 3A, 3B, 3C and 3D 211. Based on the phylogenetic analysis of 519-bp sequences at the 3C-3D (3CD junction, Aichi viruses can be divided into two genotypes A and B with approximately 90% sequence homology 12. Although only six complete genomes of Aichi virus were deposited in GenBank at present, mosaic genomes can be found in strains from different countries.

  15. Sequence analysis reveals mosaic genome of Aichi virus.

    Science.gov (United States)

    Han, Xiaohong; Zhang, Wen; Xue, Yanjun; Shao, Shihe

    2011-08-05

    Aichi virus is a positive-sense and single-stranded RNA virus, which demonstrated to be related to diarrhea of Children. In the present study, phylogenetic and recombination analysis based on the Aichi virus complete genomes available in GenBank reveal a mosaic genome sequence [GenBank: FJ890523], of which the nt 261-852 region (the nt position was based on the aligned sequence file) shows close relationship with AB010145/Japan with 97.9% sequence identity, while the other genomic regions show close relationship with AY747174/German with 90.1% sequence identity. Our results will provide valuable hints for future research on Aichi virus diversity.Aichi virus is a member of the Kobuvirus genus of the Picornaviridae family 12 and belongs to a positive-sense and single-stranded RNA virus. Its presence in fecal specimens of children suffering from diarrhea has been demonstrated in several Asian countries 3456, in Brazil and German 7, in France 8 and in Tunisia 9. Some reports showed the high level of seroprevalence in adults 710, suggesting the widespread exposure to Aichi virus during childhood.The genome of Aichi virus contains 8,280 nucleotides and a poly(A) tail. The single large open reading frame (nt 713-8014 according to the strain AB010145) encodes a polyprotein of 2,432 amino acids that is cleaved into the typical picornavirus structural proteins VP0, VP3, VP1, and nonstructural proteins 2A, 2B, 2C, 3A, 3B, 3C and 3D 211. Based on the phylogenetic analysis of 519-bp sequences at the 3C-3D (3CD) junction, Aichi viruses can be divided into two genotypes A and B with approximately 90% sequence homology 12. Although only six complete genomes of Aichi virus were deposited in GenBank at present, mosaic genomes can be found in strains from different countries.

  16. Effect of raloxifene on disease activity and vascular biomarkers in patients with systemic lupus erythematosus: subgroup analysis of a double-blind randomized controlled trial.

    Science.gov (United States)

    Mok, C C; Ying, Shirley K Y; Ma, K M; Wong, C K

    2013-12-01

    The purpose of this study was to identify the effect of raloxifene on disease activity and vascular biomarkers in patients with systemic lupus erythematosus (SLE). Subgroup data were analyzed for postmenopausal female SLE patients who participated in a randomized controlled trial of raloxifene on glucocorticoid-induced osteoporosis. Patients who were receiving a stable daily dose of prednisolone (≤10 mg) for ≥6 months were assigned to receive raloxifene (60 mg/day) or placebo on top of calcium and vitamin D. Disease activity was assessed by the Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA), SLE disease activity index (SLEDAI) and physicians' global assessment (PGA) every three months. Lupus flares were assessed by the SELENA flare instrument. Serial serum levels of homocysteine, high-sensitivity C-reactive protein (hsCRP) and soluble thrombomodulin (sTM) were measured. A total of 62 patients (30 raloxifene, 32 placebo) were studied (age 52.5 ± 6.7 years; SLE duration 9.3 ± 7.6 years; menopause duration 7.2 ± 6.6 years). The SLEDAI at entry was 1.8 ± 2.3 (SLEDAI ≥ 6 in 8%). After 12 months, a significant gain in bone mineral density (BMD) of the lumbar spine (1.6%, p = 0.02), and reduction in bone resorption and formation markers was observed in the raloxifene but not in the placebo treated patients. The SELENA-SLEDAI and PGA scores area under the curve over 12 months were not significantly different between the two groups. There were three episodes of mild/moderate lupus flares (33% musculoskeletal, 33% dermatological) in the raloxifene group, compared to nine episodes of mild/moderate flares (27% musculoskeletal, 45% dermatological) in the placebo group (p = 0.11). The low density lipoprotein (LDL) cholesterol level increased significantly in the placebo but not raloxifene treated patients. No significant changes in homocysteine, hsCRP and sTM levels were observed in either group of patients. Raloxifene significantly improves

  17. Bioinformatic analysis of the neprilysin (M13 family of peptidases reveals complex evolutionary and functional relationships

    Directory of Open Access Journals (Sweden)

    Pinney John W

    2008-01-01

    Full Text Available Abstract Background The neprilysin (M13 family of endopeptidases are zinc-metalloenzymes, the majority of which are type II integral membrane proteins. The best characterised of this family is neprilysin, which has important roles in inactivating signalling peptides involved in modulating neuronal activity, blood pressure and the immune system. Other family members include the endothelin converting enzymes (ECE-1 and ECE-2, which are responsible for the final step in the synthesis of potent vasoconstrictor endothelins. The ECEs, as well as neprilysin, are considered valuable therapeutic targets for treating cardiovascular disease. Other members of the M13 family have not been functionally characterised, but are also likely to have biological roles regulating peptide signalling. The recent sequencing of animal genomes has greatly increased the number of M13 family members in protein databases, information which can be used to reveal evolutionary relationships and to gain insight into conserved biological roles. Results The phylogenetic analysis successfully resolved vertebrate M13 peptidases into seven classes, one of which appears to be specific to mammals, and insect genes into five functional classes and a series of expansions, which may include inactive peptidases. Nematode genes primarily resolved into groups containing no other taxa, bar the two nematode genes associated with Drosophila DmeNEP1 and DmeNEP4. This analysis reconstructed only one relationship between chordate and invertebrate clusters, that of the ECE sub-group and the DmeNEP3 related genes. Analysis of amino acid utilisation in the active site of M13 peptidases reveals a basis for their biochemical properties. A relatively invariant S1' subsite gives the majority of M13 peptidases their strong preference for hydrophobic residues in P1' position. The greater variation in the S2' subsite may be instrumental in determining the specificity of M13 peptidases for their substrates

  18. Mitochondrial Genome Analysis Reveals Historical Lineages in Yellowstone Bison.

    Directory of Open Access Journals (Sweden)

    David Forgacs

    Full Text Available Yellowstone National Park is home to one of the only plains bison populations that have continuously existed on their present landscape since prehistoric times without evidence of domestic cattle introgression. Previous studies characterized the relatively high levels of nuclear genetic diversity in these bison, but little is known about their mitochondrial haplotype diversity. This study assessed mitochondrial genomes from 25 randomly selected Yellowstone bison and found 10 different mitochondrial haplotypes with a haplotype diversity of 0.78 (± 0.06. Spatial analysis of these mitochondrial DNA (mtDNA haplotypes did not detect geographic population subdivision (FST = -0.06, p = 0.76. However, we identified two independent and historically important lineages in Yellowstone bison by combining data from 65 bison (defined by 120 polymorphic sites from across North America representing a total of 30 different mitochondrial DNA haplotypes. Mitochondrial DNA haplotypes from one of the Yellowstone lineages represent descendants of the 22 indigenous bison remaining in central Yellowstone in 1902. The other mitochondrial DNA lineage represents descendants of the 18 females introduced from northern Montana in 1902 to supplement the indigenous bison population and develop a new breeding herd in the northern region of the park. Comparing modern and historical mitochondrial DNA diversity in Yellowstone bison helps uncover a historical context of park restoration efforts during the early 1900s, provides evidence against a hypothesized mitochondrial disease in bison, and reveals the signature of recent hybridization between American plains bison (Bison bison bison and Canadian wood bison (B. b. athabascae. Our study demonstrates how mitochondrial DNA can be applied to delineate the history of wildlife species and inform future conservation actions.

  19. Mitochondrial Genome Analysis Reveals Historical Lineages in Yellowstone Bison

    Science.gov (United States)

    Derr, James N.

    2016-01-01

    Yellowstone National Park is home to one of the only plains bison populations that have continuously existed on their present landscape since prehistoric times without evidence of domestic cattle introgression. Previous studies characterized the relatively high levels of nuclear genetic diversity in these bison, but little is known about their mitochondrial haplotype diversity. This study assessed mitochondrial genomes from 25 randomly selected Yellowstone bison and found 10 different mitochondrial haplotypes with a haplotype diversity of 0.78 (± 0.06). Spatial analysis of these mitochondrial DNA (mtDNA) haplotypes did not detect geographic population subdivision (FST = -0.06, p = 0.76). However, we identified two independent and historically important lineages in Yellowstone bison by combining data from 65 bison (defined by 120 polymorphic sites) from across North America representing a total of 30 different mitochondrial DNA haplotypes. Mitochondrial DNA haplotypes from one of the Yellowstone lineages represent descendants of the 22 indigenous bison remaining in central Yellowstone in 1902. The other mitochondrial DNA lineage represents descendants of the 18 females introduced from northern Montana in 1902 to supplement the indigenous bison population and develop a new breeding herd in the northern region of the park. Comparing modern and historical mitochondrial DNA diversity in Yellowstone bison helps uncover a historical context of park restoration efforts during the early 1900s, provides evidence against a hypothesized mitochondrial disease in bison, and reveals the signature of recent hybridization between American plains bison (Bison bison bison) and Canadian wood bison (B. b. athabascae). Our study demonstrates how mitochondrial DNA can be applied to delineate the history of wildlife species and inform future conservation actions. PMID:27880780

  20. Rivaroxaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a subgroup analysis of ROCKET AF.

    Science.gov (United States)

    Hankey, Graeme J; Patel, Manesh R; Stevens, Susanna R; Becker, Richard C; Breithardt, Günter; Carolei, Antonio; Diener, Hans-Christoph; Donnan, Geoffrey A; Halperin, Jonathan L; Mahaffey, Kenneth W; Mas, Jean-Louis; Massaro, Ayrton; Norrving, Bo; Nessel, Christopher C; Paolini, John F; Roine, Risto O; Singer, Daniel E; Wong, Lawrence; Califf, Robert M; Fox, Keith A A; Hacke, Werner

    2012-04-01

    In ROCKET AF, rivaroxaban was non-inferior to adjusted-dose warfarin in preventing stroke or systemic embolism among patients with atrial fibrillation (AF). We aimed to investigate whether the efficacy and safety of rivaroxaban compared with warfarin is consistent among the subgroups of patients with and without previous stroke or transient ischaemic attack (TIA). In ROCKET AF, patients with AF who were at increased risk of stroke were randomly assigned (1:1) in a double-blind manner to rivaroxaban 20 mg daily or adjusted dose warfarin (international normalised ratio 2·0-3·0). Patients and investigators were masked to treatment allocation. Between Dec 18, 2006, and June 17, 2009, 14 264 patients from 1178 centres in 45 countries were randomly assigned. The primary endpoint was the composite of stroke or non-CNS systemic embolism. In this substudy we assessed the interaction of the treatment effects of rivaroxaban and warfarin among patients with and without previous stroke or TIA. Efficacy analyses were by intention to treat and safety analyses were done in the on-treatment population. ROCKET AF is registered with ClinicalTrials.gov, number NCT00403767. 7468 (52%) patients had a previous stroke (n=4907) or TIA (n=2561) and 6796 (48%) had no previous stroke or TIA. The number of events per 100 person-years for the primary endpoint in patients treated with rivaroxaban compared with warfarin was consistent among patients with previous stroke or TIA (2·79% rivaroxaban vs 2·96% warfarin; hazard ratio [HR] 0·94, 95% CI 0·77-1·16) and those without (1·44%vs 1·88%; 0·77, 0·58-1·01; interaction p=0·23). The number of major and non-major clinically relevant bleeding events per 100 person-years in patients treated with rivaroxaban compared with warfarin was consistent among patients with previous stroke or TIA (13·31% rivaroxaban vs 13·87% warfarin; HR 0·96, 95% CI 0·87-1·07) and those without (16·69%vs 15·19%; 1·10, 0·99-1·21; interaction p=0·08

  1. Subgroup Achievement and Gap Trends: Massachusetts, 2010

    Science.gov (United States)

    Center on Education Policy, 2010

    2010-01-01

    This paper profiles the student subgroup achievement and gap trends in Massachusetts for 2010. In grade 8 (the only grade in which subgroup trends were analyzed by achievement level), Massachusetts showed across-the-board gains--improvements in both reading and math at the basic, proficient and advanced levels for all racial/ethnic subgroups, low…

  2. Subgroup Achievement and Gap Trends: Kentucky, 2010

    Science.gov (United States)

    Center on Education Policy, 2010

    2010-01-01

    This paper profiles the student subgroup achievement and gap trends in Kentucky for 2010. In grade 8 (the only grade in which subgroup trends were analyzed by achievement level), Kentucky showed mostly gains in both reading and math at the basic, proficient, and advanced levels for racial/ethnic subgroups, low income students, and boys and girls.…

  3. Additive subgroups of topological vector spaces

    CERN Document Server

    Banaszczyk, Wojciech

    1991-01-01

    The Pontryagin-van Kampen duality theorem and the Bochner theorem on positive-definite functions are known to be true for certain abelian topological groups that are not locally compact. The book sets out to present in a systematic way the existing material. It is based on the original notion of a nuclear group, which includes LCA groups and nuclear locally convex spaces together with their additive subgroups, quotient groups and products. For (metrizable, complete) nuclear groups one obtains analogues of the Pontryagin duality theorem, of the Bochner theorem and of the Lévy-Steinitz theorem on rearrangement of series (an answer to an old question of S. Ulam). The book is written in the language of functional analysis. The methods used are taken mainly from geometry of numbers, geometry of Banach spaces and topological algebra. The reader is expected only to know the basics of functional analysis and abstract harmonic analysis.

  4. Power analysis attacks revealing the secrets of smart cards

    CERN Document Server

    Mangard, Stefan; Popp, Thomas

    2008-01-01

    A comprehensive treatment of power analysis attacks and countermeasures. Based on the principle that the only way to defend against power analysis attacks is to understand them, this book explains how power analysis attacks work. It discusses simple and differential power analysis as well as advanced techniques like template attacks.

  5. Research methods for subgrouping low back pain

    DEFF Research Database (Denmark)

    Kent, Peter; Keating, Jennifer L; Leboeuf-Yde, Charlotte

    2010-01-01

    There is considerable clinician and researcher interest in whether the outcomes for patients with low back pain, and the efficiency of the health systems that treat them, can be improved by 'subgrouping research'. Subgrouping research seeks to identify subgroups of people who have clinically...... studies (a method framework). The aims of this debate article are: (1) to present a method framework to inform the design and evaluation of subgrouping research in low back pain, (2) to describe method options when investigating prognostic effects or subgroup treatment effects, and (3) to discuss...

  6. Leading Causes of Death among Asian American Subgroups (2003-2011.

    Directory of Open Access Journals (Sweden)

    Katherine G Hastings

    Full Text Available Our current understanding of Asian American mortality patterns has been distorted by the historical aggregation of diverse Asian subgroups on death certificates, masking important differences in the leading causes of death across subgroups. In this analysis, we aim to fill an important knowledge gap in Asian American health by reporting leading causes of mortality by disaggregated Asian American subgroups.We examined national mortality records for the six largest Asian subgroups (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese and non-Hispanic Whites (NHWs from 2003-2011, and ranked the leading causes of death. We calculated all-cause and cause-specific age-adjusted rates, temporal trends with annual percent changes, and rate ratios by race/ethnicity and sex. Rankings revealed that as an aggregated group, cancer was the leading cause of death for Asian Americans. When disaggregated, there was notable heterogeneity. Among women, cancer was the leading cause of death for every group except Asian Indians. In men, cancer was the leading cause of death among Chinese, Korean, and Vietnamese men, while heart disease was the leading cause of death among Asian Indians, Filipino and Japanese men. The proportion of death due to heart disease for Asian Indian males was nearly double that of cancer (31% vs. 18%. Temporal trends showed increased mortality of cancer and diabetes in Asian Indians and Vietnamese; increased stroke mortality in Asian Indians; increased suicide mortality in Koreans; and increased mortality from Alzheimer's disease for all racial/ethnic groups from 2003-2011. All-cause rate ratios revealed that overall mortality is lower in Asian Americans compared to NHWs.Our findings show heterogeneity in the leading causes of death among Asian American subgroups. Additional research should focus on culturally competent and cost-effective approaches to prevent and treat specific diseases among these growing diverse populations.

  7. Predictive and prognostic factors associated with soft tissue sarcoma response to chemotherapy: a subgroup analysis of the European Organisation for Research and Treatment of Cancer 62012 study

    NARCIS (Netherlands)

    Young, R.J.; Litiere, S.; Lia, M.; Hogendoorn, P.C.; Fisher, C.; Mechtersheimer, G.; Daugaard, S.; Sciot, R.; Collin, F.; Messiou, C.; Grunwald, V.; Gronchi, A.; Graaf, W.T.A. van der; Wardelmann, E.; Judson, I.

    2017-01-01

    BACKGROUND: The European Organization for Research and Treatment of Cancer (EORTC) 62012 study was a Phase III trial of doxorubicin versus doxorubicin-ifosfamide chemotherapy in 455 patients with advanced soft tissue sarcoma (STS). Analysis of the main study showed that combination chemotherapy

  8. Time to wean after tracheotomy differs among subgroups of critically ill patients: retrospective analysis in a mixed medical/surgical intensive care unit

    NARCIS (Netherlands)

    van der Lely, Ary-Jan Wj; Veelo, Denise P.; Dongelmans, Dave A.; Korevaar, Johanna C.; Vroom, Margreeth B.; Schultz, Marcus J.

    2006-01-01

    OBJECTIVE: To determine the time to wean from mechanical ventilation and time spent off the ventilator per day after tracheotomy in critically ill patients in a 28-bed mixed medical and surgical intensive care unit (ICU) in Amsterdam, Netherlands. METHODS: We conducted a retrospective analysis of

  9. Revealing the genomic differences between two subgroups in Lactobacillus gasseri.

    Science.gov (United States)

    Tada, Ipputa; Tanizawa, Yasuhiro; Endo, Akihito; Tohno, Masanori; Arita, Masanori

    2017-01-01

    Being an autochthonous species in humans, Lactobacillus gasseri is widely used as a probiotic for fermented products. We thoroughly compared the gene contents of 75 L. gasseri genomes and identified two intraspecific groups by the average nucleotide identity (ANI) threshold of 94%. Group I, with 48 strains, possessed 53 group-specific genes including the gassericin T cluster (9 genes) and N-acyl homoserine lactone lactonase. Group II, with 27 strains, including the type strain ATCC 33323, possessed group-specific genes with plasmid- or phage-related annotations. The genomic differences provide evidences for demarcating a new probiotic group within L. gasseri.

  10. Cilostazol decreases cerebral arterial pulsatility in patients with mild white matter hyperintensities: subgroup analysis from the Effect of Cilostazol in Acute Lacunar Infarction Based on Pulsatility Index of Transcranial Doppler (ECLIPse) study.

    Science.gov (United States)

    Han, Sang Won; Song, Tae Jin; Bushnell, Cheryl D; Lee, Sung-Soo; Kim, Seo Hyun; Lee, Jun Hong; Kim, Gyu Sik; Kim, Ok-Joon; Koh, Im-Seok; Lee, Jong Yun; Suk, Seung-Han; Lee, Sung Ik; Nam, Hyo Suk; Kim, Won-Joo; Lee, Kyung-Yul; Park, Joong Hyun; Kim, Jeong Yeon; Park, Jae Hyeon

    2014-01-01

    The Effect of Cilostazol in Acute Lacunar Infarction Based on Pulsatility Index of the Transcranial Doppler (ECLIPse) study showed a significant decrease in the transcranial Doppler (TCD) pulsatility index (PI) with cilostazol treatment at 90 days after acute lacunar infarction. The aim of the present study was to perform a subgroup analysis of the ECLIPse study in order to explore the effect of cilostazol in acute lacunar infarction based on cerebral white matter hyperintensities (WMH) volume. The ECLIPse study was a multicenter, randomized, double-blind, placebo-controlled trial that evaluated the difference between the efficacy of cilostazol and a placebo to reduce the PI in patients with acute lacunar infarction using serial TCD examinations. The primary outcome was changes in the PIs of the middle cerebral artery (MCA) and basilar artery at 14 and 90 days from the baseline TCD study. For this subgroup analysis, using semi-automated computerized software, the WMH volume was measured for those subjects for whom fluid-attenuated inversion recovery (FLAIR) images were available. Of the 203 patients in eight hospitals in the ECLIPse study, 130 participants from six hospitals were included in this subgroup analysis. Cilostazol was given to 63 patients (48.5%) and placebo to 67 patients (51.5%). All baseline characteristics were well balanced across the two groups, and there were no significant differences in these characteristics except in the changes of PI from the baseline to the 90-day point. There was a significant decrease of TCD PIs at 90-day study from baseline in the cilostazol group (p = 0.02). The mean WMH volume was 11.57 cm(3) (0.13-68.45, median 4.86) and the mean MCA PI was 0.95 (0.62-1.50). The changes in PIs from the baseline to 14 days and to 90 days were 0.09 (-0.21 to 0.33) and 0.10 (-0.22 to 0.36). While there were no significant correlations between WMH volume and the changes in PIs, a trend of inverse correlation was observed between the WMH

  11. Is the benefit of postmastectomy irradiation limited to patients with four or more positive nodes, as recommended in international consensus reports? A subgroup analysis of the DBCG 82 b & c randomized trials

    DEFF Research Database (Denmark)

    Overgaard, Marie; Nielsen, Hanne Melgaard; Overgaard, Jens

    2007-01-01

    to evaluate the loco-regional recurrence rate and survival in relation to number of positive nodes. MATERIALS AND METHODS: In the DBCG 82 b&c trials 3083 pre- and postmenopausal high-risk women were randomized to postoperative RT in addition to adjuvant systemic therapy. Since many patients had relatively few...... lymph nodes removed (median 7), the present analysis was limited to 1152 node positive patients with 8 or more nodes removed. RESULTS: The overall 15-year survival rate in the subgroup was 39% and 29% (p=0.015) after RT and no RT, respectively. RT reduced the 15-year loco-regional failure rate from 51......=0.03). CONCLUSION: The survival benefit after postmastectomy RT was substantial and similar in patients with 1-3 and 4+ positive lymph nodes. Furthermore, it was not strictly associated with the risk of loco-regional recurrence, which was most pronounced in patients with 4+ positive nodes...

  12. Rivaroxaban versus warfarin in Japanese patients with nonvalvular atrial fibrillation in relation to the CHADS2 score: a subgroup analysis of the J-ROCKET AF trial.

    Science.gov (United States)

    Hori, Masatsugu; Matsumoto, Masayasu; Tanahashi, Norio; Momomura, Shin-Ichi; Uchiyama, Shinichiro; Goto, Shinya; Izumi, Tohru; Koretsune, Yukihiro; Kajikawa, Mariko; Kato, Masaharu; Ueda, Hitoshi; Iekushi, Kazuma; Yamanaka, Satoshi; Tajiri, Masahiro

    2014-02-01

    Results from a trial of rivaroxaban versus warfarin in 1280 Japanese patients with atrial fibrillation (J-ROCKET AF) revealed that rivaroxaban was noninferior to warfarin with respect to the principal safety outcome. In this subanalysis, we investigated the safety and efficacy of rivaroxaban and warfarin in relation to patients' CHADS2 scores. The mean CHADS2 score was 3.25, and the most frequent scores were 3 and 4. No statistically significant interactions were observed between principal safety outcome event rates and CHADS2 scores with respect to treatment groups (P value for interaction = .700). Irrespective of stratification into moderate- and high-risk groups based on CHADS2 scores of 2 and 3 or more, respectively, no differences in principal safety outcome event rates were observed between rivaroxaban- and warfarin-treated patients (moderate-risk group: hazard ratio [HR], 1.06; 95% confidence interval [CI], .58-1.95; high-risk group: HR, 1.11; 95% CI, .86-1.45; P value for interaction = .488). The primary efficacy end point rate in the rivaroxaban-treated group was numerically lower than in the warfarin-treated group, regardless of risk group stratification (moderate-risk group: HR, .46; 95% CI, .09-2.37; high-risk group: HR, .49; 95% CI, .22-1.11; P value for interaction = .935). This subanalysis indicated that the safety and efficacy of rivaroxaban compared with warfarin were similar, regardless of CHADS2 score. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  13. 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.

  14. Safety and efficacy of initial combination of linagliptin and metformin in patients with type 2 diabetes: A subgroup analysis of Indian patients from a randomized, double-blind, placebo-controlled study

    Directory of Open Access Journals (Sweden)

    Vaishali Deshmukh

    2015-01-01

    Full Text Available Context and Objectives: The number of people with diabetes is increasing exponentially in India. Owing to a unique "Asian Indian Phenotype," Indians develop diabetes a decade earlier and have an earlier onset of complications than Western populations. Therefore, it is essential to evaluate more effective treatment strategies at an earlier stage of disease progression, such as initial combination therapy, in Indian patients. In this study, we evaluated the efficacy and safety of initial combination therapy with linagliptin plus metformin in comparison to linagliptin or metformin monotherapy in Indian patients with type 2 diabetes mellitus. Methods: This is a subgroup analysis of Indian patients who participated in a Phase III, 24-week, double-blind, placebo-controlled, trial. Overall, 249 Indian patients were randomized to one of six treatment arms (Two free combination therapy arms: Linagliptin 2.5 mg twice daily [bid] + either low [500 mg, n = 36] or high [1000 mg, n = 44] dose metformin bid and four monotherapy arms: Linagliptin 5 mg once daily [qd, n = 40], metformin 500 mg [n = 49] or 1000 mg bid [n = 45], or placebo [n = 23]. Results: The placebo-corrected mean change in glycated hemoglobin from baseline (8.9% to week 24 was −1.83% for linagliptin + metformin 1000 mg bid; −1.46% for linagliptin + metformin 500 mg bid; −1.30% for metformin 1000 mg bid; −1.00% for metformin 500 mg bid; and −0.77% for linagliptin 5 mg qd. None of the patients in the combination therapy arms had hypoglycemia, whereas there was one event in the metformin 1000 mg bid arm. Rates of adverse event were similar across various treatments. Conclusions: In this subgroup analysis of Indian patients, initial combination therapy with linagliptin + metformin was more efficacious in improving glycemic control than the monotherapy arms, with a comparable tolerability profile. The results were comparable to the overall population.

  15. A Subgroup Analysis Found no Diminished Response to Buprenorphine Transdermal System Treatment for Chronic Low Back Pain Patients Classified with Depression.

    Science.gov (United States)

    Yarlas, Aaron; Miller, Kate; Wen, Warren; Lynch, Shau Yu; Munera, Catherine; Dain, Bradley; Pergolizzi, Joseph V; Raffa, Robert; Ripa, Steven R

    2016-04-01

    Chronic pain (CP) patients with depression typically exhibit worse post-treatment outcomes than nondepressed CP patients. The cause is often assumed to reflect a differential response to treatment, neglecting other potential explanations, such as the continuation of differences in pretreatment outcomes. This post hoc analysis examines whether worse post-treatment outcomes for depressed patients with chronic low back pain (CLBP) are driven by reduced treatment efficacy. Data were from opioid-naïve adult patients with moderate-to-severe CLBP who participated in a randomized, placebo-controlled, double-blind clinical trial of Butrans(®) (buprenorphine) Transdermal System (BTDS) for pain relief. Depression screening was based on baseline SF-36v2 Mental Health subscale scores. Patient-reported measures of pain severity, pain interference, quality of life, sleep problems, and functional disability were administered at screening and during the study. Differential treatment efficacy for each outcome was examined using analysis of covariance models that included interaction terms between treatment arm and depression status. At baseline, patients classified as depressed showed greater pain interference, lower quality of life, more sleep problems, and greater functional disability than nondepressed patients; the two groups did not differ in pain severity. No statistically significant interactions between treatment arm and depression status were observed. The direction of improvement post-treatment favored the depressed group on nine of seventeen outcomes. Results do not support a differential response to BTDS treatment between depressed and nondepressed CLBP patients across a variety of patient-reported outcomes. These findings raise the question of whether depressed mood actually moderates the effectiveness of treatment in CP patients. © 2015 Optum. Pain Practice published by Wiley Periodicals, Inc. on behalf of World Institute of Pain.

  16. Effect of visceral fat area on outcomes of laparoscopyassisted distal gastrectomy for gastric cancer: subgroup analysis by gender and parameters of obesity.

    Science.gov (United States)

    Go, Ji-Eon; Kim, Min-Chan; Kim, Ki-Han; Oh, Jong-Young; Kim, Yoo-Min

    2015-06-01

    The aim of this study was to investigate the impact of the visceral fat area (VFA) of patients with gastric cancer undergoing laparoscopic surgery on operative outcomes such as number of retrieved lymph nodes (LNs) and operative time. We retrospectively reviewed the medical records and the CT scans of 597 patients with gastric cancer who underwent laparoscopy assisted distal gastrectomy (LADG) with partial omentectomy and LN dissection (>D1 plus beta). Patients were stratified by gender, VFA, and body mass index (BMI), and the clinicopathologic characteristics and operative outcomes were evaluated. Multiple linear regression analysis was used to assess the effects of VFA and BMI on the number of retrieved LNs and operative time in male and female patients. The mean number of retrieved LNs was significantly decreased for both male and female patients with high VFA. The operative time was significantly longer for both male and female patients with high VFA. The number of retrieved LNs had a statistically significant negative correlation with VFA in both men and women, but not with BMI. The operative time had a statistically significant positive correlation with VFA in men, whereas the operative time had a statistically significant positive correlation with BMI in women. The preoperative VFA of male patients with gastric cancer who undergo LADG may affect the number of retrieved LNs and operative time. VFA was more useful than BMI for predicting outcomes of LADG.

  17. Dabigatran, Rivaroxaban, or Apixaban versus Warfarin in Patients with Nonvalvular Atrial Fibrillation: A Systematic Review and Meta-Analysis of Subgroups

    Directory of Open Access Journals (Sweden)

    Antonio Gómez-Outes

    2013-01-01

    Full Text Available Background. New oral anticoagulants (NOAC; rivaroxaban, dabigatran, apixaban have become available as an alternative to warfarin anticoagulation in non-valvular atrial fibrillation (NVAF. Methods. MEDLINE and CENTRAL, regulatory agencies websites, clinical trials registers and conference proceedings were searched to identify randomised controlled trials of NOAC versus warfarin in NVAF. Two investigators reviewed all studies and extracted data on patient and study characteristics along with cardiovascular outcomes. Relative risks (RR and 95% confidence intervals (CI were estimated using a random effect meta-analysis. Results. Three clinical trials in 50,578 patients were included. The risk of non-hemorrhagic stroke and systemic embolic events (SEE was similar with the NOAC and warfarin (RR=0.93; 95% CI=0.83–1.04, while the risk of intracranial bleeding (ICB with the NOAC was lower than with warfarin (RR = 0.46; 95% CI = 0.33–0.65. We found differences in the effect size on all strokes and SEE depending on geographic region as well as on non-hemorrhagic stroke, SEE, bleeding and mortality depending on time in therapeutic range. Conclusion. The NOAC seem no more effective than warfarin for prevention of nonhemorrhagic stroke and SEE in the overall NVAF population, but are generally associated with a lower risk of ICB than warfarin.

  18. Efficacy and safety of rivaroxaban versus warfarin in patients from mainland China with nonvalvular atrial fibrillation: A subgroup analysis from the ROCKET AF trial.

    Science.gov (United States)

    Sun, Yihong; Hu, Dayi; Stevens, Susanna; Lokhnygina, Yuliya; Becker, Richard C; Berkowitz, Scott D; Breithardt, Günter; Hacke, Werner; Halperin, Jonathan L; Hankey, Graeme J; Mahaffey, Kenneth W; Nessel, Christopher C; Piccini, Jonathan P; Singer, Daniel E; Fox, Keith A A; Patel, Manesh R

    2017-08-01

    The ROCKET AF study evaluated once-daily rivaroxaban versus dose-adjusted warfarin for the prevention of stroke and systemic embolism in patients with atrial fibrillation (AF). In this analysis, we compared rivaroxaban with warfarin in patients with AF from China, East Asia, and the rest of the world (ROW). We assessed baseline demographics and interaction of treatment effects of rivaroxaban versus warfarin among patients from mainland China, other East Asian countries, and ROW. Of the 14,236 patients enrolled in the per-protocol population, 495 were from mainland China, 433 from other East-Asian regions, and 13,308 from the rest of the world (ROW). At baseline, patients from China had significantly higher rates of previous stroke/transient ischemic attack (TIA) compared with patients from other East Asian regions and ROW (79.6%, 44.6%, 51.6% respectively; p0.12). Numerically higher rates of intracranial bleeding were seen in patients from China receiving warfarin versus rivaroxaban. In patients from China, rates of intracranial hemorrhage were numerically lower among those receiving rivaroxaban and consistent with the overall trial. URL: https://www.clinicaltrials.gov/. Unique identifier: NCT00403767. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Health Resource Utilization Associated with Skeletal-Related Events in Patients with Advanced Prostate Cancer: A European Subgroup Analysis from an Observational, Multinational Study

    Directory of Open Access Journals (Sweden)

    Amit Bahl

    2014-07-01

    Full Text Available This study aimed to increase the understanding of health resource utilization (HRU associated with skeletal-related events (SREs occurring in patients with bone metastases secondary to advanced prostate cancer. A total of 120 patients from Germany, Italy, Spain and the United Kingdom were enrolled in this observational study. They had bone metastases secondary to prostate cancer and had experienced at least one SRE in the 97 days before giving informed consent. HRU data were collected retrospectively for 97 days before enrolment and prospectively for up to 18–21 months. HRU, including the number and duration of inpatient hospitalizations, number of outpatient and emergency department visits and procedures, was independently attributed by investigators to an SRE. Of the 222 SREs included in this analysis, 26% were associated with inpatient stays and the mean duration per SRE was 21.4 days (standard deviation (SD 17.8 days. Overall, 174 SREs (78% required an outpatient visit and the mean number of visits per SRE was 4.6 (SD 4.6. All SREs are associated with substantial HRU. Preventing SREs in patients with advanced prostate cancer and bone metastases may help to reduce the burden to both patients and European healthcare systems.

  20. Cyclophosphamide-based stem cell mobilization in relapsed multiple myeloma patients: A subgroup analysis from the phase III trial ReLApsE.

    Science.gov (United States)

    Baertsch, Marc-Andrea; Schlenzka, Jana; Lisenko, Katharina; Krzykalla, Julia; Becker, Natalia; Weisel, Katja; Noppeney, Richard; Martin, Hans; Lindemann, Hans W; Haenel, Mathias; Nogai, Axel; Scheid, Christof; Salwender, Hans; Fenk, Roland; Graeven, Ullrich; Reimer, Peter; Schmidt-Hieber, Martin; Goerner, Martin; Schmidt-Wolf, Ingo G H; Klein, Stefan; Ho, Anthony D; Goldschmidt, Hartmut; Wuchter, Patrick

    2017-07-01

    Analysis of the efficiency and toxicity of cyclophosphamide-based stem cell mobilization in patients with relapsed multiple myeloma (RMM). Peripheral blood stem cells (PBSCs) were mobilized with high dose cyclophosphamide (2 g/m2 daily on days 1 and 2) and G-CSF plus pre-emptive/rescue plerixafor in RMM patients (first to third relapse) treated within the ReLApsE trial of the German-Speaking Myeloma Multicenter Group (GMMG). Mobilization was initiated with high-dose cyclophosphamide (HD-CY) and G-CSF in 30 patients. Fifteen patients received additional pre-emptive/rescue administration of plerixafor. Stem cell collection was successful (≥2×106 CD34+ cells per kg bw) in 77% (23/30 patients). Patients with prior high-dose melphalan collected a significantly lower median total number of PBSCs than patients without prior high-dose melphalan (3.3×106 vs 17×106 CD34+ cells/kg bw). Toxicity of HD-CY was frequent with 12 serious adverse events (SAE) in 37% of patients (11/30 patients). Infections accounted for the majority of SAE reports. In two patients, SAEs were lethal (septic shock). These data proof feasibility of PBSC collection at relapse but emphasize the importance of collection and storage of additional PBSC transplants during first-line treatment when mobilization is more efficient and less toxic. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Edoxaban vs. warfarin in patients with atrial fibrillation on amiodarone: a subgroup analysis of the ENGAGE AF-TIMI 48 trial.

    Science.gov (United States)

    Steffel, J; Giugliano, R P; Braunwald, E; Murphy, S A; Atar, D; Heidbuchel, H; Camm, A J; Antman, E M; Ruff, C T

    2015-09-01

    In the ENGAGE AF-TIMI 48 trial, the higher-dose edoxaban (HDE) regimen had a similar incidence of ischaemic stroke compared with warfarin, whereas a higher incidence was observed with the lower-dose regimen (LDE). Amiodarone increases edoxaban plasma levels via P-glycoprotein inhibition. The current pre-specified exploratory analysis was performed to determine the effect of amiodarone on the relative efficacy and safety profile of edoxaban. At randomization, 2492 patients (11.8%) were receiving amiodarone. The primary efficacy endpoint of stroke or systemic embolic event was significantly lower with LDE compared with warfarin in amiodarone treated patients vs. patients not on amiodarone (hazard ratio [HR] 0.60, 95% confidence intervals [CIs] 0.36-0.99 and HR 1.20, 95% CI 1.03-1.40, respectively; P interaction amiodarone use. Patients randomized to the LDE treated with amiodarone at the time of randomization demonstrated a significant reduction in ischaemic events vs. warfarin when compared with those not on amiodarone, while preserving a favourable bleeding profile. In contrast, amiodarone had no effect on the relative efficacy and safety of HDE. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

  2. G-protein coupled receptor expression patterns delineate medulloblastoma subgroups

    Science.gov (United States)

    2013-01-01

    Background Medulloblastoma is the most common malignant brain tumor in children. Genetic profiling has identified four principle tumor subgroups; each subgroup is characterized by different initiating mutations, genetic and clinical profiles, and prognoses. The two most well-defined subgroups are caused by overactive signaling in the WNT and SHH mitogenic pathways; less is understood about Groups 3 and 4 medulloblastoma. Identification of tumor subgroup using molecular classification is set to become an important component of medulloblastoma diagnosis and staging, and will likely guide therapeutic options. However, thus far, few druggable targets have emerged. G-protein coupled receptors (GPCRs) possess characteristics that make them ideal targets for molecular imaging and therapeutics; drugs targeting GPCRs account for 30-40% of all current pharmaceuticals. While expression patterns of many proteins in human medulloblastoma subgroups have been discerned, the expression pattern of GPCRs in medulloblastoma has not been investigated. We hypothesized that analysis of GPCR expression would identify clear subsets of medulloblastoma and suggest distinct GPCRs that might serve as molecular targets for both imaging and therapy. Results Our study found that medulloblastoma tumors fall into distinct clusters based solely on GPCR expression patterns. Normal cerebellum clustered separately from the tumor samples. Further, two of the tumor clusters correspond with high fidelity to the WNT and SHH subgroups of medulloblastoma. Distinct over-expressed GPCRs emerge; for example, LGR5 and GPR64 are significantly and uniquely over-expressed in the WNT subgroup of tumors, while PTGER4 is over-expressed in the SHH subgroup. Uniquely under-expressed GPCRs were also observed. Our key findings were independently validated using a large international dataset. Conclusions Our results identify GPCRs with potential to act as imaging and therapeutic targets. Elucidating tumorigenic pathways

  3. Calcipotriol Plus Betamethasone Dipropionate Aerosol Foam in Patients with Moderate-to-Severe Psoriasis: Sub-Group Analysis of the PSO-ABLE Study.

    Science.gov (United States)

    Paul, Carle; Leonardi, Craig; Menter, Alan; Reich, Kristian; Gold, Linda Stein; Warren, Richard B; Møller, Anders; Lebwohl, Mark

    2017-06-01

    Fixed-combination calcipotriol 50 μg/g plus betamethasone 0.5 mg/g (Cal/BD) aerosol foam is a new topical treatment for psoriasis. Although moderate-to-severe psoriasis is typically treated with systemic/biologic therapies, a topical treatment that is efficacious in these patients may be a significant cost-saving alternative to systemic therapy. The objective of this study was to assess the response to Cal/BD foam and gel in patients with moderate-to-severe psoriasis enrolled in the phase III, 12-week PSO-ABLE study. Patients eligible for this analysis had moderate-to-severe psoriasis, defined by the 'Rule of Tens': body surface area ≥10% or Psoriasis Area and Severity Index (PASI) [excluding head; modified PASI (mPASI)] >10 or Dermatology Life-Quality Index >10. Endpoints included: proportion of patients achieving mPASI75 or mPASI90; change in body surface area; proportion of patients clear/almost clear with a ≥2 grade improvement (i.e., treatment success); change in Dermatology Life-Quality Index. Seventy-seven Cal/BD foam patients and 82 gel patients had moderate-to-severe psoriasis. A greater proportion achieved mPASI75 and mPASI90 with Cal/BD foam than gel at weeks 4, 8, and 12 (57.1 vs. 35.4%; p = 0.006 and 15.6 vs. 12.2% at week 12, respectively); overall reduction in mPASI from baseline to week 12 was 64% with the foam vs. 51% with the gel. Overall reduction in body surface area at week 12 was 50% with the foam and 39% with the gel. Treatment success rates were higher with the Cal/BD foam than the gel at weeks 1, 2, 4, 8 (p = 0.0089), and 12, and a greater proportion of foam patients achieved a Dermatology Life-Quality Index score of 0/1 at weeks 4 (p = 0.004), 8, and 12 (p = 0.001). Cal/BD foam can be considered as a treatment option in some patients with moderate-to-severe psoriasis who are potential candidates for systemic therapy. CLINICALTRIALS. NCT02132936.

  4. RAPD analysis reveals genetic variation in different populations of ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-09-15

    Sep 15, 2009 ... ginseng (Um et al., 2001). Naugzemys et al. (2007) analyzed Lonicera caerulea germplasm accessions using. RAPD markers and found that RAPD analysis is efficient for genotyping of accessions. DNA polymorphism signifi- cantly exceeds the morphological diversity of the sam- ples. A total of 105 bands ...

  5. Network analysis reveals multiscale controls on streamwater chemistry

    Science.gov (United States)

    Kevin J. McGuire; Christian E. Torgersen; Gene E. Likens; Donald C. Buso; Winsor H. Lowe; Scott W. Bailey

    2014-01-01

    By coupling synoptic data from a basin-wide assessment of streamwater chemistry with network-based geostatistical analysis, we show that spatial processes differentially affect biogeochemical condition and pattern across a headwater stream network. We analyzed a high-resolution dataset consisting of 664 water samples collected every 100 m throughout 32 tributaries in...

  6. Revealing the underlying drivers of disaster risk: a global analysis

    Science.gov (United States)

    Peduzzi, Pascal

    2017-04-01

    Disasters events are perfect examples of compound events. Disaster risk lies at the intersection of several independent components such as hazard, exposure and vulnerability. Understanding the weight of each component requires extensive standardisation. Here, I show how footprints of past disastrous events were generated using GIS modelling techniques and used for extracting population and economic exposures based on distribution models. Using past event losses, it was possible to identify and quantify a wide range of socio-politico-economic drivers associated with human vulnerability. The analysis was applied to about nine thousand individual past disastrous events covering earthquakes, floods and tropical cyclones. Using a multiple regression analysis on these individual events it was possible to quantify each risk component and assess how vulnerability is influenced by various hazard intensities. The results show that hazard intensity, exposure, poverty, governance as well as other underlying factors (e.g. remoteness) can explain the magnitude of past disasters. Analysis was also performed to highlight the role of future trends in population and climate change and how this may impacts exposure to tropical cyclones in the future. GIS models combined with statistical multiple regression analysis provided a powerful methodology to identify, quantify and model disaster risk taking into account its various components. The same methodology can be applied to various types of risk at local to global scale. This method was applied and developed for the Global Risk Analysis of the Global Assessment Report on Disaster Risk Reduction (GAR). It was first applied on mortality risk in GAR 2009 and GAR 2011. New models ranging from global assets exposure and global flood hazard models were also recently developed to improve the resolution of the risk analysis and applied through CAPRA software to provide probabilistic economic risk assessments such as Average Annual Losses (AAL

  7. Sensitization trajectories in childhood revealed by using a cluster analysis

    DEFF Research Database (Denmark)

    Schoos, Ann-Marie M.; Chawes, Bo L.; Melen, Erik

    2017-01-01

    biologically and clinically relevant. OBJECTIVE: We sought to explore latent patterns of sensitization during the first 6 years of life and investigate whether such patterns associate with the development of asthma, rhinitis, and eczema. METHODS: We investigated 398 children from the at-risk Copenhagen...... Prospective Studies on Asthma in Childhood 2000 (COPSAC2000) birth cohort with specific IgE against 13 common food and inhalant allergens at the ages of ½, 1½, 4, and 6 years. An unsupervised cluster analysis for 3-dimensional data (nonnegative sparse parallel factor analysis) was used to extract latent...... patterns explicitly characterizing temporal development of sensitization while clustering allergens and children. Subsequently, these patterns were investigated in relation to asthma, rhinitis, and eczema. Verification was sought in an independent unselected birth cohort (BAMSE) constituting 3051 children...

  8. Fractal analysis reveals reduced complexity of retinal vessels in CADASIL.

    Directory of Open Access Journals (Sweden)

    Michele Cavallari

    Full Text Available The Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL affects mainly small cerebral arteries and leads to disability and dementia. The relationship between clinical expression of the disease and progression of the microvessel pathology is, however, uncertain as we lack tools for imaging brain vessels in vivo. Ophthalmoscopy is regarded as a window into the cerebral microcirculation. In this study we carried out an ophthalmoscopic examination in subjects with CADASIL. Specifically, we performed fractal analysis of digital retinal photographs. Data are expressed as mean fractal dimension (mean-D, a parameter that reflects complexity of the retinal vessel branching. Ten subjects with genetically confirmed diagnosis of CADASIL and 10 sex and age-matched control subjects were enrolled. Fractal analysis of retinal digital images was performed by means of a computer-based program, and the data expressed as mean-D. Brain MRI lesion volume in FLAIR and T1-weighted images was assessed using MIPAV software. Paired t-test was used to disclose differences in mean-D between CADASIL and control groups. Spearman rank analysis was performed to evaluate potential associations between mean-D values and both disease duration and disease severity, the latter expressed as brain MRI lesion volumes, in the subjects with CADASIL. The results showed that mean-D value of patients (1.42±0.05; mean±SD was lower than control (1.50±0.04; p = 0.002. Mean-D did not correlate with disease duration nor with MRI lesion volumes of the subjects with CADASIL. The findings suggest that fractal analysis is a sensitive tool to assess changes of retinal vessel branching, likely reflecting early brain microvessel alterations, in CADASIL patients.

  9. Demographic analysis reveals gradual senescence in the flatworm Macrostomum lignano

    OpenAIRE

    Mouton, Stijn; Willems, Maxime; Back, Patricia; Braeckman, Bart; Borgonie, Gaetan

    2009-01-01

    Abstract Free-living flatworms ("Turbellaria") are appropriate model organisms to gain better insight into the role of stem cells in ageing and rejuvenation. Ageing research in flatworms is, however, still scarce. This is partly due to culture difficulties and the lack of a complete set of demographic data, including parameters such as median lifespan and age-specific mortality rate. In this paper, we report on the first flatworm survival analysis. We used the species Macrostomum lignano, whi...

  10. Tracking cohesive subgroups over time in inferred social networks

    Science.gov (United States)

    Chin, Alvin; Chignell, Mark; Wang, Hao

    2010-04-01

    As a first step in the development of community trackers for large-scale online interaction, this paper shows how cohesive subgroup analysis using the Social Cohesion Analysis of Networks (SCAN; Chin and Chignell 2008) and Data-Intensive Socially Similar Evolving Community Tracker (DISSECT; Chin and Chignell 2010) methods can be applied to the problem of identifying cohesive subgroups and tracking them over time. Three case studies are reported, and the findings are used to evaluate how well the SCAN and DISSECT methods work for different types of data. In the largest of the case studies, variations in temporal cohesiveness are identified across a set of subgroups extracted from the inferred social network. Further modifications to the DISSECT methodology are suggested based on the results obtained. The paper concludes with recommendations concerning further research that would be beneficial in addressing the community tracking problem for online data.

  11. Revealing metabolic phenotypes in plants: inputs from NMR analysis.

    Science.gov (United States)

    Ratcliffe, R G; Shachar-Hill, Y

    2005-02-01

    Assessing the performance of the plant metabolic network, with its varied biosynthetic capacity and its characteristic subcellular compartmentation, remains a considerable challenge. The complexity of the network is such that it is not yet possible to build large-scale predictive models of the fluxes it supports, whether on the basis of genomic and gene expression analysis or on the basis of more traditional measurements of metabolites and their interconversions. This limits the agronomic and biotechnological exploitation of plant metabolism, and it undermines the important objective of establishing a rational metabolic engineering strategy. Metabolic analysis is central to removing this obstacle and currently there is particular interest in harnessing high-throughput and/or large-scale analyses to the task of defining metabolic phenotypes. Nuclear magnetic resonance (NMR) spectroscopy contributes to this objective by providing a versatile suite of analytical techniques for the detection of metabolites and the fluxes between them. The principles that underpin the analysis of plant metabolism by NMR are described, including a discussion of the measurement options for the detection of metabolites in vivo and in vitro, and a description of the stable isotope labelling experiments that provide the basis for metabolic flux analysis. Despite a relatively low sensitivity, NMR is suitable for high-throughput system-wide analyses of the metabolome, providing methods for both metabolite fingerprinting and metabolite profiling, and in these areas NMR can contribute to the definition of plant metabolic phenotypes that are based on metabolic composition. NMR can also be used to investigate the operation of plant metabolic networks. Labelling experiments provide information on the operation of specific pathways within the network, and the quantitative analysis of steady-state labelling experiments leads to the definition of large-scale flux maps for heterotrophic carbon

  12. Subgroup Achievement and Gap Trends: Delaware

    Science.gov (United States)

    Center on Education Policy, 2010

    2010-01-01

    In grade 8 (the only grade in which subgroup trends were analyzed by achievement level), Delaware students showed consistent gains in math at the basic, proficient, and advanced levels for racial/ethnic subgroups, low income students, and boys and girls. There were mixed results in reading. Achievement gaps narrowed in both reading and math in…

  13. Subgroup Achievement and Gap Trends: Maine

    Science.gov (United States)

    Center on Education Policy, 2010

    2010-01-01

    In grade 8 (the only grade in which subgroup trends were analyzed by achievement level), Maine students had across-the-board gains. There were improvements in both reading and math at the basic, proficient and advanced levels for the subgroups large enough to count, which were white students, low income students, and boys and girls. Results on…

  14. Subgroup Achievement and Gap Trends: Illinois

    Science.gov (United States)

    Center on Education Policy, 2010

    2010-01-01

    In grade 8 (the only grade in which subgroup trends were analyzed by achievement level), Illinois students showed mostly gains in both reading and math at the basic, proficient, and advanced levels for racial/ethnic subgroups, low income students, and boys and girls. There was mixed progress made in narrowing achievement gaps in reading and math…

  15. Subgroup Achievement and Gap Trends: Florida

    Science.gov (United States)

    Center on Education Policy, 2010

    2010-01-01

    In grade 8 (the only grade in which subgroup trends were analyzed by achievement level), Florida students showed gains almost across the board in both reading and math at the basic, proficient, and advanced levels for racial/ethnic subgroups, low income students, and boys and girls. Progress has been made in narrowing achievement gaps in both…

  16. ∗-supplemented subgroups of finite groups

    Indian Academy of Sciences (India)

    supplemented maximal and minimal subgroups of Sylow subgroups of finite groups, Proc. Amer. Math. Soc. 132(8) (2004) 2197–2204. [17] Wang Y, Wei H and Li Y, A generalization of Kramer's theorem and its applications,. Bull. Austral. Math.

  17. Proteogenomic analysis reveals exosomes are more oncogenic than ectosomes

    Science.gov (United States)

    Liem, Michael; Fonseka, Pamali; Atukorala, Ishara; Ozcitti, Cemil; Mechler, Adam; Adda, Christopher G.; Ang, Ching-Seng; Mathivanan, Suresh

    2015-01-01

    Extracellular vesicles (EVs) include the exosomes (30-100 nm) that are produced through the endocytic pathway via the multivesicular bodies and the ectosomes (100-1000 nm) that are released through the budding of the plasma membrane. Despite the differences in the mode of biogenesis and size, reliable markers that can distinguish between exosomes and ectosomes are non-existent. Moreover, the precise functional differences between exosomes and ectosomes remains poorly characterised. Here, using label-free quantitative proteomics, we highlight proteins that could be exploited as markers to discriminate between exosomes and ectosomes. For the first time, a global proteogenomics analysis unveiled the secretion of mutant proteins that are implicated in cancer progression through tumor-derived EVs. Follow up integrated bioinformatics analysis highlighted the enrichment of oncogenic cargo in exosomes and ectosomes. Interestingly, exosomes induced significant cell proliferation and migration in recipient cells compared to ectosomes confirming the oncogenic nature of exosomes. These findings ascertain that cancer cells facilitate oncogenesis by the secretion of mutant and oncoproteins into the tumor microenvironment via exosomes and ectosomes. The integrative proteogenomics approach utilized in this study has the potential to identify disease biomarker candidates which can be later assayed in liquid biopsies obtained from cancer patients. PMID:25944692

  18. Extensive exometabolome analysis reveals extended overflow metabolism in various microorganisms

    Directory of Open Access Journals (Sweden)

    Paczia Nicole

    2012-09-01

    Full Text Available Abstract Overflow metabolism is well known for yeast, bacteria and mammalian cells. It typically occurs under glucose excess conditions and is characterized by excretions of by-products such as ethanol, acetate or lactate. This phenomenon, also denoted the short-term Crabtree effect, has been extensively studied over the past few decades, however, its basic regulatory mechanism and functional role in metabolism is still unknown. Here we present a comprehensive quantitative and time-dependent analysis of the exometabolome of Escherichia coli, Corynebacterium glutamicum, Bacillus licheniformis, and Saccharomyces cerevisiae during well-controlled bioreactor cultivations. Most surprisingly, in all cases a great diversity of central metabolic intermediates and amino acids is found in the culture medium with extracellular concentrations varying in the micromolar range. Different hypotheses for these observations are formulated and experimentally tested. As a result, the intermediates in the culture medium during batch growth must originate from passive or active transportation due to a new phenomenon termed “extended” overflow metabolism. Moreover, we provide broad evidence that this could be a common feature of all microorganism species when cultivated under conditions of carbon excess and non-inhibited carbon uptake. In turn, this finding has consequences for metabolite balancing and, particularly, for intracellular metabolite quantification and 13C-metabolic flux analysis.

  19. Factors associated with prolonged time to treatment failure with fulvestrant 500 mg in patients with postmenopausal estrogen receptor-positive advanced breast cancer: a subgroup analysis of the JBCRG-C06 Safari study.

    Science.gov (United States)

    Kawaguchi, Hidetoshi; Masuda, Norikazu; Nakayama, Takahiro; Aogi, Kenjiro; Anan, Keisei; Ito, Yoshinori; Ohtani, Shoichiro; Sato, Nobuaki; Saji, Shigehira; Takano, Toshimi; Tokunaga, Eriko; Nakamura, Seigo; Hasegawa, Yoshie; Hattori, Masaya; Fujisawa, Tomomi; Morita, Satoshi; Yamaguchi, Miki; Yamashita, Hiroko; Yamashita, Toshinari; Yamamoto, Yutaka; Yotsumoto, Daisuke; Toi, Masakazu; Ohno, Shinji

    2017-11-02

    The JBCRG-C06 Safari study showed that earlier fulvestrant 500 mg (F500) use, a longer time from diagnosis to F500 use, and no prior palliative chemotherapy were associated with significantly longer time to treatment failure (TTF) among Japanese patients with estrogen receptor-positive (ER+) advanced breast cancer (ABC). The objective of this subgroup analysis was to further examine data from the Safari study, focusing on ER+ and human epidermal growth factor receptor-negative (HER2-) cases. The Safari study (UMIN000015168) was a retrospective, multicenter cohort study, conducted in 1072 patients in Japan taking F500 for ER+ ABC. The subanalysis included only patients administered F500 as second-line or later therapy (n = 960). Of these, 828 patients were HER2-. Multivariate analysis showed that advanced age (≥65 years; p = 0.035), longer time (≥3 years) from AMBC ABC diagnosis to F500 use (p < 0.001), no prior chemotherapy (p < 0.001), and F500 treatment line (p < 0.001) were correlated with prolonged TTF (median 5.39 months). In ER+/HER2- patients receiving F500 as a second-line or later therapy, treatment line, advanced age, no prior palliative chemotherapy use, and a longer period from ABC diagnosis to F500 use were associated with longer TTF.

  20. Sensitization trajectories in childhood revealed by using a cluster analysis.

    Science.gov (United States)

    Schoos, Ann-Marie M; Chawes, Bo L; Melén, Erik; Bergström, Anna; Kull, Inger; Wickman, Magnus; Bønnelykke, Klaus; Bisgaard, Hans; Rasmussen, Morten A

    2017-12-01

    Assessment of sensitization at a single time point during childhood provides limited clinical information. We hypothesized that sensitization develops as specific patterns with respect to age at debut, development over time, and involved allergens and that such patterns might be more biologically and clinically relevant. We sought to explore latent patterns of sensitization during the first 6 years of life and investigate whether such patterns associate with the development of asthma, rhinitis, and eczema. We investigated 398 children from the at-risk Copenhagen Prospective Studies on Asthma in Childhood 2000 (COPSAC2000) birth cohort with specific IgE against 13 common food and inhalant allergens at the ages of ½, 1½, 4, and 6 years. An unsupervised cluster analysis for 3-dimensional data (nonnegative sparse parallel factor analysis) was used to extract latent patterns explicitly characterizing temporal development of sensitization while clustering allergens and children. Subsequently, these patterns were investigated in relation to asthma, rhinitis, and eczema. Verification was sought in an independent unselected birth cohort (BAMSE) constituting 3051 children with specific IgE against the same allergens at 4 and 8 years of age. The nonnegative sparse parallel factor analysis indicated a complex latent structure involving 7 age- and allergen-specific patterns in the COPSAC2000 birth cohort data: (1) dog/cat/horse, (2) timothy grass/birch, (3) molds, (4) house dust mites, (5) peanut/wheat flour/mugwort, (6) peanut/soybean, and (7) egg/milk/wheat flour. Asthma was solely associated with pattern 1 (odds ratio [OR], 3.3; 95% CI, 1.5-7.2), rhinitis with patterns 1 to 4 and 6 (OR, 2.2-4.3), and eczema with patterns 1 to 3 and 5 to 7 (OR, 1.6-2.5). All 7 patterns were verified in the independent BAMSE cohort (R2 > 0.89). This study suggests the presence of specific sensitization patterns in early childhood differentially associated with development of clinical

  1. Image analysis of weaverbird nests reveals signature weave textures.

    Science.gov (United States)

    Bailey, Ida E; Backes, André; Walsh, Patrick T; Morgan, Kate V; Meddle, Simone L; Healy, Susan D

    2015-06-01

    In nature, many animals build structures that can be readily measured at the scale of their gross morphology (e.g. length, volume and weight). Capturing individuality as can be done with the structures designed and built by human architects or artists, however, is more challenging. Here, we tested whether computer-aided image texture classification approaches can be used to describe textural variation in the nests of weaverbirds (Ploceus species) in order to attribute nests to the individual weaverbird that built them. We found that a computer-aided texture analysis approach does allow the assignment of a signature to weaverbirds' nests. We suggest that this approach will be a useful tool with which to examine individual variation across a range of animal constructions, not just for nests.

  2. Genome analysis of the platypus reveals unique signatures of evolution

    Science.gov (United States)

    Warren, Wesley C.; Hillier, LaDeana W.; Marshall Graves, Jennifer A.; Birney, Ewan; Ponting, Chris P.; Grützner, Frank; Belov, Katherine; Miller, Webb; Clarke, Laura; Chinwalla, Asif T.; Yang, Shiaw-Pyng; Heger, Andreas; Locke, Devin P.; Miethke, Pat; Waters, Paul D.; Veyrunes, Frédéric; Fulton, Lucinda; Fulton, Bob; Graves, Tina; Wallis, John; Puente, Xose S.; López-Otín, Carlos; Ordóñez, Gonzalo R.; Eichler, Evan E.; Chen, Lin; Cheng, Ze; Deakin, Janine E.; Alsop, Amber; Thompson, Katherine; Kirby, Patrick; Papenfuss, Anthony T.; Wakefield, Matthew J.; Olender, Tsviya; Lancet, Doron; Huttley, Gavin A.; Smit, Arian F. A.; Pask, Andrew; Temple-Smith, Peter; Batzer, Mark A.; Walker, Jerilyn A.; Konkel, Miriam K.; Harris, Robert S.; Whittington, Camilla M.; Wong, Emily S. W.; Gemmell, Neil J.; Buschiazzo, Emmanuel; Vargas Jentzsch, Iris M.; Merkel, Angelika; Schmitz, Juergen; Zemann, Anja; Churakov, Gennady; Kriegs, Jan Ole; Brosius, Juergen; Murchison, Elizabeth P.; Sachidanandam, Ravi; Smith, Carly; Hannon, Gregory J.; Tsend-Ayush, Enkhjargal; McMillan, Daniel; Attenborough, Rosalind; Rens, Willem; Ferguson-Smith, Malcolm; Lefèvre, Christophe M.; Sharp, Julie A.; Nicholas, Kevin R.; Ray, David A.; Kube, Michael; Reinhardt, Richard; Pringle, Thomas H.; Taylor, James; Jones, Russell C.; Nixon, Brett; Dacheux, Jean-Louis; Niwa, Hitoshi; Sekita, Yoko; Huang, Xiaoqiu; Stark, Alexander; Kheradpour, Pouya; Kellis, Manolis; Flicek, Paul; Chen, Yuan; Webber, Caleb; Hardison, Ross; Nelson, Joanne; Hallsworth-Pepin, Kym; Delehaunty, Kim; Markovic, Chris; Minx, Pat; Feng, Yucheng; Kremitzki, Colin; Mitreva, Makedonka; Glasscock, Jarret; Wylie, Todd; Wohldmann, Patricia; Thiru, Prathapan; Nhan, Michael N.; Pohl, Craig S.; Smith, Scott M.; Hou, Shunfeng; Renfree, Marilyn B.; Mardis, Elaine R.; Wilson, Richard K.

    2009-01-01

    We present a draft genome sequence of the platypus, Ornithorhynchus anatinus. This monotreme exhibits a fascinating combination of reptilian and mammalian characters. For example, platypuses have a coat of fur adapted to an aquatic lifestyle; platypus females lactate, yet lay eggs; and males are equipped with venom similar to that of reptiles. Analysis of the first monotreme genome aligned these features with genetic innovations. We find that reptile and platypus venom proteins have been co-opted independently from the same gene families; milk protein genes are conserved despite platypuses laying eggs; and immune gene family expansions are directly related to platypus biology. Expansions of protein, non-protein-coding RNA and microRNA families, as well as repeat elements, are identified. Sequencing of this genome now provides a valuable resource for deep mammalian comparative analyses, as well as for monotreme biology and conservation. PMID:18464734

  3. Existence of a dictatorial subgroup in social choice with independent subgroup utility scales, an alternative proof

    NARCIS (Netherlands)

    Khmelnitskaya, Anna Borisovna; van Deemen, Adrian; Rusinowska, Agnieszka

    2010-01-01

    Social welfare orderings for different scales of individual utility measurement in distinct population subgroups are studied. In Khmelnitskaya (2000), employing the continuous version of Arrow’s impossibility theorem, it was shown that for combinations of independent subgroups scales every

  4. Clinical outcomes according to diabetic status in patients treated with biodegradable polymer sirolimus-eluting stents versus durable polymer everolimus-eluting stents: prespecified subgroup analysis of the BIOSCIENCE trial.

    Science.gov (United States)

    Franzone, Anna; Pilgrim, Thomas; Heg, Dik; Roffi, Marco; Tüller, David; Vuilliomenet, André; Muller, Olivier; Cook, Stéphane; Weilenmann, Daniel; Kaiser, Christoph; Jamshidi, Peiman; Räber, Lorenz; Stortecky, Stefan; Wenaweser, Peter; Jüni, Peter; Windecker, Stephan

    2015-06-01

    Ultrathin strut biodegradable polymer sirolimus-eluting stents (BP-SES) proved noninferior to durable polymer everolimus-eluting stents (DP-EES) for a composite clinical end point in a population with minimal exclusion criteria. We performed a prespecified subgroup analysis of the Ultrathin Strut Biodegradable Polymer Sirolimus-Eluting Stent Versus Durable Polymer Everolimus-Eluting Stent for Percutaneous Coronary Revascularisation (BIOSCIENCE) trial to compare the performance of BP-SES and DP-EES in patients with diabetes mellitus. BIOSCIENCE trial was an investigator-initiated, single-blind, multicentre, randomized, noninferiority trial comparing BP-SES versus DP-EES. The primary end point, target lesion failure, was a composite of cardiac death, target-vessel myocardial infarction, and clinically indicated target lesion revascularization within 12 months. Among a total of 2119 patients enrolled between February 2012 and May 2013, 486 (22.9%) had diabetes mellitus. Overall diabetic patients experienced a significantly higher risk of target lesion failure compared with patients without diabetes mellitus (10.1% versus 5.7%; hazard ratio [HR], 1.80; 95% confidence interval [CI], 1.27-2.56; P=0.001). At 1 year, there were no differences between BP-SES versus DP-EES in terms of the primary end point in both diabetic (10.9% versus 9.3%; HR, 1.19; 95% CI, 0.67-2.10; P=0.56) and nondiabetic patients (5.3% versus 6.0%; HR, 0.88; 95% CI, 0.58-1.33; P=0.55). Similarly, no significant differences in the risk of definite or probable stent thrombosis were recorded according to treatment arm in both study groups (4.0% versus 3.1%; HR, 1.30; 95% CI, 0.49-3.41; P=0.60 for diabetic patients and 2.4% versus 3.4%; HR, 0.70; 95% CI, 0.39-1.25; P=0.23, in nondiabetics). In the prespecified subgroup analysis of the BIOSCIENCE trial, clinical outcomes among diabetic patients treated with BP-SES or DP-EES were comparable at 1 year. URL: http://www.clinicaltrials.gov. Unique identifier

  5. Systematic Epigenomic Analysis Reveals Chromatin States Associated with Melanoma Progression

    Directory of Open Access Journals (Sweden)

    Petko Fiziev

    2017-04-01

    Full Text Available The extent and nature of epigenomic changes associated with melanoma progression is poorly understood. Through systematic epigenomic profiling of 35 epigenetic modifications and transcriptomic analysis, we define chromatin state changes associated with melanomagenesis by using a cell phenotypic model of non-tumorigenic and tumorigenic states. Computation of specific chromatin state transitions showed loss of histone acetylations and H3K4me2/3 on regulatory regions proximal to specific cancer-regulatory genes in important melanoma-driving cell signaling pathways. Importantly, such acetylation changes were also observed between benign nevi and malignant melanoma human tissues. Intriguingly, only a small fraction of chromatin state transitions correlated with expected changes in gene expression patterns. Restoration of acetylation levels on deacetylated loci by histone deacetylase (HDAC inhibitors selectively blocked excessive proliferation in tumorigenic cells and human melanoma cells, suggesting functional roles of observed chromatin state transitions in driving hyperproliferative phenotype. Through these results, we define functionally relevant chromatin states associated with melanoma progression.

  6. Transcriptomic analysis of autistic brain reveals convergent molecular pathology.

    Science.gov (United States)

    Voineagu, Irina; Wang, Xinchen; Johnston, Patrick; Lowe, Jennifer K; Tian, Yuan; Horvath, Steve; Mill, Jonathan; Cantor, Rita M; Blencowe, Benjamin J; Geschwind, Daniel H

    2011-05-25

    Autism spectrum disorder (ASD) is a common, highly heritable neurodevelopmental condition characterized by marked genetic heterogeneity. Thus, a fundamental question is whether autism represents an aetiologically heterogeneous disorder in which the myriad genetic or environmental risk factors perturb common underlying molecular pathways in the brain. Here, we demonstrate consistent differences in transcriptome organization between autistic and normal brain by gene co-expression network analysis. Remarkably, regional patterns of gene expression that typically distinguish frontal and temporal cortex are significantly attenuated in the ASD brain, suggesting abnormalities in cortical patterning. We further identify discrete modules of co-expressed genes associated with autism: a neuronal module enriched for known autism susceptibility genes, including the neuronal specific splicing factor A2BP1 (also known as FOX1), and a module enriched for immune genes and glial markers. Using high-throughput RNA sequencing we demonstrate dysregulated splicing of A2BP1-dependent alternative exons in the ASD brain. Moreover, using a published autism genome-wide association study (GWAS) data set, we show that the neuronal module is enriched for genetically associated variants, providing independent support for the causal involvement of these genes in autism. In contrast, the immune-glial module showed no enrichment for autism GWAS signals, indicating a non-genetic aetiology for this process. Collectively, our results provide strong evidence for convergent molecular abnormalities in ASD, and implicate transcriptional and splicing dysregulation as underlying mechanisms of neuronal dysfunction in this disorder.

  7. Consanguinity and late fertility: spatial analysis reveals positive association patterns.

    Science.gov (United States)

    Lisa, Antonella; Astolfi, Paola; Zei, Gianna; Tentoni, Stefania

    2015-01-01

    The role of consanguinity on human complex traits is an important and controversial issue. In this work we focused on the Sardinian population and examined the effect of consanguineous unions on late female fertility. During the last century the island has been characterized by a high incidence of marriages between relatives, favoured by socio economic conditions and geographical isolation, and by high fertility despite a widespread tendency to delay reproduction. Through spatial analysis techniques, we explored the geographical heterogeneity of consanguinity and late fertility, and identified in Central-Eastern Sardinia a common area with an excess of both traits, where the traits are positively associated. We found that their association did not significantly affect women's fertility in the area, despite the expected negative role of both traits. Intriguingly, this critical zone corresponds well to areas reported by previous studies as being peculiar for a high frequency of centenarians and for lower risk in pregnancy outcome. The proposed approach can be generally exploited to identify target populations on which socioeconomic, biodemographic and genetic data can be collected at the individual level, and deeper analyses carried out to disentangle the determinants of complex biological traits and to investigate their association. © 2014 John Wiley & Sons Ltd/University College London.

  8. Systematic Epigenomic Analysis Reveals Chromatin States Associated with Melanoma Progression.

    Science.gov (United States)

    Fiziev, Petko; Akdemir, Kadir C; Miller, John P; Keung, Emily Z; Samant, Neha S; Sharma, Sneha; Natale, Christopher A; Terranova, Christopher J; Maitituoheti, Mayinuer; Amin, Samirkumar B; Martinez-Ledesma, Emmanuel; Dhamdhere, Mayura; Axelrad, Jacob B; Shah, Amiksha; Cheng, Christine S; Mahadeshwar, Harshad; Seth, Sahil; Barton, Michelle C; Protopopov, Alexei; Tsai, Kenneth Y; Davies, Michael A; Garcia, Benjamin A; Amit, Ido; Chin, Lynda; Ernst, Jason; Rai, Kunal

    2017-04-25

    The extent and nature of epigenomic changes associated with melanoma progression is poorly understood. Through systematic epigenomic profiling of 35 epigenetic modifications and transcriptomic analysis, we define chromatin state changes associated with melanomagenesis by using a cell phenotypic model of non-tumorigenic and tumorigenic states. Computation of specific chromatin state transitions showed loss of histone acetylations and H3K4me2/3 on regulatory regions proximal to specific cancer-regulatory genes in important melanoma-driving cell signaling pathways. Importantly, such acetylation changes were also observed between benign nevi and malignant melanoma human tissues. Intriguingly, only a small fraction of chromatin state transitions correlated with expected changes in gene expression patterns. Restoration of acetylation levels on deacetylated loci by histone deacetylase (HDAC) inhibitors selectively blocked excessive proliferation in tumorigenic cells and human melanoma cells, suggesting functional roles of observed chromatin state transitions in driving hyperproliferative phenotype. Through these results, we define functionally relevant chromatin states associated with melanoma progression. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  9. Candida albicans morphologies revealed by scanning electron microscopy analysis

    Directory of Open Access Journals (Sweden)

    M. Staniszewska

    2013-09-01

    Full Text Available Scanning electron microscope (SEM observations were used to analyze particular morphologies of Candida albicans clinical isolate (strain 82 and mutants defective in hyphae-promoting genes EFG1 (strain HLC52 and/ or CPH1 (strains HLC54 and Can16. Transcription factors Efg1 and Cph1 play role in regulating filamentation and adhesion of C. albicans' morphologies. Comparative analysis of such mutants and clinical isolate showed that Efg1 is required for human serum-induced cell growth and morphological switching. In the study, distinct differences between ultrastructural patterns of clinical strain's and null mutants' morphologies were observed (spherical vs tube-like blastoconidia, or solid and fragile constricted septa vs only the latter observed in strains with EFG1 deleted. In addition, wild type strain displayed smooth colonies of cells in comparison to mutants which exhibited wrinkled phenotype. It was observed that blastoconidia of clinical strain exhibited either polarly or randomly located budding. Contrariwise, morphotypes of mutants showed either multiple polar budding or a centrally located single bud scar (mother-daughter cell junction distinguishing tube-like yeast/ pseudohyphal growth (the length-to-width ratios larger than 1.5. In their planktonic form of growth, blastoconidia of clinical bloodstream isolate formed constitutively true hyphae under undiluted human serum inducing conditions. It was found that true hyphae are essential elements for developing structural integrity of conglomerate, as mutants displaying defects in their flocculation and conglomerate-forming abilities in serum. While filamentation is an important virulence trait in C. albicans the true hyphae are the morphologies which may be expected to play a role in bloodstream infections.

  10. Demographic analysis reveals gradual senescence in the flatworm Macrostomum lignano

    Directory of Open Access Journals (Sweden)

    Braeckman Bart P

    2009-07-01

    Full Text Available Abstract Free-living flatworms ("Turbellaria" are appropriate model organisms to gain better insight into the role of stem cells in ageing and rejuvenation. Ageing research in flatworms is, however, still scarce. This is partly due to culture difficulties and the lack of a complete set of demographic data, including parameters such as median lifespan and age-specific mortality rate. In this paper, we report on the first flatworm survival analysis. We used the species Macrostomum lignano, which is an emerging model for studying the reciprocal influence between stem cells, ageing and rejuvenation. This species has a median lifespan of 205 ± 13 days (average ± standard deviation [SD] and a 90th percentile lifespan of 373 ± 32 days. The maximum lifespan, however, is more than 745 days, and the average survival curve is characterised by a long tail because a small number of individuals lives twice as long as 90% of the population. Similar to earlier observations in a wide range of animals, in M. lignano the age-specific mortality rate increases exponentially, but levels off at the oldest ages. To compare the senescence of M. lignano with that of other ageing models, we determined the mortality rate doubling time, which is 0.20 ± 0.02 years. As a result, we can conclude that M. lignano shows gradual senescence at a rate similar to the vertebrate ageing models Rattus norvegicus and Mus musculus. We argue that M. lignano is a suitable model for ageing and rejuvenation research, and especially for the role of stem cells in these processes, due to its accessible stem cell system and regeneration capacity, and the possibility of combining stem cell studies with demographic analyses.

  11. Demographic analysis reveals gradual senescence in the flatworm Macrostomum lignano.

    Science.gov (United States)

    Mouton, Stijn; Willems, Maxime; Back, Patricia; Braeckman, Bart P; Borgonie, Gaetan

    2009-07-30

    Free-living flatworms ("Turbellaria") are appropriate model organisms to gain better insight into the role of stem cells in ageing and rejuvenation. Ageing research in flatworms is, however, still scarce. This is partly due to culture difficulties and the lack of a complete set of demographic data, including parameters such as median lifespan and age-specific mortality rate. In this paper, we report on the first flatworm survival analysis. We used the species Macrostomum lignano, which is an emerging model for studying the reciprocal influence between stem cells, ageing and rejuvenation. This species has a median lifespan of 205 +/- 13 days (average +/- standard deviation [SD]) and a 90th percentile lifespan of 373 +/- 32 days. The maximum lifespan, however, is more than 745 days, and the average survival curve is characterised by a long tail because a small number of individuals lives twice as long as 90% of the population. Similar to earlier observations in a wide range of animals, in M. lignano the age-specific mortality rate increases exponentially, but levels off at the oldest ages. To compare the senescence of M. lignano with that of other ageing models, we determined the mortality rate doubling time, which is 0.20 +/- 0.02 years. As a result, we can conclude that M. lignano shows gradual senescence at a rate similar to the vertebrate ageing models Rattus norvegicus and Mus musculus. We argue that M. lignano is a suitable model for ageing and rejuvenation research, and especially for the role of stem cells in these processes, due to its accessible stem cell system and regeneration capacity, and the possibility of combining stem cell studies with demographic analyses.

  12. Changes in cod muscle proteins during frozen storage revealed by proteome analysis and multivariate data analysis

    DEFF Research Database (Denmark)

    Kjærsgård, Inger Vibeke Holst; Nørrelykke, M.R.; Jessen, Flemming

    2006-01-01

    packing did not lead to distinct changes in protein pattern. Applying DPLSR to the 2-DE data enabled the selection of protein spots critical for differentiation between 3 and 6months frozen storage with 12months frozen storage. Some of these protein spots have been identified by MS/MS, revealing myosin...... light chain 1, 2 and 3, triose-phosphate isomerase, glyceraldehyde-3-phosphate dehydrogenase, aldolase A and two ?-actin fragments, and a nuclease diphosphate kinase B fragment to change in concentration, during frozen storage. Application of proteomics, multivariate data analysis and MS/MS to analyse...

  13. The effects of status on subgroup relations.

    Science.gov (United States)

    Hornsey, Matthew J; Hogg, Michael A

    2002-06-01

    Two experiments were conducted to assess the impact of status differentials on subgroup attitudes and behaviours. In Experiment 1, 73 math-science students were led to believe they had higher or lower status than humanities students. They then performed a non-interactive decision-making task during which they were categorized exclusively as a university student (superordinate condition), or as a university student and math-science student simultaneously (subgroups condition). Experiment 2 (N = 98) differed from Experiment 1 in that perceptions of relative subgroup status were measured rather than manipulated. Consistent with social identity theory, subgroup members tended to categorize themselves more at the superordinate (university) level the lower status they considered their subgroup to be. In Experiment 2, a series of interactions also emerged, showing that status and inter-subgroup bias were positively related when the participants had been categorized exclusively at the superordinate level. When superordinate and subgroup identities were activated simultaneously, perceptions of status had no effect on levels of bias. The results were interpreted in terms of participants' needs for identity enhancement and identity distinctiveness.

  14. Clinical outcome of elderly patients with unresectable pancreatic cancer treated with gemcitabine plus S-1, S-1 alone, or gemcitabine alone: Subgroup analysis of a randomised phase III trial, GEST study.

    Science.gov (United States)

    Imaoka, Hiroshi; Kou, Tadayuki; Tanaka, Masao; Egawa, Shinichi; Mizuno, Nobumasa; Hijioka, Susumu; Hara, Kazuo; Yazumi, Shujiro; Shimizu, Yasuhiro; Yamao, Kenji

    2016-02-01

    In the GEST study of unresectable pancreatic cancer, S-1 demonstrated non-inferiority compared to gemcitabine, but gemcitabine plus S-1 (GS) did not show superiority over gemcitabine for overall survival (OS). We performed subgroup analysis of these data focused on the efficacy and safety of these regimens as a first-line treatment for elderly patients. Elderly patients (≥ 70 years, n = 261) treated for unresectable pancreatic cancer (GS: n = 90, S-1: n = 85 and gemcitabine: n = 86) were analysed. No significant differences between the GS, S-1, or gemcitabine groups in OS (median: 10.2, 8.0 and 8.5 months, respectively) or objective response rates (27.6%, 25.3% and 14.3%, respectively) were noted. Grade ≥ III adverse haematological events were observed more frequently in GS-treated than in S-1- or gemcitabine-treated elderly patients (p < 0.001 and p = 0.016, respectively). Four of 8 patients aged ≥ 80 years experienced serious adverse events. S-1 and gemcitabine are both efficacious options for treatment of elderly patients with unresectable pancreatic cancer. Conversely, first-line treatment of elderly patients with GS should only be used after careful consideration. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Omega-3 fatty acid supplementation in adolescents with borderline personality disorder and ultra-high risk criteria for psychosis: a post hoc subgroup analysis of a double-blind, randomized controlled trial.

    Science.gov (United States)

    Amminger, G Paul; Chanen, Andrew M; Ohmann, Susanne; Klier, Claudia M; Mossaheb, Nilufar; Bechdolf, Andreas; Nelson, Barnaby; Thompson, Andrew; McGorry, Patrick D; Yung, Alison R; Schäfer, Miriam R

    2013-07-01

    To investigate whether long-chain omega-3 (n-3) polyunsaturated fatty acids (PUFAs) improve functioning and psychiatric symptoms in young people with borderline personality disorder (BPD) who also meet ultra-high risk criteria for psychosis. We conducted a post hoc subgroup analysis of a double-blind, randomized controlled trial. Fifteen adolescents with BPD (mean age 16.2 years, [SD 2.1]) were randomized to either 1.2 g/day n-3 PUFAs or placebo. The intervention period was 12 weeks. Study measures included the Positive and Negative Syndrome Scale, the Montgomery-Åsberg Depression Rating Scale, and the Global Assessment of Functioning. Side effects were documented with the Udvalg for Kliniske Undersøgelser. Fatty acids in erythrocytes were analyzed using capillary gas chromatography. At baseline, erythrocyte n-3 PUFA levels correlated positively with psychosocial functioning and negatively with psychopathology. By the end of the intervention, n-3 PUFAs significantly improved functioning and reduced psychiatric symptoms, compared with placebo. Side effects did not differ between the treatment groups. Long-chain n-3 PUFAs should be further explored as a viable treatment strategy with minimal associated risk in young people with BPD. ( NCT00396643).

  16. Efficacy and safety of radium-223 dichloride in patients with castration-resistant prostate cancer and symptomatic bone metastases, with or without previous docetaxel use: a prespecified subgroup analysis from the randomised, double-blind, phase 3 ALSYMPCA trial.

    Science.gov (United States)

    Hoskin, Peter; Sartor, Oliver; O'Sullivan, Joe M; Johannessen, Dag Clement; Helle, Svein I; Logue, John; Bottomley, David; Nilsson, Sten; Vogelzang, Nicholas J; Fang, Fang; Wahba, Mona; Aksnes, Anne-Kirsti; Parker, Christopher

    2014-11-01

    Primary results from the phase 3 ALSYMPCA trial showed that radium-223 dichloride (radium-223), a targeted α-emitter, improved overall survival compared with placebo and was well tolerated in patients with castration-resistant prostate cancer and symptomatic bone metastases. We did a prespecified subgroup analysis from ALSYMPCA to assess the effect of previous docetaxel use on the efficacy and safety of radium-223. In the phase 3, randomised, double-blind ALSYMPCA trial, patients with symptomatic castration-resistant prostate cancer, at least two symptomatic bone metastases, no known visceral metastases, and who were receiving best standard of care were randomly assigned (2:1) via an interactive voice response system to receive six injections of radium-223 (50 kBq/kg intravenously) or matching placebo, with one injection given every 4 weeks. Patients had either received previous docetaxel treatment or were unsuitable for or declined docetaxel; previous docetaxel use (yes or no) was a trial stratification factor. We investigated the effect of previous docetaxel use on radium-223 treatment for the primary endpoint of overall survival, the main secondary efficacy endpoints, and safety. Efficacy analyses were done for the intention-to-treat population; safety analyses were done for the safety population. The trial has been completed and is registered with ClinicalTrials.gov, number NCT00699751. Randomisation took place between June 12, 2008, and Feb 1, 2011. 526 (57%) of 921 randomly assigned patients had received previous docetaxel treatment (352 in the radium-223 group and 174 in the placebo group) and 395 (43%) had not (262 in the radium-223 group and 133 in the placebo group). Radium-223 prolonged median overall survival compared with placebo, irrespective of previous docetaxel use (previous docetaxel use, hazard ratio [HR] 0·70, 95% CI 0·56-0·88; p=0·002; no previous docetaxel use, HR 0·69, 0·52-0·92; p=0·01). The benefit of radium-223 compared with

  17. RNA-seq Analysis Reveals Unique Transcriptome Signatures in Systemic Lupus Erythematosus Patients with Distinct Autoantibody Specificities.

    Directory of Open Access Journals (Sweden)

    Richa Rai

    Full Text Available Systemic lupus erythematosus (SLE patients exhibit immense heterogeneity which is challenging from the diagnostic perspective. Emerging high throughput sequencing technologies have been proved to be a useful platform to understand the complex and dynamic disease processes. SLE patients categorised based on autoantibody specificities are reported to have differential immuno-regulatory mechanisms. Therefore, we performed RNA-seq analysis to identify transcriptomics of SLE patients with distinguished autoantibody specificities. The SLE patients were segregated into three subsets based on the type of autoantibodies present in their sera (anti-dsDNA+ group with anti-dsDNA autoantibody alone; anti-ENA+ group having autoantibodies against extractable nuclear antigens (ENA only, and anti-dsDNA+ENA+ group having autoantibodies to both dsDNA and ENA. Global transcriptome profiling for each SLE patients subsets was performed using Illumina® Hiseq-2000 platform. The biological relevance of dysregulated transcripts in each SLE subsets was assessed by ingenuity pathway analysis (IPA software. We observed that dysregulation in the transcriptome expression pattern was clearly distinct in each SLE patients subsets. IPA analysis of transcripts uniquely expressed in different SLE groups revealed specific biological pathways to be affected in each SLE subsets. Multiple cytokine signaling pathways were specifically dysregulated in anti-dsDNA+ patients whereas Interferon signaling was predominantly dysregulated in anti-ENA+ patients. In anti-dsDNA+ENA+ patients regulation of actin based motility by Rho pathway was significantly affected. The granulocyte gene signature was a common feature to all SLE subsets; however, anti-dsDNA+ group showed relatively predominant expression of these genes. Dysregulation of Plasma cell related transcripts were higher in anti-dsDNA+ and anti-ENA+ patients as compared to anti-dsDNA+ ENA+. Association of specific canonical pathways

  18. Key predictive factors for efficacy of axitinib in first-line metastatic renal cell carcinoma: subgroup analysis in Japanese patients from a randomized, double-blind phase II study

    Science.gov (United States)

    Tomita, Yoshihiko; Fukasawa, Satoshi; Oya, Mototsugu; Uemura, Hirotsugu; Shinohara, Nobuo; Habuchi, Tomonori; Rini, Brian I.; Chen, Ying; Bair, Angel H.; Ozono, Seiichiro; Naito, Seiji; Akaza, Hideyuki

    2016-01-01

    Objectives To conduct Japanese subgroup analyses of a randomized, global Phase II study of axitinib with and without dose titration in first-line metastatic renal cell carcinoma and to explore predictive factors for axitinib efficacy in first-line metastatic renal cell carcinoma. Methods The data included 44 Japanese and 169 non-Japanese treatment-naïve patients with metastatic renal cell carcinoma. Patients received twice-daily axitinib 5 mg during a 4-week lead-in period. Patients who met the pre-defined randomization criteria were stratified by Eastern Cooperative Oncology Group performance status and randomly assigned (1:1) to axitinib or placebo titration. The primary endpoint was objective response rate; secondary endpoints included progression-free survival and safety. Predictive factors were analyzed using data from all patients. Results The objective response rate (95% confidence interval) was 66% (50–80%) vs. 44% (36–52%) in Japanese and non-Japanese patients, respectively. At the primary analysis, median progression-free survival could not be estimated for Japanese patients, and was 27.6 months (95% confidence interval: 16.6–33.2) in an updated analysis. Hypertension, diarrhea, hand–foot syndrome, dysphonia, hypothyroidism and proteinuria were common adverse events in Japanese patients. Due to a small number of randomized patients, effects of axitinib dose titration could not sufficiently be confirmed among Japanese patients. The multivariate analysis identified time from histopathological diagnosis to treatment and sum of the longest diameter for target lesion at baseline as independent predictive factors for progression-free survival. Conclusions Axitinib is effective and well tolerated as first-line metastatic renal cell carcinoma therapy in Japanese patients. Predictive factors for axitinib efficacy endpoints identified in this setting warrant further investigation. PMID:27572087

  19. SUBGR: A Program to Generate Subgroup Data for the Subgroup Resonance Self-Shielding Calculation

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Kang Seog [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2016-06-06

    The Subgroup Data Generation (SUBGR) program generates subgroup data, including levels and weights from the resonance self-shielded cross section table as a function of background cross section. Depending on the nuclide and the energy range, these subgroup data can be generated by (a) narrow resonance approximation, (b) pointwise flux calculations for homogeneous media; and (c) pointwise flux calculations for heterogeneous lattice cells. The latter two options are performed by the AMPX module IRFFACTOR. These subgroup data are to be used in the Consortium for Advanced Simulation of Light Water Reactors (CASL) neutronic simulator MPACT, for which the primary resonance self-shielding method is the subgroup method.

  20. Genome-wide analysis of the Dof transcription factor gene family reveals soybean-specific duplicable and functional characteristics.

    Directory of Open Access Journals (Sweden)

    Yong Guo

    Full Text Available The Dof domain protein family is a classic plant-specific zinc-finger transcription factor family involved in a variety of biological processes. There is great diversity in the number of Dof genes in different plants. However, there are only very limited reports on the characterization of Dof transcription factors in soybean (Glycine max. In the present study, 78 putative Dof genes were identified from the whole-genome sequence of soybean. The predicted GmDof genes were non-randomly distributed within and across 19 out of 20 chromosomes and 97.4% (38 pairs were preferentially retained duplicate paralogous genes located in duplicated regions of the genome. Soybean-specific segmental duplications contributed significantly to the expansion of the soybean Dof gene family. These Dof proteins were phylogenetically clustered into nine distinct subgroups among which the gene structure and motif compositions were considerably conserved. Comparative phylogenetic analysis of these Dof proteins revealed four major groups, similar to those reported for Arabidopsis and rice. Most of the GmDofs showed specific expression patterns based on RNA-seq data analyses. The expression patterns of some duplicate genes were partially redundant while others showed functional diversity, suggesting the occurrence of sub-functionalization during subsequent evolution. Comprehensive expression profile analysis also provided insights into the soybean-specific functional divergence among members of the Dof gene family. Cis-regulatory element analysis of these GmDof genes suggested diverse functions associated with different processes. Taken together, our results provide useful information for the functional characterization of soybean Dof genes by combining phylogenetic analysis with global gene-expression profiling.

  1. TERT promoter mutation and its interaction with IDH mutations in glioma: Combined TERT promoter and IDH mutations stratifies lower-grade glioma into distinct survival subgroups-A meta-analysis of aggregate data.

    Science.gov (United States)

    Vuong, Huy Gia; Altibi, Ahmed M A; Duong, Uyen N P; Ngo, Hanh T T; Pham, Thong Quang; Chan, Aden Ka-Yin; Park, Chul-Kee; Fung, Kar-Ming; Hassell, Lewis

    2017-12-01

    The clinical significance of telomerase reverse transcriptase (TERT) promoter mutation in glioma remains unclear. The aim of our meta-analysis is to investigate the prognostic impact TERT promoter mutation in glioma patients and its interaction with other molecular markers, particularly Isocitrate Dehydrogenase (IDH) mutation from aggregate level data. Relevant articles were searched in four electronic databases including PubMed, Scopus, Web of Science and Virtual Health Library. Pooled HRs were calculated using random effect model weighted by inverse variance method. From 1010 studies, we finally included 28 studies with 11519 patients for meta-analyses. TERT mutation is significantly associated with compromised overall survival (OS) (HR=1.38; 95% CI=1.15-1.67) and progression-free survival (PFS) (HR=1.31; 95% CI=1.06-1.63) in glioma patients. In studying its reaction with IDH, TERT promoter mutation was associated with reduced OS in both IDH-mutant (IDH-mut) and IDH-wild type (IDH-wt) glioblastomas but shown to have inverse effects on IDH-mut and IDH-wt grade II/III tumors. Our analysis categorized WHO grade II/III glioma patients into four distinct survival subgroups with descending survival as follow: TERT-mut/IDH-mut≫TERT-wt/IDH-mut≫TERT-wt/IDH-wt≫TERT-mut/IDH-wt. Prognostic value of TERT promoter mutations in gliomas is dependent on tumor grade and the IDH mutational status. With the same tumor grade in WHO grade II and III tumors and the same IDH mutation status, TERT-mut is a prognostic factor. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Revealing the association between cerebrovascular accidents and ambient temperature: a meta-analysis

    Science.gov (United States)

    Zorrilla-Vaca, Andrés; Healy, Ryan Jacob; Silva-Medina, Melissa M.

    2017-05-01

    The association between cerebrovascular accidents (CVA) and weather has been described across several studies showing multiple conflicting results. In this paper, we aim to conduct a meta-analysis to further clarify this association, as well as to find the potential sources of heterogeneity. PubMed, EMBASE, and Google Scholar were searched from inception through 2015, for articles analyzing the correlation between the incidence of CVA and temperature. A pooled effect size (ES) was estimated using random effects model and expressed as absolute values. Subgroup analyses by type of CVA were also performed. Heterogeneity and influence of covariates—including geographic latitude of the study site, male percentage, average temperature, and time interval—were assessed by meta-regression analysis. Twenty-six articles underwent full data extraction and scoring. A total of 19,736 subjects with CVA from 12 different countries were included and grouped as ischemic strokes (IS; n = 14,199), intracerebral hemorrhages (ICH; n = 3798), and subarachnoid hemorrhages (SAH; n = 1739). Lower ambient temperature was significantly associated with increase in incidence of overall CVA when using unadjusted (pooled ES = 0.23, P < 0.001) and adjusted data (pooled ES = 0.03, P = 0.003). Subgroup analyses showed that lower temperature has higher impact on the incidence of ICH (pooled ES = 0.34, P < 0.001), than that of IS (pooled ES = 0.22, P < 0.001) and SAH (pooled ES = 0.11, P = 0.012). In meta-regression analysis, the geographic latitude of the study site was the most influencing factor on this association ( Z-score = 8.68). Synthesis of the existing data provides evidence supporting that a lower ambient temperature increases the incidence of CVA. Further population-based studies conducted at negative latitudes are needed to clarify the influence of this factor.

  3. Clinical Subgroups in Bilateral Meniere Disease

    Science.gov (United States)

    Frejo, Lidia; Soto-Varela, Andres; Santos-Perez, Sofía; Aran, Ismael; Batuecas-Caletrio, Angel; Perez-Guillen, Vanesa; Perez-Garrigues, Herminio; Fraile, Jesus; Martin-Sanz, Eduardo; Tapia, Maria C.; Trinidad, Gabriel; García-Arumi, Ana María; González-Aguado, Rocío; Espinosa-Sanchez, Juan M.; Marques, Pedro; Perez, Paz; Benitez, Jesus; Lopez-Escamez, Jose A.

    2016-01-01

    Meniere disease (MD) is a heterogeneous clinical condition characterized by sensorineural hearing loss, episodic vestibular symptoms, and tinnitus associated with several comorbidities, such as migraine or autoimmune disorders (AD). The frequency of bilateral involvement may range from 5 to 50%, and it depends on the duration of the disease. We have performed a two-step cluster analysis in 398 patients with bilateral MD (BMD) to identify the best predictors to define clinical subgroups with a potential different etiology to improve the phenotyping of BMD and to develop new treatments. We have defined five clinical variants in BMD. Group 1 is the most frequently found, includes 46% of patients, and is defined by metachronic hearing loss without migraine and without AD. Group 2 is found in 17% of patients, and it is defined by synchronic hearing loss without migraine or AD. Group 3, with 13% of patients, is characterized by familial MD, while group 4, that includes 12% of patients, is associated by the presence of migraine in all cases. Group 5 is found in 11% of patients and is defined by AD. This approach can be helpful in selecting patients for genetic and clinical research. However, further studies will be required to improve the phenotyping in these clinical variants for a better understanding of the diverse etiological factors contributing to BMD. PMID:27822199

  4. Biosynthetic Pathway for the Epipolythiodioxopiperazine Acetylaranotin in Aspergillus terreus Revealed by Genome-based Deletion Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Chun-Jun; Yeh, Hsu-Hua; Chiang, Yi Ming; Sanchez, James F.; Chang, ShuLin; Bruno, Kenneth S.; Wang, Clay C.

    2013-04-15

    Abstract Epipolythiodioxopiperazines (ETPs) are a class of fungal secondary metabolites derived from cyclic peptides. Acetylaranotin belongs to one structural subgroup of ETPs characterized by the presence of a seven-membered dihydrooxepine ring. Defining the genes involved in acetylaranotin biosynthesis should provide a means to increase production of these compounds and facilitate the engineering of second-generation molecules. The filamentous fungus Aspergillus terreus produces acetylaranotin and related natural products. Using targeted gene deletions, we have identified a cluster of 9 genes including one nonribosomal peptide synthase gene, ataP, that is required for acetylaranotin biosynthesis. Chemical analysis of the wild type and mutant strains enabled us to isolate seventeen natural products that are either intermediates in the normal biosynthetic pathway or shunt products that are produced when the pathway is interrupted through mutation. Nine of the compounds identified in this study are novel natural products. Our data allow us to propose a complete biosynthetic pathway for acetylaranotin and related natural products.

  5. Insulin degludec/insulin aspart versus biphasic insulin aspart 30 twice daily in insulin-experienced Japanese subjects with uncontrolled type 2 diabetes: Subgroup analysis of a Pan-Asian, treat-to-target Phase 3 Trial.

    Science.gov (United States)

    Taneda, Shinji; Hyllested-Winge, Jacob; Gall, Mari-Anne; Kaneko, Shizuka; Hirao, Koichi

    2017-03-01

    The present study was a subgroup analysis of a Pan-Asian Phase 3 open-label randomized treat-to-target trial evaluating insulin degludec/insulin aspart (IDegAsp) and biphasic insulin aspart 30 (BIAsp 30) in Japanese subjects with type 2 diabetes inadequately controlled on insulin. Eligible subjects (n = 178) were randomized (2: 1) to twice-daily (b.i.d.) IDegAsp or BIAsp 30 with or without metformin for 26 weeks, titrated to a blood glucose target of between 3.9 and <5.0 mmol/L. Changes in HbA1c , the proportion of responders reaching the HbA1c target, and changes in fasting plasma glucose, nine-point self-monitored plasma glucose profiles, and body weight were assessed. At 26 weeks, the decrease in HbA1c was similar in both groups. Fasting plasma glucose was lower with IDegAsp than BIAsp 30 (estimated treatment difference -1.50 mmol/L; 95 % confidence interval [CI] -1.98, -1.01). Overall confirmed hypoglycemia rates were similar; the nocturnal confirmed hypoglycemia rate was lower with IDegAsp than BIAsp 30 (estimated rate ratio 0.44; 95 % CI 0.20, 0.99). No severe hypoglycemic episodes were reported. The results indicate that IDegAsp b.i.d. improves glycemic control and, compared with BIAsp 30, lowers the rate of nocturnal confirmed hypoglycemia. © 2016 The Authors. Journal of Diabetes published John Wiley & Sons Australia, Ltd and Ruijin Hospital, Shanghai Jiaotong University School of Medicine.

  6. GPR99, a new G protein-coupled receptor with homology to a new subgroup of nucleotide receptors

    Directory of Open Access Journals (Sweden)

    Chica Schaller H

    2002-07-01

    Full Text Available Abstract Background Based on sequence similarity, the superfamily of G protein-coupled receptors (GPRs can be subdivided into several subfamilies, the members of which often share similar ligands. The sequence data provided by the human genome project allows us to identify new GPRs by in silico homology screening, and to predict their ligands. Results By searching the human genomic database with known nucleotide receptors we discovered the gene for GPR99, a new orphan GPR. The mRNA of GPR99 was found in kidney and placenta. Phylogenetic analysis groups GPR99 into the P2Y subfamily of GPRs. Based on the phylogenetic tree we propose a new classification of P2Y nucleotide receptors into two subgroups predicting a nucleotide ligand for GPR99. By assaying known nucleotide ligands on heterologously expressed GPR99, we could not identify specifically activating substances, indicating that either they are not agonists of GPR99 or that GPR99 was not expressed at the cell surface. Analysis of the chromosomal localization of all genes of the P2Y subfamily revealed that all members of subgroup "a" are encoded by less than 370 kb on chromosome 3q24, and that the genes of subgroup "b" are clustered on one hand to chromosome 11q13.5 and on the other on chromosome 3q24-25.1 close to the subgroup "a" position. Therefore, the P2Y subfamily is a striking example for local gene amplification. Conclusions We identified a new orphan receptor, GPR99, with homology to the family of G protein-coupled nucleotide receptors. Phylogenetic analysis separates this family into different subgroups predicting a nucleotide ligand for GPR99.

  7. Functional divergence of the NIP III subgroup proteins involved altered selective constraints and positive selection

    Directory of Open Access Journals (Sweden)

    Zhu Zhujun

    2010-11-01

    Full Text Available Abstract Background Nod26-like intrinsic proteins (NIPs that belong to the aquaporin superfamily are unique to plants. According to homology modeling and phylogenetic analysis, the NIP subfamily can be further divided into three subgroups with distinct biological functions (NIP I, NIP II, and NIP III. In some grasses, the NIP III subgroup proteins (NIP2s were demonstrated to be permeable to solutes with larger diameter, such as silicic acid and arsenous acids. However, to date there is no data-mining or direct experimental evidences for the permeability of such larger solutes for dicot NIP2s, although they exhibit similar three-dimensional structures as those in grasses. It is therefore intriguing to investigate the molecular mechanisms that drive the evolution of plant NIP2s. Results The NIP III subgroup is more ancient with a divergence time that predates the monocot-dicot split. The proliferation of NIP2 genes in modern grass species is primarily attributed to whole genome and segmental chromosomal duplication events. The structure of NIP2 genes is relatively conserved, possessing five exons and four introns. All NIP2s possess an ar/R filter consisting of G, S, G, and R, except for the cucumber CsNIP2;2, where a small G in the H2 is substituted with the bulkier C residue. Our maximum likelihood analysis revealed that NIP2s, especially the loop A (LA region, have undergone strong selective pressure for adaptive evolution. The analysis at the amino acid level provided strong statistical evidences for the functional divergence between monocot and dicot NIP III subgroup proteins. In addition, several SDPs (Specificity Determining Positions responsible for functional specificity were predicted. Conclusions The present study provides the first evidences of functional divergence between dicot and monocot NIP2s, and suggests that positive selection, as well as a radical shift of evolutionary rate at some critical amino acid sites is the primary

  8. Differential gene expression analysis by RNA-seq reveals the importance of actin cytoskeletal proteins in erythroleukemia cells

    Directory of Open Access Journals (Sweden)

    Vanessa Fernández-Calleja

    2017-06-01

    Full Text Available Development of drug resistance limits the effectiveness of anticancer treatments. Understanding the molecular mechanisms triggering this event in tumor cells may lead to improved therapeutic strategies. Here we used RNA-seq to compare the transcriptomes of a murine erythroleukemia cell line (MEL and a derived cell line with induced resistance to differentiation (MEL-R. RNA-seq analysis identified a total of 596 genes (Benjamini–Hochberg adjusted p-value < 0.05 that were differentially expressed by more than two-fold, of which 81.5% (486/596 of genes were up-regulated in MEL cells and 110 up-regulated in MEL-R cells. These observations revealed that for some genes the relative expression of mRNA amount in the MEL cell line has decreased as the cells acquired the resistant phenotype. Clustering analysis of a group of genes showing the highest differential expression allowed identification of a sub-group among genes up-regulated in MEL cells. These genes are related to the organization of the actin cytoskeleton network. Moreover, the majority of these genes are preferentially expressed in the hematopoietic lineage and at least three of them, Was (Wiskott Aldrich syndrome, Btk (Bruton’s tyrosine kinase and Rac2, when mutated in humans, give rise to severe hematopoietic deficiencies. Among the group of genes that were up-regulated in MEL-R cells, 16% of genes code for histone proteins, both canonical and variants. A potential implication of these results on the blockade of differentiation in resistant cells is discussed.

  9. Differential gene expression analysis by RNA-seq reveals the importance of actin cytoskeletal proteins in erythroleukemia cells.

    Science.gov (United States)

    Fernández-Calleja, Vanessa; Hernández, Pablo; Schvartzman, Jorge B; García de Lacoba, Mario; Krimer, Dora B

    2017-01-01

    Development of drug resistance limits the effectiveness of anticancer treatments. Understanding the molecular mechanisms triggering this event in tumor cells may lead to improved therapeutic strategies. Here we used RNA-seq to compare the transcriptomes of a murine erythroleukemia cell line (MEL) and a derived cell line with induced resistance to differentiation (MEL-R). RNA-seq analysis identified a total of 596 genes (Benjamini-Hochberg adjusted p-value < 0.05) that were differentially expressed by more than two-fold, of which 81.5% (486/596) of genes were up-regulated in MEL cells and 110 up-regulated in MEL-R cells. These observations revealed that for some genes the relative expression of mRNA amount in the MEL cell line has decreased as the cells acquired the resistant phenotype. Clustering analysis of a group of genes showing the highest differential expression allowed identification of a sub-group among genes up-regulated in MEL cells. These genes are related to the organization of the actin cytoskeleton network. Moreover, the majority of these genes are preferentially expressed in the hematopoietic lineage and at least three of them, Was (Wiskott Aldrich syndrome), Btk (Bruton's tyrosine kinase) and Rac2, when mutated in humans, give rise to severe hematopoietic deficiencies. Among the group of genes that were up-regulated in MEL-R cells, 16% of genes code for histone proteins, both canonical and variants. A potential implication of these results on the blockade of differentiation in resistant cells is discussed.

  10. Outpatient treatment of acute bacterial skin and skin structure infections (ABSSSI) with tedizolid phosphate and linezolid in patients in the United States: Subgroup analysis of 2 randomized phase 3 trials.

    Science.gov (United States)

    De Anda, Carisa; Anuskiewicz, Steven; Prokocimer, Philippe; Vazquez, Jose

    2017-12-01

    Acute bacterial skin and skin structure infections (ABSSSI) are a frequent cause of hospital admissions in the United States. Safe and effective outpatient treatments may lower ABSSSI-associated health care costs by reducing unnecessary hospital admissions. Using data from 2 phase 3 trials (ESTABLISH-1, NCT01170221; ESTABLISH-2, NCT01421511), this post-hoc analysis explored the efficacy and safety of tedizolid in an outpatient setting. Subgroup analysis was performed on US outpatients (defined as patients who were not in hospital at the time of treatment initiation) with ABSSSI caused by presumed or proven gram-positive pathogens. Patients were randomly assigned to receive tedizolid phosphate 200 mg once daily for 6 days (n = 403) or linezolid 600 mg twice daily for 10 days (n = 410). The primary end point was early clinical response (48-72 hours after the start of treatment). Secondary end points included investigator-assessed clinical response at end of therapy (EOT) and post-therapy evaluation (PTE; 7-14 days after therapy). Additional assessments included the patient-reported level of pain using a visual analog scale (VAS) and the per-pathogen favorable microbiological response rate at the PTE visit. Compliance with treatment and safety outcomes was also recorded. Early clinical response was similar between treatment groups (tedizolid, 82.4%; linezolid, 79.0%), as was investigator-assessed clinical response at EOT (tedizolid, 87.1%; linezolid, 86.1%) and PTE (tedizolid, 83.1%; linezolid, 83.7%). Mean changes from baseline to days 10 to 13 in VAS scores were identical between treatment groups (tedizolid, -51.9 mm; linezolid, -51.9 mm). Microbiological eradication rates were generally similar in both treatment groups for all key pathogens. Patients in both groups had favorable response at PTE. More tedizolid-treated patients (89.3%) than linezolid-treated patients (77.3%) were compliant with treatment. The most frequently reported drug

  11. Fast determination of structurally cohesive subgroups in large networks.

    Science.gov (United States)

    Sinkovits, Robert S; Moody, James; Oztan, B Tolga; White, Douglas R

    2016-11-01

    Structurally cohesive subgroups are a powerful and mathematically rigorous way to characterize network robustness. Their strength lies in the ability to detect strong connections among vertices that not only have no neighbors in common, but that may be distantly separated in the graph. Unfortunately, identifying cohesive subgroups is a computationally intensive problem, which has limited empirical assessments of cohesion to relatively small graphs of at most a few thousand vertices. We describe here an approach that exploits the properties of cliques, k-cores and vertex separators to iteratively reduce the complexity of the graph to the point where standard algorithms can be used to complete the analysis. As a proof of principle, we apply our method to the cohesion analysis of a 29,462-vertex biconnected component extracted from a 128,151-vertex co-authorship data set.

  12. On Preferential sylow fuzzy subgroups | Makamba | Quaestiones ...

    African Journals Online (AJOL)

    In this paper, for a prime p, we propose some plausible denitions for the notion of Sylow fuzzy p-subgroup of a nite group. We derive a number of results for nite fuzzy groups using one of the proposed denitions. We also discuss some of the relationships between various proposed denitions for suitability, including the crisp ...

  13. Zero-sum problems with subgroup weights

    Indian Academy of Sciences (India)

    In this note, we generalize some theorems on zero-sums with weights from [1], [4] and [5] in two directions. In particular, we consider Z Z p d for a general and subgroups of Z p ∗ as weights. Author Affiliations. S D Adhikari1 A A Ambily2 B Sury2. Harish-Chandra Research Institute, Chhatnag Road, Jhunsi, Allahabad 211 ...

  14. Interpretation of Subgroup Effects in Published Trials

    DEFF Research Database (Denmark)

    Hancock, Mark J; Kjær, Per; Korsholm, Lars

    2013-01-01

    that report on treatment effect modifiers (subgroups) for specific physical therapy interventions. The key messages are: (1) point estimates of treatment modifier effect size (interaction effect) and their confidence intervals can be calculated using group-level data when individual patient-level data...

  15. Efficacy and safety of ticagrelor versus aspirin in acute stroke or transient ischaemic attack of atherosclerotic origin: a subgroup analysis of SOCRATES, a randomised, double-blind, controlled trial.

    Science.gov (United States)

    Amarenco, Pierre; Albers, Gregory W; Denison, Hans; Easton, J Donald; Evans, Scott R; Held, Peter; Hill, Michael D; Jonasson, Jenny; Kasner, Scott E; Ladenvall, Per; Minematsu, Kazuo; Molina, Carlos A; Wang, Yongjun; Wong, K S Lawrence; Johnston, S Claiborne

    2017-04-01

    Ticagrelor is an effective antiplatelet therapy for patients with coronary atherosclerotic disease and might be more effective than aspirin in preventing recurrent stroke and cardiovascular events in patients with acute cerebral ischaemia of atherosclerotic origin. Our aim was to test for a treatment-by-ipsilateral atherosclerotic stenosis interaction in a subgroup analysis of patients in the Acute Stroke or Transient Ischaemic Attack Treated with Aspirin or Ticagrelor and Patient Outcomes (SOCRATES) trial. SOCRATES was a randomised, double-blind, controlled trial of ticagrelor versus aspirin in patients aged 40 years or older with a non-cardioembolic, non-severe acute ischaemic stroke, or high-risk transient ischaemic attack from 674 hospitals in 33 countries. We randomly allocated patients (1:1) to ticagrelor (180 mg loading dose on day 1 followed by 90 mg twice daily for days 2-90, given orally) or aspirin (300 mg on day 1 followed by 100 mg daily for days 2-90, given orally) within 24 h of symptom onset. Investigators classified all patients into atherosclerotic and non-atherosclerotic groups for the prespecified, exploratory analysis reported in this study. The primary endpoint was the time to occurrence of stroke, myocardial infarction, or death within 90 days. Efficacy analysis was by intention to treat. The SOCRATES trial is registered with ClinicalTrials.gov, number NCT01994720. Between Jan 7, 2014, and Oct 29, 2015, we randomly allocated 13 199 patients (6589 [50%] to ticagrelor and 6610 [50%] to aspirin). Potentially symptomatic ipsilateral atherosclerotic stenosis was reported in 3081 (23%) of 13 199 patients. We found a treatment-by-atherosclerotic stenosis interaction (p=0·017). 103 (6·7%) of 1542 patients with ipsilateral stenosis in the ticagrelor group and 147 (9·6%) of 1539 patients with ipsilateral stenosis in the aspirin group had an occurrence of stroke, myocardial infarction, or death within 90 days (hazard ratio 0·68 [95% CI 0·53-0

  16. Gardnerella vaginalis Subgroups Defined by cpn60 Sequencing and Sialidase Activity in Isolates from Canada, Belgium and Kenya.

    Directory of Open Access Journals (Sweden)

    John J Schellenberg

    Full Text Available Increased abundance of Gardnerella vaginalis and sialidase activity in vaginal fluid is associated with bacterial vaginosis (BV, a common but poorly understood clinical entity associated with poor reproductive health outcomes. Since most women are colonized with G. vaginalis, its status as a normal member of the vaginal microbiota or pathogen causing BV remains controversial, and numerous classification schemes have been described. Since 2005, sequencing of the chaperonin-60 universal target (cpn60 UT has distinguished four subgroups in isolate collections, clone libraries and deep sequencing datasets. To clarify potential clinical and diagnostic significance of cpn60 subgroups, we undertook phenotypic and molecular characterization of 112 G. vaginalis isolates from three continents. A total of 36 subgroup A, 33 B, 35 C and 8 D isolates were identified through phylogenetic analysis of cpn60 sequences as corresponding to four "clades" identified in a recently published study, based on sequencing 473 genes across 17 isolates. cpn60 subgroups were compared with other previously described molecular methods for classification of Gardnerella subgroups, including amplified ribosomal DNA restriction analysis (ARDRA and real-time PCR assays designed to quantify subgroups in vaginal samples. Although two ARDRA patterns were observed in isolates, each was observed in three cpn60 subgroups (A/B/D and B/C/D. Real-time PCR assays corroborated cpn60 subgroups overall, but 13 isolates from subgroups A, B and D were negative in all assays. A putative sialidase gene was detected in all subgroup B, C and D isolates, but only in a single subgroup A isolate. In contrast, sialidase activity was observed in all subgroup B isolates, 3 (9% subgroup C isolates and no subgroup A or D isolates. These observations suggest distinct roles for G. vaginalis subgroups in BV pathogenesis. We conclude that cpn60 UT sequencing is a robust approach for defining G. vaginalis

  17. Gardnerella vaginalis Subgroups Defined by cpn60 Sequencing and Sialidase Activity in Isolates from Canada, Belgium and Kenya.

    Science.gov (United States)

    Schellenberg, John J; Paramel Jayaprakash, Teenus; Withana Gamage, Niradha; Patterson, Mo H; Vaneechoutte, Mario; Hill, Janet E

    2016-01-01

    Increased abundance of Gardnerella vaginalis and sialidase activity in vaginal fluid is associated with bacterial vaginosis (BV), a common but poorly understood clinical entity associated with poor reproductive health outcomes. Since most women are colonized with G. vaginalis, its status as a normal member of the vaginal microbiota or pathogen causing BV remains controversial, and numerous classification schemes have been described. Since 2005, sequencing of the chaperonin-60 universal target (cpn60 UT) has distinguished four subgroups in isolate collections, clone libraries and deep sequencing datasets. To clarify potential clinical and diagnostic significance of cpn60 subgroups, we undertook phenotypic and molecular characterization of 112 G. vaginalis isolates from three continents. A total of 36 subgroup A, 33 B, 35 C and 8 D isolates were identified through phylogenetic analysis of cpn60 sequences as corresponding to four "clades" identified in a recently published study, based on sequencing 473 genes across 17 isolates. cpn60 subgroups were compared with other previously described molecular methods for classification of Gardnerella subgroups, including amplified ribosomal DNA restriction analysis (ARDRA) and real-time PCR assays designed to quantify subgroups in vaginal samples. Although two ARDRA patterns were observed in isolates, each was observed in three cpn60 subgroups (A/B/D and B/C/D). Real-time PCR assays corroborated cpn60 subgroups overall, but 13 isolates from subgroups A, B and D were negative in all assays. A putative sialidase gene was detected in all subgroup B, C and D isolates, but only in a single subgroup A isolate. In contrast, sialidase activity was observed in all subgroup B isolates, 3 (9%) subgroup C isolates and no subgroup A or D isolates. These observations suggest distinct roles for G. vaginalis subgroups in BV pathogenesis. We conclude that cpn60 UT sequencing is a robust approach for defining G. vaginalis subgroups within the

  18. Pain and Fatigue Variability Patterns Distinguish Subgroups of Fibromyalgia Patients.

    Science.gov (United States)

    Bartley, Emily J; Robinson, Michael E; Staud, Roland

    2017-12-15

    The current study examined between- and within-subject variability in pain-related symptoms as predictors of pain and fatigue, and identified patient subgroups based upon symptom variability characteristics. Two hundred and fifty-six fibromyalgia (FM) patients completed daily diaries up to a period of 154 days and reported on symptoms of pain intensity, pain unpleasantness, fatigue, anxiety, and depressed mood. Measures of health status, quality of life, and somatic symptoms were obtained at baseline, and hierarchical linear modeling and cluster analyses were employed. Significant intra- and inter-individual variability in daily FM symptoms was observed. Higher levels of pain were associated with greater fluctuations in pain unpleasantness, fatigue, and depressed mood. Similar effects were observed for fatigue and individual variability in anxiety also emerged as a robust predictor. Three FM subgroups were revealed: low variability in symptoms (Cluster 1), high symptom variability (Cluster 2), and a mixed variability group characterized by low fluctuation in pain unpleasantness; moderate pain, fatigue, and depressed mood variability; and high anxiety variability (Cluster 3). Cluster 3 exhibited lower social functioning and higher levels of pain, compared to Cluster 1. These findings support the dynamic nature of FM pain and suggest the presence of FM subgroups based upon variation in mood and pain symptomatology. Fibromyalgia patients display significant intra- and inter-individual variability in pain, mood, and fatigue. Subgroups in mood and pain-related variability emerged, with phenotypic clusters differing across levels of pain intensity and social functioning. Better understanding of the processes impacting pain variability may facilitate targeted treatments for the control of pain. Copyright © 2017. Published by Elsevier Inc.

  19. Post hoc analysis of a single IV infusion of zoledronic acid versus daily oral risedronate on lumbar spine bone mineral density in different subgroups with glucocorticoid-induced osteoporosis.

    Science.gov (United States)

    Roux, C; Reid, D M; Devogelaer, J-P; Saag, K; Lau, C S; Reginster, J-Y; Papanastasiou, P; Bucci-Rechtweg, C; Su, G; Sambrook, P N

    2012-03-01

    This study summarizes the treatment effect of zoledronic acid infusion on lumbar spine bone mineral density in different subgroups with glucocorticoid-induced osteoporosis. Zoledronic acid is significantly more effective than risedronate in increasing lumbar spine (LS) bone mineral density (BMD) in both prevention and treatment of glucocorticoid-induced osteoporosis. Introduction In patients on glucocorticoids, a single zoledronic acid infusion significantly increased BMD versus daily oral risedronate. We assessed treatment effect on LS BMD in different patient subgroups at month 12 that contributed to the risk of osteoporosis in addition to glucocorticoids. Methods Patients randomized to a single IV infusion of zoledronic acid 5 mg or risedronate (5 mg/day) and stratified based on glucocorticoids duration [treatment (>3 months) and prevention (≤ 3 months) subpopulations]were subgrouped by age; gender; menopausal status in women; dose and duration of prednisone during the trial; and baseline serum 25-OH vitamin D, LS BMD T-score, creatinine clearance, and concomitant medication use. Results At month 12, zoledronic acid significantly increased LS BMD versus risedronate in patients ≤ 74 years (Pinduced osteoporosis across a wide range of patients.

  20. A novel subgroup 16SrVII-D phytoplasma identified in association with Erigeron witches' broom.

    Science.gov (United States)

    Flôres, Daniela; Amaral Mello, Ana Paula de Oliveira; Pereira, Thays Benites Camargo; Rezende, Jorge Alberto Marques; Bedendo, Ivan Paulo

    2015-08-01

    Erigeron sp. plants showing symptoms of witches' broom and stunting were found near orchards of passion fruit in São Paulo state, Brazil. These symptoms were indicative of infection by phytoplasmas. Thus, the aim of this study was to detect and identify possible phytoplasmas associated with diseased plants. Total DNA was extracted from symptomatic and asymptomatic plants and used in nested PCR conducted with the primer pairs P1/Tint and R16F2n/16R2. Amplification of genomic fragments of 1.2 kb from the 16S rRNA gene confirmed the presence of phytoplasma in all symptomatic samples. The sequence identity scores between the 16S rRNA gene of the phytoplasma strain identified in the current study and those of previously reported 'Candidatus Phytoplasma fraxini'-related strains ranged from 98% to 99% indicating the phytoplasma to be a strain affiliated with 'Candidatus Phytoplasma fraxini'. The results from a phylogenetic analysis and virtual RFLP analysis of the 16S rRNA gene sequence with 17 restriction enzymes revealed that the phytoplasma strain belongs to the ash yellows phytoplasma group (16SrVII); the similarity coefficient of RFLP patterns further suggested that the phytoplasma represents a novel subgroup, designated 16SrVII-D. The representative of this new subgroup was named EboWB phytoplasma (Erigeron bonariensis Witches' Broom).

  1. Oral rivaroxaban versus enoxaparin with vitamin K antagonist for the treatment of symptomatic venous thromboembolism in patients with cancer (EINSTEIN-DVT and EINSTEIN-PE): a pooled subgroup analysis of two randomised controlled trials.

    Science.gov (United States)

    Prins, Martin H; Lensing, Anthonie W A; Brighton, Tim A; Lyons, Roger M; Rehm, Jeffrey; Trajanovic, Mila; Davidson, Bruce L; Beyer-Westendorf, Jan; Pap, Ákos F; Berkowitz, Scott D; Cohen, Alexander T; Kovacs, Michael J; Wells, Philip S; Prandoni, Paolo

    2014-10-01

    Patients with venous thromboembolism and cancer have a substantial risk of recurrent venous thromboembolism and bleeding during anticoagulant therapy. Although monotherapy with low-molecular-weight heparin is recommended in these patients, in clinical practice many patients with venous thromboembolism and cancer do not receive this treatment. We aimed to assess the efficacy and safety of a single-drug regimen with oral rivaroxaban compared with enoxaparin followed by vitamin K antagonists, in the subgroup of patients with cancer enrolled in the EINSTEIN-DVT and EINSTEIN-PE randomised controlled trials. We did a subgroup analysis of patients with active cancer (either at baseline or diagnosed during the study), a history of cancer, or no cancer who were enrolled in the EINSTEIN-DVT and EINSTEIN-PE trials. Eligible patients with deep-vein thrombosis (EINSTEIN-DVT) or pulmonary embolism (EINSTEIN-PE) were randomly assigned in a 1:1 ratio to receive rivaroxaban (15 mg twice daily for 21 days, followed by 20 mg once daily) or standard therapy (enoxaparin 1·0 mg/kg twice daily and warfarin or acenocoumarol; international normalised ratio 2·0-3·0). Randomisation with a computerised voice-response system was stratified according to country and intended treatment duration (3, 6, or 12 months). The prespecified primary efficacy and safety outcomes of both the trials and this subanalysis were symptomatic recurrent venous thromboembolism and clinically relevant bleeding, respectively. We did efficacy and mortality analyses in the intention-to-treat population, and bleeding analyses for time spent receiving treatment plus 2 days in the safety population (all patients who received at least one dose of study drug). The EINSTEIN-DVT and EINSTEIN-PE studies are registered at ClinicalTrials.gov, numbers NCT00440193 and NCT00439777. In patients with active cancer (diagnosed at baseline or during treatment), recurrent venous thromboembolism occurred in 16 (5%) of 354 patients

  2. Transcriptome analysis reveals key differentially expressed genes involved in wheat grain development

    Directory of Open Access Journals (Sweden)

    Yonglong Yu

    2016-04-01

    Full Text Available Wheat seed development is an important physiological process of seed maturation and directly affects wheat yield and quality. In this study, we performed dynamic transcriptome microarray analysis of an elite Chinese bread wheat cultivar (Jimai 20 during grain development using the GeneChip Wheat Genome Array. Grain morphology and scanning electron microscope observations showed that the period of 11–15 days post-anthesis (DPA was a key stage for the synthesis and accumulation of seed starch. Genome-wide transcriptional profiling and significance analysis of microarrays revealed that the period from 11 to 15 DPA was more important than the 15–20 DPA stage for the synthesis and accumulation of nutritive reserves. Series test of cluster analysis of differential genes revealed five statistically significant gene expression profiles. Gene ontology annotation and enrichment analysis gave further information about differentially expressed genes, and MapMan analysis revealed expression changes within functional groups during seed development. Metabolic pathway network analysis showed that major and minor metabolic pathways regulate one another to ensure regular seed development and nutritive reserve accumulation. We performed gene co-expression network analysis to identify genes that play vital roles in seed development and identified several key genes involved in important metabolic pathways. The transcriptional expression of eight key genes involved in starch and protein synthesis and stress defense was further validated by qRT-PCR. Our results provide new insight into the molecular mechanisms of wheat seed development and the determinants of yield and quality.

  3. Topological groups with dense compactly generated subgroups

    Directory of Open Access Journals (Sweden)

    Hiroshi Fujita

    2002-04-01

    Full Text Available A topological group G is: (i compactly generated if it contains a compact subset algebraically generating G, (ii -compact if G is a union of countably many compact subsets, (iii 0-bounded if arbitrary neighborhood U of the identity element of G has countably many translates xU that cover G, and (iv finitely generated modulo open sets if for every non-empty open subset U of G there exists a finite set F such that F  U algebraically generates G. We prove that: (1 a topological group containing a dense compactly generated subgroup is both 0-bounded and finitely generated modulo open sets, (2 an almost metrizable topological group has a dense compactly generated subgroup if and only if it is both 0-bounded and finitely generated modulo open sets, and (3 an almost metrizable topological group is compactly generated if and only if it is -compact and finitely generated modulo open sets.

  4. Factorizing profinite groups into two Abelian subgroups

    Directory of Open Access Journals (Sweden)

    Wolfgang Herfort

    2013-03-01

    Full Text Available We prove that the class of profinite groups $G$ that have a factorization $G=AB$with $A$ and $B$ abelian closed subgroups, is closed under taking strict projective limits.This is a generalization of a recent result by K.H.~Hofmann and F.G.~Russo.As an application we reprove their generalization of Iwasawa's structure theorem forquasihamiltonian pro-$p$ groups.

  5. Network-based analysis reveals functional connectivity related to internet addiction tendency

    Directory of Open Access Journals (Sweden)

    Tanya eWen

    2016-02-01

    Full Text Available IntroductionPreoccupation and compulsive use of the internet can have negative psychological effects, such that it is increasingly being recognized as a mental disorder. The present study employed network-based statistics to explore how whole-brain functional connections at rest is related to the extent of individual’s level of internet addiction, indexed by a self-rated questionnaire. We identified two topologically significant networks, one with connections that are positively correlated with internet addiction tendency, and one with connections negatively correlated with internet addiction tendency. The two networks are interconnected mostly at frontal regions, which might reflect alterations in the frontal region for different aspects of cognitive control (i.e., for control of internet usage and gaming skills. Next, we categorized the brain into several large regional subgroupings, and found that the majority of proportions of connections in the two networks correspond to the cerebellar model of addiction which encompasses the four-circuit model. Lastly, we observed that the brain regions with the most inter-regional connections associated with internet addiction tendency replicate those often seen in addiction literature, and is corroborated by our meta-analysis of internet addiction studies. This research provides a better understanding of large-scale networks involved in internet addiction tendency and shows that pre-clinical levels of internet addiction are associated with similar regions and connections as clinical cases of addiction.

  6. MPACT Subgroup Self-Shielding Efficiency Improvements

    Energy Technology Data Exchange (ETDEWEB)

    Stimpson, Shane [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Liu, Yuxuan [Univ. of Michigan, Ann Arbor, MI (United States); Collins, Benjamin S. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Clarno, Kevin T. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2016-08-31

    Recent developments to improve the efficiency of the MOC solvers in MPACT have yielded effective kernels that loop over several energy groups at once, rather that looping over one group at a time. These kernels have produced roughly a 2x speedup on the MOC sweeping time during eigenvalue calculation. However, the self-shielding subgroup calculation had not been reevaluated to take advantage of these new kernels, which typically requires substantial solve time. The improvements covered in this report start by integrating the multigroup kernel concepts into the subgroup calculation, which are then used as the basis for further extensions. The next improvement that is covered is what is currently being termed as “Lumped Parameter MOC”. Because the subgroup calculation is a purely fixed source problem and multiple sweeps are performed only to update the boundary angular fluxes, the sweep procedure can be condensed to allow for the instantaneous propagation of the flux across a spatial domain, without the need to sweep along all segments in a ray. Once the boundary angular fluxes are considered to be converged, an additional sweep that will tally the scalar flux is completed. The last improvement that is investigated is the possible reduction of the number of azimuthal angles per octant in the shielding sweep. Typically 16 azimuthal angles per octant are used for self-shielding and eigenvalue calculations, but it is possible that the self-shielding sweeps are less sensitive to the number of angles than the full eigenvalue calculation.

  7. Proteomic analysis of three gonad types of swamp eel reveals genes differentially expressed during sex reversal

    OpenAIRE

    Yue Sheng; Wei Zhao; Ying Song; Zhigang Li; Majing Luo; Quan Lei; Hanhua Cheng; Rongjia Zhou

    2015-01-01

    A variety of mechanisms are engaged in sex determination in vertebrates. The teleost fish swamp eel undergoes sex reversal naturally and is an ideal model for vertebrate sexual development. However, the importance of proteome-wide scanning for gonad reversal was not previously determined. We report a 2-D electrophoresis analysis of three gonad types of proteomes during sex reversal. MS/MS analysis revealed a group of differentially expressed proteins during ovary to ovotestis to testis transf...

  8. Using team cognitive work analysis to reveal healthcare team interactions in a birthing unit

    Science.gov (United States)

    Ashoori, Maryam; Burns, Catherine M.; d'Entremont, Barbara; Momtahan, Kathryn

    2014-01-01

    Cognitive work analysis (CWA) as an analytical approach for examining complex sociotechnical systems has shown success in modelling the work of single operators. The CWA approach incorporates social and team interactions, but a more explicit analysis of team aspects can reveal more information for systems design. In this paper, Team CWA is explored to understand teamwork within a birthing unit at a hospital. Team CWA models are derived from theories and models of teamworkand leverage the existing CWA approaches to analyse team interactions. Team CWA is explained and contrasted with prior approaches to CWA. Team CWA does not replace CWA, but supplements traditional CWA to more easily reveal team information. As a result, Team CWA may be a useful approach to enhance CWA in complex environments where effective teamwork is required. Practitioner Summary: This paper looks at ways of analysing cognitive work in healthcare teams. Team Cognitive Work Analysis, when used to supplement traditional Cognitive Work Analysis, revealed more team information than traditional Cognitive Work Analysis. Team Cognitive Work Analysis should be considered when studying teams PMID:24837514

  9. Using team cognitive work analysis to reveal healthcare team interactions in a birthing unit.

    Science.gov (United States)

    Ashoori, Maryam; Burns, Catherine M; d'Entremont, Barbara; Momtahan, Kathryn

    2014-01-01

    Cognitive work analysis (CWA) as an analytical approach for examining complex sociotechnical systems has shown success in modelling the work of single operators. The CWA approach incorporates social and team interactions, but a more explicit analysis of team aspects can reveal more information for systems design. In this paper, Team CWA is explored to understand teamwork within a birthing unit at a hospital. Team CWA models are derived from theories and models of teamwork and leverage the existing CWA approaches to analyse team interactions. Team CWA is explained and contrasted with prior approaches to CWA. Team CWA does not replace CWA, but supplements traditional CWA to more easily reveal team information. As a result, Team CWA may be a useful approach to enhance CWA in complex environments where effective teamwork is required. This paper looks at ways of analysing cognitive work in healthcare teams. Team Cognitive Work Analysis, when used to supplement traditional Cognitive Work Analysis, revealed more team information than traditional Cognitive Work Analysis. Team Cognitive Work Analysis should be considered when studying teams.

  10. Genomewide analysis of MATE-type gene family in maize reveals ...

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Genetics; Volume 95; Issue 3. Genomewide analysis of MATE-type gene family in maize reveals microsynteny and their expression patterns under aluminum treatment. HUASHENG ZHU JIANDONG WU YINGLI JIANG JING JIN WEI ZHOU YU WANG GUOMIN HAN YANG ZHAO BEIJIU CHENG.

  11. Using risk analysis to reveal opportunities for the management of unplanned ignitions in wilderness

    Science.gov (United States)

    Kevin Barnett; Carol Miller; Tyron J. Venn

    2016-01-01

    A goal of fire management in wilderness is to allow fire to play its natural ecological role without intervention. Unfortunately, most unplanned ignitions in wilderness are suppressed, in part because of the risk they might pose to values outside of the wilderness. We capitalize on recent advances in fire risk analysis to demonstrate a risk-based approach for revealing...

  12. How young can children reliably and validly self-report their health-related quality of life?: An analysis of 8,591 children across age subgroups with the PedsQL™ 4.0 Generic Core Scales

    Directory of Open Access Journals (Sweden)

    Burwinkle Tasha M

    2007-01-01

    Full Text Available Abstract Background The last decade has evidenced a dramatic increase in the development and utilization of pediatric health-related quality of life (HRQOL measures in an effort to improve pediatric patient health and well-being and determine the value of healthcare services. The emerging paradigm shift toward patient-reported outcomes (PROs in clinical trials has provided the opportunity to further emphasize the value and essential need for pediatric patient self-reported outcomes measurement. Data from the PedsQL™ DatabaseSM were utilized to test the hypothesis that children as young as 5 years of age can reliably and validly report their HRQOL. Methods The sample analyzed represented child self-report age data on 8,591 children ages 5 to 16 years from the PedsQL™ 4.0 Generic Core Scales DatabaseSM. Participants were recruited from general pediatric clinics, subspecialty clinics, and hospitals in which children were being seen for well-child checks, mild acute illness, or chronic illness care (n = 2,603, 30.3%, and from a State Children's Health Insurance Program (SCHIP in California (n = 5,988, 69.7%. Results Items on the PedsQL™ 4.0 Generic Core Scales had minimal missing responses for children as young as 5 years old, supporting feasibility. The majority of the child self-report scales across the age subgroups, including for children as young as 5 years, exceeded the minimum internal consistency reliability standard of 0.70 required for group comparisons, while the Total Scale Scores across the age subgroups approached or exceeded the reliability criterion of 0.90 recommended for analyzing individual patient scale scores. Construct validity was demonstrated utilizing the known groups approach. For each PedsQL™ scale and summary score, across age subgroups, including children as young as 5 years, healthy children demonstrated a statistically significant difference in HRQOL (better HRQOL than children with a known chronic health

  13. A method for identifying genetic heterogeneity within phenotypically defined disease subgroups.

    Science.gov (United States)

    Liley, James; Todd, John A; Wallace, Chris

    2017-02-01

    Many common diseases show wide phenotypic variation. We present a statistical method for determining whether phenotypically defined subgroups of disease cases represent different genetic architectures, in which disease-associated variants have different effect sizes in two subgroups. Our method models the genome-wide distributions of genetic association statistics with mixture Gaussians. We apply a global test without requiring explicit identification of disease-associated variants, thus maximizing power in comparison to standard variant-by-variant subgroup analysis. Where evidence for genetic subgrouping is found, we present methods for post hoc identification of the contributing genetic variants. We demonstrate the method on a range of simulated and test data sets, for which expected results are already known. We investigate subgroups of individuals with type 1 diabetes (T1D) defined by autoantibody positivity, establishing evidence for differential genetic architecture with positivity for thyroid-peroxidase-specific antibody, driven generally by variants in known T1D-associated genomic regions.

  14. Heterogeneity in chronic fatigue syndrome - empirically defined subgroups from the PACE trial.

    Science.gov (United States)

    Williams, T E; Chalder, T; Sharpe, M; White, P D

    2017-06-01

    Chronic fatigue syndrome is likely to be a heterogeneous condition. Previous studies have empirically defined subgroups using combinations of clinical and biological variables. We aimed to explore the heterogeneity of chronic fatigue syndrome. We used baseline data from the PACE trial, which included 640 participants with chronic fatigue syndrome. Variable reduction, using a combination of clinical knowledge and principal component analyses, produced a final dataset of 26 variables for 541 patients. Latent class analysis was then used to empirically define subgroups. The most statistically significant and clinically recognizable model comprised five subgroups. The largest, 'core' subgroup (33% of participants), had relatively low scores across all domains and good self-efficacy. A further three subgroups were defined by: the presence of mood disorders (21%); the presence of features of other functional somatic syndromes (such as fibromyalgia or irritable bowel syndrome) (21%); or by many symptoms - a group which combined features of both of the above (14%). The smallest 'avoidant-inactive' subgroup was characterized by physical inactivity, belief that symptoms were entirely physical in nature, and fear that they indicated harm (11%). Differences in the severity of fatigue and disability provided some discriminative validation of the subgroups. In addition to providing further evidence for the heterogeneity of chronic fatigue syndrome, the subgroups identified may aid future research into the important aetiological factors of specific subtypes of chronic fatigue syndrome and the development of more personalized treatment approaches.

  15. Individualizing antipsychotic treatment selection in schizophrenia: characteristics of empirically derived patient subgroups.

    Science.gov (United States)

    Correll, C U; Cañas, F; Larmo, I; Levy, P; Montes, J-M; Fagiolini, A; Papageorgiou, G; Rossi, A; Sturlason, R; Zink, M

    2011-03-01

    Treatment of schizophrenia with antipsychotic drugs is frequently sub-optimal. One reason for this may be heterogeneity between patients with schizophrenia. The objectives of this study were to identify patient, disease and treatment attributes that are important for physicians in choosing an antipsychotic drug, and to identify empirically subgroups of patients who may respond differentially to antipsychotic drugs. The survey was conducted by structured interview of 744 randomly-selected psychiatrists in four European countries who recruited 3996 patients with schizophrenia. Information on 39 variables was collected. Multiple component analysis was used to identify dimensions that explained the variance between patients. Three axes, accounting for 99% of the variance, were associated with disease severity (64%), socioeconomic status (27%) and patient autonomy (8%). These dimensions discriminated between six discrete patient subgroups, identified using ascending hierarchical classification analysis. The six subgroups differed regarding educational level, illness severity, autonomy, symptom presentation, addictive behaviors, comorbidities and cardiometabolic risk factors. Subgroup 1 patients had moderately severe physician-rated disease and addictive behaviours (23.2%); Subgroup 2 patients were well-integrated and autonomous with mild to moderate disease (6.7%); Subgroup 3 patients were less well-integrated with mild to moderate disease, living alone (11.2%); Subgroup 4 patients were women with low education levels (5.4%), Subgroup 5 patients were young men with severe disease (36.8%); and Subgroup 6 patients were poorly-integrated with moderately severe disease, needing caregiver support (16.7%). The presence of these subgroups, which require confirmation and extension regarding potentially identifiable biological markers, may help individualizing treatment in patients with schizophrenia. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  16. Driver style and driver skill – Clustering sub-groups of drivers differing in their potential danger in traffic

    DEFF Research Database (Denmark)

    Martinussen, Laila Marianne; Møller, Mette; Prato, Carlo Giacomo

    mirrored the self-reported frequency of aberrant driving behaviors. K-means cluster analysis revealed four distinct clusters that differed in the frequency of aberrant driving behavior and driving skills, as well as individual characteristics and driving related factors such as annual mileage, accident...... frequency and number of tickets and fines. These differences between the clusters suggest that two of the sub-groups are less safe than the two others. The present findings highlight the need to look into driver’s attitudes towards safety, in order to improve the motivation to drive safely. Information from...

  17. A Case-Control Study and Meta-Analysis Reveal BDNF Val66Met Is a Possible Risk Factor for PTSD

    Directory of Open Access Journals (Sweden)

    Dagmar Bruenig

    2016-01-01

    Full Text Available Posttraumatic stress disorder (PTSD is a debilitating condition that develops in some people after exposure to a traumatic event. Brain-derived neurotrophic factor (BDNF is highly expressed in the mammalian brain and is thought to be involved in learning and memory processes. A nonsynonymous polymorphism in the BDNF gene, rs6265 (Val66Met, has been hypothesised to be associated with PTSD. Association studies examining the Val66Met polymorphism and PTSD have been inconclusive, likely due to the variability in type of trauma exposure analysed. Vietnam veterans (n=257 screened for PTSD and controlled for trauma exposure were genotyped for BDNF Val66Met. The association was not significant so we incorporated our data into a meta-analysis to obtain greater statistical power. A comprehensive search of more than 1237 articles revealed eight additional studies suitable for meta-analysis (n=3625. A random-effects meta-analysis observed a potential protective factor of the Val/Val genotype. After removing two studies with violation of Hardy-Weinberg equilibrium, findings for the Val/Val genotype reached significance. Subgroup analyses confirmed a trend for this finding. Limitations of some studies that inform this meta-analysis include poorly screened controls and a lack of examination of population stratification. Effectively designed studies should inform this line of research in the future.

  18. Analysis of self-overlap reveals trade-offs in plankton swimming trajectories

    DEFF Research Database (Denmark)

    Mariani, Patrizio; Visser, Andre W.; Mazzocchi, Maria Grazia

    2014-01-01

    these contrasting processes. This trade-off can be hypothesized as being evident in the behaviour of plankton, which inhabit a dilute three-dimensional environment with few refuges or orienting landmarks. We present an analysis of the swimming path geometries based on a volumetric Monte Carlo sampling approach......, which is particularly adept at revealing such trade-offs by measuring the self-overlap of the trajectories. Application of this method to experimentally measured trajectories reveals that swimming patterns in copepods are shaped to efficiently explore volumes at small scales, while achieving a large...

  19. EXPLORATORY DATA ANALYSIS AND MULTIVARIATE STRATEGIES FOR REVEALING MULTIVARIATE STRUCTURES IN CLIMATE DATA

    Directory of Open Access Journals (Sweden)

    2016-12-01

    Full Text Available This paper is on data analysis strategy in a complex, multidimensional, and dynamic domain. The focus is on the use of data mining techniques to explore the importance of multivariate structures; using climate variables which influences climate change. Techniques involved in data mining exercise vary according to the data structures. The multivariate analysis strategy considered here involved choosing an appropriate tool to analyze a process. Factor analysis is introduced into data mining technique in order to reveal the influencing impacts of factors involved as well as solving for multicolinearity effect among the variables. The temporal nature and multidimensionality of the target variables is revealed in the model using multidimensional regression estimates. The strategy of integrating the method of several statistical techniques, using climate variables in Nigeria was employed. R2 of 0.518 was obtained from the ordinary least square regression analysis carried out and the test was not significant at 5% level of significance. However, factor analysis regression strategy gave a good fit with R2 of 0.811 and the test was significant at 5% level of significance. Based on this study, model building should go beyond the usual confirmatory data analysis (CDA, rather it should be complemented with exploratory data analysis (EDA in order to achieve a desired result.

  20. The ergodic theory of lattice subgroups

    CERN Document Server

    Gorodnik, Alexander

    2010-01-01

    The results established in this book constitute a new departure in ergodic theory and a significant expansion of its scope. Traditional ergodic theorems focused on amenable groups, and relied on the existence of an asymptotically invariant sequence in the group, the resulting maximal inequalities based on covering arguments, and the transference principle. Here, Alexander Gorodnik and Amos Nevo develop a systematic general approach to the proof of ergodic theorems for a large class of non-amenable locally compact groups and their lattice subgroups. Simple general conditions on the spectral theory of the group and the regularity of the averaging sets are formulated, which suffice to guarantee convergence to the ergodic mean

  1. iSubgraph: integrative genomics for subgroup discovery in hepatocellular carcinoma using graph mining and mixture models.

    Directory of Open Access Journals (Sweden)

    Bahadir Ozdemir

    Full Text Available The high tumor heterogeneity makes it very challenging to identify key tumorigenic pathways as therapeutic targets. The integration of multiple omics data is a promising approach to identify driving regulatory networks in patient subgroups. Here, we propose a novel conceptual framework to discover patterns of miRNA-gene networks, observed frequently up- or down-regulated in a group of patients and to use such networks for patient stratification in hepatocellular carcinoma (HCC. We developed an integrative subgraph mining approach, called iSubgraph, and identified altered regulatory networks frequently observed in HCC patients. The miRNA and gene expression profiles were jointly analyzed in a graph structure. We defined a method to transform microarray data into graph representation that encodes miRNA and gene expression levels and the interactions between them as well. The iSubgraph algorithm was capable to detect cooperative regulation of miRNAs and genes even if it occurred only in some patients. Next, the miRNA-mRNA modules were used in an unsupervised class prediction model to discover HCC subgroups via patient clustering by mixture models. The robustness analysis of the mixture model showed that the class predictions are highly stable. Moreover, the Kaplan-Meier survival analysis revealed that the HCC subgroups identified by the algorithm have different survival characteristics. The pathway analyses of the miRNA-mRNA co-modules identified by the algorithm demonstrate key roles of Myc, E2F1, let-7, TGFB1, TNF and EGFR in HCC subgroups. Thus, our method can integrate various omics data derived from different platforms and with different dynamic scales to better define molecular tumor subtypes. iSubgraph is available as MATLAB code at http://www.cs.umd.edu/~ozdemir/isubgraph/.

  2. Dynamic transcriptional signature and cell fate analysis reveals plasticity of individual neural plate border cells.

    Science.gov (United States)

    Roellig, Daniela; Tan-Cabugao, Johanna; Esaian, Sevan; Bronner, Marianne E

    2017-03-29

    The 'neural plate border' of vertebrate embryos contains precursors of neural crest and placode cells, both defining vertebrate characteristics. How these lineages segregate from neural and epidermal fates has been a matter of debate. We address this by performing a fine-scale quantitative temporal analysis of transcription factor expression in the neural plate border of chick embryos. The results reveal significant overlap of transcription factors characteristic of multiple lineages in individual border cells from gastrula through neurula stages. Cell fate analysis using a Sox2 (neural) enhancer reveals that cells that are initially Sox2+ cells can contribute not only to neural tube but also to neural crest and epidermis. Moreover, modulating levels of Sox2 or Pax7 alters the apportionment of neural tube versus neural crest fates. Our results resolve a long-standing question and suggest that many individual border cells maintain ability to contribute to multiple ectodermal lineages until or beyond neural tube closure.

  3. Safety and efficacy of single-agent bevacizumab-containing therapy in elderly patients with platinum-resistant recurrent ovarian cancer: Subgroup analysis of the randomised phase III AURELIA trial.

    Science.gov (United States)

    Sorio, Roberto; Roemer-Becuwe, Célia; Hilpert, Felix; Gibbs, Emma; García, Yolanda; Kaern, Janne; Huizing, Manon; Witteveen, Petronella; Zagouri, Flora; Coeffic, David; Lück, Hans-Joachim; González-Martín, Antonio; Kristensen, Gunnar; Levaché, Charles-Briac; Lee, Chee Khoon; Gebski, Val; Pujade-Lauraine, Eric

    2017-01-01

    The AURELIA trial demonstrated significantly improved progression-free survival (PFS) with bevacizumab added to chemotherapy for platinum-resistant ovarian cancer (PROC). Patients with PROC were randomised to receive investigator-selected single-agent chemotherapy alone or with bevacizumab. Post-hoc exploratory analyses assessed efficacy, safety and patient-reported outcomes according to age <65 versus ≥65years. In the 133 patients (37%) aged ≥65years, baseline hypertension was more frequent and ascites was less common than in patients <65years. The magnitude of PFS benefit from bevacizumab was similar in patients ≥65 versus <65years (hazard ratio 0.44 [95% CI, 0.31-0.64] versus 0.49 [95% CI, 0.37-0.64], respectively, treatment-age interaction p=0.58), with similar improvements in response rates. Grade≥3 hypertension was more common with bevacizumab than chemotherapy alone in both subgroups, and more common in older than younger patients irrespective of treatment. However, there was no excess of other adverse events of specific interest for bevacizumab, including venous thromboembolic events, in older patients. More patients receiving bevacizumab in the younger but not the older subgroup showed improved gastrointestinal/abdominal symptoms. In exploratory analyses, PFS and response rate improvement with bevacizumab were consistent in older and younger patients. Grade≥3 hypertension was more common in elderly bevacizumab-treated patients; careful monitoring is recommended. Overall, bevacizumab-containing therapy was well tolerated in a selected population aged ≥65years, suggesting a favourable benefit:risk profile. However, geriatric assessments are needed to improve selection of elderly patients potentially gaining symptom and quality of life improvements from bevacizumab-containing therapy. ClinicalTrials.govNCT00976911. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Promoter analysis reveals cis-regulatory motifs associated with the expression of the WRKY transcription factor CrWRKY1 in Catharanthus roseus.

    Science.gov (United States)

    Yang, Zhirong; Patra, Barunava; Li, Runzhi; Pattanaik, Sitakanta; Yuan, Ling

    2013-12-01

    WRKY transcription factors (TFs) are emerging as an important group of regulators of plant secondary metabolism. However, the cis-regulatory elements associated with their regulation have not been well characterized. We have previously demonstrated that CrWRKY1, a member of subgroup III of the WRKY TF family, regulates biosynthesis of terpenoid indole alkaloids in the ornamental and medicinal plant, Catharanthus roseus. Here, we report the isolation and functional characterization of the CrWRKY1 promoter. In silico analysis of the promoter sequence reveals the presence of several potential TF binding motifs, indicating the involvement of additional TFs in the regulation of the TIA pathway. The CrWRKY1 promoter can drive the expression of a β-glucuronidase (GUS) reporter gene in native (C. roseus protoplasts and transgenic hairy roots) and heterologous (transgenic tobacco seedlings) systems. Analysis of 5'- or 3'-end deletions indicates that the sequence located between positions -140 to -93 bp and -3 to +113 bp, relative to the transcription start site, is critical for promoter activity. Mutation analysis shows that two overlapping as-1 elements and a CT-rich motif contribute significantly to promoter activity. The CrWRKY1 promoter is induced in response to methyl jasmonate (MJ) treatment and the promoter region between -230 and -93 bp contains a putative MJ-responsive element. The CrWRKY1 promoter can potentially be used as a tool to isolate novel TFs involved in the regulation of the TIA pathway.

  5. Proteomics analysis reveals a dynamic diurnal pattern of photosynthesis-related pathways in maize leaves

    OpenAIRE

    Feng, Dan; Wang, Yanwei; Lu, Tiegang; Zhang, Zhiguo; Han, Xiao

    2017-01-01

    Plant leaves exhibit differentiated patterns of photosynthesis rates under diurnal light regulation. Maize leaves show a single-peak pattern without photoinhibition at midday when the light intensity is maximized. This mechanism contributes to highly efficient photosynthesis in maize leaves. To understand the molecular basis of this process, an isobaric tag for relative and absolute quantitation (iTRAQ)-based proteomics analysis was performed to reveal the dynamic pattern of proteins related ...

  6. Proteomic Analysis of Human Brown Adipose Tissue Reveals Utilization of Coupled and Uncoupled Energy Expenditure Pathways

    OpenAIRE

    M?ller, Sebastian; Balaz, Miroslav; Stefanicka, Patrik; Varga, Lukas; Amri, Ez-Zoubir; Ukropec, Jozef; Wollscheid, Bernd; Wolfrum, Christian

    2016-01-01

    Human brown adipose tissue (BAT) has become an attractive target to combat the current epidemical spread of obesity and its associated co-morbidities. Currently, information on its functional role is primarily derived from rodent studies. Here, we present the first comparative proteotype analysis of primary human brown adipose tissue versus adjacent white adipose tissue, which reveals significant quantitative differences in protein abundances and in turn differential functional capabilities. ...

  7. Comparative analysis of fungal genomes reveals different plant cell wall degrading capacity in fungi

    Science.gov (United States)

    2013-01-01

    Background Fungi produce a variety of carbohydrate activity enzymes (CAZymes) for the degradation of plant polysaccharide materials to facilitate infection and/or gain nutrition. Identifying and comparing CAZymes from fungi with different nutritional modes or infection mechanisms may provide information for better understanding of their life styles and infection models. To date, over hundreds of fungal genomes are publicly available. However, a systematic comparative analysis of fungal CAZymes across the entire fungal kingdom has not been reported. Results In this study, we systemically identified glycoside hydrolases (GHs), polysaccharide lyases (PLs), carbohydrate esterases (CEs), and glycosyltransferases (GTs) as well as carbohydrate-binding modules (CBMs) in the predicted proteomes of 103 representative fungi from Ascomycota, Basidiomycota, Chytridiomycota, and Zygomycota. Comparative analysis of these CAZymes that play major roles in plant polysaccharide degradation revealed that fungi exhibit tremendous diversity in the number and variety of CAZymes. Among them, some families of GHs and CEs are the most prevalent CAZymes that are distributed in all of the fungi analyzed. Importantly, cellulases of some GH families are present in fungi that are not known to have cellulose-degrading ability. In addition, our results also showed that in general, plant pathogenic fungi have the highest number of CAZymes. Biotrophic fungi tend to have fewer CAZymes than necrotrophic and hemibiotrophic fungi. Pathogens of dicots often contain more pectinases than fungi infecting monocots. Interestingly, besides yeasts, many saprophytic fungi that are highly active in degrading plant biomass contain fewer CAZymes than plant pathogenic fungi. Furthermore, analysis of the gene expression profile of the wheat scab fungus Fusarium graminearum revealed that most of the CAZyme genes related to cell wall degradation were up-regulated during plant infection. Phylogenetic analysis also

  8. Comparative analysis of fungal genomes reveals different plant cell wall degrading capacity in fungi.

    Science.gov (United States)

    Zhao, Zhongtao; Liu, Huiquan; Wang, Chenfang; Xu, Jin-Rong

    2013-04-23

    Fungi produce a variety of carbohydrate activity enzymes (CAZymes) for the degradation of plant polysaccharide materials to facilitate infection and/or gain nutrition. Identifying and comparing CAZymes from fungi with different nutritional modes or infection mechanisms may provide information for better understanding of their life styles and infection models. To date, over hundreds of fungal genomes are publicly available. However, a systematic comparative analysis of fungal CAZymes across the entire fungal kingdom has not been reported. In this study, we systemically identified glycoside hydrolases (GHs), polysaccharide lyases (PLs), carbohydrate esterases (CEs), and glycosyltransferases (GTs) as well as carbohydrate-binding modules (CBMs) in the predicted proteomes of 103 representative fungi from Ascomycota, Basidiomycota, Chytridiomycota, and Zygomycota. Comparative analysis of these CAZymes that play major roles in plant polysaccharide degradation revealed that fungi exhibit tremendous diversity in the number and variety of CAZymes. Among them, some families of GHs and CEs are the most prevalent CAZymes that are distributed in all of the fungi analyzed. Importantly, cellulases of some GH families are present in fungi that are not known to have cellulose-degrading ability. In addition, our results also showed that in general, plant pathogenic fungi have the highest number of CAZymes. Biotrophic fungi tend to have fewer CAZymes than necrotrophic and hemibiotrophic fungi. Pathogens of dicots often contain more pectinases than fungi infecting monocots. Interestingly, besides yeasts, many saprophytic fungi that are highly active in degrading plant biomass contain fewer CAZymes than plant pathogenic fungi. Furthermore, analysis of the gene expression profile of the wheat scab fungus Fusarium graminearum revealed that most of the CAZyme genes related to cell wall degradation were up-regulated during plant infection. Phylogenetic analysis also revealed a complex

  9. Debate: Subgroup analyses in clinical trials: fun to look at - but don't believe them!

    Directory of Open Access Journals (Sweden)

    Sleight Peter

    2000-07-01

    Full Text Available Abstract Analysis of subgroup results in a clinical trial is surprisingly unreliable, even in a large trial. This is the result of a combination of reduced statistical power, increased variance and the play of chance. Reliance on such analyses is likely to be more erroneous, and hence harmful, than application of the overall proportional (or relative result in the whole trial to the estimate of absolute risk in that subgroup. Plausible explanations can usually be found for effects that are, in reality, simply due to the play of chance. When clinicians believe such subgroup analyses, there is a real danger of harm to the individual patient.

  10. Fecal metagenomic profiles in subgroups of patients with myalgic encephalomyelitis/chronic fatigue syndrome.

    Science.gov (United States)

    Nagy-Szakal, Dorottya; Williams, Brent L; Mishra, Nischay; Che, Xiaoyu; Lee, Bohyun; Bateman, Lucinda; Klimas, Nancy G; Komaroff, Anthony L; Levine, Susan; Montoya, Jose G; Peterson, Daniel L; Ramanan, Devi; Jain, Komal; Eddy, Meredith L; Hornig, Mady; Lipkin, W Ian

    2017-04-26

    Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by unexplained persistent fatigue, commonly accompanied by cognitive dysfunction, sleeping disturbances, orthostatic intolerance, fever, lymphadenopathy, and irritable bowel syndrome (IBS). The extent to which the gastrointestinal microbiome and peripheral inflammation are associated with ME/CFS remains unclear. We pursued rigorous clinical characterization, fecal bacterial metagenomics, and plasma immune molecule analyses in 50 ME/CFS patients and 50 healthy controls frequency-matched for age, sex, race/ethnicity, geographic site, and season of sampling. Topological analysis revealed associations between IBS co-morbidity, body mass index, fecal bacterial composition, and bacterial metabolic pathways but not plasma immune molecules. IBS co-morbidity was the strongest driving factor in the separation of topological networks based on bacterial profiles and metabolic pathways. Predictive selection models based on bacterial profiles supported findings from topological analyses indicating that ME/CFS subgroups, defined by IBS status, could be distinguished from control subjects with high predictive accuracy. Bacterial taxa predictive of ME/CFS patients with IBS were distinct from taxa associated with ME/CFS patients without IBS. Increased abundance of unclassified Alistipes and decreased Faecalibacterium emerged as the top biomarkers of ME/CFS with IBS; while increased unclassified Bacteroides abundance and decreased Bacteroides vulgatus were the top biomarkers of ME/CFS without IBS. Despite findings of differences in bacterial taxa and metabolic pathways defining ME/CFS subgroups, decreased metabolic pathways associated with unsaturated fatty acid biosynthesis and increased atrazine degradation pathways were independent of IBS co-morbidity. Increased vitamin B6 biosynthesis/salvage and pyrimidine ribonucleoside degradation were the top metabolic pathways in ME/CFS without IBS as well as in the

  11. Pain rating schema: three distinct subgroups of individuals emerge when rating mild, moderate, and severe pain

    Directory of Open Access Journals (Sweden)

    Frey-Law LA

    2013-12-01

    Full Text Available Laura A Frey-Law,1 Jennifer E Lee,2,3 Alex M Wittry,4 Myles Melyon5 1Department of Physical Therapy and Rehabilitation Science, The University of Iowa, Iowa City, IA, USA; 2Mount Mercy University, Department of Psychology, Cedar Rapids, IA, USA; ³College of Nursing, The University of Iowa, 4Department of Emergency Medicine, The University of Iowa Hospitals and Clinics, Iowa City, IA, USA; 5Midwestern University, Glendale, AZ, USA Background: While the validity of pain assessment has been well documented, the underlying schema (ie, organized, preconceived ideas of how individuals interpret numerical pain ratings is not well understood. This study's objectives were to examine numerical pain intensity ratings, from (0 to 10 cm on the visual analog scale [VAS] across multiple severities of commonly experienced acute pain conditions to determine whether the ratings differed between these pain conditions and/or between individuals. Methods: A community sample (N=365, 66% female rated their anticipated pain intensity (VAS for threshold, mild, moderate, severe, and tolerance level, using several common pain conditions: headache, toothache, joint injury, delayed-onset muscle soreness, burns, and “general pain.” Results: Cluster analysis revealed three subgroups of individuals, suggesting three types of underlying pain rating schema: 1 Low Rating subgroup (low VAS pain intensity ratings across all the pain severity categories; 2 Low/High Rating subgroup (low VAS pain intensity rating for mild, but high VAS pain intensity rating for severe pain; and 3 High Rating subgroup (high VAS pain intensity ratings across all the pain severity categories. Overall, differences between pain conditions were small: muscle soreness pain intensity was consistently rated lower than the other pain types across severities. The highest pain ratings varied between joint injury and general pain, depending on severity level. No effects of sex or current experience of pain

  12. Complete nucleotide sequence of a Polish strain of Peanut stunt virus (PSV-P) that is related to but not a typical member of subgroup I.

    Science.gov (United States)

    Obrepalska-Steplowska, Aleksandra; Budziszewska, Marta; Pospieszny, Henryk

    2008-01-01

    Peanut stunt virus (PSV) is a common legume pathogen present worldwide. It is also infectious for many other plants including peanut and some vegetables. Viruses of this species are classified at present into three subgroups based on their serology and nucleotide homology. Some of them may also carry an additional subviral element - satellite RNA. Analysis of the full genome sequence of a Polish strain - PSV-P - associated with satRNA was performed and showed that it may be classified as a derivative of the subgroup I sharing 83.9-87.9% nucleotide homology with other members of this subgroup. A comparative study of sequenced PSV strains indicates that PSV-P shows the highest identity level with PSV-ER or PSV-J depending on the region used for analysis. Phylogenetic analyses, on the other hand, have revealed that PSV-P is related to representatives of the subgroup I to the same degree, with the exception of the coat protein coding sequence where PSV-P is clustered together with PSV-ER.

  13. AKT pathway genes define 5 prognostic subgroups in glioblastoma.

    Directory of Open Access Journals (Sweden)

    Anna Joy

    Full Text Available Activity of GFR/PI3K/AKT pathway inhibitors in glioblastoma clinical trials has not been robust. We hypothesized variations in the pathway between tumors contribute to poor response. We clustered GBM based on AKT pathway genes and discovered new subtypes then characterized their clinical and molecular features. There are at least 5 GBM AKT subtypes having distinct DNA copy number alterations, enrichment in oncogenes and tumor suppressor genes and patterns of expression for PI3K/AKT/mTOR signaling components. Gene Ontology terms indicate a different cell of origin or dominant phenotype for each subgroup. Evidence suggests one subtype is very sensitive to BCNU or CCNU (median survival 5.8 vs. 1.5 years; BCNU/CCNU vs other treatments; respectively. AKT subtyping advances previous approaches by revealing additional subgroups with unique clinical and molecular features. Evidence indicates it is a predictive marker for response to BCNU or CCNU and PI3K/AKT/mTOR pathway inhibitors. We anticipate Akt subtyping may help stratify patients for clinical trials and augment discovery of class-specific therapeutic targets.

  14. AKT Pathway Genes Define 5 Prognostic Subgroups in Glioblastoma

    Science.gov (United States)

    Smirnov, Ivan; Reiser, Mark; Misra, Anjan; Shapiro, William R.; Mills, Gordon B.; Kim, Seungchan; Feuerstein, Burt G.

    2014-01-01

    Activity of GFR/PI3K/AKT pathway inhibitors in glioblastoma clinical trials has not been robust. We hypothesized variations in the pathway between tumors contribute to poor response. We clustered GBM based on AKT pathway genes and discovered new subtypes then characterized their clinical and molecular features. There are at least 5 GBM AKT subtypes having distinct DNA copy number alterations, enrichment in oncogenes and tumor suppressor genes and patterns of expression for PI3K/AKT/mTOR signaling components. Gene Ontology terms indicate a different cell of origin or dominant phenotype for each subgroup. Evidence suggests one subtype is very sensitive to BCNU or CCNU (median survival 5.8 vs. 1.5 years; BCNU/CCNU vs other treatments; respectively). AKT subtyping advances previous approaches by revealing additional subgroups with unique clinical and molecular features. Evidence indicates it is a predictive marker for response to BCNU or CCNU and PI3K/AKT/mTOR pathway inhibitors. We anticipate Akt subtyping may help stratify patients for clinical trials and augment discovery of class-specific therapeutic targets. PMID:24984002

  15. AKT pathway genes define 5 prognostic subgroups in glioblastoma.

    Science.gov (United States)

    Joy, Anna; Ramesh, Archana; Smirnov, Ivan; Reiser, Mark; Misra, Anjan; Shapiro, William R; Mills, Gordon B; Kim, Seungchan; Feuerstein, Burt G

    2014-01-01

    Activity of GFR/PI3K/AKT pathway inhibitors in glioblastoma clinical trials has not been robust. We hypothesized variations in the pathway between tumors contribute to poor response. We clustered GBM based on AKT pathway genes and discovered new subtypes then characterized their clinical and molecular features. There are at least 5 GBM AKT subtypes having distinct DNA copy number alterations, enrichment in oncogenes and tumor suppressor genes and patterns of expression for PI3K/AKT/mTOR signaling components. Gene Ontology terms indicate a different cell of origin or dominant phenotype for each subgroup. Evidence suggests one subtype is very sensitive to BCNU or CCNU (median survival 5.8 vs. 1.5 years; BCNU/CCNU vs other treatments; respectively). AKT subtyping advances previous approaches by revealing additional subgroups with unique clinical and molecular features. Evidence indicates it is a predictive marker for response to BCNU or CCNU and PI3K/AKT/mTOR pathway inhibitors. We anticipate Akt subtyping may help stratify patients for clinical trials and augment discovery of class-specific therapeutic targets.

  16. Subgrouping the autism "spectrum": reflections on DSM-5.

    Directory of Open Access Journals (Sweden)

    Meng-Chuan Lai

    Full Text Available DSM-5 has moved autism from the level of subgroups ("apples and oranges" to the prototypical level ("fruit". But making progress in research, and ultimately improving clinical practice, will require identifying subgroups within the autism spectrum.

  17. Notes on relatively hyperbolic groups and relatively quasiconvex subgroups

    OpenAIRE

    Matsuda, Yoshifumi; Oguni, Shin-ichi; Yamagata, Saeko

    2013-01-01

    We define relatively quasiconvex subgroups of relatively hyperbolic groups in the sense of Osin and show that such subgroups have expected properties. Also we state several definitions equivalent to the definition of relatively hyperbolic groups in the sense of Osin.

  18. Chromosomal phylogeny of the Drosophila fasciola species subgroup revisited (Diptera, Drosophilidae

    Directory of Open Access Journals (Sweden)

    Nilda Maria Diniz

    2004-01-01

    Full Text Available The analysis of polytene chromosomes in 26 strains of seven species in the Drosophila fasciola subgroup, from several locations in Brazil, in addition to strains of two species belonging to the Drosophila mulleri subgroup (D. aldrichi and D. mulleri, enabled us to determine that the 3c inversion found in the latter species differ in one of its break points from that present in the species of the fasciola subgroup. Therefore, a change in the mulleri complex denomination from inversion 3c to inversion 3u is proposed. Accordingly, the fasciola subgroup is no longer a lesser phylogenetic part within the mulleri subgroup. Rather, it is directly related to the likely ancestor of the repleta group, called Primitive I. This information removes the main obstacle to considering the Drosophila fasciola subgroup as an ancestral group within the Drosophila repleta species group, according to the hypothesis of Throckmorton. Our data also support the conclusion that D. onca and D. carolinae are closely related species based on one new inversion in chromosome 4 (4f², in both species. D. fascioloides and D. ellisoni also form a pair of sister species based on the presence of fusions of chromosomes 2-4 and 3-5. D. rosinae is related only to the likely ancestor of the fasciola subgroup, where the 3c inversion was fixed.

  19. Can the tinnitus spectrum identify tinnitus subgroups?

    Directory of Open Access Journals (Sweden)

    Karin M Heijneman

    2013-01-01

    Full Text Available The tinnitus spectrum is a psycho-acoustic metric of tinnitus. Previous work found a tight relation between the spectrum and the tone audiogram. This suggests that the spectrum and the audiogram provide essentially the same information, and the added value of the spectrum is limited. In order to test whether the spectrum shows tinnitus characteristics that cannot be inferred from the audiogram, we re-examined the relation between the tinnitus spectrum and the tone audiogram, in a group of 80 tinnitus patients. We defined three subgroups of patients, using the shape of their tinnitus spectrum: (1 patients with a spectrum, monotonously increasing with frequency (2 patients with a distinct peak in their spectrum, (3 all other patients. Patients in group 3 typically showed low frequency tinnitus spectra. In all three groups, the largest hearing loss was at high frequencies (>2 kHz. The mean audiograms of group 1 and 2 were remarkably similar; group 3 had an additional hearing loss for the lower frequencies (<2 kHz. The three groups did not differ with respect to age, sex, or tinnitus questionnaire outcomes. In subgroups 2 and 3, the shape of the spectrum clearly differed from that of the tone audiogram. In other words, the spectrum technique provided information that could not have been obtained by tone audiometry alone. Therefore, the spectrum measurement may develop into a technique that can differentiate between classes of tinnitus. This may eventually contribute to the effective management of tinnitus, as various classes of tinnitus may require different therapeutic interventions.

  20. Meta-analysis of small RNA-sequencing errors reveals ubiquitous post-transcriptional RNA modifications.

    Science.gov (United States)

    Ebhardt, H Alexander; Tsang, Herbert H; Dai, Denny C; Liu, Yifeng; Bostan, Babak; Fahlman, Richard P

    2009-05-01

    Recent advances in DNA-sequencing technology have made it possible to obtain large datasets of small RNA sequences. Here we demonstrate that not all non-perfectly matched small RNA sequences are simple technological sequencing errors, but many hold valuable biological information. Analysis of three small RNA datasets originating from Oryza sativa and Arabidopsis thaliana small RNA-sequencing projects demonstrates that many single nucleotide substitution errors overlap when aligning homologous non-identical small RNA sequences. Investigating the sites and identities of substitution errors reveal that many potentially originate as a result of post-transcriptional modifications or RNA editing. Modifications include N1-methyl modified purine nucleotides in tRNA, potential deamination or base substitutions in micro RNAs, 3' micro RNA uridine extensions and 5' micro RNA deletions. Additionally, further analysis of large sequencing datasets reveal that the combined effects of 5' deletions and 3' uridine extensions can alter the specificity by which micro RNAs associate with different Argonaute proteins. Hence, we demonstrate that not all sequencing errors in small RNA datasets are technical artifacts, but that these actually often reveal valuable biological insights to the sites of post-transcriptional RNA modifications.

  1. Comparative Transcriptome Analysis Reveals Related Regulatory Mechanisms of Androgenic Gland in Eriocheir sinensis

    Directory of Open Access Journals (Sweden)

    Chunpeng Fu

    2017-01-01

    Full Text Available Chinese mitten crab (Eriocheir sinensis is one of the most commercially important aquaculture species in China. The androgenic gland (AG of crustaceans plays pivotal roles in the regulation of male differentiation and in maintaining the male sexual characteristics. In order to reveal related mechanisms in AG, we compared transcriptomes of AG between proliferation and secretion phase. A total of 72,000 unigenes and 4,027 differentially expressed genes were obtained. Gene ontology enrichment analysis indicated that biological processes and metabolic pathways related to protein synthesis and secretion such as transcription, translation, and signal transduction were significantly enriched. Critical genes such as IAG, SXL, TRA-2, SRY, FTZ-F1, FOXL2, and FEM-1 were identified and potentially involved in maintaining the testis development and spermatogenesis. Ribosomes pathway revealed the cause of insulin-like androgenic gland hormone secretion increase. Three insulin-like receptors were thought to be associated with growth and spermatogenesis. In the neuroactive ligand-receptor interaction pathway, the expression of octopamine receptor, 5-HT receptor 1, and melatonin receptor was significantly changed, which revealed the key regulation mechanism of aggressive and mating behavior of males. Comparative transcriptome analysis provided new insights into the genome-wide molecular mechanisms of AG development and the regulatory mechanisms of male development.

  2. Transcriptomic analysis of human retinal detachment reveals both inflammatory response and photoreceptor death.

    Directory of Open Access Journals (Sweden)

    Marie-Noëlle Delyfer

    Full Text Available BACKGROUND: Retinal detachment often leads to a severe and permanent loss of vision and its therapeutic management remains to this day exclusively surgical. We have used surgical specimens to perform a differential analysis of the transcriptome of human retinal tissues following detachment in order to identify new potential pharmacological targets that could be used in combination with surgery to further improve final outcome. METHODOLOGY/PRINCIPAL FINDINGS: Statistical analysis reveals major involvement of the immune response in the disease. Interestingly, using a novel approach relying on coordinated expression, the interindividual variation was monitored to unravel a second crucial aspect of the pathological process: the death of photoreceptor cells. Within the genes identified, the expression of the major histocompatibility complex I gene HLA-C enables diagnosis of the disease, while PKD2L1 and SLCO4A1 -which are both down-regulated- act synergistically to provide an estimate of the duration of the retinal detachment process. Our analysis thus reveals the two complementary cellular and molecular aspects linked to retinal detachment: an immune response and the degeneration of photoreceptor cells. We also reveal that the human specimens have a higher clinical value as compared to artificial models that point to IL6 and oxidative stress, not implicated in the surgical specimens studied here. CONCLUSIONS/SIGNIFICANCE: This systematic analysis confirmed the occurrence of both neurodegeneration and inflammation during retinal detachment, and further identifies precisely the modification of expression of the different genes implicated in these two phenomena. Our data henceforth give a new insight into the disease process and provide a rationale for therapeutic strategies aimed at limiting inflammation and photoreceptor damage associated with retinal detachment and, in turn, improving visual prognosis after retinal surgery.

  3. Network analysis of oyster transcriptome revealed a cascade of cellular responses during recovery after heat shock.

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    Lingling Zhang

    Full Text Available Oysters, as a major group of marine bivalves, can tolerate a wide range of natural and anthropogenic stressors including heat stress. Recent studies have shown that oysters pretreated with heat shock can result in induced heat tolerance. A systematic study of cellular recovery from heat shock may provide insights into the mechanism of acquired thermal tolerance. In this study, we performed the first network analysis of oyster transcriptome by reanalyzing microarray data from a previous study. Network analysis revealed a cascade of cellular responses during oyster recovery after heat shock and identified responsive gene modules and key genes. Our study demonstrates the power of network analysis in a non-model organism with poor gene annotations, which can lead to new discoveries that go beyond the focus on individual genes.

  4. An exploratory data analysis method to reveal modular latent structures in high-throughput data

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    Yu Tianwei

    2010-08-01

    Full Text Available Abstract Background Modular structures are ubiquitous across various types of biological networks. The study of network modularity can help reveal regulatory mechanisms in systems biology, evolutionary biology and developmental biology. Identifying putative modular latent structures from high-throughput data using exploratory analysis can help better interpret the data and generate new hypotheses. Unsupervised learning methods designed for global dimension reduction or clustering fall short of identifying modules with factors acting in linear combinations. Results We present an exploratory data analysis method named MLSA (Modular Latent Structure Analysis to estimate modular latent structures, which can find co-regulative modules that involve non-coexpressive genes. Conclusions Through simulations and real-data analyses, we show that the method can recover modular latent structures effectively. In addition, the method also performed very well on data generated from sparse global latent factor models. The R code is available at http://userwww.service.emory.edu/~tyu8/MLSA/.

  5. An exploratory data analysis method to reveal modular latent structures in high-throughput data.

    Science.gov (United States)

    Yu, Tianwei

    2010-08-27

    Modular structures are ubiquitous across various types of biological networks. The study of network modularity can help reveal regulatory mechanisms in systems biology, evolutionary biology and developmental biology. Identifying putative modular latent structures from high-throughput data using exploratory analysis can help better interpret the data and generate new hypotheses. Unsupervised learning methods designed for global dimension reduction or clustering fall short of identifying modules with factors acting in linear combinations. We present an exploratory data analysis method named MLSA (Modular Latent Structure Analysis) to estimate modular latent structures, which can find co-regulative modules that involve non-coexpressive genes. Through simulations and real-data analyses, we show that the method can recover modular latent structures effectively. In addition, the method also performed very well on data generated from sparse global latent factor models. The R code is available at http://userwww.service.emory.edu/~tyu8/MLSA/.

  6. The Revealed Competitiveness of Major Ports in the East Asian Region: An Additive Market Share Analysis

    Directory of Open Access Journals (Sweden)

    Tae Seung Kim

    2015-12-01

    Full Text Available In the single cargo market, the ordinary market share analysis method has been the representative tool for revealed competitiveness analysis. This paper develops and employs an applied market share index called the additive market share (AMS. Data are collected from 15 major container ports for the 1998-2013 period. In comparison to the results of an ordinary market share analysis, the highest AMS is observed for the Bohai Rim port cluster from 2008, not for the Yangtze River cluster or the Pearl River cluster. There are substitutable relationships between Yangtze River and non-Chinese ports and between Pearl River and Bohai Rim ports from 2001. Finally, there is an internal competition at Pearl River and Yangtze River ports, whereas Bohai Rim and non-Chinese ports show internally complementary relationships.

  7. Proteomic and genomic analysis reveals novel Campylobacter jejuni outer membrane proteins and potential heterogeneity

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    Eleanor Watson

    2014-09-01

    Full Text Available Gram-negative bacterial outer membrane proteins play important roles in the interaction of bacteria with their environment including nutrient acquisition, adhesion and invasion, and antibiotic resistance. In this study we identified 47 proteins within the Sarkosyl-insoluble fraction of Campylobacter jejuni 81-176, using LC–ESI-MS/MS. Comparative analysis of outer membrane protein sequences was visualised to reveal protein distribution within a panel of Campylobacter spp., identifying several C. jejuni-specific proteins. Smith–Waterman analyses of C. jejuni homologues revealed high sequence conservation amongst a number of hypothetical proteins, sequence heterogeneity of other proteins and several proteins which are absent in a proportion of strains.

  8. Proteome-wide analysis of arginine monomethylation reveals widespread occurrence in human cells

    DEFF Research Database (Denmark)

    Larsen, Sara C; Sylvestersen, Kathrine B; Mund, Andreas

    2016-01-01

    The posttranslational modification of proteins by arginine methylation is functionally important, yet the breadth of this modification is not well characterized. Using high-resolution mass spectrometry, we identified 8030 arginine methylation sites within 3300 human proteins in human embryonic...... kidney 293 cells, indicating that the occurrence of this modification is comparable to phosphorylation and ubiquitylation. A site-level conservation analysis revealed that arginine methylation sites are less evolutionarily conserved compared to arginines that were not identified as modified...... as coactivator-associated arginine methyltransferase 1 (CARM1)] or PRMT1 increased the RNA binding function of HNRNPUL1. High-content single-cell imaging additionally revealed that knocking down CARM1 promoted the nuclear accumulation of SRSF2, independent of cell cycle phase. Collectively, the presented human...

  9. A 6-gene signature identifies four molecular subgroups of neuroblastoma

    LENUS (Irish Health Repository)

    Abel, Frida

    2011-04-14

    Abstract Background There are currently three postulated genomic subtypes of the childhood tumour neuroblastoma (NB); Type 1, Type 2A, and Type 2B. The most aggressive forms of NB are characterized by amplification of the oncogene MYCN (MNA) and low expression of the favourable marker NTRK1. Recently, mutations or high expression of the familial predisposition gene Anaplastic Lymphoma Kinase (ALK) was associated to unfavourable biology of sporadic NB. Also, various other genes have been linked to NB pathogenesis. Results The present study explores subgroup discrimination by gene expression profiling using three published microarray studies on NB (47 samples). Four distinct clusters were identified by Principal Components Analysis (PCA) in two separate data sets, which could be verified by an unsupervised hierarchical clustering in a third independent data set (101 NB samples) using a set of 74 discriminative genes. The expression signature of six NB-associated genes ALK, BIRC5, CCND1, MYCN, NTRK1, and PHOX2B, significantly discriminated the four clusters (p < 0.05, one-way ANOVA test). PCA clusters p1, p2, and p3 were found to correspond well to the postulated subtypes 1, 2A, and 2B, respectively. Remarkably, a fourth novel cluster was detected in all three independent data sets. This cluster comprised mainly 11q-deleted MNA-negative tumours with low expression of ALK, BIRC5, and PHOX2B, and was significantly associated with higher tumour stage, poor outcome and poor survival compared to the Type 1-corresponding favourable group (INSS stage 4 and\\/or dead of disease, p < 0.05, Fisher\\'s exact test). Conclusions Based on expression profiling we have identified four molecular subgroups of neuroblastoma, which can be distinguished by a 6-gene signature. The fourth subgroup has not been described elsewhere, and efforts are currently made to further investigate this group\\'s specific characteristics.

  10. Multilocus sequence analysis of nectar pseudomonads reveals high genetic diversity and contrasting recombination patterns.

    Directory of Open Access Journals (Sweden)

    Sergio Alvarez-Pérez

    Full Text Available The genetic and evolutionary relationships among floral nectar-dwelling Pseudomonas 'sensu stricto' isolates associated to South African and Mediterranean plants were investigated by multilocus sequence analysis (MLSA of four core housekeeping genes (rrs, gyrB, rpoB and rpoD. A total of 35 different sequence types were found for the 38 nectar bacterial isolates characterised. Phylogenetic analyses resulted in the identification of three main clades [nectar groups (NGs 1, 2 and 3] of nectar pseudomonads, which were closely related to five intrageneric groups: Pseudomonas oryzihabitans (NG 1; P. fluorescens, P. lutea and P. syringae (NG 2; and P. rhizosphaerae (NG 3. Linkage disequilibrium analysis pointed to a mostly clonal population structure, even when the analysis was restricted to isolates from the same floristic region or belonging to the same NG. Nevertheless, signatures of recombination were observed for NG 3, which exclusively included isolates retrieved from the floral nectar of insect-pollinated Mediterranean plants. In contrast, the other two NGs comprised both South African and Mediterranean isolates. Analyses relating diversification to floristic region and pollinator type revealed that there has been more unique evolution of the nectar pseudomonads within the Mediterranean region than would be expected by chance. This is the first work analysing the sequence of multiple loci to reveal geno- and ecotypes of nectar bacteria.

  11. High-speed image analysis reveals chaotic vibratory behaviors of pathological vocal folds

    Energy Technology Data Exchange (ETDEWEB)

    Zhang Yu, E-mail: yuzhang@xmu.edu.c [Key Laboratory of Underwater Acoustic Communication and Marine Information Technology of the Ministry of Education, Xiamen University, Xiamen Fujian 361005 (China); Shao Jun [Shanghai EENT Hospital of Fudan University, Shanghai (China); Krausert, Christopher R. [Department of Surgery, Division of Otolaryngology - Head and Neck Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792-7375 (United States); Zhang Sai [Key Laboratory of Underwater Acoustic Communication and Marine Information Technology of the Ministry of Education, Xiamen University, Xiamen Fujian 361005 (China); Jiang, Jack J. [Shanghai EENT Hospital of Fudan University, Shanghai (China); Department of Surgery, Division of Otolaryngology - Head and Neck Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792-7375 (United States)

    2011-01-15

    Research highlights: Low-dimensional human glottal area data. Evidence of chaos in human laryngeal activity from high-speed digital imaging. Traditional perturbation analysis should be cautiously applied to aperiodic high speed image signals. Nonlinear dynamic analysis may be helpful for understanding disordered behaviors in pathological laryngeal systems. - Abstract: Laryngeal pathology is usually associated with irregular dynamics of laryngeal activity. High-speed imaging facilitates direct observation and measurement of vocal fold vibrations. However, chaotic dynamic characteristics of aperiodic high-speed image data have not yet been investigated in previous studies. In this paper, we will apply nonlinear dynamic analysis and traditional perturbation methods to quantify high-speed image data from normal subjects and patients with various laryngeal pathologies including vocal fold nodules, polyps, bleeding, and polypoid degeneration. The results reveal the low-dimensional dynamic characteristics of human glottal area data. In comparison to periodic glottal area series from a normal subject, aperiodic glottal area series from pathological subjects show complex reconstructed phase space, fractal dimension, and positive Lyapunov exponents. The estimated positive Lyapunov exponents provide the direct evidence of chaos in pathological human vocal folds from high-speed digital imaging. Furthermore, significant differences between the normal and pathological groups are investigated for nonlinear dynamic and perturbation analyses. Jitter in the pathological group is significantly higher than in the normal group, but shimmer does not show such a difference. This finding suggests that the traditional perturbation analysis should be cautiously applied to high speed image signals. However, the correlation dimension and the maximal Lyapunov exponent reveal a statistically significant difference between normal and pathological groups. Nonlinear dynamic analysis is capable of

  12. Correction: Comparative analysis of fungal genomes reveals different plant cell wall degrading capacity in fungi.

    Science.gov (United States)

    Zhao, Zhongtao; Liu, Huiquan; Wang, Chenfang; Xu, Jin-Rong

    2014-01-03

    The version of this article published in BMC Genomics 2013, 14: 274, contains 9 unpublished genomes (Botryobasidium botryosum, Gymnopus luxurians, Hypholoma sublateritium, Jaapia argillacea, Hebeloma cylindrosporum, Conidiobolus coronatus, Laccaria amethystina, Paxillus involutus, and P. rubicundulus) downloaded from JGI website. In this correction, we removed these genomes after discussion with editors and data producers whom we should have contacted before downloading these genomes. Removing these data did not alter the principle results and conclusions of our original work. The relevant Figures 1, 2, 3, 4 and 6; and Table 1 have been revised. Additional files 1, 3, 4, and 5 were also revised. We would like to apologize for any confusion or inconvenience this may have caused. Fungi produce a variety of carbohydrate activity enzymes (CAZymes) for the degradation of plant polysaccharide materials to facilitate infection and/or gain nutrition. Identifying and comparing CAZymes from fungi with different nutritional modes or infection mechanisms may provide information for better understanding of their life styles and infection models. To date, over hundreds of fungal genomes are publicly available. However, a systematic comparative analysis of fungal CAZymes across the entire fungal kingdom has not been reported. In this study, we systemically identified glycoside hydrolases (GHs), polysaccharide lyases (PLs), carbohydrate esterases (CEs), and glycosyltransferases (GTs) as well as carbohydrate-binding modules (CBMs) in the predicted proteomes of 94 representative fungi from Ascomycota, Basidiomycota, Chytridiomycota, and Zygomycota. Comparative analysis of these CAZymes that play major roles in plant polysaccharide degradation revealed that fungi exhibit tremendous diversity in the number and variety of CAZymes. Among them, some families of GHs and CEs are the most prevalent CAZymes that are distributed in all of the fungi analyzed. Importantly, cellulases of some GH

  13. Correction: Comparative analysis of fungal genomes reveals different plant cell wall degrading capacity in fungi

    Science.gov (United States)

    2014-01-01

    Abstract The version of this article published in BMC Genomics 2013, 14: 274, contains 9 unpublished genomes (Botryobasidium botryosum, Gymnopus luxurians, Hypholoma sublateritium, Jaapia argillacea, Hebeloma cylindrosporum, Conidiobolus coronatus, Laccaria amethystina, Paxillus involutus, and P. rubicundulus) downloaded from JGI website. In this correction, we removed these genomes after discussion with editors and data producers whom we should have contacted before downloading these genomes. Removing these data did not alter the principle results and conclusions of our original work. The relevant Figures 1, 2, 3, 4 and 6; and Table 1 have been revised. Additional files 1, 3, 4, and 5 were also revised. We would like to apologize for any confusion or inconvenience this may have caused. Background Fungi produce a variety of carbohydrate activity enzymes (CAZymes) for the degradation of plant polysaccharide materials to facilitate infection and/or gain nutrition. Identifying and comparing CAZymes from fungi with different nutritional modes or infection mechanisms may provide information for better understanding of their life styles and infection models. To date, over hundreds of fungal genomes are publicly available. However, a systematic comparative analysis of fungal CAZymes across the entire fungal kingdom has not been reported. Results In this study, we systemically identified glycoside hydrolases (GHs), polysaccharide lyases (PLs), carbohydrate esterases (CEs), and glycosyltransferases (GTs) as well as carbohydrate-binding modules (CBMs) in the predicted proteomes of 94 representative fungi from Ascomycota, Basidiomycota, Chytridiomycota, and Zygomycota. Comparative analysis of these CAZymes that play major roles in plant polysaccharide degradation revealed that fungi exhibit tremendous diversity in the number and variety of CAZymes. Among them, some families of GHs and CEs are the most prevalent CAZymes that are distributed in all of the fungi analyzed

  14. VNTR analysis reveals unexpected genetic diversity within Mycoplasma agalactiae, the main causative agent of contagious agalactia

    Directory of Open Access Journals (Sweden)

    Ayling Roger D

    2008-11-01

    Full Text Available Abstract Background Mycoplasma agalactiae is the main cause of contagious agalactia, a serious disease of sheep and goats, which has major clinical and economic impacts. Previous studies of M. agalactiae have shown it to be unusually homogeneous and there are currently no available epidemiological techniques which enable a high degree of strain differentiation. Results We have developed variable number tandem repeat (VNTR analysis using the sequenced genome of the M. agalactiae type strain PG2. The PG2 genome was found to be replete with tandem repeat sequences and 4 were chosen for further analysis. VNTR 5 was located within the hypothetical protein MAG6170 a predicted lipoprotein. VNTR 14 was intergenic between the hypothetical protein MAG3350 and the hypothetical protein MAG3340. VNTR 17 was intergenic between the hypothetical protein MAG4060 and the hypothetical protein MAG4070 and VNTR 19 spanned the 5' end of the pseudogene for a lipoprotein MAG4310 and the 3' end of the hypothetical lipoprotein MAG4320. We have investigated the genetic diversity of 88 M. agalactiae isolates of wide geographic origin using VNTR analysis and compared it with pulsed field gel electrophoresis (PFGE and random amplified polymorphic DNA (RAPD analysis. Simpson's index of diversity was calculated to be 0.324 for PFGE and 0.574 for VNTR analysis. VNTR analysis revealed unexpected diversity within M. agalactiae with 9 different VNTR types discovered. Some correlation was found between geographical origin and the VNTR type of the isolates. Conclusion VNTR analysis represents a useful, rapid first-line test for use in molecular epidemiological analysis of M. agalactiae for outbreak tracing and control.

  15. Accelerated partial breast irradiation using intensity-modulated radiotherapy technique compared to whole breast irradiation for patients aged 70 years or older: subgroup analysis from a randomized phase 3 trial.

    Science.gov (United States)

    Meattini, Icro; Saieva, Calogero; Marrazzo, Livia; Di Brina, Lucia; Pallotta, Stefania; Mangoni, Monica; Meacci, Fiammetta; Bendinelli, Benedetta; Francolini, Giulio; Desideri, Isacco; De Luca Cardillo, Carla; Scotti, Vieri; Furfaro, Ilaria Francesca; Rossi, Francesca; Greto, Daniela; Bonomo, Pierluigi; Casella, Donato; Bernini, Marco; Sanchez, Luis; Orzalesi, Lorenzo; Simoncini, Roberta; Nori, Jacopo; Bianchi, Simonetta; Livi, Lorenzo

    2015-10-01

    The purpose of this study was to report the efficacy and the safety profile on the subset of selected early breast cancer (BC) patients aged 70 years or older from a single-center phase 3 trial comparing whole breast irradiation (WBI) to accelerated partial breast irradiation (APBI) using intensity-modulated radiation therapy technique. Between 2005 and 2013, 520 patients aged more than 40 years old were enrolled and randomly assigned to receive either WBI or APBI in a 1:1 ratio. Eligible patients were women with early BC (maximum diameter 2.5 cm) suitable for breast conserving surgery. This study is registered with ClinicalTrials.gov, NCT02104895. A total of 117 patients aged 70 years or more were analyzed (58 in the WBI arm, 59 in the APBI arm). At a median follow-up of 5-years (range 3.4-7.0), the ipsilateral breast tumor recurrence (IBTR) rate was 1.9 % in both groups. No significant difference between the two groups was identified (log-rank test p = 0.96). The 5-year disease-free survival (DFS) rates in the WBI group and APBI group were 6.1 and 1.9 %, respectively (p = 0.33). The APBI group presented significantly better results in terms of acute skin toxicity, considering both any grade (p = 0.0001) and grade 2 or higher (p = 0.0001). Our subgroup analyses showed a very low rate and no significant difference in terms of IBTR, using both WBI and APBI. A significant impact on patients compliance in terms of acute and early late toxicity was shown, which could translate in a consistent improvement of overall quality of life.

  16. Proteomic analysis reveals novel proteins associated with progression and differentiation of colorectal carcinoma

    Directory of Open Access Journals (Sweden)

    Yi Gan

    2014-01-01

    Full Text Available Aim: The objective of this study is to characterize differential proteomic expression among well-differentiation and poor-differentiation colorectal carcinoma tissues and normal mucous epithelium. Materials and Methods: The study is based on quantitative 2-dimensional gel electrophoresis and analyzed by PDquest. Results: Excluding redundancies due to proteolysis and posttranslational modified isoforms of over 600 protein spots, 11 proteins were revealed as regulated with statistical variance being within the 95 th confidence level and were identified by peptide mass fingerprinting in matrix assisted laser desorption/ionization time-of-flight mass spectrometry. Progression-associated proteins belong to the functional complexes of tumorigenesis, proliferation, differentiation, metabolism, and the regulation of major histocompatibility complex processing and other functions. Partial but significant overlap was revealed with previous proteomics and transcriptomics studies in CRC. Among various differentiation stage of CRC tissues, we identified calreticulin precursor, MHC class I antigen (human leukocyte antigen A , glutathione S-transferase pi1, keratin 8, heat shock protein 27, tubulin beta chain, triosephosphate, fatty acid-binding protein, hemoglobin (deoxy mutant with val b 1 replaced by met (HBB, and zinc finger protein 312 (FEZF2. Conclusions: Their functional networks were analyzed by Ingenuity systems Ingenuity Pathways Analysis and revealed the potential roles as novel biomarkers for progression in various differentiation stages of CRC.

  17. Comprehensive genomic analysis of Oesophageal Squamous Cell Carcinoma reveals clinical relevance

    DEFF Research Database (Denmark)

    Du, Peina; Huang, Peide; Huang, Xuanlin

    2017-01-01

    was relatively small, and the molecular basis of ESCC has not been fully elucidated. Here, we performed an integrated analysis of 490 tumours by combining the genomic data from 7 previous ESCC projects. We identified 18 significantly mutated genes (SMGs). PTEN, DCDC1 and CUL3 were first reported as SMGs in ESCC....... Notably, the AJUBA mutations and mutational signature4 were significantly correlated with a poorer survival in patients with ESCC. Hierarchical clustering analysis of the copy number alteration (CNA) of cancer gene census (CGC) genes in ESCC patients revealed three subtypes, and subtype3 exhibited more...... and shed some light into the clinical relevance, which would help improve the therapy and prognosis of ESCC patients....

  18. In Vivo Phosphoproteomics Analysis Reveals the Cardiac Targets of β-Adrenergic Receptor Signaling

    DEFF Research Database (Denmark)

    Lundby, Alicia; Andersen, Martin N; Steffensen, Annette B

    2013-01-01

    used quantitative in vivo phosphoproteomics to identify 670 site-specific phosphorylation changes in murine hearts in response to acute treatment with specific βAR agonists. The residues adjacent to the regulated phosphorylation sites exhibited a sequence-specific preference (R......) of the potassium channel KV7.1, increased current amplitude. Our data set represents a quantitative analysis of phosphorylated proteins regulated in vivo upon stimulation of seven-transmembrane receptors, and our findings reveal previously unknown phosphorylation sites that regulate myocardial contractility......-X-X-pS/T), and integrative analysis of sequence motifs and interaction networks suggested that the kinases AMPK (adenosine 5'-monophosphate-activated protein kinase), Akt, and mTOR (mammalian target of rapamycin) mediate βAR signaling, in addition to the well-established pathways mediated by PKA (cyclic adenosine...

  19. Proteomic analysis of three gonad types of swamp eel reveals genes differentially expressed during sex reversal.

    Science.gov (United States)

    Sheng, Yue; Zhao, Wei; Song, Ying; Li, Zhigang; Luo, Majing; Lei, Quan; Cheng, Hanhua; Zhou, Rongjia

    2015-05-18

    A variety of mechanisms are engaged in sex determination in vertebrates. The teleost fish swamp eel undergoes sex reversal naturally and is an ideal model for vertebrate sexual development. However, the importance of proteome-wide scanning for gonad reversal was not previously determined. We report a 2-D electrophoresis analysis of three gonad types of proteomes during sex reversal. MS/MS analysis revealed a group of differentially expressed proteins during ovary to ovotestis to testis transformation. Cbx3 is up-regulated during gonad reversal and is likely to have a role in spermatogenesis. Rab37 is down-regulated during the reversal and is mainly associated with oogenesis. Both Cbx3 and Rab37 are linked up in a protein network. These datasets in gonadal proteomes provide a new resource for further studies in gonadal development.

  20. Proteomic analysis of MG132-treated germinating pollen reveals expression signatures associated with proteasome inhibition.

    Directory of Open Access Journals (Sweden)

    Candida Vannini

    Full Text Available Chemical inhibition of the proteasome has been previously found to effectively impair pollen germination and tube growth in vitro. However, the mediators of these effects at the molecular level are unknown. By performing 2DE proteomic analysis, 24 differentially expressed protein spots, representing 14 unique candidate proteins, were identified in the pollen of kiwifruit (Actinidia deliciosa germinated in the presence of the MG132 proteasome inhibitor. qPCR analysis revealed that 11 of these proteins are not up-regulated at the mRNA level, but are most likely stabilized by proteasome inhibition. These differentially expressed proteins are predicted to function in various pathways including energy and lipid metabolism, cell wall synthesis, protein synthesis/degradation and stress responses. In line with this evidence, the MG132-induced changes in the proteome were accompanied by an increase in ATP and ROS content and by an alteration in fatty acid composition.

  1. Integrative analysis of RNA, translation, and protein levels reveals distinct regulatory variation across humans

    Science.gov (United States)

    Cenik, Can; Cenik, Elif Sarinay; Byeon, Gun W.; Grubert, Fabian; Candille, Sophie I.; Spacek, Damek; Alsallakh, Bilal; Tilgner, Hagen; Araya, Carlos L.; Tang, Hua; Ricci, Emiliano; Snyder, Michael P.

    2015-01-01

    Elucidating the consequences of genetic differences between humans is essential for understanding phenotypic diversity and personalized medicine. Although variation in RNA levels, transcription factor binding, and chromatin have been explored, little is known about global variation in translation and its genetic determinants. We used ribosome profiling, RNA sequencing, and mass spectrometry to perform an integrated analysis in lymphoblastoid cell lines from a diverse group of individuals. We find significant differences in RNA, translation, and protein levels suggesting diverse mechanisms of personalized gene expression control. Combined analysis of RNA expression and ribosome occupancy improves the identification of individual protein level differences. Finally, we identify genetic differences that specifically modulate ribosome occupancy—many of these differences lie close to start codons and upstream ORFs. Our results reveal a new level of gene expression variation among humans and indicate that genetic variants can cause changes in protein levels through effects on translation. PMID:26297486

  2. Are there distinct cognitive and motivational sub-groups of children with ADHD?

    Science.gov (United States)

    Lambek, Rikke; Sonuga-Barke, Edmund; Tannock, Rosemary; Sørensen, Anne Virring; Damm, Dorte; Thomsen, Per Hove

    2017-11-16

    Attention-deficit/hyperactivity disorder (ADHD) is proposed to be a neuropsychologically heterogeneous disorder that encompasses two distinct sub-groups, one with executive function (EF) deficits and one with delay aversion (DA). However, such claims have often been based on studies that have operationalized neuropsychological deficits using a categorical approach - using intuitive but rather arbitrary, clinical cut-offs. The current study applied an alternative empirical approach to sub-grouping in ADHD, latent profile analysis (LPA), and attempted to validate emerging subgroups through clinically relevant correlates. One-hundred medication-naïve children with ADHD and 96 typically developing children (6-14 years) completed nine EF and three DA tasks as well as an odor identification test. Parents and teachers provided reports of the children's behavior (ADHD and EF). Models of the latent structure of scores on EF and DA tests were contrasted using confirmatory factor analysis (CFA). LPA was carried out based on factor scores from the CFA and sub-groups were compared in terms of odor identification and behavior. A model with one DA and two EF factors best fit the data. LPA resulted in four sub-groups that differed in terms of general level of neuropsychological performance (ranging from high to very low), odor identification, and behavior. The sub-groups did not differ in terms of the relative EF and DA performance. Results in the ADHD group were replicated in the control group. While EF and DA appear to be dissociable constructs; they do not yield distinct sub-groups when sub-grouping is based on a statistical approach such as LPA.

  3. Dynamic transcriptional signature and cell fate analysis reveals plasticity of individual neural plate border cells

    Science.gov (United States)

    Roellig, Daniela; Tan-Cabugao, Johanna; Esaian, Sevan; Bronner, Marianne E

    2017-01-01

    The ‘neural plate border’ of vertebrate embryos contains precursors of neural crest and placode cells, both defining vertebrate characteristics. How these lineages segregate from neural and epidermal fates has been a matter of debate. We address this by performing a fine-scale quantitative temporal analysis of transcription factor expression in the neural plate border of chick embryos. The results reveal significant overlap of transcription factors characteristic of multiple lineages in individual border cells from gastrula through neurula stages. Cell fate analysis using a Sox2 (neural) enhancer reveals that cells that are initially Sox2+ cells can contribute not only to neural tube but also to neural crest and epidermis. Moreover, modulating levels of Sox2 or Pax7 alters the apportionment of neural tube versus neural crest fates. Our results resolve a long-standing question and suggest that many individual border cells maintain ability to contribute to multiple ectodermal lineages until or beyond neural tube closure. DOI: http://dx.doi.org/10.7554/eLife.21620.001 PMID:28355135

  4. Transcriptome analysis reveals distinct gene expression profiles in astrocytoma grades II-IV.

    Science.gov (United States)

    Narsia, Nato; Ramagiri, Pradeep; Ehrmann, Jiri; Kolar, Zdenek

    2017-09-01

    Astrocytoma is the most prevalent form of primary brain cancer categorized into four histological grades by the World Health Organization. Investigation into individual grades of astrocytoma by previous studies has provided some insight into dysregulation of regulatory networks associated with increasing astrocytoma grades. However, further understanding of key mechanisms that distinguish different astrocytoma grades is required to facilitate targeted therapies. In this study, we utilized a large cohort of publicly available RNA sequencing data from patients with diffuse astrocytoma (grade II), anaplastic astrocytoma (grade III), primary glioblastoma (grade IV), secondary glioblastoma (grade IV), recurrent glioblastoma (grade IV), and normal brain samples to identify genetic similarities and differences between these grades using bioinformatics applications. Our analysis revealed a distinct gene expression pattern between grade II astrocytoma and grade IV glioblastoma (GBM). We also identified genes that were exclusively expressed in each of the astrocytoma grades. Furthermore, we identified known and novel genes involved in key pathways in our study. Gene set enrichment analysis revealed a distinct expression pattern of transcriptional regulators in primary GBM. Further investigation into molecular processes showed that the genes involved in cell proliferation and invasion were shared across all subtypes of astrocytoma. Also, the number of genes involved in metastasis, regulation of cell proliferation, and apoptosis increased with tumor grade. We confirmed existing findings and shed light on some important genes and molecular processes that will improve our understanding of glioma biology.

  5. Proteomics Analysis of Tissue Samples Reveals Changes in Mitochondrial Protein Levels in Parathyroid Hyperplasia over Adenoma.

    Science.gov (United States)

    Akpinar, Gurler; Kasap, Murat; Canturk, Nuh Zafer; Zulfigarova, Mehin; Islek, Eylül Ece; Guler, Sertac Ata; Simsek, Turgay; Canturk, Zeynep

    2017-01-01

    To unveil the pathophysiology of primary hyperparathyroidism, molecular details of parathyroid hyperplasia and adenoma have to be revealed. Such details will provide the tools necessary for differentiation of these two look-alike diseases. Therefore, in the present study, a comparative proteomic study using postoperative tissue samples from the parathyroid adenoma and parathyroid hyperplasia patients was performed. Protein extracts were prepared from tissue samples (n=8 per group). Protein pools were created for each group and subjected to DIGE and conventional 2DE. Following image analysis, spots representing the differentially regulated proteins were excised from the and used for identification via MALDI-TOF/TOF analysis. The identities of 40 differentially-expressed proteins were revealed. Fourteen of these proteins were over-expressed in the hyperplasia while 26 of them were over-expressed in the adenoma. Most proteins found to be over-expressed in the hyperplasia samples were mitochondrial, underlying the importance of the mitochondrial activity as a potential biomarker for differentiation of parathyroid hyperplasia from adenoma. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  6. Genomic and functional analysis of Romboutsia ilealis CRIBT reveals adaptation to the small intestine

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    Jacoline Gerritsen

    2017-09-01

    Full Text Available Background The microbiota in the small intestine relies on their capacity to rapidly import and ferment available carbohydrates to survive in a complex and highly competitive ecosystem. Understanding how these communities function requires elucidating the role of its key players, the interactions among them and with their environment/host. Methods The genome of the gut bacterium Romboutsia ilealis CRIBT was sequenced with multiple technologies (Illumina paired-end, mate-pair and PacBio. The transcriptome was sequenced (Illumina HiSeq after growth on three different carbohydrate sources, and short chain fatty acids were measured via HPLC. Results We present the complete genome of Romboutsia ilealis CRIBT, a natural inhabitant and key player of the small intestine of rats. R. ilealis CRIBT possesses a circular chromosome of 2,581,778 bp and a plasmid of 6,145 bp, carrying 2,351 and eight predicted protein coding sequences, respectively. Analysis of the genome revealed limited capacity to synthesize amino acids and vitamins, whereas multiple and partially redundant pathways for the utilization of different relatively simple carbohydrates are present. Transcriptome analysis allowed identification of the key components in the degradation of glucose, L-fucose and fructo-oligosaccharides. Discussion This revealed that R. ilealis CRIBT is adapted to a nutrient-rich environment where carbohydrates, amino acids and vitamins are abundantly available.

  7. Evolutionary Meta-Analysis of Association Studies Reveals Ancient Constraints Affecting Disease Marker Discovery

    Science.gov (United States)

    Dudley, Joel T.; Chen, Rong; Sanderford, Maxwell; Butte, Atul J.; Kumar, Sudhir

    2012-01-01

    Genome-wide disease association studies contrast genetic variation between disease cohorts and healthy populations to discover single nucleotide polymorphisms (SNPs) and other genetic markers revealing underlying genetic architectures of human diseases. Despite scores of efforts over the past decade, many reproducible genetic variants that explain substantial proportions of the heritable risk of common human diseases remain undiscovered. We have conducted a multispecies genomic analysis of 5,831 putative human risk variants for more than 230 disease phenotypes reported in 2,021 studies. We find that the current approaches show a propensity for discovering disease-associated SNPs (dSNPs) at conserved genomic positions because the effect size (odds ratio) and allelic P value of genetic association of an SNP relates strongly to the evolutionary conservation of their genomic position. We propose a new measure for ranking SNPs that integrates evolutionary conservation scores and the P value (E-rank). Using published data from a large case-control study, we demonstrate that E-rank method prioritizes SNPs with a greater likelihood of bona fide and reproducible genetic disease associations, many of which may explain greater proportions of genetic variance. Therefore, long-term evolutionary histories of genomic positions offer key practical utility in reassessing data from existing disease association studies, and in the design and analysis of future studies aimed at revealing the genetic basis of common human diseases. PMID:22389448

  8. Genomic and functional analysis of Romboutsia ilealis CRIBT reveals adaptation to the small intestine.

    Science.gov (United States)

    Gerritsen, Jacoline; Hornung, Bastian; Renckens, Bernadette; van Hijum, Sacha A F T; Martins Dos Santos, Vitor A P; Rijkers, Ger T; Schaap, Peter J; de Vos, Willem M; Smidt, Hauke

    2017-01-01

    The microbiota in the small intestine relies on their capacity to rapidly import and ferment available carbohydrates to survive in a complex and highly competitive ecosystem. Understanding how these communities function requires elucidating the role of its key players, the interactions among them and with their environment/host. The genome of the gut bacterium Romboutsia ilealis CRIBT was sequenced with multiple technologies (Illumina paired-end, mate-pair and PacBio). The transcriptome was sequenced (Illumina HiSeq) after growth on three different carbohydrate sources, and short chain fatty acids were measured via HPLC. We present the complete genome of Romboutsia ilealis CRIBT, a natural inhabitant and key player of the small intestine of rats. R. ilealis CRIBT possesses a circular chromosome of 2,581,778 bp and a plasmid of 6,145 bp, carrying 2,351 and eight predicted protein coding sequences, respectively. Analysis of the genome revealed limited capacity to synthesize amino acids and vitamins, whereas multiple and partially redundant pathways for the utilization of different relatively simple carbohydrates are present. Transcriptome analysis allowed identification of the key components in the degradation of glucose, L-fucose and fructo-oligosaccharides. This revealed that R. ilealis CRIBT is adapted to a nutrient-rich environment where carbohydrates, amino acids and vitamins are abundantly available.

  9. Cerebral degeneration in amyotrophic lateral sclerosis revealed by 3-dimensional texture analysis

    Directory of Open Access Journals (Sweden)

    Rouzbeh eMaani

    2016-03-01

    Full Text Available Introduction: Routine MR images do not consistently reveal pathological changes in the brain in ALS. Texture analysis, a method to quantitate voxel intensities and their patterns and interrelationships, can detect changes in images not apparent to the naked eye. Our objective was to evaluate cerebral degeneration in ALS using 3-dimensional texture analysis of MR images of the brain. Methods: In a case-control design, voxel-based texture analysis was performed on T1-weighted MR images of 20 healthy subjects and 19 patients with ALS. Four texture features, namely, autocorrelation, sum of squares variance, sum average, and sum variance were computed. Texture features were compared between the groups by statistical parametric mapping and correlated with clinical measures of disability and upper motor neuron dysfunction.Results: Texture features were different in ALS in motor regions including the precentral gyrus and corticospinal tracts. To a lesser extent, changes were also found in the thalamus, cingulate gyrus, and temporal lobe. Texture features in the precentral gyrus correlated with disease duration, and in the corticospinal tract they correlated with finger tapping speed. Conclusions: Changes in MR image textures are present in motor and non-motor regions in ALS and correlate with clinical features. Whole brain texture analysis has potential in providing biomarkers of cerebral degeneration in ALS.

  10. Gene expression analysis of endometrium reveals progesterone resistance and candidate susceptibility genes in women with endometriosis.

    Science.gov (United States)

    Burney, Richard O; Talbi, Said; Hamilton, Amy E; Vo, Kim Chi; Nyegaard, Mette; Nezhat, Camran R; Lessey, Bruce A; Giudice, Linda C

    2007-08-01

    The identification of molecular differences in the endometrium of women with endometriosis is an important step toward understanding the pathogenesis of this condition and toward developing novel strategies for the treatment of associated infertility and pain. In this study, we conducted global gene expression analysis of endometrium from women with and without moderate/severe stage endometriosis and compared the gene expression signatures across various phases of the menstrual cycle. The transcriptome analysis revealed molecular dysregulation of the proliferative-to-secretory transition in endometrium of women with endometriosis. Paralleled gene expression analysis of endometrial specimens obtained during the early secretory phase demonstrated a signature of enhanced cellular survival and persistent expression of genes involved in DNA synthesis and cellular mitosis in the setting of endometriosis. Comparative gene expression analysis of progesterone-regulated genes in secretory phase endometrium confirmed the observation of attenuated progesterone response. Additionally, interesting candidate susceptibility genes were identified that may be associated with this disorder, including FOXO1A, MIG6, and CYP26A1. Collectively these findings provide a framework for further investigations on causality and mechanisms underlying attenuated progesterone response in endometrium of women with endometriosis.

  11. Metabolomic analysis reveals the composition differences in 13 Chinese tea cultivars of different manufacturing suitabilities.

    Science.gov (United States)

    Li, Pengliang; Dai, Weidong; Lu, Meiling; Xie, Dongchao; Tan, Junfeng; Yang, Chen; Zhu, Yin; Lv, Haipeng; Peng, Qunhua; Zhang, Yue; Guo, Li; Ni, Dejiang; Lin, Zhi

    2018-02-01

    Green tea and black tea are manufactured using appropriate tea cultivars in China. However, the metabolite differences relating to the manufacturing suitability of tea cultivars are unclear. In the present study, we performed a non-targeted metabolomic analysis on 13 Chinese tea cultivars using ultra-high performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry to investigate comprehensively the metabolite differences between cultivars suitable for manufacturing green tea (GT cultivars) and cultivars suitable for manufacturing both green tea and black tea (G&BT cultivars). Multivariate statistical analysis and cluster analysis divided the 13 cultivars into two groups, namely GT cultivars and G&BT cultivars, which correlated with their manufacturing suitability. The GT cultivars contained higher levels of flavonoid glycosides, whereas the G&BT cultivars contained higher levels of catechins, dimeric catechins, phenolic acids and alkaloids. Metabolic pathway analysis revealed that the flavonoid pathway inclined toward the synthesis of flavonoid glycosides in GT cultivars, whereas it inclined toward the synthesis of catechins and phenolic acids in G&BT cultivars. The results of the present study will be helpful for discriminating the manufacturing suitability of tea cultivars and investigating their breeding. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  12. Network Analysis of a Comprehensive Knowledge Repository Reveals a Dual Role for Ceramide in Alzheimer's Disease.

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    Satoshi Mizuno

    Full Text Available Alzheimer's disease (AD is the most common cause of senile dementia. Many inflammatory factors such as amyloid-β and pro-inflammatory cytokines are known to contribute to the inflammatory response in the AD brain. Sphingolipids are widely known to have roles in the pathogenesis of inflammatory diseases, where the precise roles for sphingolipids in inflammation-associated pathogenesis of AD are not well understood. Here we performed a network analysis to clarify the importance of sphingolipids and to model relationships among inflammatory factors and sphingolipids in AD. In this study, we have updated sphingolipid signaling and metabolic cascades in a map of AD signaling networks that we named "AlzPathway," a comprehensive knowledge repository of signaling pathways in AD. Our network analysis of the updated AlzPathway indicates that the pathways related to ceramide are one of the primary pathways and that ceramide is one of the important players in the pathogenesis of AD. The results of our analysis suggest the following two prospects about inflammation in AD: (1 ceramide could play important roles in both inflammatory and anti-inflammatory pathways of AD, and (2 several factors such as Sphingomyelinase and Siglec-11 may be associated with ceramide related inflammation and anti-inflammation pathways in AD. In this study, network analysis of comprehensive knowledge repository reveals a dual role for ceramide in AD. This result provides a clue to clarify sphingolipids related inflammatory and anti-inflammatory pathways in AD.

  13. Gene set based integrated data analysis reveals phenotypic differences in a brain cancer model.

    Directory of Open Access Journals (Sweden)

    Kjell Petersen

    Full Text Available A key challenge in the data analysis of biological high-throughput experiments is to handle the often low number of samples in the experiments compared to the number of biomolecules that are simultaneously measured. Combining experimental data using independent technologies to illuminate the same biological trends, as well as complementing each other in a larger perspective, is one natural way to overcome this challenge. In this work we investigated if integrating proteomics and transcriptomics data from a brain cancer animal model using gene set based analysis methodology, could enhance the biological interpretation of the data relative to more traditional analysis of the two datasets individually. The brain cancer model used is based on serial passaging of transplanted human brain tumor material (glioblastoma--GBM through several generations in rats. These serial transplantations lead over time to genotypic and phenotypic changes in the tumors and represent a medically relevant model with a rare access to samples and where consequent analyses of individual datasets have revealed relatively few significant findings on their own. We found that the integrated analysis both performed better in terms of significance measure of its findings compared to individual analyses, as well as providing independent verification of the individual results. Thus a better context for overall biological interpretation of the data can be achieved.

  14. Metatranscriptomic analysis of diverse microbial communities reveals core metabolic pathways and microbiome-specific functionality.

    Science.gov (United States)

    Jiang, Yue; Xiong, Xuejian; Danska, Jayne; Parkinson, John

    2016-01-12

    Metatranscriptomics is emerging as a powerful technology for the functional characterization of complex microbial communities (microbiomes). Use of unbiased RNA-sequencing can reveal both the taxonomic composition and active biochemical functions of a complex microbial community. However, the lack of established reference genomes, computational tools and pipelines make analysis and interpretation of these datasets challenging. Systematic studies that compare data across microbiomes are needed to demonstrate the ability of such pipelines to deliver biologically meaningful insights on microbiome function. Here, we apply a standardized analytical pipeline to perform a comparative analysis of metatranscriptomic data from diverse microbial communities derived from mouse large intestine, cow rumen, kimchi culture, deep-sea thermal vent and permafrost. Sequence similarity searches allowed annotation of 19 to 76% of putative messenger RNA (mRNA) reads, with the highest frequency in the kimchi dataset due to its relatively low complexity and availability of closely related reference genomes. Metatranscriptomic datasets exhibited distinct taxonomic and functional signatures. From a metabolic perspective, we identified a common core of enzymes involved in amino acid, energy and nucleotide metabolism and also identified microbiome-specific pathways such as phosphonate metabolism (deep sea) and glycan degradation pathways (cow rumen). Integrating taxonomic and functional annotations within a novel visualization framework revealed the contribution of different taxa to metabolic pathways, allowing the identification of taxa that contribute unique functions. The application of a single, standard pipeline confirms that the rich taxonomic and functional diversity observed across microbiomes is not simply an artefact of different analysis pipelines but instead reflects distinct environmental influences. At the same time, our findings show how microbiome complexity and availability of

  15. Live imaging analysis of human gastric epithelial spheroids reveals spontaneous rupture, rotation and fusion events.

    Science.gov (United States)

    Sebrell, T Andrew; Sidar, Barkan; Bruns, Rachel; Wilkinson, Royce A; Wiedenheft, Blake; Taylor, Paul J; Perrino, Brian A; Samuelson, Linda C; Wilking, James N; Bimczok, Diane

    2018-02-01

    Three-dimensional cultures of primary epithelial cells including organoids, enteroids and epithelial spheroids have become increasingly popular for studies of gastrointestinal development, mucosal immunology and epithelial infection. However, little is known about the behavior of these complex cultures in their three-dimensional culture matrix. Therefore, we performed extended time-lapse imaging analysis (up to 4 days) of human gastric epithelial spheroids generated from adult tissue samples in order to visualize the dynamics of the spheroids in detail. Human gastric epithelial spheroids cultured in our laboratory grew to an average diameter of 443.9 ± 34.6 μm after 12 days, with the largest spheroids reaching diameters of >1000 μm. Live imaging analysis revealed that spheroid growth was associated with cyclic rupture of the epithelial shell at a frequency of 0.32 ± 0.1/day, which led to the release of luminal contents. Spheroid rupture usually resulted in an initial collapse, followed by spontaneous re-formation of the spheres. Moreover, spheroids frequently rotated around their axes within the Matrigel matrix, possibly propelled by basolateral pseudopodia-like formations of the epithelial cells. Interestingly, adjacent spheroids occasionally underwent luminal fusion, as visualized by injection of individual spheroids with FITC-Dextran (4 kDa). In summary, our analysis revealed unexpected dynamics in human gastric spheroids that challenge our current view of cultured epithelia as static entities and that may need to be considered when performing spheroid infection experiments.

  16. Association genetics and transcriptome analysis reveal a gibberellin-responsive pathway involved in regulating photosynthesis.

    Science.gov (United States)

    Xie, Jianbo; Tian, Jiaxing; Du, Qingzhang; Chen, Jinhui; Li, Ying; Yang, Xiaohui; Li, Bailian; Zhang, Deqiang

    2016-05-01

    Gibberellins (GAs) regulate a wide range of important processes in plant growth and development, including photosynthesis. However, the mechanism by which GAs regulate photosynthesis remains to be understood. Here, we used multi-gene association to investigate the effect of genes in the GA-responsive pathway, as constructed by RNA sequencing, on photosynthesis, growth, and wood property traits, in a population of 435 Populus tomentosa By analyzing changes in the transcriptome following GA treatment, we identified many key photosynthetic genes, in agreement with the observed increase in measurements of photosynthesis. Regulatory motif enrichment analysis revealed that 37 differentially expressed genes related to photosynthesis shared two essential GA-related cis-regulatory elements, the GA response element and the pyrimidine box. Thus, we constructed a GA-responsive pathway consisting of 47 genes involved in regulating photosynthesis, including GID1, RGA, GID2, MYBGa, and 37 photosynthetic differentially expressed genes. Single nucleotide polymorphism (SNP)-based association analysis showed that 142 SNPs, representing 40 candidate genes in this pathway, were significantly associated with photosynthesis, growth, and wood property traits. Epistasis analysis uncovered interactions between 310 SNP-SNP pairs from 37 genes in this pathway, revealing possible genetic interactions. Moreover, a structural gene-gene matrix based on a time-course of transcript abundances provided a better understanding of the multi-gene pathway affecting photosynthesis. The results imply a functional role for these genes in mediating photosynthesis, growth, and wood properties, demonstrating the potential of combining transcriptome-based regulatory pathway construction and genetic association approaches to detect the complex genetic networks underlying quantitative traits. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights

  17. Diversity of eukaryotic DNA replication origins revealed by genome-wide analysis of chromatin structure.

    Directory of Open Access Journals (Sweden)

    Nicolas M Berbenetz

    2010-09-01

    Full Text Available Eukaryotic DNA replication origins differ both in their efficiency and in the characteristic time during S phase when they become active. The biological basis for these differences remains unknown, but they could be a consequence of chromatin structure. The availability of genome-wide maps of nucleosome positions has led to an explosion of information about how nucleosomes are assembled at transcription start sites, but no similar maps exist for DNA replication origins. Here we combine high-resolution genome-wide nucleosome maps with comprehensive annotations of DNA replication origins to identify patterns of nucleosome occupancy at eukaryotic replication origins. On average, replication origins contain a nucleosome depleted region centered next to the ACS element, flanked on both sides by arrays of well-positioned nucleosomes. Our analysis identified DNA sequence properties that correlate with nucleosome occupancy at replication origins genome-wide and that are correlated with the nucleosome-depleted region. Clustering analysis of all annotated replication origins revealed a surprising diversity of nucleosome occupancy patterns. We provide evidence that the origin recognition complex, which binds to the origin, acts as a barrier element to position and phase nucleosomes on both sides of the origin. Finally, analysis of chromatin reconstituted in vitro reveals that origins are inherently nucleosome depleted. Together our data provide a comprehensive, genome-wide view of chromatin structure at replication origins and suggest a model of nucleosome positioning at replication origins in which the underlying sequence occludes nucleosomes to permit binding of the origin recognition complex, which then (likely in concert with nucleosome modifiers and remodelers positions nucleosomes adjacent to the origin to promote replication origin function.

  18. An association network analysis among microeukaryotes and bacterioplankton reveals algal bloom dynamics.

    Science.gov (United States)

    Tan, Shangjin; Zhou, Jin; Zhu, Xiaoshan; Yu, Shichen; Zhan, Wugen; Wang, Bo; Cai, Zhonghua

    2015-02-01

    Algal blooms are a worldwide phenomenon and the biological interactions that underlie their regulation are only just beginning to be understood. It is established that algal microorganisms associate with many other ubiquitous, oceanic organisms, but the interactions that lead to the dynamics of bloom formation are currently unknown. To address this gap, we used network approaches to investigate the association patterns among microeukaryotes and bacterioplankton in response to a natural Scrippsiella trochoidea bloom. This is the first study to apply network approaches to bloom dynamics. To this end, terminal restriction fragment (T-RF) length polymorphism analysis showed dramatic changes in community compositions of microeukaryotes and bacterioplankton over the blooming period. A variance ratio test revealed significant positive overall associations both within and between microeukaryotic and bacterioplankton communities. An association network generated from significant correlations between T-RFs revealed that S. trochoidea had few connections to other microeukaryotes and bacterioplankton and was placed on the edge. This lack of connectivity allowed for the S. trochoidea sub-network to break off from the overall network. These results allowed us to propose a conceptual model for explaining how changes in microbial associations regulate the dynamics of an algal bloom. In addition, key T-RFs were screened by principal components analysis, correlation coefficients, and network analysis. Dominant T-RFs were then identified through 18S and 16S rRNA gene clone libraries. Results showed that microeukaryotes clustered predominantly with Dinophyceae and Perkinsea while the majority of bacterioplankton identified were Alphaproteobacteria, Gammaproteobacteria, and Bacteroidetes. The ecologi-cal roles of both were discussed in the context of these findings. © 2014 Phycological Society of America.

  19. The interest of gait markers in the identification of subgroups among fibromyalgia patients.

    Science.gov (United States)

    Auvinet, Bernard; Chaleil, Denis; Cabane, Jean; Dumolard, Anne; Hatron, Pierre; Juvin, Robert; Lanteri-Minet, Michel; Mainguy, Yves; Negre-Pages, Laurence; Pillard, Fabien; Riviere, Daniel; Maugars, Yves-Michel

    2011-11-11

    Fibromyalgia (FM) is a heterogeneous syndrome and its classification into subgroups calls for broad-based discussion. FM subgrouping, which aims to adapt treatment according to different subgroups, relies in part, on psychological and cognitive dysfunctions. Since motor control of gait is closely related to cognitive function, we hypothesized that gait markers could be of interest in the identification of FM patients' subgroups. This controlled study aimed at characterizing gait disorders in FM, and subgrouping FM patients according to gait markers such as stride frequency (SF), stride regularity (SR), and cranio-caudal power (CCP) which measures kinesia. A multicentre, observational open trial enrolled patients with primary FM (44.1 ± 8.1 y), and matched controls (44.1 ± 7.3 y). Outcome measurements and gait analyses were available for 52 pairs. A 3-step statistical analysis was carried out. A preliminary single blind analysis using k-means cluster was performed as an initial validation of gait markers. Then in order to quantify FM patients according to psychometric and gait variables an open descriptive analysis comparing patients and controls were made, and correlations between gait variables and main outcomes were calculated. Finally using cluster analysis, we described subgroups for each gait variable and looked for significant differences in self-reported assessments. SF was the most discriminating gait variable (73% of patients and controls). SF, SR, and CCP were different between patients and controls. There was a non-significant association between SF, FIQ and physical components from Short-Form 36 (p = 0.06). SR was correlated to FIQ (p = 0.01) and catastrophizing (p = 0.05) while CCP was correlated to pain (p = 0.01). The SF cluster identified 3 subgroups with a particular one characterized by normal SF, low pain, high activity and hyperkinesia. The SR cluster identified 2 distinct subgroups: the one with a reduced SR was distinguished by high FIQ

  20. The interest of gait markers in the identification of subgroups among fibromyalgia patients

    Directory of Open Access Journals (Sweden)

    Auvinet Bernard

    2011-11-01

    Full Text Available Abstract Background Fibromyalgia (FM is a heterogeneous syndrome and its classification into subgroups calls for broad-based discussion. FM subgrouping, which aims to adapt treatment according to different subgroups, relies in part, on psychological and cognitive dysfunctions. Since motor control of gait is closely related to cognitive function, we hypothesized that gait markers could be of interest in the identification of FM patients' subgroups. This controlled study aimed at characterizing gait disorders in FM, and subgrouping FM patients according to gait markers such as stride frequency (SF, stride regularity (SR, and cranio-caudal power (CCP which measures kinesia. Methods A multicentre, observational open trial enrolled patients with primary FM (44.1 ± 8.1 y, and matched controls (44.1 ± 7.3 y. Outcome measurements and gait analyses were available for 52 pairs. A 3-step statistical analysis was carried out. A preliminary single blind analysis using k-means cluster was performed as an initial validation of gait markers. Then in order to quantify FM patients according to psychometric and gait variables an open descriptive analysis comparing patients and controls were made, and correlations between gait variables and main outcomes were calculated. Finally using cluster analysis, we described subgroups for each gait variable and looked for significant differences in self-reported assessments. Results SF was the most discriminating gait variable (73% of patients and controls. SF, SR, and CCP were different between patients and controls. There was a non-significant association between SF, FIQ and physical components from Short-Form 36 (p = 0.06. SR was correlated to FIQ (p = 0.01 and catastrophizing (p = 0.05 while CCP was correlated to pain (p = 0.01. The SF cluster identified 3 subgroups with a particular one characterized by normal SF, low pain, high activity and hyperkinesia. The SR cluster identified 2 distinct subgroups: the one with a

  1. Report of the Production and Delivery Subgroup

    Energy Technology Data Exchange (ETDEWEB)

    Glass, R; Zalesky, R

    2004-11-01

    The Production and Delivery Subgroup was tasked with evaluating the various options that could be used for hydrogen production and delivery in terms of availability/industry readiness, technical and economic barriers, and environmental considerations. Hydrogen can be produced using a variety of feedstocks and conversion technologies. The feedstock options include water, natural gas, coal, petroleum, methanol, ethanol, biomass, and organic waste streams. Ultimately, using these domestic resources we will be able to produce all the hydrogen we will need for the complete conversion of our transportation infrastructure. The various conversion technologies include electrolysis, reforming (principally of natural gas, but also ethanol and methanol), photobiological and photoelectrochemical, biofermentation, pyrolysis and gasification of biomass and coal, high temperature thermochemical, and catalytic membranes. All of these production technologies are being actively researched by DOE's Office of Hydrogen, Fuel Cells and Infrastructure Technologies (HFCIT); and other offices within DOE support work that complements the HFCIT Program activities. In addition, private industry is also dedicating significant resources to these efforts. In establishing the California Hydrogen Highway Network (CA H2 Net) we must utilize both distributed (that is, hydrogen that is produced at the point of use) as well as centralized production of hydrogen. Because of technical and economic barriers, most of the technologies for hydrogen production listed above will not become practical for either mode of hydrogen production in large quantities until at least the 2015-2030 timeframe. In the near term, that is, the transitional period between now and 2010 when we will establish a widely available hydrogen fueling infrastructure in California, the distributed production options of reforming and electrolysis will play the dominant role. In addition, production of hydrogen at centralized plants

  2. Cluster analysis

    CERN Document Server

    Everitt, Brian S; Leese, Morven; Stahl, Daniel

    2011-01-01

    Cluster analysis comprises a range of methods for classifying multivariate data into subgroups. By organizing multivariate data into such subgroups, clustering can help reveal the characteristics of any structure or patterns present. These techniques have proven useful in a wide range of areas such as medicine, psychology, market research and bioinformatics.This fifth edition of the highly successful Cluster Analysis includes coverage of the latest developments in the field and a new chapter dealing with finite mixture models for structured data.Real life examples are used throughout to demons

  3. Expression profiling and functional analysis of Populus WRKY23 reveals a regulatory role in defense.

    Science.gov (United States)

    Levée, Valérie; Major, Ian; Levasseur, Caroline; Tremblay, Laurence; MacKay, John; Séguin, Armand

    2009-01-01

    WRKY transcription factors are key regulators that activate and fine-tune stress responses, including defense responses against pathogens. We isolated a poplar (Populus tremulaxPopulus alba) cDNA sequence, PtWRKY23, that encodes the ortholog of Arabidopsis WRKY23 and present the functional analysis of WRKY23, with emphasis on its potential role in resistance to rust infection. To investigate the function of PtWRKY23, we examined PtWRKY23 expression after stress treatments by qRT-PCR and generated PtWRKY23-misexpressing plants. Transgenic plants were assessed for resistance to Melampsora rust and were analyzed using the poplar Affymetrix GeneChip and histological techniques to study the consequences of PtWRKY23 misexpression. PtWRKY23 is rapidly induced by Melampsora infection and elicitor treatments and poplars overexpressing and underexpressing PtWRKY23 were both more susceptible to Melampsora infection than wild type. Transcriptome analysis of PtWRKY23 overexpressors revealed a significant overlap with the Melampsora-infection response. Transcriptome analysis also suggests that PtWRKY23 affects redox homeostasis and cell wall-related metabolism, which was confirmed by analyses that showed that PtWRKY23-misexpressing plants have altered peroxidase activity, apparent H(2)O(2) accumulation and lignin deposition. Our results show that PtWRKY23 affects resistance to Melampsora infection and that this may be caused by deregulation of genes that disrupt redox homeostasis and cell wall metabolism.

  4. Comparative Analysis of 35 Basidiomycete Genomes Reveals Diversity and Uniqueness of the Phylum

    Energy Technology Data Exchange (ETDEWEB)

    Riley, Robert; Salamov, Asaf; Otillar, Robert; Fagnan, Kirsten; Boussau, Bastien; Brown, Daren; Henrissat, Bernard; Levasseur, Anthony; Held, Benjamin; Nagy, Laszlo; Floudas, Dimitris; Morin, Emmanuelle; Manning, Gerard; Baker, Scott; Martin, Francis; Blanchette, Robert; Hibbett, David; Grigoriev, Igor V.

    2013-03-11

    Fungi of the phylum Basidiomycota (basidiomycetes), make up some 37percent of the described fungi, and are important in forestry, agriculture, medicine, and bioenergy. This diverse phylum includes symbionts, pathogens, and saprobes including wood decaying fungi. To better understand the diversity of this phylum we compared the genomes of 35 basidiomycete fungi including 6 newly sequenced genomes. The genomes of basidiomycetes span extremes of genome size, gene number, and repeat content. A phylogenetic tree of Basidiomycota was generated using the Phyldog software, which uses all available protein sequence data to simultaneously infer gene and species trees. Analysis of core genes reveals that some 48percent of basidiomycete proteins are unique to the phylum with nearly half of those (22percent) comprising proteins found in only one organism. Phylogenetic patterns of plant biomass-degrading genes suggest a continuum rather than a sharp dichotomy between the white rot and brown rot modes of wood decay among the members of Agaricomycotina subphylum. There is a correlation of the profile of certain gene families to nutritional mode in Agaricomycotina. Based on phylogenetically-informed PCA analysis of such profiles, we predict that that Botryobasidium botryosum and Jaapia argillacea have properties similar to white rot species, although neither has liginolytic class II fungal peroxidases. Furthermore, we find that both fungi exhibit wood decay with white rot-like characteristics in growth assays. Analysis of the rate of discovery of proteins with no or few homologs suggests the high value of continued sequencing of basidiomycete fungi.

  5. Network analysis reveals that bacteria and fungi form modules that correlate independently with soil parameters.

    Science.gov (United States)

    de Menezes, Alexandre B; Prendergast-Miller, Miranda T; Richardson, Alan E; Toscas, Peter; Farrell, Mark; Macdonald, Lynne M; Baker, Geoff; Wark, Tim; Thrall, Peter H

    2015-08-01

    Network and multivariate statistical analyses were performed to determine interactions between bacterial and fungal community terminal restriction length polymorphisms as well as soil properties in paired woodland and pasture sites. Canonical correspondence analysis (CCA) revealed that shifts in woodland community composition correlated with soil dissolved organic carbon, while changes in pasture community composition correlated with moisture, nitrogen and phosphorus. Weighted correlation network analysis detected two distinct microbial modules per land use. Bacterial and fungal ribotypes did not group separately, rather all modules comprised of both bacterial and fungal ribotypes. Woodland modules had a similar fungal : bacterial ribotype ratio, while in the pasture, one module was fungal dominated. There was no correspondence between pasture and woodland modules in their ribotype composition. The modules had different relationships to soil variables, and these contrasts were not detected without the use of network analysis. This study demonstrated that fungi and bacteria, components of the soil microbial communities usually treated as separate functional groups as in a CCA approach, were co-correlated and formed distinct associations in these adjacent habitats. Understanding these distinct modular associations may shed more light on their niche space in the soil environment, and allow a more realistic description of soil microbial ecology and function. © 2014 Society for Applied Microbiology and John Wiley & Sons Ltd.

  6. Genomic and physiological analysis reveals versatile metabolic capacity of deep-sea Photobacterium phosphoreum ANT-2200.

    Science.gov (United States)

    Zhang, Sheng-Da; Santini, Claire-Lise; Zhang, Wei-Jia; Barbe, Valérie; Mangenot, Sophie; Guyomar, Charlotte; Garel, Marc; Chen, Hai-Tao; Li, Xue-Gong; Yin, Qun-Jian; Zhao, Yuan; Armengaud, Jean; Gaillard, Jean-Charles; Martini, Séverine; Pradel, Nathalie; Vidaud, Claude; Alberto, François; Médigue, Claudine; Tamburini, Christian; Wu, Long-Fei

    2016-05-01

    Bacteria of the genus Photobacterium thrive worldwide in oceans and show substantial eco-physiological diversity including free-living, symbiotic and piezophilic life styles. Genomic characteristics underlying this variability across species are poorly understood. Here we carried out genomic and physiological analysis of Photobacterium phosphoreum strain ANT-2200, the first deep-sea luminous bacterium of which the genome has been sequenced. Using optical mapping we updated the genomic data and reassembled it into two chromosomes and a large plasmid. Genomic analysis revealed a versatile energy metabolic potential and physiological analysis confirmed its growth capacity by deriving energy from fermentation of glucose or maltose, by respiration with formate as electron donor and trimethlyamine N-oxide (TMAO), nitrate or fumarate as electron acceptors, or by chemo-organo-heterotrophic growth in rich media. Despite that it was isolated at a site with saturated dissolved oxygen, the ANT-2200 strain possesses four gene clusters coding for typical anaerobic enzymes, the TMAO reductases. Elevated hydrostatic pressure enhances the TMAO reductase activity, mainly due to the increase of isoenzyme TorA1. The high copy number of the TMAO reductase isoenzymes and pressure-enhanced activity might imply a strategy developed by bacteria to adapt to deep-sea habitats where the instant TMAO availability may increase with depth.

  7. Differential Network Analysis Reveals Evolutionary Complexity in Secondary Metabolism of Rauvolfia serpentina over Catharanthus roseus

    Science.gov (United States)

    Pathania, Shivalika; Bagler, Ganesh; Ahuja, Paramvir S.

    2016-01-01

    Comparative co-expression analysis of multiple species using high-throughput data is an integrative approach to determine the uniformity as well as diversification in biological processes. Rauvolfia serpentina and Catharanthus roseus, both members of Apocyanacae family, are reported to have remedial properties against multiple diseases. Despite of sharing upstream of terpenoid indole alkaloid pathway, there is significant diversity in tissue-specific synthesis and accumulation of specialized metabolites in these plants. This led us to implement comparative co-expression network analysis to investigate the modules and genes responsible for differential tissue-specific expression as well as species-specific synthesis of metabolites. Toward these goals differential network analysis was implemented to identify candidate genes responsible for diversification of metabolites profile. Three genes were identified with significant difference in connectivity leading to differential regulatory behavior between these plants. These genes may be responsible for diversification of secondary metabolism, and thereby for species-specific metabolite synthesis. The network robustness of R. serpentina, determined based on topological properties, was also complemented by comparison of gene-metabolite networks of both plants, and may have evolved to have complex metabolic mechanisms as compared to C. roseus under the influence of various stimuli. This study reveals evolution of complexity in secondary metabolism of R. serpentina, and key genes that contribute toward diversification of specific metabolites. PMID:27588023

  8. Differential network analysis reveals evolutionary complexity in secondary metabolism of Rauvolfia serpentina over Catharanthus roseus

    Directory of Open Access Journals (Sweden)

    Shivalika Pathania

    2016-08-01

    Full Text Available Comparative co-expression analysis of multiple species using high-throughput data is an integrative approach to determine the uniformity as well as diversification in biological processes. Rauvolfia serpentina and Catharanthus roseus, both members of Apocyanacae family, are reported to have remedial properties against multiple diseases. Despite of sharing upstream of terpenoid indole alkaloid pathway, there is significant diversity in tissue-specific synthesis and accumulation of specialized metabolites in these plants. This led us to implement comparative co-expression network analysis to investigate the modules and genes responsible for differential tissue-specific expression as well as species-specific synthesis of metabolites. Towards these goals differential network analysis was implemented to identify candidate genes responsible for diversification of metabolites profile. Three genes were identified with significant difference in connectivity leading to differential regulatory behavior between these plants. These mechanisms may be responsible for diversification of secondary metabolism, and thereby for species-specific metabolite synthesis. The network robustness of R. serpentina, determined based on topological properties, was also complemented by comparison of gene-metabolite networks of both plants, and may have evolved to have complex metabolic mechanisms as compared to C. roseus under the influence of various stimuli. This study reveals evolution of complexity in secondary metabolism of Rauvolfia serpentina, and key genes that contribute towards diversification of specific metabolites.

  9. Comprehensive DNA Adduct Analysis Reveals Pulmonary Inflammatory Response Contributes to Genotoxic Action of Magnetite Nanoparticles

    Directory of Open Access Journals (Sweden)

    Kousuke Ishino

    2015-02-01

    Full Text Available Nanosized-magnetite (MGT is widely utilized in medicinal and industrial fields; however, its toxicological properties are not well documented. In our previous report, MGT showed genotoxicity in both in vitro and in vivo assay systems, and it was suggested that inflammatory responses exist behind the genotoxicity. To further clarify mechanisms underlying the genotoxicity, a comprehensive DNA adduct (DNA adductome analysis was conducted using DNA samples derived from the lungs of mice exposed to MGT. In total, 30 and 42 types of DNA adducts were detected in the vehicle control and MGT-treated groups, respectively. Principal component analysis (PCA against a subset of DNA adducts was applied and several adducts, which are deduced to be formed by inflammation or oxidative stress, as the case of etheno-deoxycytidine (εdC, revealed higher contributions to MGT exposure. By quantitative-LC-MS/MS analysis, εdC levels were significantly higher in MGT-treated mice than those of the vehicle control. Taken together with our previous data, it is suggested that inflammatory responses might be involved in the genotoxicity induced by MGT in the lungs of mice.

  10. Multiple maternal origins of Indonesian crowing chickens revealed by mitochondrial DNA analysis.

    Science.gov (United States)

    Ulfah, Maria; Perwitasari, Dyah; Jakaria, Jakaria; Muladno, Muhammad; Farajallah, Achmad

    2017-03-01

    The utilization of Indonesian crowing chickens is increasing; as such, assessing their genetic structures is important to support the conservation of their genetic resources. This study analyzes the matrilineal evolution of Indonesian crowing chickens based on the mtDNA displacement loop D-loop region to clarify their phylogenetic relationships, possible maternal origin, and possible routes of chicken dispersal. The neighbor-joining tree reveals that the majority of Indonesian crowing chickens belong to haplogroups B, D, and E, but haplogroup D harbored most of them. The Bayesian analysis also reveals that Indonesian crowing chickens derive from Bekisar chicken, a hybrid of the green junglefowl, suggesting the possible contribution of green junglefowl to chicken domestication. There appear at least three maternal lineages of Indonesian chicken origins indicated by the median network profile of mtDNA D-loop haplotypes, namely (1) Chinese; (2) Chinese, Indian, and other Southeast Asian chickens; and (3) Indian, Chinese, Southeast Asian, Japanese, and European chickens. Chicken domestication might be centered in China, India, Indonesia, and other Southeast Asian countries, supporting multiple maternal origins of Indonesian crowing chickens. A systematic breeding program of indigenous chickens will be very important to retain the genetic diversity for future use and conservation.

  11. Dependency Network Analysis (DEPNA) Reveals Context Related Influence of Brain Network Nodes.

    Science.gov (United States)

    Jacob, Yael; Winetraub, Yonatan; Raz, Gal; Ben-Simon, Eti; Okon-Singer, Hadas; Rosenberg-Katz, Keren; Hendler, Talma; Ben-Jacob, Eshel

    2016-06-07

    Communication between and within brain regions is essential for information processing within functional networks. The current methods to determine the influence of one region on another are either based on temporal resolution, or require a predefined model for the connectivity direction. However these requirements are not always achieved, especially in fMRI studies, which have poor temporal resolution. We thus propose a new graph theory approach that focuses on the correlation influence between selected brain regions, entitled Dependency Network Analysis (DEPNA). Partial correlations are used to quantify the level of influence of each node during task performance. As a proof of concept, we conducted the DEPNA on simulated datasets and on two empirical motor and working memory fMRI tasks. The simulations revealed that the DEPNA correctly captures the network's hierarchy of influence. Applying DEPNA to the functional tasks reveals the dynamics between specific nodes as would be expected from prior knowledge. To conclude, we demonstrate that DEPNA can capture the most influencing nodes in the network, as they emerge during specific cognitive processes. This ability opens a new horizon for example in delineating critical nodes for specific clinical interventions.

  12. Novel molecular subgroups for clinical classification and outcome prediction in childhood medulloblastoma: a cohort study.

    Science.gov (United States)

    Schwalbe, Edward C; Lindsey, Janet C; Nakjang, Sirintra; Crosier, Stephen; Smith, Amanda J; Hicks, Debbie; Rafiee, Gholamreza; Hill, Rebecca M; Iliasova, Alice; Stone, Thomas; Pizer, Barry; Michalski, Antony; Joshi, Abhijit; Wharton, Stephen B; Jacques, Thomas S; Bailey, Simon; Williamson, Daniel; Clifford, Steven C

    2017-07-01

    International consensus recognises four medulloblastoma molecular subgroups: WNT (MBWNT), SHH (MBSHH), group 3 (MBGrp3), and group 4 (MBGrp4), each defined by their characteristic genome-wide transcriptomic and DNA methylomic profiles. These subgroups have distinct clinicopathological and molecular features, and underpin current disease subclassification and initial subgroup-directed therapies that are underway in clinical trials. However, substantial biological heterogeneity and differences in survival are apparent within each subgroup, which remain to be resolved. We aimed to investigate whether additional molecular subgroups exist within childhood medulloblastoma and whether these could be used to improve disease subclassification and prognosis predictions. In this retrospective cohort study, we assessed 428 primary medulloblastoma samples collected from UK Children's Cancer and Leukaemia Group (CCLG) treatment centres (UK), collaborating European institutions, and the UKCCSG-SIOP-PNET3 European clinical trial. An independent validation cohort (n=276) of archival tumour samples was also analysed. We analysed samples from patients with childhood medulloblastoma who were aged 0-16 years at diagnosis, and had central review of pathology and comprehensive clinical data. We did comprehensive molecular profiling, including DNA methylation microarray analysis, and did unsupervised class discovery of test and validation cohorts to identify consensus primary molecular subgroups and characterise their clinical and biological significance. We modelled survival of patients aged 3-16 years in patients (n=215) who had craniospinal irradiation and had been treated with a curative intent. Seven robust and reproducible primary molecular subgroups of childhood medulloblastoma were identified. MBWNT remained unchanged and each remaining consensus subgroup was split in two. MBSHH was split into age-dependent subgroups corresponding to infant (<4·3 years; MBSHH-Infant; n=65) and

  13. Bifidobacterium asteroides PRL2011 genome analysis reveals clues for colonization of the insect gut.

    Science.gov (United States)

    Bottacini, Francesca; Milani, Christian; Turroni, Francesca; Sánchez, Borja; Foroni, Elena; Duranti, Sabrina; Serafini, Fausta; Viappiani, Alice; Strati, Francesco; Ferrarini, Alberto; Delledonne, Massimo; Henrissat, Bernard; Coutinho, Pedro; Fitzgerald, Gerald F; Margolles, Abelardo; van Sinderen, Douwe; Ventura, Marco

    2012-01-01

    Bifidobacteria are known as anaerobic/microaerophilic and fermentative microorganisms, which commonly inhabit the gastrointestinal tract of various animals and insects. Analysis of the 2,167,301 bp genome of Bifidobacterium asteroides PRL2011, a strain isolated from the hindgut of Apis mellifera var. ligustica, commonly known as the honey bee, revealed its predicted capability for respiratory metabolism. Conservation of the latter gene clusters in various B. asteroides strains enforces the notion that respiration is a common metabolic feature of this ancient bifidobacterial species, which has been lost in currently known mammal-derived Bifidobacterium species. In fact, phylogenomic based analyses suggested an ancient origin of B. asteroides and indicates it as an ancestor of the genus Bifidobacterium. Furthermore, the B. asteroides PRL2011 genome encodes various enzymes for coping with toxic products that arise as a result of oxygen-mediated respiration.

  14. Microarray analysis reveals novel features of the muscle aging process in men and women.

    Science.gov (United States)

    Liu, Dongmei; Sartor, Maureen A; Nader, Gustavo A; Pistilli, Emidio E; Tanton, Leah; Lilly, Charles; Gutmann, Laurie; IglayReger, Heidi B; Visich, Paul S; Hoffman, Eric P; Gordon, Paul M

    2013-09-01

    To develop a global view of muscle transcriptional differences between older men and women and sex-specific aging, we obtained muscle biopsies from the biceps brachii of young and older men and women and profiled the whole-genome gene expression using microarray. A logistic regression-based method in combination with an intensity-based Bayesian moderated t test was used to identify significant sex- and aging-related gene functional groups. Our analysis revealed extensive sex differences in the muscle transcriptome of older individuals and different patterns of transcriptional changes with aging in men and women. In older women, we observed a coordinated transcriptional upregulation of immune activation, extracellular matrix remodeling, and lipids storage; and a downregulation of mitochondrial biogenesis and function and muscle regeneration. The effect of aging results in sexual dimorphic alterations in the skeletal muscle transcriptome, which may modify the risk for developing musculoskeletal and metabolic diseases in men and women.

  15. Peptidomic analysis reveals proteolytic activity of kefir microorganisms on bovine milk proteins.

    Science.gov (United States)

    Dallas, David C; Citerne, Florine; Tian, Tian; Silva, Vitor L M; Kalanetra, Karen M; Frese, Steven A; Robinson, Randall C; Mills, David A; Barile, Daniela

    2016-04-15

    The microorganisms that make up kefir grains are well known for lactose fermentation, but the extent to which they hydrolyze and consume milk proteins remains poorly understood. Peptidomics technologies were used to examine the proteolytic activity of kefir grains on bovine milk proteins. Gel electrophoresis revealed substantial digestion of milk proteins by kefir grains, with mass spectrometric analysis showing the release of 609 protein fragments and alteration of the abundance of >1500 peptides that derived from 27 milk proteins. Kefir contained 25 peptides identified from the literature as having biological activity, including those with antihypertensive, antimicrobial, immunomodulatory, opioid and anti-oxidative functions. 16S rRNA and shotgun metagenomic sequencing identified the principle taxa in the culture as Lactobacillus species. The model kefir sample contained thousands of protein fragments released in part by kefir microorganisms and in part by native milk proteases. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Proteomics analysis reveals a dynamic diurnal pattern of photosynthesis-related pathways in maize leaves.

    Science.gov (United States)

    Feng, Dan; Wang, Yanwei; Lu, Tiegang; Zhang, Zhiguo; Han, Xiao

    2017-01-01

    Plant leaves exhibit differentiated patterns of photosynthesis rates under diurnal light regulation. Maize leaves show a single-peak pattern without photoinhibition at midday when the light intensity is maximized. This mechanism contributes to highly efficient photosynthesis in maize leaves. To understand the molecular basis of this process, an isobaric tag for relative and absolute quantitation (iTRAQ)-based proteomics analysis was performed to reveal the dynamic pattern of proteins related to photosynthetic reactions. Steady, single-peak and double-peak protein expression patterns were discovered in maize leaves, and antenna proteins in these leaves displayed a steady pattern. In contrast, the photosystem, carbon fixation and citrate pathways were highly controlled by diurnal light intensity. Most enzymes in the limiting steps of these pathways were major sites of regulation. Thus, maize leaves optimize photosynthesis and carbon fixation outside of light harvesting to adapt to the changes in diurnal light intensity at the protein level.

  17. Bifidobacterium asteroides PRL2011 genome analysis reveals clues for colonization of the insect gut.

    Directory of Open Access Journals (Sweden)

    Francesca Bottacini

    Full Text Available Bifidobacteria are known as anaerobic/microaerophilic and fermentative microorganisms, which commonly inhabit the gastrointestinal tract of various animals and insects. Analysis of the 2,167,301 bp genome of Bifidobacterium asteroides PRL2011, a strain isolated from the hindgut of Apis mellifera var. ligustica, commonly known as the honey bee, revealed its predicted capability for respiratory metabolism. Conservation of the latter gene clusters in various B. asteroides strains enforces the notion that respiration is a common metabolic feature of this ancient bifidobacterial species, which has been lost in currently known mammal-derived Bifidobacterium species. In fact, phylogenomic based analyses suggested an ancient origin of B. asteroides and indicates it as an ancestor of the genus Bifidobacterium. Furthermore, the B. asteroides PRL2011 genome encodes various enzymes for coping with toxic products that arise as a result of oxygen-mediated respiration.

  18. Global analysis of asymmetric RNA enrichment in oocytes reveals low conservation between closely related Xenopus species

    Science.gov (United States)

    Claußen, Maike; Lingner, Thomas; Pommerenke, Claudia; Opitz, Lennart; Salinas, Gabriela; Pieler, Tomas

    2015-01-01

    RNAs that localize to the vegetal cortex during Xenopus laevis oogenesis have been reported to function in germ layer patterning, axis determination, and development of the primordial germ cells. Here we report on the genome-wide, comparative analysis of differentially localizing RNAs in Xenopus laevis and Xenopus tropicalis oocytes, revealing a surprisingly weak degree of conservation in respect to the identity of animally as well as vegetally enriched transcripts in these closely related species. Heterologous RNA injections and protein binding studies indicate that the different RNA localization patterns in these two species are due to gain/loss of cis-acting localization signals rather than to differences in the RNA-localizing machinery. PMID:26337391

  19. Conformational Dynamics of apo-GlnBP Revealed by Experimental and Computational Analysis

    KAUST Repository

    Feng, Yitao

    2016-10-13

    The glutamine binding protein (GlnBP) binds l-glutamine and cooperates with its cognate transporters during glutamine uptake. Crystal structure analysis has revealed an open and a closed conformation for apo- and holo-GlnBP, respectively. However, the detailed conformational dynamics have remained unclear. Herein, we combined NMR spectroscopy, MD simulations, and single-molecule FRET techniques to decipher the conformational dynamics of apo-GlnBP. The NMR residual dipolar couplings of apo-GlnBP were in good agreement with a MD-derived structure ensemble consisting of four metastable states. The open and closed conformations are the two major states. This four-state model was further validated by smFRET experiments and suggests the conformational selection mechanism in ligand recognition of GlnBP. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

  20. Cluster analysis reveals risk factors for repeated suicide attempts in a multi-ethnic Asian population.

    Science.gov (United States)

    Choo, Carol; Diederich, Joachim; Song, Insu; Ho, Roger

    2014-04-01

    This study explores underlying patterns in suicide risk factors using data mining techniques. Medical records of suicide attempters who were admitted to a teaching hospital in January 2004 - December 2006 were studied. Cluster analysis revealed hidden patterns for repeated and single attempters (n=418). Repeated attempters had a more complex clinical picture. Symptoms of psychotic illness, borderline personality disorder, and psychosomatic complaints of insomnia and headaches, reports of adverse life events such as unemployment, divorce and quarrels, experience of negative feelings, and usage of alcohol were associated with risk of repeated overdoses with benzodiazepines and paracetamol. The findings have implications for suicide assessments and interventions. Copyright © 2013 Elsevier B.V. All rights reserved.

  1. EEG Cortical Connectivity Analysis of Working Memory Reveals Topological Reorganization in Theta and Alpha Bands

    Directory of Open Access Journals (Sweden)

    Zhongxiang Dai

    2017-05-01

    Full Text Available Numerous studies have revealed various working memory (WM-related brain activities that originate from various cortical regions and oscillate at different frequencies. However, multi-frequency band analysis of the brain network in WM in the cortical space remains largely unexplored. In this study, we employed a graph theoretical framework to characterize the topological properties of the brain functional network in the theta and alpha frequency bands during WM tasks. Twenty-eight subjects performed visual n-back tasks at two difficulty levels, i.e., 0-back (control task and 2-back (WM task. After preprocessing, Electroencephalogram (EEG signals were projected into the source space and 80 cortical brain regions were selected for further analysis. Subsequently, the theta- and alpha-band networks were constructed by calculating the Pearson correlation coefficients between the power series (obtained by concatenating the power values of all epochs in each session of all pairs of brain regions. Graph theoretical approaches were then employed to estimate the topological properties of the brain networks at different WM tasks. We found higher functional integration in the theta band and lower functional segregation in the alpha band in the WM task compared with the control task. Moreover, compared to the 0-back task, altered regional centrality was revealed in the 2-back task in various brain regions that mainly resided in the frontal, temporal and occipital lobes, with distinct presentations in the theta and alpha bands. In addition, significant negative correlations were found between the reaction time with the average path length of the theta-band network and the local clustering of the alpha-band network, which demonstrates the potential for using the brain network metrics as biomarkers for predicting the task performance during WM tasks.

  2. Comparative transcriptional analysis reveals differential gene expression between asymmetric and symmetric zygotic divisions in tobacco.

    Directory of Open Access Journals (Sweden)

    Tian-Xiang Hu

    Full Text Available Asymmetric cell divisions occur widely during many developmental processes in plants. In most angiosperms, the first zygotic cell division is asymmetric resulting in two daughter cells of unequal size and with distinct fates. However, the critical molecular mechanisms regulating this division remain unknown. Previously we showed that treatment of tobacco zygotes with beta-glucosyl Yariv (βGlcY could dramatically alter the first zygotic asymmetric division to produce symmetric two-celled proembryos. In the present study, we isolated zygotes and two-celled asymmetric proembryos in vivo by micromanipulation, and obtained symmetric, two-celled proembryos by in vitro cell cultures. Using suppression-subtractive hybridization (SSH and macroarray analysis differential gene expression between the zygote and the asymmetric and symmetric two-celled proembryos was investigated. After sequencing of the differentially expressed clones, a total of 1610 EST clones representing 685 non-redundant transcripts were obtained. Gene ontology (GO term analysis revealed that these transcripts include those involved in physiological processes such as response to stimulus, regulation of gene expression, and localization and formation of anatomical structures. A homology search against known genes from Arabidopsis indicated that some of the above transcripts are involved in asymmetric cell division and embryogenesis. Quantitative real-time PCR confirmed the up- or down-regulation of the selected candidate transcripts during zygotic division. A few of these transcripts were expressed exclusively in the zygote, or in either type of the two-celled proembryos. Expression analyses of select genes in different tissues and organs also revealed potential roles of these transcripts in fertilization, seed maturation and organ development. The putative roles of few of the identified transcripts in the regulation of zygotic division are discussed. Further functional work on these

  3. Comparative transcriptomic analysis reveals similarities and dissimilarities in Saccharomyces cerevisiae wine strains response to nitrogen availability.

    Directory of Open Access Journals (Sweden)

    Catarina Barbosa

    Full Text Available Nitrogen levels in grape-juices are of major importance in winemaking ensuring adequate yeast growth and fermentation performance. Here we used a comparative transcriptome analysis to uncover wine yeasts responses to nitrogen availability during fermentation. Gene expression was assessed in three genetically and phenotypically divergent commercial wine strains (CEG, VL1 and QA23, under low (67 mg/L and high nitrogen (670 mg/L regimes, at three time points during fermentation (12 h, 24 h and 96 h. Two-way ANOVA analysis of each fermentation condition led to the identification of genes whose expression was dependent on strain, fermentation stage and on the interaction of both factors. The high fermenter yeast strain QA23 was more clearly distinct from the other two strains, by differential expression of genes involved in flocculation, mitochondrial functions, energy generation and protein folding and stabilization. For all strains, higher transcriptional variability due to fermentation stage was seen in the high nitrogen fermentations. A positive correlation between maximum fermentation rate and the expression of genes involved in stress response was observed. The finding of common genes correlated with both fermentation activity and nitrogen up-take underlies the role of nitrogen on yeast fermentative fitness. The comparative analysis of genes differentially expressed between both fermentation conditions at 12 h, where the main difference was the level of nitrogen available, showed the highest variability amongst strains revealing strain-specific responses. Nevertheless, we were able to identify a small set of genes whose expression profiles can quantitatively assess the common response of the yeast strains to varying nitrogen conditions. The use of three contrasting yeast strains in gene expression analysis prompts the identification of more reliable, accurate and reproducible biomarkers that will facilitate the diagnosis of deficiency of this

  4. Comparative Transcriptomic Analysis Reveals Similarities and Dissimilarities in Saccharomyces cerevisiae Wine Strains Response to Nitrogen Availability

    Science.gov (United States)

    Barbosa, Catarina; García-Martínez, José; Pérez-Ortín, José E.; Mendes-Ferreira, Ana

    2015-01-01

    Nitrogen levels in grape-juices are of major importance in winemaking ensuring adequate yeast growth and fermentation performance. Here we used a comparative transcriptome analysis to uncover wine yeasts responses to nitrogen availability during fermentation. Gene expression was assessed in three genetically and phenotypically divergent commercial wine strains (CEG, VL1 and QA23), under low (67 mg/L) and high nitrogen (670 mg/L) regimes, at three time points during fermentation (12h, 24h and 96h). Two-way ANOVA analysis of each fermentation condition led to the identification of genes whose expression was dependent on strain, fermentation stage and on the interaction of both factors. The high fermenter yeast strain QA23 was more clearly distinct from the other two strains, by differential expression of genes involved in flocculation, mitochondrial functions, energy generation and protein folding and stabilization. For all strains, higher transcriptional variability due to fermentation stage was seen in the high nitrogen fermentations. A positive correlation between maximum fermentation rate and the expression of genes involved in stress response was observed. The finding of common genes correlated with both fermentation activity and nitrogen up-take underlies the role of nitrogen on yeast fermentative fitness. The comparative analysis of genes differentially expressed between both fermentation conditions at 12h, where the main difference was the level of nitrogen available, showed the highest variability amongst strains revealing strain-specific responses. Nevertheless, we were able to identify a small set of genes whose expression profiles can quantitatively assess the common response of the yeast strains to varying nitrogen conditions. The use of three contrasting yeast strains in gene expression analysis prompts the identification of more reliable, accurate and reproducible biomarkers that will facilitate the diagnosis of deficiency of this nutrient in the grape

  5. Breast Cancer Prevalence and Mortality among Hispanic Subgroups in the United States, 2009–2013

    Directory of Open Access Journals (Sweden)

    Bijou R. Hunt

    2016-01-01

    Full Text Available Background. This paper presents data on breast cancer prevalence and mortality among US Hispanics and Hispanic subgroups, including Cuban, Mexican, Puerto Rican, Central American, and South American. Methods. Five-year average annual female breast cancer prevalence and mortality rates for 2009–2013 were examined using data from the National Health Interview Survey (prevalence and the National Center for Health Statistics and the American Community Survey (mortality rates. Results. Overall breast cancer prevalence among US Hispanic women was 1.03%. Although the estimates varied slightly by Hispanic subgroup, these differences were not statistically significant. The breast cancer mortality rate for Hispanics overall was 17.71 per 100,000 women. Higher rates were observed among Cubans (17.89, Mexicans (18.78, and Puerto Ricans (19.04, and a lower rate was observed among Central and South Americans (10.15. With the exception of the rate for Cubans, all Hispanic subgroup rates were statistically significantly different from the overall Hispanic rate. Additionally, all Hispanic subgroups rates were statistically significantly higher than the Central and South American rate. Conclusion. The data reveal significant differences in mortality across Hispanic subgroups. These data enable public health officials to develop targeted interventions to help lower breast cancer mortality among the highest risk populations.

  6. Intraspecific Variation and Phylogenetic Relationships Are Revealed by ITS1 Secondary Structure Analysis and Single-Nucleotide Polymorphism in Ganoderma lucidum.

    Directory of Open Access Journals (Sweden)

    Xiuqing Zhang

    Full Text Available Ganoderma lucidum is a typical polypore fungus used for traditional Chinese medical purposes. The taxonomic delimitation of Ganoderma lucidum is still debated. In this study, we sequenced seven internal transcribed spacer (ITS sequences of Ganoderma lucidum strains and annotated the ITS1 and ITS2 regions. Phylogenetic analysis of ITS1 differentiated the strains into three geographic groups. Groups 1-3 were originated from Europe, tropical Asia, and eastern Asia, respectively. While ITS2 could only differentiate the strains into two groups in which Group 2 originated from tropical Asia gathered with Groups 1 and 3 originated from Europe and eastern Asia. By determining the secondary structures of the ITS1 sequences, these three groups exhibited similar structures with a conserved central core and differed helices. While compared to Group 2, Groups 1 and 3 of ITS2 sequences shared similar structures with the difference in helix 4. Large-scale evaluation of ITS1 and ITS2 both exhibited that the majority of subgroups in the same group shared the similar structures. Further Weblogo analysis of ITS1 sequences revealed two main variable regions located in helix 2 in which C/T or A/G substitutions frequently occurred and ITS1 exhibited more nucleotide variances compared to ITS2. ITS1 multi-alignment of seven spawn strains and culture tests indicated that a single-nucleotide polymorphism (SNP site at position 180 correlated with strain antagonism. The HZ, TK and 203 fusion strains of Ganoderma lucidum had a T at position 180, whereas other strains exhibiting antagonism, including DB, RB, JQ, and YS, had a C. Taken together, compared to ITS2 region, ITS1 region could differentiated Ganoderma lucidum into three geographic originations based on phylogenetic analysis and secondary structure prediction. Besides, a SNP in ITS 1 could delineate Ganoderma lucidum strains at the intraspecific level. These findings will be implemented to improve species quality

  7. Intraspecific Variation and Phylogenetic Relationships Are Revealed by ITS1 Secondary Structure Analysis and Single-Nucleotide Polymorphism in Ganoderma lucidum

    Science.gov (United States)

    Pei, Haisheng; Chen, Zhou; Tan, Xiaoyan; Hu, Jing; Yang, Bin; Sun, Junshe

    2017-01-01

    Ganoderma lucidum is a typical polypore fungus used for traditional Chinese medical purposes. The taxonomic delimitation of Ganoderma lucidum is still debated. In this study, we sequenced seven internal transcribed spacer (ITS) sequences of Ganoderma lucidum strains and annotated the ITS1 and ITS2 regions. Phylogenetic analysis of ITS1 differentiated the strains into three geographic groups. Groups 1–3 were originated from Europe, tropical Asia, and eastern Asia, respectively. While ITS2 could only differentiate the strains into two groups in which Group 2 originated from tropical Asia gathered with Groups 1 and 3 originated from Europe and eastern Asia. By determining the secondary structures of the ITS1 sequences, these three groups exhibited similar structures with a conserved central core and differed helices. While compared to Group 2, Groups 1 and 3 of ITS2 sequences shared similar structures with the difference in helix 4. Large-scale evaluation of ITS1 and ITS2 both exhibited that the majority of subgroups in the same group shared the similar structures. Further Weblogo analysis of ITS1 sequences revealed two main variable regions located in helix 2 in which C/T or A/G substitutions frequently occurred and ITS1 exhibited more nucleotide variances compared to ITS2. ITS1 multi-alignment of seven spawn strains and culture tests indicated that a single-nucleotide polymorphism (SNP) site at position 180 correlated with strain antagonism. The HZ, TK and 203 fusion strains of Ganoderma lucidum had a T at position 180, whereas other strains exhibiting antagonism, including DB, RB, JQ, and YS, had a C. Taken together, compared to ITS2 region, ITS1 region could differentiated Ganoderma lucidum into three geographic originations based on phylogenetic analysis and secondary structure prediction. Besides, a SNP in ITS 1 could delineate Ganoderma lucidum strains at the intraspecific level. These findings will be implemented to improve species quality control in the

  8. A comparison of three clustering methods for finding subgroups in MRI, SMS or clinical data

    DEFF Research Database (Denmark)

    Kent, Peter; Jensen, Rikke K; Kongsted, Alice

    2014-01-01

    intensity data collected for 52 weeks by text (SMS) messaging (n = 1,121 people), and the last dataset contained a range of clinical variables measured in low back pain patients (n = 543 people). Four artificial datasets (n = 1,000 each) containing subgroups of varying complexity were also analysed testing......BACKGROUND: There are various methodological approaches to identifying clinically important subgroups and one method is to identify clusters of characteristics that differentiate people in cross-sectional and/or longitudinal data using Cluster Analysis (CA) or Latent Class Analysis (LCA...

  9. Social Network Analysis: Applied Tool to Enhance Effective Collaboration between Child Protection Organisations by Revealing and Strengthening Work Relationships

    National Research Council Canada - National Science Library

    Beáta Dávid

    2013-01-01

    .... The qualitative approach was complemented by social network analysis. Revealing the mechanism based on the actors' perception on how the child protection network operates, we identifi ed and named the strengths and weaknesses of its structure...

  10. Analysis of wheat SAGE tags reveals evidence for widespread antisense transcription

    Directory of Open Access Journals (Sweden)

    Gibbings J George

    2008-10-01

    role in the regulation of gene expression. Conclusion Our results indicate that the detailed analysis of transcriptome data, such as SAGE tags, is essential to understand fully the factors that regulate gene expression and that such analysis of the wheat grain transcriptome reveals that antisense transcripts maybe widespread and hence probably play a significant role in the regulation of gene expression during grain development.

  11. Comparative Metagenomic Analysis Reveals Mechanisms for Stress Response in Hypoliths from Extreme Hyperarid Deserts

    Science.gov (United States)

    Le, Phuong Thi; Makhalanyane, Thulani P.; Guerrero, Leandro D.; Vikram, Surendra; Van de Peer, Yves; Cowan, Don A.

    2016-01-01

    Abstract Understanding microbial adaptation to environmental stressors is crucial for interpreting broader ecological patterns. In the most extreme hot and cold deserts, cryptic niche communities are thought to play key roles in ecosystem processes and represent excellent model systems for investigating microbial responses to environmental stressors. However, relatively little is known about the genetic diversity underlying such functional processes in climatically extreme desert systems. This study presents the first comparative metagenome analysis of cyanobacteria-dominated hypolithic communities in hot (Namib Desert, Namibia) and cold (Miers Valley, Antarctica) hyperarid deserts. The most abundant phyla in both hypolith metagenomes were Actinobacteria, Proteobacteria, Cyanobacteria and Bacteroidetes with Cyanobacteria dominating in Antarctic hypoliths. However, no significant differences between the two metagenomes were identified. The Antarctic hypolithic metagenome displayed a high number of sequences assigned to sigma factors, replication, recombination and repair, translation, ribosomal structure, and biogenesis. In contrast, the Namib Desert metagenome showed a high abundance of sequences assigned to carbohydrate transport and metabolism. Metagenome data analysis also revealed significant divergence in the genetic determinants of amino acid and nucleotide metabolism between these two metagenomes and those of soil from other polar deserts, hot deserts, and non-desert soils. Our results suggest extensive niche differentiation in hypolithic microbial communities from these two extreme environments and a high genetic capacity for survival under environmental extremes. PMID:27503299

  12. Bioinformatic and proteomic analysis of bulk histones reveals PTM crosstalk and chromatin features.

    Science.gov (United States)

    Zhang, Chunchao; Gao, Shan; Molascon, Anthony J; Wang, Zhe; Gorovsky, Martin A; Liu, Yifan; Andrews, Philip C

    2014-07-03

    Systems analysis of chromatin has been constrained by complex patterns and dynamics of histone post-translational modifications (PTMs), which represent major challenges for both mass spectrometry (MS) and immuno-based approaches (e.g., chromatin immuno-precipitation, ChIP). Here we present a proof-of-concept study demonstrating that crosstalk among PTMs and their functional significance can be revealed via systematic bioinformatic and proteomic analysis of steady-state histone PTM levels from cells under various perturbations. Using high resolution tandem MS, we quantified 53 modification states from all core histones and their conserved variants in the unicellular eukaryotic model organism Tetrahymena. By correlating histone PTM patterns across 15 different conditions, including various physiological states and mutations of key histone modifying enzymes, we identified 5 specific chromatin states with characteristic covarying histone PTMs and associated them with distinctive functions in replication, transcription, and DNA repair. In addition to providing a detailed picture on histone PTM crosstalk at global levels, this work has established a novel bioinformatic and proteomic approach, which can be adapted to other organisms and readily scaled up to allow increased resolution of chromatin states.

  13. Arsenic metabolism in high altitude modern stromatolites revealed by metagenomic analysis.

    Science.gov (United States)

    Kurth, Daniel; Amadio, Ariel; Ordoñez, Omar F; Albarracín, Virginia H; Gärtner, Wolfgang; Farías, María E

    2017-04-21

    Modern stromatolites thrive only in selected locations in the world. Socompa Lake, located in the Andean plateau at 3570 masl, is one of the numerous extreme Andean microbial ecosystems described over recent years. Extreme environmental conditions include hypersalinity, high UV incidence, and high arsenic content, among others. After Socompa's stromatolite microbial communities were analysed by metagenomic DNA sequencing, taxonomic classification showed dominance of Proteobacteria, Bacteroidetes and Firmicutes, and a remarkably high number of unclassified sequences. A functional analysis indicated that carbon fixation might occur not only by the Calvin-Benson cycle, but also through alternative pathways such as the reverse TCA cycle, and the reductive acetyl-CoA pathway. Deltaproteobacteria were involved both in sulfate reduction and nitrogen fixation. Significant differences were found when comparing the Socompa stromatolite metagenome to the Shark Bay (Australia) smooth mat metagenome: namely, those involving stress related processes, particularly, arsenic resistance. An in-depth analysis revealed a surprisingly diverse metabolism comprising all known types of As resistance and energy generating pathways. While the ars operon was the main mechanism, an important abundance of arsM genes was observed in selected phyla. The data resulting from this work will prove a cornerstone for further studies on this rare microbial community.

  14. Proteogenomic analysis reveals unanticipated adaptations of colorectal tumor cells to deficiencies in DNA mismatch repair.

    Science.gov (United States)

    Halvey, Patrick J; Wang, Xiaojing; Wang, Jing; Bhat, Ajaz A; Dhawan, Punita; Li, Ming; Zhang, Bing; Liebler, Daniel C; Slebos, Robbert J C

    2014-01-01

    A growing body of genomic data on human cancers poses the critical question of how genomic variations translate to cancer phenotypes. We used standardized shotgun proteomics and targeted protein quantitation platforms to analyze a panel of 10 colon cancer cell lines differing by mutations in DNA mismatch repair (MMR) genes. In addition, we performed transcriptome sequencing (RNA-seq) to enable detection of protein sequence variants from the proteomic data. Biologic replicate cultures yielded highly consistent proteomic inventories with a cumulative total of 6,513 protein groups with a protein false discovery rate of 3.17% across all cell lines. Networks of coexpressed proteins with differential expression based on MMR status revealed impact on protein folding, turnover and transport, on cellular metabolism and on DNA and RNA synthesis and repair. Analysis of variant amino acid sequences suggested higher stability of proteins affected by naturally occurring germline polymorphisms than of proteins affected by somatic protein sequence changes. The data provide evidence for multisystem adaptation to MMR deficiency with a stress response that targets misfolded proteins for degradation through the ubiquitin-dependent proteasome pathway. Enrichment analysis suggested epithelial-to-mesenchymal transition in RKO cells, as evidenced by increased mobility and invasion properties compared with SW480. The observed proteomic profiles demonstrate previously unknown consequences of altered DNA repair and provide an expanded basis for mechanistic interpretation of MMR phenotypes.

  15. Comparative Transcriptome Analysis Reveals Different Silk Yields of Two Silkworm Strains.

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    Juan Li

    Full Text Available Cocoon and silk yields are the most important characteristics of sericulture. However, few studies have examined the genes that modulate these features. Further studies of these genes will be useful for improving the products of sericulture. JingSong (JS and Lan10 (L10 are two strains having significantly different cocoon and silk yields. In the current study, RNA-Seq and quantitative polymerase chain reaction (qPCR were performed on both strains in order to determine divergence of the silk gland, which controls silk biosynthesis in silkworms. Compared with L10, JS had 1375 differentially expressed genes (DEGs; 738 up-regulated genes and 673 down-regulated genes. Nine enriched gene ontology (GO terms were identified by GO enrichment analysis based on these DEGs. KEGG enrichment analysis results showed that the DEGs were enriched in three pathways, which were mainly associated with the processing and biosynthesis of proteins. The representative genes in the enrichment pathways and ten significant DEGs were further verified by qPCR, the results of which were consistent with the RNA-Seq data. Our study has revealed differences in silk glands between the two silkworm strains and provides a perspective for understanding the molecular mechanisms determining silk yield.

  16. Genetic analysis of hyperemesis gravidarum reveals association with intracellular calcium release channel (RYR2).

    Science.gov (United States)

    Fejzo, Marlena Schoenberg; Myhre, Ronny; Colodro-Conde, Lucía; MacGibbon, Kimber W; Sinsheimer, Janet S; Reddy, M V Prasad Linga; Pajukanta, Päivi; Nyholt, Dale R; Wright, Margaret J; Martin, Nicholas G; Engel, Stephanie M; Medland, Sarah E; Magnus, Per; Mullin, Patrick M

    2017-01-05

    Hyperemesis Gravidarum (HG), severe nausea/vomiting in pregnancy (NVP), can cause poor maternal/fetal outcomes. Genetic predisposition suggests the genetic component is essential in discovering an etiology. We performed whole-exome sequencing of 5 families followed by analysis of variants in 584 cases/431 controls. Variants in RYR2 segregated with disease in 2 families. The novel variant L3277R was not found in any case/control. The rare variant, G1886S was more common in cases (p = 0.046) and extreme cases (p = 0.023). Replication of G1886S using Norwegian/Australian data was supportive. Common variants rs790899 and rs1891246 were significantly associated with HG and weight loss. Copy-number analysis revealed a deletion in a patient. RYR2 encodes an intracellular calcium release channel involved in vomiting, cyclic-vomiting syndrome, and is a thyroid hormone target gene. Additionally, RYR2 is a downstream drug target of Inderal, used to treat HG and CVS. Thus, herein we provide genetic evidence for a pathway and therapy for HG. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  17. Complementarity in the supramolecular design of arenaviruses and retroviruses revealed by electron cryomicroscopy and image analysis.

    Science.gov (United States)

    Neuman, Benjamin W; Adair, Brian D; Burns, John W; Milligan, Ronald A; Buchmeier, Michael J; Yeager, Mark

    2005-03-01

    Arenaviruses are rodent-borne agents of diseases, including potentially lethal human hemorrhagic fevers. These enveloped viruses encapsidate a bisegmented ambisense single-stranded RNA genome that can be packaged in variable copy number. Electron cryomicroscopy and image analysis of New World Pichinde and Tacaribe arenaviruses and Old World lymphocytic choriomeningitis virus revealed pleomorphic enveloped particles ranging in diameter from approximately 400 to approximately 2,000 A. The surface spikes were spaced approximately 100 A apart and extended approximately 90 A from the maximum phospholipid headgroup density of the outer bilayer leaflet. Distinctive stalk and head regions extended radially approximately 30 and approximately 60 A from the outer bilayer leaflet, respectively. Two interior layers of density apposed to the inner leaflet of the viral lipid bilayer were assigned as protein Z and nucleoprotein (NP) molecules on the basis of their appearance, spacing, and projected volume. Analysis of en face views of virions lacking the GP-C spikes showed reflections consistent with paracrystalline packing of the NP molecules in a lattice with edges of approximately 57 and approximately 74 A. The structural proteins of retroviruses and arenaviruses assemble with similar radial density distributions, using common cellular components.

  18. Metagenomic analysis reveals wastewater treatment plants as hotspots of antibiotic resistance genes and mobile genetic elements.

    Science.gov (United States)

    Guo, Jianhua; Li, Jie; Chen, Hui; Bond, Philip L; Yuan, Zhiguo

    2017-10-15

    The intensive use of antibiotics results in their continuous release into the environment and the subsequent widespread occurrence of antibiotic resistant bacteria (ARB), antibiotic resistance genes (ARGs) and mobile genetic elements (MGEs). This study used Illumina high-throughput sequencing to investigate the broad-spectrum profiles of both ARGs and MGEs in activated sludge and anaerobically digested sludge from a full-scale wastewater treatment plant. A pipeline for identifying antibiotic resistance determinants was developed that consisted of four categories: gene transfer potential, ARG potential, ARGs pathway and ARGs phylogenetic origin. The metagenomic analysis showed that the activated sludge and the digested sludge exhibited different microbial communities and changes in the types and occurrence of ARGs and MGEs. In total, 42 ARGs subtypes were identified in the activated sludge, while 51 ARG subtypes were detected in the digested sludge. Additionally, MGEs including plasmids, transposons, integrons (intI1) and insertion sequences (e.g. ISSsp4, ISMsa21 and ISMba16) were abundant in the two sludge samples. The co-occurrence pattern between ARGs and microbial taxa revealed by network analysis indicated that some environmental bacteria (e.g. Clostridium and Nitrosomonas) might be potential hosts of multiple ARGs. The findings increase our understanding of WWTPs as hotspots of ARGs and MGEs, and contribute towards preventing their release into the downstream environment. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Integrative microbial community analysis reveals full-scale enhanced biological phosphorus removal under tropical conditions

    Science.gov (United States)

    Law, Yingyu; Kirkegaard, Rasmus Hansen; Cokro, Angel Anisa; Liu, Xianghui; Arumugam, Krithika; Xie, Chao; Stokholm-Bjerregaard, Mikkel; Drautz-Moses, Daniela I.; Nielsen, Per Halkjær; Wuertz, Stefan; Williams, Rohan B. H.

    2016-05-01

    Management of phosphorus discharge from human waste is essential for the control of eutrophication in surface waters. Enhanced biological phosphorus removal (EBPR) is a sustainable, efficient way of removing phosphorus from waste water without employing chemical precipitation, but is assumed unachievable in tropical temperatures due to conditions that favour glycogen accumulating organisms (GAOs) over polyphosphate accumulating organisms (PAOs). Here, we show these assumptions are unfounded by studying comparative community dynamics in a full-scale plant following systematic perturbation of operational conditions, which modified community abundance, function and physicochemical state. A statistically significant increase in the relative abundance of the PAO Accumulibacter was associated with improved EBPR activity. GAO relative abundance also increased, challenging the assumption of competition. An Accumulibacter bin-genome was identified from a whole community metagenomic survey, and comparative analysis against extant Accumulibacter genomes suggests a close relationship to Type II. Analysis of the associated metatranscriptome data revealed that genes encoding proteins involved in the tricarboxylic acid cycle and glycolysis pathways were highly expressed, consistent with metabolic modelling results. Our findings show that tropical EBPR is indeed possible, highlight the translational potential of studying competition dynamics in full-scale waste water communities and carry implications for plant design in tropical regions.

  20. Large-scale analysis by SAGE reveals new mechanisms of v-erbA oncogene action

    Directory of Open Access Journals (Sweden)

    Faure Claudine

    2007-10-01

    Full Text Available Abstract Background: The v-erbA oncogene, carried by the Avian Erythroblastosis Virus, derives from the c-erbAα proto-oncogene that encodes the nuclear receptor for triiodothyronine (T3R. v-ErbA transforms erythroid progenitors in vitro by blocking their differentiation, supposedly by interference with T3R and RAR (Retinoic Acid Receptor. However, v-ErbA target genes involved in its transforming activity still remain to be identified. Results: By using Serial Analysis of Gene Expression (SAGE, we identified 110 genes deregulated by v-ErbA and potentially implicated in the transformation process. Bioinformatic analysis of promoter sequence and transcriptional assays point out a potential role of c-Myb in the v-ErbA effect. Furthermore, grouping of newly identified target genes by function revealed both expected (chromatin/transcription and unexpected (protein metabolism functions potentially deregulated by v-ErbA. We then focused our study on 15 of the new v-ErbA target genes and demonstrated by real time PCR that in majority their expression was activated neither by T3, nor RA, nor during differentiation. This was unexpected based upon the previously known role of v-ErbA. Conclusion: This paper suggests the involvement of a wealth of new unanticipated mechanisms of v-ErbA action.

  1. Comparative transcriptome and proteome analysis to reveal the biosynthesis of gold nanoparticles in Arabidopsis.

    Science.gov (United States)

    Tiwari, Manish; Krishnamurthy, Sneha; Shukla, Devesh; Kiiskila, Jeffrey; Jain, Ajay; Datta, Rupali; Sharma, Nilesh; Sahi, Shivendra V

    2016-02-23

    A large number of plants have been tested and exploited in search of a green chemistry approach for the fabrication of gold or other precious metal nanomaterials. Despite the potential of plant based methods, very little is known about the underlying biochemical reactions and genes involved in the biotransformation mechanism of AuCl4 into gold nanoparticles (AuNPs). In this research, we thus focused on studying the effect of Au on growth and nanoparticles formation by analyses of transcriptome, proteome and ionome shift in Arabidopsis. Au exposure favored the growth of Arabidopsis seedling and induced formation of nanoparticles in root and shoot, as indicated by optical and hyperspectral imaging. Root transcriptome analysis demonstrated the differential expression of the members of WRKY, MYB and BHLH gene families, which are involved in the Fe and other essential metals homeostasis. The proteome analysis revealed that Glutathione S-transferases were induced in the shoot and suggested its potential role in the biosynthesis AuNPs. This study also demonstrated the role of plant hormone auxin in determining the Au induced root system architecture. This is the first study using an integrated approach to understand the in planta biotransformation of KAuCl4 into AuNPs.

  2. Metagenomic analysis reveals that bacteriophages are reservoirs of antibiotic resistance genes.

    Science.gov (United States)

    Subirats, Jéssica; Sànchez-Melsió, Alexandre; Borrego, Carles M; Balcázar, José Luis; Simonet, Pascal

    2016-08-01

    A metagenomics approach was applied to explore the presence of antibiotic resistance genes (ARGs) in bacteriophages from hospital wastewater. Metagenomic analysis showed that most phage sequences affiliated to the order Caudovirales, comprising the tailed phage families Podoviridae, Siphoviridae and Myoviridae. Moreover, the relative abundance of ARGs in the phage DNA fraction (0.26%) was higher than in the bacterial DNA fraction (0.18%). These differences were particularly evident for genes encoding ATP-binding cassette (ABC) and resistance-nodulation-cell division (RND) proteins, phosphotransferases, β-lactamases and plasmid-mediated quinolone resistance. Analysis of assembled contigs also revealed that blaOXA-10, blaOXA-58 and blaOXA-24 genes belonging to class D β-lactamases as well as a novel blaTEM (98.9% sequence similarity to the blaTEM-1 gene) belonging to class A β-lactamases were detected in a higher proportion in phage DNA. Although preliminary, these findings corroborate the role of bacteriophages as reservoirs of resistance genes and thus highlight the necessity to include them in future studies on the emergence and spread of antibiotic resistance in the environment. Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  3. Automated image analysis reveals the dynamic 3-dimensional organization of multi-ciliary arrays

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    Domenico F. Galati

    2016-01-01

    Full Text Available Multi-ciliated cells (MCCs use polarized fields of undulating cilia (ciliary array to produce fluid flow that is essential for many biological processes. Cilia are positioned by microtubule scaffolds called basal bodies (BBs that are arranged within a spatially complex 3-dimensional geometry (3D. Here, we develop a robust and automated computational image analysis routine to quantify 3D BB organization in the ciliate, Tetrahymena thermophila. Using this routine, we generate the first morphologically constrained 3D reconstructions of Tetrahymena cells and elucidate rules that govern the kinetics of MCC organization. We demonstrate the interplay between BB duplication and cell size expansion through the cell cycle. In mutant cells, we identify a potential BB surveillance mechanism that balances large gaps in BB spacing by increasing the frequency of closely spaced BBs in other regions of the cell. Finally, by taking advantage of a mutant predisposed to BB disorganization, we locate the spatial domains that are most prone to disorganization by environmental stimuli. Collectively, our analyses reveal the importance of quantitative image analysis to understand the principles that guide the 3D organization of MCCs.

  4. Bach Is the Father of Harmony: Revealed by a 1/f Fluctuation Analysis across Musical Genres.

    Science.gov (United States)

    Wu, Dan; Kendrick, Keith M; Levitin, Daniel J; Li, Chaoyi; Yao, Dezhong

    2015-01-01

    Harmony is a fundamental attribute of music. Close connections exist between music and mathematics since both pursue harmony and unity. In music, the consonance of notes played simultaneously partly determines our perception of harmony; associates with aesthetic responses; and influences the emotion expression. The consonance could be considered as a window to understand and analyze harmony. Here for the first time we used a 1/f fluctuation analysis to investigate whether the consonance fluctuation structure in music with a wide range of composers and genres followed the scale free pattern that has been found for pitch, melody, rhythm, human body movements, brain activity, natural images and geographical features. We then used a network graph approach to investigate which composers were the most influential both within and across genres. Our results showed that patterns of consonance in music did follow scale-free characteristics, suggesting that this feature is a universally evolved one in both music and the living world. Furthermore, our network analysis revealed that Bach's harmony patterns were having the most influence on those used by other composers, followed closely by Mozart.

  5. Glycoproteomic analysis of seven major allergenic proteins reveals novel post-translational modifications.

    Science.gov (United States)

    Halim, Adnan; Carlsson, Michael C; Madsen, Caroline Benedicte; Brand, Stephanie; Møller, Svenning Rune; Olsen, Carl Erik; Vakhrushev, Sergey Y; Brimnes, Jens; Wurtzen, Peter Adler; Ipsen, Henrik; Petersen, Bent L; Wandall, Hans H

    2015-01-01

    Allergenic proteins such as grass pollen and house dust mite (HDM) proteins are known to trigger hypersensitivity reactions of the immune system, leading to what is commonly known as allergy. Key allergenic proteins including sequence variants have been identified but characterization of their post-translational modifications (PTMs) is still limited. Here, we present a detailed PTM(1) characterization of a series of the main and clinically relevant allergens used in allergy tests and vaccines. We employ Orbitrap-based mass spectrometry with complementary fragmentation techniques (HCD/ETD) for site-specific PTM characterization by bottom-up analysis. In addition, top-down mass spectrometry is utilized for targeted analysis of individual proteins, revealing hitherto unknown PTMs of HDM allergens. We demonstrate the presence of lysine-linked polyhexose glycans and asparagine-linked N-acetylhexosamine glycans on HDM allergens. Moreover, we identified more complex glycan structures than previously reported on the major grass pollen group 1 and 5 allergens, implicating important roles for carbohydrates in allergen recognition and response by the immune system. The new findings are important for understanding basic disease-causing mechanisms at the cellular level, which ultimately may pave the way for instigating novel approaches for targeted desensitization strategies and improved allergy vaccines. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  6. Structure analysis reveals the flexibility of the ADAMTS-5 active site

    Energy Technology Data Exchange (ETDEWEB)

    Shieh, Huey-Sheng; Tomasselli, Alfredo G.; Mathis, Karl J.; Schnute, Mark E.; Woodard, Scott S.; Caspers, Nicole; Williams, Jennifer M.; Kiefer, James R.; Munie, Grace; Wittwer, Arthur; Malfait, Anne-Marie; Tortorella, Micky D. (Pfizer)

    2012-03-02

    A ((1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl) succinamide derivative (here referred to as Compound 12) shows significant activity toward many matrix metalloproteinases (MMPs), including MMP-2, MMP-8, MMP-9, and MMP-13. Modeling studies had predicted that this compound would not bind to ADAMTS-5 (a disintegrin and metalloproteinase with thrombospondin motifs-5) due to its shallow S1' pocket. However, inhibition analysis revealed it to be a nanomolar inhibitor of both ADAMTS-4 and -5. The observed inconsistency was explained by analysis of crystallographic structures, which showed that Compound 12 in complex with the catalytic domain of ADAMTS-5 (cataTS5) exhibits an unusual conformation in the S1' pocket of the protein. This first demonstration that cataTS5 can undergo an induced conformational change in its active site pocket by a molecule like Compound 12 should enable the design of new aggrecanase inhibitors with better potency and selectivity profiles.

  7. Transcriptional analysis reveals gender-specific changes in the aging of the human immune system.

    Directory of Open Access Journals (Sweden)

    Saara Marttila

    Full Text Available Aging and gender have a strong influence on the functional capacity of the immune system. In general, the immune response in females is stronger than that in males, but there is scant information about the effect of aging on the gender difference in the immune response. To address this question, we performed a transcriptomic analysis of peripheral blood mononuclear cells derived from elderly individuals (nonagenarians, n = 146 and young controls (aged 19-30 years, n = 30. When compared to young controls, we found 339 and 248 genes that were differentially expressed (p1.5 or <-1.5 in nonagenarian females and males, respectively, 180 of these genes were changed in both genders. An analysis of the affected signaling pathways revealed a clear gender bias: there were 48 pathways that were significantly changed in females, while only 29 were changed in males. There were 24 pathways that were shared between both genders. Our results indicate that female nonagenarians have weaker T cell defenses and a more prominent pro-inflammatory response as compared to males. In males significantly fewer pathways were affected, two of which are known to be regulated by estrogen. These data show that the effects of aging on the human immune system are significantly different in males and females.

  8. Transcriptional analysis reveals gender-specific changes in the aging of the human immune system.

    Science.gov (United States)

    Marttila, Saara; Jylhävä, Juulia; Nevalainen, Tapio; Nykter, Matti; Jylhä, Marja; Hervonen, Antti; Tserel, Liina; Peterson, Pärt; Hurme, Mikko

    2013-01-01

    Aging and gender have a strong influence on the functional capacity of the immune system. In general, the immune response in females is stronger than that in males, but there is scant information about the effect of aging on the gender difference in the immune response. To address this question, we performed a transcriptomic analysis of peripheral blood mononuclear cells derived from elderly individuals (nonagenarians, n = 146) and young controls (aged 19-30 years, n = 30). When compared to young controls, we found 339 and 248 genes that were differentially expressed (p1.5 or genders. An analysis of the affected signaling pathways revealed a clear gender bias: there were 48 pathways that were significantly changed in females, while only 29 were changed in males. There were 24 pathways that were shared between both genders. Our results indicate that female nonagenarians have weaker T cell defenses and a more prominent pro-inflammatory response as compared to males. In males significantly fewer pathways were affected, two of which are known to be regulated by estrogen. These data show that the effects of aging on the human immune system are significantly different in males and females.

  9. Singularity analysis of the AKT signaling pathway reveals connections between cancer and metabolic diseases

    Science.gov (United States)

    Wang, Guanyu

    2010-12-01

    Connections between cancer and metabolic diseases may consist in the complex network of interactions among a common set of biomolecules. By applying singularity and bifurcation analysis, the phenotypes constrained by the AKT signaling pathway are identified and mapped onto the parameter space, which include cancer and certain metabolic diseases. By considering physiologic properties (sensitivity, robustness and adaptivity) the AKT pathway must possess in order to efficiently sense growth factors and nutrients, the region of normal responses is located. To optimize these properties, the intracellular concentration of the AKT protein must be sufficiently high to saturate its enzymes; the strength of the positive feedback must be stronger than that of the negative feedback. The analysis illuminates the parameter space and reveals system-level mechanisms in regulating biological functions (cell growth, survival, proliferation and metabolism) and how their deregulation may lead to the development of diseases. The analytical expressions summarize the synergistic interactions among many molecules, which provides valuable insights into therapeutic interventions. In particular, a strategy for overcoming the limitations of mTOR inhibition is proposed for cancer therapy.

  10. Analysis of spatial-temporal gene expression patterns reveals dynamics and regionalization in developing mouse brain.

    Science.gov (United States)

    Chou, Shen-Ju; Wang, Chindi; Sintupisut, Nardnisa; Niou, Zhen-Xian; Lin, Chih-Hsu; Li, Ker-Chau; Yeang, Chen-Hsiang

    2016-01-20

    Allen Brain Atlas (ABA) provides a valuable resource of spatial/temporal gene expressions in mammalian brains. Despite rich information extracted from this database, current analyses suffer from several limitations. First, most studies are either gene-centric or region-centric, thus are inadequate to capture the superposition of multiple spatial-temporal patterns. Second, standard tools of expression analysis such as matrix factorization can capture those patterns but do not explicitly incorporate spatial dependency. To overcome those limitations, we proposed a computational method to detect recurrent patterns in the spatial-temporal gene expression data of developing mouse brains. We demonstrated that regional distinction in brain development could be revealed by localized gene expression patterns. The patterns expressed in the forebrain, medullary and pontomedullary, and basal ganglia are enriched with genes involved in forebrain development, locomotory behavior, and dopamine metabolism respectively. In addition, the timing of global gene expression patterns reflects the general trends of molecular events in mouse brain development. Furthermore, we validated functional implications of the inferred patterns by showing genes sharing similar spatial-temporal expression patterns with Lhx2 exhibited differential expression in the embryonic forebrains of Lhx2 mutant mice. These analysis outcomes confirm the utility of recurrent expression patterns in studying brain development.

  11. Genome-Wide SNP Analysis Reveals Distinct Origins of Trypanosoma evansi and Trypanosoma equiperdum.

    Science.gov (United States)

    Cuypers, Bart; Van den Broeck, Frederik; Van Reet, Nick; Meehan, Conor J; Cauchard, Julien; Wilkes, Jonathan M; Claes, Filip; Goddeeris, Bruno; Birhanu, Hadush; Dujardin, Jean-Claude; Laukens, Kris; Büscher, Philippe; Deborggraeve, Stijn

    2017-08-01

    Trypanosomes cause a variety of diseases in man and domestic animals in Africa, Latin America, and Asia. In the Trypanozoon subgenus, Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense cause human African trypanosomiasis, whereas Trypanosoma brucei brucei, Trypanosoma evansi, and Trypanosoma equiperdum are responsible for nagana, surra, and dourine in domestic animals, respectively. The genetic relationships between T. evansi and T. equiperdum and other Trypanozoon species remain unclear because the majority of phylogenetic analyses has been based on only a few genes. In this study, we have conducted a phylogenetic analysis based on genome-wide SNP analysis comprising 56 genomes from the Trypanozoon subgenus. Our data reveal that T. equiperdum has emerged at least once in Eastern Africa and T. evansi at two independent occasions in Western Africa. The genomes within the T. equiperdum and T. evansi monophyletic clusters show extremely little variation, probably due to the clonal spread linked to the independence from tsetse flies for their transmission. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  12. Comparative Genomic Analysis of Lactococcus garvieae Strains Isolated from Different Sources Reveals Candidate Virulence Genes

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    Eiji Miyauchi

    2012-01-01

    Full Text Available Lactococcus garvieae is a major pathogen for fish. Two complete (ATCC 49156 and Lg2 and three draft (UNIUD074, 8831, and 21881 genome sequences of L. garvieae have recently been released. We here present the results of a comparative genomic analysis of these fish and human isolates of L. garvieae. The pangenome comprised 1,542 core and 1,378 dispensable genes. The sequenced L. garvieae strains shared most of the possible virulence genes, but the capsule gene cluster was found only in fish-pathogenic strain Lg2. The absence of the capsule gene cluster in other nonpathogenic strains isolated from mastitis and vegetable was also confirmed by PCR. The fish and human isolates of L. garvieae contained the specific two and four adhesin genes, respectively, indicating that these adhesion proteins may be involved in the host specificity differences of L. garvieae. The discoveries revealed by the pangenomic analysis may provide significant insights into the biology of L. garvieae.

  13. Spatial and temporal variation of total electron content as revealed by principal component analysis

    Science.gov (United States)

    Talaat, Elsayed R.; Zhu, Xun

    2016-11-01

    Eleven years of global total electron content (TEC) data derived from the assimilated thermosphere-ionosphere electrodynamics general circulation model are analyzed using empirical orthogonal function (EOF) decomposition and the corresponding principal component analysis (PCA) technique. For the daily averaged TEC field, the first EOF explains more than 89 % and the first four EOFs explain more than 98 % of the total variance of the TEC field, indicating an effective data compression and clear separation of different physical processes. The effectiveness of the PCA technique for TEC is nearly insensitive to the horizontal resolution and the length of the data records. When the PCA is applied to global TEC including local-time variations, the rich spatial and temporal variations of field can be represented by the first three EOFs that explain 88 % of the total variance. The spectral analysis of the time series of the EOF coefficients reveals how different mechanisms such as solar flux variation, change in the orbital declination, nonlinear mode coupling and geomagnetic activity are separated and expressed in different EOFs. This work demonstrates the usefulness of using the PCA technique to assimilate and monitor the global TEC field.

  14. Genome-Wide Association Analysis Reveals Different Genetic Control in Panicle Architecture Between and Rice.

    Science.gov (United States)

    Bai, Xufeng; Zhao, Hu; Huang, Yong; Xie, Weibo; Han, Zhongmin; Zhang, Bo; Guo, Zilong; Yang, Lin; Dong, Haijiao; Xue, Weiya; Li, Guangwei; Hu, Gang; Hu, Yong; Xing, Yongzhong

    2016-07-01

    Panicle architecture determines the number of spikelets per panicle (SPP) and is highly associated with grain yield in rice ( L.). Understanding the genetic basis of panicle architecture is important for improving the yield of rice grain. In this study, we dissected panicle architecture traits into eight components, which were phenotyped from a germplasm collection of 529 cultivars. Multiple regression analysis revealed that the number of secondary branch (NSB) was the major factor that contributed to SPP. Genome-wide association analysis was performed independently for the eight particle architecture traits observed in the and rice subpopulations compared with the whole rice population. In total, 30 loci were associated with these traits. Of these, 13 loci were closely linked to known panicle architecture genes, and 17 novel loci were repeatedly identified in different environments. An association signal cluster was identified for NSB and number of spikelets per secondary branch (NSSB) in the region of 31.6 to 31.7 Mb on chromosome 4. In addition to the common associations detected in both and subpopulations, many associated loci were unique to one subpopulation. For example, and were specifically associated with panicle length (PL) in and rice, respectively. Moreover, the -mediated flowering genes and were associated with the formation of panicle architecture in rice. These results suggest that different gene networks regulate panicle architecture in and rice. Copyright © 2016 Crop Science Society of America.

  15. Comprehensive Proteomics Analysis of Laticifer Latex Reveals New Insights into Ethylene Stimulation of Natural Rubber Production.

    Science.gov (United States)

    Wang, Xuchu; Wang, Dan; Sun, Yong; Yang, Qian; Chang, Lili; Wang, Limin; Meng, Xueru; Huang, Qixing; Jin, Xiang; Tong, Zheng

    2015-09-08

    Ethylene is a stimulant to increase natural rubber latex. After ethylene application, both fresh yield and dry matter of latex are substantially improved. Moreover, we found that ethylene improves the generation of small rubber particles. However, most genes involved in rubber biosynthesis are inhibited by exogenous ethylene. Therefore, we conducted a proteomics analysis of ethylene-stimulated rubber latex, and identified 287 abundant proteins as well as 143 ethylene responsive latex proteins (ERLPs) with mass spectrometry from the 2-DE and DIGE gels, respectively. In addition, more than 1,600 proteins, including 404 ERLPs, were identified by iTRAQ. Functional classification of ERLPs revealed that enzymes involved in post-translational modification, carbohydrate metabolism, hydrolase activity, and kinase activity were overrepresented. Some enzymes for rubber particle aggregation were inhibited to prolong latex flow, and thus finally improved latex production. Phosphoproteomics analysis identified 59 differential phosphoproteins; notably, specific isoforms of rubber elongation factor and small rubber particle protein that were phosphorylated mainly at serine residues. This post-translational modification and isoform-specific phosphorylation might be important for ethylene-stimulated latex production. These results not only deepen our understanding of the rubber latex proteome but also provide new insights into the use of ethylene to stimulate rubber latex production.

  16. Bach Is the Father of Harmony: Revealed by a 1/f Fluctuation Analysis across Musical Genres.

    Directory of Open Access Journals (Sweden)

    Dan Wu

    Full Text Available Harmony is a fundamental attribute of music. Close connections exist between music and mathematics since both pursue harmony and unity. In music, the consonance of notes played simultaneously partly determines our perception of harmony; associates with aesthetic responses; and influences the emotion expression. The consonance could be considered as a window to understand and analyze harmony. Here for the first time we used a 1/f fluctuation analysis to investigate whether the consonance fluctuation structure in music with a wide range of composers and genres followed the scale free pattern that has been found for pitch, melody, rhythm, human body movements, brain activity, natural images and geographical features. We then used a network graph approach to investigate which composers were the most influential both within and across genres. Our results showed that patterns of consonance in music did follow scale-free characteristics, suggesting that this feature is a universally evolved one in both music and the living world. Furthermore, our network analysis revealed that Bach's harmony patterns were having the most influence on those used by other composers, followed closely by Mozart.

  17. Metagenomic analysis reveals symbiotic relationship among bacteria in Microcystis-dominated community

    Directory of Open Access Journals (Sweden)

    Meili eXie

    2016-02-01

    Full Text Available Microcystis bloom, a cyanobacterial mass occurrence often found in eutrophicated water bodies, is one of the most serious threats to freshwater ecosystems worldwide. In nature, Microcystis forms aggregates or colonies that contain heterotrophic bacteria. The Microcystis-bacteria colonies were persistent even when they were maintained in lab culture for a long period. The relationship between Microcystis and the associated bacteria was investigated by a metagenomic approach in this study. We developed a visualization-guided method of binning for genome assembly after total colony DNA sequencing. We found that the method was effective in grouping sequences and it did not require reference genome sequence. Individual genomes of the colony bacteria were obtained and they provided valuable insights into microbial community structures. Analysis of metabolic pathways based on these genomes revealed that while all heterotrophic bacteria were dependent upon Microcystis for carbon and energy, Vitamin B12 biosynthesis, which is required for growth by Microcystis, was accomplished in a cooperative fashion among the bacteria. Our analysis also suggests that individual bacteria in the colony community contributed a complete pathway for degradation of benzoate, which is inhibitory to the cyanobacterial growth, and its ecological implication for Microcystis bloom is discussed.

  18. Comparative proteomics and codon substitution analysis reveal mechanisms of differential resistance to hypoxia in congeneric snails

    KAUST Repository

    Mu, Huawei

    2017-11-06

    Although high-throughput proteomics has been widely applied to study mechanisms of environmental adaptation, the conclusions from studies that are based on one species can be confounded by phylogeny. We compare the freshwater snail Pomacea canaliculata (a notorious invasive species) and its congener Pomacea diffusa (a non-invasive species) to understand the molecular mechanisms of their differential resistance to hypoxia. A 72-h acute exposure experiment showed that P. canaliculata is more tolerant to hypoxia than P. diffusa. The two species were then exposed to three levels of dissolved oxygen (6.7, 2.0 and 1.0mgL−1) for 8h, and their gill proteins were analyzed using iTRAQ-coupled LC-MS/MS. The two species showed striking differences in protein expression profiles, with the more hypoxia tolerant P. canaliculata having more up-regulated proteins in signal transduction and down-regulated proteins in glycolysis and the tricarboxylic acid cycle. Evolutionary analysis revealed five orthologous genes encoding differentially expressed proteins having clear signal of positive selection, indicating selection has acted on some of the hypoxia responsive genes. Our case study has highlighted the potential of integrated proteomics and comparative evolutionary analysis for understanding the genetic basis of adaptation to global environmental change in non-model species. SignificanceRapid globalization in recent decades has greatly facilitated species introduction around the world. Successfully established introduced species, so-called invasive species, have threatened the invaded ecosystems. There has been substantial interest in studying how invasive species respond to extreme environmental conditions because the results can help not only predict their range of expansion and manage their impact, but also may reveal the adaptive mechanisms underlying their invasiveness. Our study has adopted a comparative approach to study the differential physiological and proteomic

  19. Genome-wide analysis of UDP-glycosyltransferase super family in Brassica rapa and Brassica oleracea reveals its evolutionary history and functional characterization.

    Science.gov (United States)

    Yu, Jingyin; Hu, Fan; Dossa, Komivi; Wang, Zhaokai; Ke, Tao

    2017-06-23

    Glycosyltransferases comprise a highly divergent and polyphyletic multigene family that is involved in widespread modification of plant secondary metabolites in a process called glycosylation. According to conserved domains identified in their amino acid sequences, these glycosyltransferases can be classified into a single UDP-glycosyltransferase (UGT) 1 superfamily. We performed genome-wide comparative analysis of UGT genes to trace evolutionary history in algae, bryophytes, pteridophytes, and angiosperms; then, we further investigated the expansion mechanisms and function characterization of UGT gene families in Brassica rapa and Brassica oleracea. Using Hidden Markov Model search, we identified 3, 21, 140, 200, 115, 147, and 147 UGTs in Chlamydomonas reinhardtii, Physcomitrella patens, Selaginella moellendorffii, Oryza sativa, Arabidopsis thaliana, B. rapa, and B. oleracea, respectively. Phylogenetic analysis revealed that UGT80 gene family is an ancient gene family, which is shared by all plants and UGT74 gene family is shared by ferns and angiosperms, but the remaining UGT gene families were shared by angiosperms. In dicot lineage, UGTs among three species were classified into three subgroups containing 3, 6, and 12 UGT gene families. Analysis of chromosomal distribution indicates that 98.6 and 71.4% of UGTs were located on B. rapa and B. oleracea pseudo-molecules, respectively. Expansion mechanism analyses uncovered that whole genome duplication event exerted larger influence than tandem duplication on expansion of UGT gene families in B. rapa, and B. oleracea. Analysis of selection forces of UGT orthologous gene pairs in B. rapa, and B. oleracea compared to A. thaliana suggested that orthologous genes in B. rapa, and B. oleracea have undergone negative selection, but there were no significant differences between A. thaliana -B. rapa and A. thaliana -B. oleracea lineages. Our comparisons of expression profiling illustrated that UGTs in B. rapa performed more

  20. Transcriptional Regulation of Rod Photoreceptor Homeostasis Revealed by In Vivo NRL Targetome Analysis

    Science.gov (United States)

    Hao, Hong; Kim, Douglas S.; Klocke, Bernward; Johnson, Kory R.; Cui, Kairong; Gotoh, Norimoto; Zang, Chongzhi; Gregorski, Janina; Gieser, Linn; Peng, Weiqun; Fann, Yang; Seifert, Martin; Zhao, Keji; Swaroop, Anand

    2012-01-01

    A stringent control of homeostasis is critical for functional maintenance and survival of neurons. In the mammalian retina, the basic motif leucine zipper transcription factor NRL determines rod versus cone photoreceptor cell fate and activates the expression of many rod-specific genes. Here, we report an integrated analysis of NRL-centered gene regulatory network by coupling chromatin immunoprecipitation followed by high-throughput sequencing (ChIP–Seq) data from Illumina and ABI platforms with global expression profiling and in vivo knockdown studies. We identified approximately 300 direct NRL target genes. Of these, 22 NRL targets are associated with human retinal dystrophies, whereas 95 mapped to regions of as yet uncloned retinal disease loci. In silico analysis of NRL ChIP–Seq peak sequences revealed an enrichment of distinct sets of transcription factor binding sites. Specifically, we discovered that genes involved in photoreceptor function include binding sites for both NRL and homeodomain protein CRX. Evaluation of 26 ChIP–Seq regions validated their enhancer functions in reporter assays. In vivo knockdown of 16 NRL target genes resulted in death or abnormal morphology of rod photoreceptors, suggesting their importance in maintaining retinal function. We also identified histone demethylase Kdm5b as a novel secondary node in NRL transcriptional hierarchy. Exon array analysis of flow-sorted photoreceptors in which Kdm5b was knocked down by shRNA indicated its role in regulating rod-expressed genes. Our studies identify candidate genes for retinal dystrophies, define cis-regulatory module(s) for photoreceptor-expressed genes and provide a framework for decoding transcriptional regulatory networks that dictate rod homeostasis. PMID:22511886

  1. Co-expression network analysis reveals transcription factors associated to cell wall biosynthesis in sugarcane.

    Science.gov (United States)

    Ferreira, Savio Siqueira; Hotta, Carlos Takeshi; Poelking, Viviane Guzzo de Carli; Leite, Debora Chaves Coelho; Buckeridge, Marcos Silveira; Loureiro, Marcelo Ehlers; Barbosa, Marcio Henrique Pereira; Carneiro, Monalisa Sampaio; Souza, Glaucia Mendes

    2016-05-01

    Sugarcane is a hybrid of Saccharum officinarum and Saccharum spontaneum, with minor contributions from other species in Saccharum and other genera. Understanding the molecular basis of cell wall metabolism in sugarcane may allow for rational changes in fiber quality and content when designing new energy crops. This work describes a comparative expression profiling of sugarcane ancestral genotypes: S. officinarum, S. spontaneum and S. robustum and a commercial hybrid: RB867515, linking gene expression to phenotypes to identify genes for sugarcane improvement. Oligoarray experiments of leaves, immature and intermediate internodes, detected 12,621 sense and 995 antisense transcripts. Amino acid metabolism was particularly evident among pathways showing natural antisense transcripts expression. For all tissues sampled, expression analysis revealed 831, 674 and 648 differentially expressed genes in S. officinarum, S. robustum and S. spontaneum, respectively, using RB867515 as reference. Expression of sugar transporters might explain sucrose differences among genotypes, but an unexpected differential expression of histones were also identified between high and low Brix° genotypes. Lignin biosynthetic genes and bioenergetics-related genes were up-regulated in the high lignin genotype, suggesting that these genes are important for S. spontaneum to allocate carbon to lignin, while S. officinarum allocates it to sucrose storage. Co-expression network analysis identified 18 transcription factors possibly related to cell wall biosynthesis while in silico analysis detected cis-elements involved in cell wall biosynthesis in their promoters. Our results provide information to elucidate regulatory networks underlying traits of interest that will allow the improvement of sugarcane for biofuel and chemicals production.

  2. The optimal regulation mode of Bcl-2 apoptotic switch revealed by bistability analysis.

    Science.gov (United States)

    Yin, Zhiyong; Qi, Hong; Liu, Lili; Jin, Zhen

    2017-12-01

    In most cell types, apoptosis occurs by the mitochondrial outer membrane permeability (MOMP)-mediated pathway, which is controlled by Bcl-2 family proteins (often referred to as Bcl-2 apoptotic switch). These proteins, which display a range of bioactivities, can be divided into four types: effectors, inhibitors, activators and sensitizers. Although the complex interactions among Bcl-2 family members have been studied intensively, a unifying hypothesis for the mechanism they use to regulate MOMP remains elusive. The bistable behaviors are often used to explain the all-or-none decisions of apoptosis. Here, we attempt to reveal the optimal interaction mode by comparing the bistable performances of three different modes (direct activation, indirect activation, and unified mode) proposed by biologists. Using the method that combines mathematical analysis and numerical simulation, we discover that bistability can only emerge from the unified mode when proteins synthesis and degradation are considered, which is in favor of it as an optimal regulation mode of Bcl-2 apoptotic switch. The parameter sensitivity analysis for the unified mode further consolidates this view. Moreover, two-parameter bifurcation analysis suggests that the sensitizers lower the threshold of activation of Bax, but have a negative influence on the width of the bistability region. Our study may provide mechanistic insights into the heterogeneity of tumor cells and the efficiency of BH3 mimetic-mediated killing of cancer cells, and suggest that a combination treatment might be required to overcome apoptosis resistance in the Bcl-2 family targeted therapies. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Transcriptional regulation of rod photoreceptor homeostasis revealed by in vivo NRL targetome analysis.

    Directory of Open Access Journals (Sweden)

    Hong Hao

    Full Text Available A stringent control of homeostasis is critical for functional maintenance and survival of neurons. In the mammalian retina, the basic motif leucine zipper transcription factor NRL determines rod versus cone photoreceptor cell fate and activates the expression of many rod-specific genes. Here, we report an integrated analysis of NRL-centered gene regulatory network by coupling chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-Seq data from Illumina and ABI platforms with global expression profiling and in vivo knockdown studies. We identified approximately 300 direct NRL target genes. Of these, 22 NRL targets are associated with human retinal dystrophies, whereas 95 mapped to regions of as yet uncloned retinal disease loci. In silico analysis of NRL ChIP-Seq peak sequences revealed an enrichment of distinct sets of transcription factor binding sites. Specifically, we discovered that genes involved in photoreceptor function include binding sites for both NRL and homeodomain protein CRX. Evaluation of 26 ChIP-Seq regions validated their enhancer functions in reporter assays. In vivo knockdown of 16 NRL target genes resulted in death or abnormal morphology of rod photoreceptors, suggesting their importance in maintaining retinal function. We also identified histone demethylase Kdm5b as a novel secondary node in NRL transcriptional hierarchy. Exon array analysis of flow-sorted photoreceptors in which Kdm5b was knocked down by shRNA indicated its role in regulating rod-expressed genes. Our studies identify candidate genes for retinal dystrophies, define cis-regulatory module(s for photoreceptor-expressed genes and provide a framework for decoding transcriptional regulatory networks that dictate rod homeostasis.

  4. Nonlinear cardio-respiratory interactions revealed by time-phase bispectral analysis

    Energy Technology Data Exchange (ETDEWEB)

    Jamsek, Janez [Group of Nonlinear Dynamics and Synergetics, Faculty of Electrical Engineering, University of Ljubljana, Trzaska 25, 1000 Ljubljana (Slovenia); Stefanovska, Aneta [Group of Nonlinear Dynamics and Synergetics, Faculty of Electrical Engineering, University of Ljubljana, Trzaska 25, 1000 Ljubljana (Slovenia); McClintock, Peter V E [Department of Physics, University of Lancaster, Lancaster LA1 4YB (United Kingdom)

    2004-09-21

    Bispectral analysis based on high order statistics, introduced recently as a technique for revealing time-phase relationships among interacting noisy oscillators, has been used to study the nature of the coupling between cardiac and respiratory activity. Univariate blood flow signals recorded simultaneously by laser-Doppler flowmetry on both legs and arms were analysed. Coupling between cardiac and respiratory activity was also checked by use of bivariate data and computation of the cross-bispectrum between the ECG and respiratory signals. Measurements were made on six healthy males aged 25-27 years. Recordings were taken during spontaneous breathing (20 min), and during paced respiration at frequencies both lower and higher than that of spontaneous respiration (either two or three recordings with a constant frequency in the interval between 0.09 and 0.35 Hz). At each paced frequency recordings were taken for 12 min. It was confirmed that the dynamics of blood flow can usefully be considered in terms of coupled oscillators, and demonstrated that interactions between the cardiac and respiratory processes are weak and time-varying, and that they can be nonlinear. Nonlinear coupling was revealed to exist during both spontaneous and paced respiration. When present, it was detected in all four blood flow signals and in the cross-bispectrum between the ECG and respiratory signal. The episodes with nonlinear coupling were detected in 11 out of 22 recordings and lasted between 19 s in the case of high frequency (0.34 Hz) and 106 s in the case of low frequency paced respiration (0.11 Hz)

  5. Nonlinear cardio-respiratory interactions revealed by time-phase bispectral analysis

    Science.gov (United States)

    Jamsek, Janez; Stefanovska, Aneta; McClintock, Peter V. E.

    2004-09-01

    Bispectral analysis based on high order statistics, introduced recently as a technique for revealing time-phase relationships among interacting noisy oscillators, has been used to study the nature of the coupling between cardiac and respiratory activity. Univariate blood flow signals recorded simultaneously by laser-Doppler flowmetry on both legs and arms were analysed. Coupling between cardiac and respiratory activity was also checked by use of bivariate data and computation of the cross-bispectrum between the ECG and respiratory signals. Measurements were made on six healthy males aged 25-27 years. Recordings were taken during spontaneous breathing (20 min), and during paced respiration at frequencies both lower and higher than that of sponta