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Sample records for subgroup analysis showed

  1. Identifying Tinnitus Subgroups With Cluster Analysis

    Science.gov (United States)

    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

  2. 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.

  3. Cluster Analysis of Clinical Data Identifies Fibromyalgia Subgroups

    Science.gov (United States)

    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

  4. 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 ...

  5. 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.

  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

    Directory of Open Access Journals (Sweden)

    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 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

  9. 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

    Directory of Open Access Journals (Sweden)

    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

  10. 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.

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

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    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.

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

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    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.

  13. 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

  14. 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.

  15. 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...

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

    Science.gov (United States)

    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…

  17. 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

  18. 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.

  19. 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.

  20. 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

    -effective. However, subgroups with ASPECTS ≤5 or with M2 occlusions showed considerably higher incremental cost-effectiveness ratios ($14 273/QALY and $28 812/QALY, respectively) and only reached suboptimal acceptability in the probabilistic sensitivity analysis (75.5% and 59.4%, respectively). All other subgroups had acceptability rates of 90% to 100%. EVT+SC is cost-effective in most subgroups. In patients with ASPECTS ≤5 or with M2 occlusions, cost-effectiveness remains uncertain based on current data. © 2016 American Heart Association, Inc.

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

    Science.gov (United States)

    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.

  2. 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.

  3. 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.

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

    Science.gov (United States)

    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. [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.

  6. 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...

  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

    . 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....

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

    Directory of Open Access Journals (Sweden)

    Safiri S

    2016-07-01

    also estimated. Three latent classes were determined: 1 low risk; 2 cigarette and hookah smoker; and 3 high risk. It is worth mentioning that 3.7% of males and 0.4% of females were in the high risk group.Conclusion: Subgrouping of college students showed that a considerable percentage of them, especially males, were classified into the high risk and cigarette and hookah smoker groups. Appropriate preventive measures that consider multiple different risky behaviors simultaneously are needed for this part of the population. Keywords: alcohol drinking, sexual behavior, latent class analysis, risk behaviors, drug abuse, substance abuse

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

    Science.gov (United States)

    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.

  11. 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.

  12. 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. 

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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

    .04). Average ODI scores in the subgroup of patients that had reached the one year postoperative time point were 46.5 pre-op (n = 46), and 26.2 at 1 year post-op (n = 40, p = 0.0001). There was significant improvement in VAS scores: pre-operative (back = 6.7, leg = 5.4, n = 46), and 1 year post-operative (back = 3.2, leg = 1.7, n = 40, p = 0.0001). Patients with pre-operative ODI scores greater than 50 demonstrated significant improvement starting at the 6 week post-operative time point (24 point improvement, n = 46, p < 0.001). A pre-operative ODI between 35-50 showed significant improvement starting at 3 months (15.5 point improvement, n = 29, p = 0.05). Patients with a pre-operative ODI score less than 35 had an initial period of increased disability with a trend towards significant improvement by 3 months post-op (n = 20). Conclusions Initial findings of the MIS Prospective Registry show patients can be enrolled in a relatively short time period and patient based questionnaires can successfully be obtained through a combination of clinic follow-up appointments and remote correspondence. Outcomes of the MIS Registry MIS TLIF subgroup were consistent with previously published MIS TLIF studies. Sub-analysis of data collected through level-specific patient diagnosis and treatment modalities permits outcome analysis of a wide breadth of spinal conditions and interventions. PMID:25694921

  19. 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...

  20. 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

  1. 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.

  2. 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

  3. 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...

  4. 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...

  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. 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.

  7. 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...

  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. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. 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...

  3. 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 ...

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. 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.

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

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    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.

  13. 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.

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

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    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

  15. 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.

  16. 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.

  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. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

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    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.

  1. 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

  2. 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.

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

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    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

  4. 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

  5. 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

  6. 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

  7. 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.

  8. 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

  9. 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

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

    Science.gov (United States)

    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.

  11. 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

  12. 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...

  13. 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...

  14. 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

  15. 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).

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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\

  1. 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

  2. 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.

  3. 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.

  4. 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…

  5. 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.…

  6. Advertising Discourse Analysis of FES stores: Killing Love, Cowards Show

    OpenAIRE

    Cristian Venegas Ahumada

    2013-01-01

    The objective is to analyze the structural and photographic discourse of the Autumn-Winter campaign 2008 of FES stores for young people. This was done by a semiotic theory and a critical-structural methodology of discourse. An analysis of 4 advertising photographs was done, and at once an analysis of the discourse “FES says no to violence against Women”, which explains the campaign’s target. The result is: The discourse was subjected to production condition (society of control) and makes adve...

  7. 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

  8. Advertising Discourse Analysis of FES stores: Killing Love, Cowards Show

    Directory of Open Access Journals (Sweden)

    Cristian Venegas Ahumada

    2013-08-01

    Full Text Available The objective is to analyze the structural and photographic discourse of the Autumn-Winter campaign 2008 of FES stores for young people. This was done by a semiotic theory and a critical-structural methodology of discourse. An analysis of 4 advertising photographs was done, and at once an analysis of the discourse “FES says no to violence against Women”, which explains the campaign’s target. The result is: The discourse was subjected to production condition (society of control and makes advertising a way to homogenize subjectivity of masses to consume. Recognition conditions demonstrate that this advertising discourse of symbolic violence means a type of violation of Men and Women Rights. An action like this requires commitment of Psychology in order to promote the social humanizing change, by means of university teaching and professional tasks.

  9. Authenticity and TV Shows: A Multidimensional Analysis Perspective

    Science.gov (United States)

    Al-Surmi, Mansoor

    2012-01-01

    Television shows, especially soap operas and sitcoms, are usually considered by English as a second language practitioners as a source of authentic spoken conversational materials presumably because they reflect the linguistic features of natural conversation. However, practitioners are faced with the dilemma of how to assess whether such…

  10. 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

  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

    Directory of Open Access Journals (Sweden)

    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. 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

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

    Directory of Open Access Journals (Sweden)

    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

  16. 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

  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

    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.

  18. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  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. 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...

  6. 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

  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. 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.

  9. 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.

  10. 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 ...

  11. 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)

  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: 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…

  14. 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…

  15. A Subgroup of First-Degree Relatives of Crohn's Disease Patients Shows a Profile of Inflammatory Markers in the Blood Which is More Typical of Crohn's Disease Patients Than of Normal Individuals

    Directory of Open Access Journals (Sweden)

    2006-01-01

    Full Text Available Introduction. Family member with IBD is the greatest risk factor for developing the disease. The hematological profileof first-degree relatives (FDRs of Crohn's disease (CD patients was studied in order to identify healthy FDRs at risk to develop disease. Materials and methods. Thirty CD patients, 90 FDRs, and 28 non-related individuals (controls were enrolled. Hematological profile and C-reactive protein were determined. Results. All hematological parameters were significantly different in CD patients compared to controls, with significantly higher levels of CRP, WBC, PMN, MONO, and PLT and lower Hb and lymphocyte count. The hematological profile of FDRs showed values between the controls and CD patients with ten FDRs that their parameters matched those of CD patients and significantly different from other FDRs. This group was defined as high-risk relatives (HRRs. Conclusions. Analysis of the hematological profile and CRP level might be proven as a fast, reliable, and less money-consuming tool to identify FDRs with a probable increased risk to develop the disease.

  16. 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...

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. 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

  2. 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

  3. 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…

  4. 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....

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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

  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. Importance Performance Analysis as a Trade Show Performance Evaluation and Benchmarking Tool

    OpenAIRE

    Tafesse, Wondwesen; Skallerud, Kåre; Korneliussen, Tor

    2010-01-01

    The purpose of this study is to introduce importance performance analysis as a trade show performance evaluation and benchmarking tool. Importance performance analysis considers exhibitors’ performance expectation and perceived performance in unison to evaluate and benchmark trade show performance. The present study uses data obtained from exhibitors of an international trade show to demonstrate how importance performance analysis can be used to evaluate and benchmark trade show performance. ...

  15. 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

  16. 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.

  17. Importance Performance Analysis as a Trade Show Performance Evaluation and Benchmarking Tool

    OpenAIRE

    Tafesse, Wondwesen; Skallerud, Kåre; Korneliussen, Tor

    2010-01-01

    Author's accepted version (post-print). The purpose of this study is to introduce importance performance analysis as a trade show performance evaluation and benchmarking tool. Importance performance analysis considers exhibitors’ performance expectation and perceived performance in unison to evaluate and benchmark trade show performance. The present study uses data obtained from exhibitors of an international trade show to demonstrate how importance performance analysis can be used to eval...

  18. [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.

  19. 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.

  20. 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 ...

  1. 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

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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).

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. 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

  2. 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.

  3. 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

  4. 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

  5. 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.

  6. 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.

  7. 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...

  8. Osteopathic manipulative treatment showed reduction of length of stay and costs in preterm infants: A systematic review and meta-analysis.

    Science.gov (United States)

    Lanaro, Diego; Ruffini, Nuria; Manzotti, Andrea; Lista, Gianluca

    2017-03-01

    Osteopathic medicine is an emerging and complementary method used in neonatology. Outcomes were the mean difference in length of stay (LOS) and costs between osteopathy and alternative treatment group. A comprehensive literature search of (quasi)- randomized controlled trials (RCTs), was conducted from journal inception to May, 2015. Eligible studies must have treated preterm infants directly in the crib or bed and Osteopathic Manipulative Treatment (OMT) must have been performed by osteopaths. A rigorous Cochrane-like method was used for study screening and selection, risk of bias assessment and data reporting. Fixed effect meta-analysis was performed to synthesize data. 5 trials enrolling 1306 infants met our inclusion criteria. Although the heterogeneity was moderate (I = 61%, P = 0.03), meta-analysis of all five studies showed that preterm infants treated with OMT had a significant reduction of LOS by 2.71 days (95% CI -3.99, -1.43; P < 0.001). Considering costs, meta-analysis showed reduction in the OMT group (-1,545.66&OV0556;, -1,888.03&OV0556;, -1,203.29&OV0556;, P < 0.0001). All studies reported no adverse events associated to OMT. Subgroup analysis showed that the benefit of OMT is inversely associated to gestational age. The present systematic review showed the clinical effectiveness of OMT on the reduction of LOS and costs in a large population of preterm infants.

  9. 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.

  10. 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.

  11. Analysis of allergen immunotherapy studies shows increased clinical efficacy in highly symptomatic patients

    DEFF Research Database (Denmark)

    Howarth, P; Malling, Hans-Jørgen; Molimard, M

    2011-01-01

    To cite this article: Howarth P, Malling H-J, Molimard M, Devillier P. Analysis of allergen immunotherapy studies shows increased clinical efficacy in highly symptomatic patients. Allergy 2012; 67: 321-327. ABSTRACT: Background:  The assessment of allergen immunotherapy (AIT) efficacy...... them. Thus, clinical studies of AIT can neither establish baseline symptom levels nor limit the enrolment of patients to those with the most severe symptoms. Allergen immunotherapy treatment effects are therefore diluted by patients with low symptoms for a particular pollen season. The objective...... of this analysis was to assess the effect possible to achieve with AIT in the groups of patients presenting the most severe allergic symptoms. Methods:  Study centres were grouped into tertiles categorized according to symptom severity scores observed in the placebo patients in each centre (low, middle and high...

  12. 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

  13. Subgroup Achievement and Gap Trends: District of Columbia

    Science.gov (United States)

    Center on Education Policy, 2010

    2010-01-01

    The District's demographics are such that achievement trends could only be determined for African American, male and female, and low income subgroups. In grade 8 (the only grade in which subgroup trends were analyzed by achievement level), Washington, DC students showed gains in both reading and math at the basic, proficient, and advanced levels…

  14. 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.

  15. 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...

  16. Combined analysis of 19 common validated type 2 diabetes susceptibility gene variants shows moderate discriminative value and no evidence of gene-gene interaction

    DEFF Research Database (Denmark)

    Sparsø, T; Grarup, N; Andreasen, C

    2009-01-01

    the area under a ROC curve to estimate the discrimination rate between glucose-tolerant individuals and type 2 diabetes patients based on the 19 variants. We found an area under the ROC curve of 0.60. Two-way gene-gene interaction showed few nominal interaction effects. CONCLUSIONS/INTERPRETATION: Combined...... analysis of the 19 validated variants enables detection of subgroups at substantially increased risk of type 2 diabetes; however, the discrimination between glucose-tolerant and type 2 diabetes individuals is still too inaccurate to achieve clinical value.......AIMS/HYPOTHESIS: The list of validated type 2 diabetes susceptibility variants has recently been expanded from three to 19. The variants identified are common and have low penetrance in the general population. The aim of the study is to investigate the combined effect of the 19 variants by applying...

  17. 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

  18. 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.

  19. Cross-platform single cell analysis of kidney development shows stromal cells express Gdnf.

    Science.gov (United States)

    Magella, Bliss; Adam, Mike; Potter, Andrew S; Venkatasubramanian, Meenakshi; Chetal, Kashish; Hay, Stuart B; Salomonis, Nathan; Potter, S Steven

    2018-02-01

    The developing kidney provides a useful model for study of the principles of organogenesis. In this report we use three independent platforms, Drop-Seq, Chromium 10x Genomics and Fluidigm C1, to carry out single cell RNA-Seq (scRNA-Seq) analysis of the E14.5 mouse kidney. Using the software AltAnalyze, in conjunction with the unsupervised approach ICGS, we were unable to identify and confirm the presence of 16 distinct cell populations during this stage of active nephrogenesis. Using a novel integrative supervised computational strategy, we were able to successfully harmonize and compare the cell profiles across all three technological platforms. Analysis of possible cross compartment receptor/ligand interactions identified the nephrogenic zone stroma as a source of GDNF. This was unexpected because the cap mesenchyme nephron progenitors had been thought to be the sole source of GDNF, which is a key driver of branching morphogenesis of the collecting duct system. The expression of Gdnf by stromal cells was validated in several ways, including Gdnf in situ hybridization combined with immunohistochemistry for SIX2, and marker of nephron progenitors, and MEIS1, a marker of stromal cells. Finally, the single cell gene expression profiles generated in this study confirmed and extended previous work showing the presence of multilineage priming during kidney development. Nephron progenitors showed stochastic expression of genes associated with multiple potential differentiation lineages. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Proteome Analysis of the Plant Pathogenic Fungus Monilinia laxa Showing Host Specificity

    Directory of Open Access Journals (Sweden)

    Olja Bregar

    2012-01-01

    Full Text Available Brown rot fungus Monilinia laxa (Aderh. & Ruhl. Honey is an important plant pathogen in stone and pome fruits in Europe. We applied a proteomic approach in a study of M. laxa isolates obtained from apples and apricots in order to show the host specifity of the isolates and to analyse differentially expressed proteins in terms of host specifity, fungal pathogenicity and identification of candidate proteins for diagnostic marker development. Extracted mycelium proteins were separated by 2-D electrophoresis (2-DE and visualized by Coomassie staining in a non-linear pH range of 3–11 and Mr of 14–116 kDa. We set up a 2-DE reference map of M. laxa, resolving up to 800 protein spots, and used it for image analysis. The average technical coefficient of variance (13 % demonstrated a high reproducibility of protein extraction and 2-D polyacrylamide gel electrophoresis (2-DE PAGE, and the average biological coefficient of variance (23 % enabled differential proteomic analysis of the isolates. Multivariate statistical analysis (principal component analysis discriminated isolates from two different hosts, providing new data that support the existence of a M. laxa specialized form f. sp. mali, which infects only apples. A total of 50 differentially expressed proteins were further analyzed by LC-MS/MS, yielding 41 positive identifications. The identified mycelial proteins were functionally classified into 6 groups: amino acid and protein metabolism, energy production, carbohydrate metabolism, stress response, fatty acid metabolism and other proteins. Some proteins expressed only in apple isolates have been described as virulence factors in other fungi. The acetolactate synthase was almost 11-fold more abundant in apple-specific isolates than in apricot isolates and it might be implicated in M. laxa host specificity. Ten proteins identified only in apple isolates are potential candidates for the development of M. laxa host-specific diagnostic markers.

  1. Patients with schizophrenia show aberrant patterns of basal ganglia activation: Evidence from ALE meta-analysis.

    Science.gov (United States)

    Bernard, Jessica A; Russell, Courtney E; Newberry, Raeana E; Goen, James R M; Mittal, Vijay A

    2017-01-01

    The diverse circuits and functional contributions of the basal ganglia, coupled with known differences in dopaminergic function in patients with schizophrenia, suggest they may be an important contributor to the etiology of the hallmark symptoms and cognitive dysfunction experienced by these patients. Using activation-likelihood-estimation meta-analysis of functional imaging research, we investigated differences in activation patterns in the basal ganglia in patients with schizophrenia, relative to healthy controls across task domains. This analysis included 42 functional neuroimaging studies, representing a variety of behavioral domains that have been linked to basal ganglia function in prior work. We provide important new information about the functional activation patterns and functional topography of the basal ganglia for different task domains in healthy controls. Crucially however, we demonstrate that across task domains, patients with schizophrenia show markedly decreased activation in the basal ganglia relative to healthy controls. Our results provide further support for basal ganglia dysfunction in patients with schizophrenia, and the broad dysfunction across task domains may contribute to the symptoms and cognitive deficits associated with schizophrenia.

  2. HIV-1 Phylogenetic analysis shows HIV-1 transits through the meninges to brain and peripheral tissues

    Science.gov (United States)

    Lamers, Susanna L.; Gray, Rebecca R.; Salemi, Marco; Huysentruyt, Leanne C.; McGrath, Michael

    2010-01-01

    Brain infection by the human immunodeficiency virus type 1 (HIV-1) has been investigated in many reports with a variety of conclusions concerning the time of entry and degree of viral compartmentalization. To address these diverse findings, we sequenced HIV-1 gp120 clones from a wide range of brain, peripheral and meningeal tissues from five patients who died from several HIV-1 associated disease pathologies. High-resolution phylogenetic analysis confirmed previous studies that showed a significant degree of compartmentalization in brain and peripheral tissue subpopulations. Some intermixing between the HIV-1 subpopulations was evident, especially in patients that died from pathologies other than HIV-associated dementia. Interestingly, the major tissue harboring virus from both the brain and peripheral tissues was the meninges. These results show that 1) HIV-1 is clearly capable of migrating out of the brain, 2) the meninges are the most likely primary transport tissues, and 3) infected brain macrophages comprise an important HIV reservoir during highly active antiretroviral therapy. PMID:21055482

  3. Gambaran Populasi Golongan Darah Subgroup A (A1, A2 di PMI Kulon Progo

    Directory of Open Access Journals (Sweden)

    Hieronymus Rayi Prasetya

    2017-08-01

    Full Text Available Subgroup A1 and A2 are the most important in the blood group A. Subgroup A1 has the A antigen more than A2 subgroup, the A2 subgroup can cause misidentification of blood group due to poor A antigen and genetic variation possessed. Misidentification of the blood group will increase the risk of transfusion reactions. This research aims to describe the A1 and A2 subgroup population in Kulon Progo district. This study was conducted with a cross sectional sampling technique. The sample in this study were taken from donors of blood group A in Kulon Progo Red Cross. Identification of A1 and A2 subgroup is done by using lectin (Dolichos biflorus extract. The result of the examination of 53 samples showed that 96,2% was A1 subgroup and 3,8% was A2 subgroup. Key words : Subgroup A1, Subgroup A2, Population, Kulon Progo

  4. 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.

  5. 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.

  6. 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.

  7. 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...

  8. 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...

  9. 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.

  10. 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.

  11. Factor analysis shows association between family activity environment and children's health behaviour.

    Science.gov (United States)

    Hendrie, Gilly A; Coveney, John; Cox, David N

    2011-12-01

    To characterise the family activity environment in a questionnaire format, assess the questionnaire's reliability and describe its predictive ability by examining the relationships between the family activity environment and children's health behaviours - physical activity, screen time and fruit and vegetable intake. This paper describes the creation of a tool, based on previously validated scales, adapted from the food domain. Data are from 106 children and their parents (Adelaide, South Australia). Factor analysis was used to characterise factors within the family activity environment. Pearson-Product Moment correlations between the family environment and child outcomes, controlling for demographic variation, were examined. Three factors described the family activity environment - parental activity involvement, opportunity for role modelling and parental support for physical activity - and explained 37.6% of the variance. Controlling for demographic factors, the scale was significantly correlated with children's health behaviour - physical activity (r=0.27), screen time (r=-0.24) and fruit and vegetable intake (r=0.34). The family activity environment questionnaire shows high internal consistency and moderate predictive ability. This study has built on previous research by taking a more comprehensive approach to measuring the family activity environment. This research suggests the family activity environment should be considered in family-based health promotion interventions. © 2011 The Authors. ANZJPH © 2011 Public Health Association of Australia.

  12. Analysis of experimental evidence that shows adverse effects of salt and its relation to hypertension

    Directory of Open Access Journals (Sweden)

    Ignacio Bravo A.

    2012-02-01

    Full Text Available The study by Taylor et al published in June 2010 in the American Journal of Hypertension questions the effectiveness of reducing salt intake in the diet in the prevention and treatment of high blood pressure and other cardiovascular conditions. The publication of this article has lead to great controversy and medical associations and learned societies responded promptly. The response criticized the results of the meta-analysis and pointed out its methodological shortcomings. In this review we critically appraise the experimental evidence that shows the importance of diet salt intake and its role as a determinant of blood pressure. We briefly describe the paradigm that explains the role of salt intake in contributing in the regulation of blood pressure (Guyton hypothesis and model and we mention the experimental evidence that supports this. We briefly comment on the classical studies that indicate that salt intake (NaCl contributes directly to the development of high blood pressure and target tissues. Finally, we briefly mention the experimental data that is related with the controversy on the role of salt (NaCl or sodium as prohypertensive agents.

  13. Gut Transcriptome Analysis Shows Different Food Utilization Efficiency by the Grasshopper Oedaleous asiaticus (Orthoptera: Acrididae).

    Science.gov (United States)

    Huang, Xunbing; McNeill, Mark Richard; Ma, Jingchuan; Qin, Xinghu; Tu, Xiongbing; Cao, Guangchun; Wang, Guangjun; Nong, Xiangqun; Zhang, Zehua

    2017-08-01

    Oedaleus asiaticus B. Bienko is a persistent pest occurring in north Asian grasslands. We found that O. asiaticus feeding on Stipa krylovii Roshev. had higher approximate digestibility (AD), efficiency of conversion of ingested food (ECI), and efficiency of conversion of digested food (ECD), compared with cohorts feeding on Leymus chinensis (Trin.) Tzvel, Artemisia frigida Willd., or Cleistogenes squarrosa (Trin.) Keng. Although this indicated high food utilization efficiency for S. krylovii, the physiological processes and molecular mechanisms underlying these biological observations are not well understood. Transcriptome analysis was used to examine how gene expression levels in O. asiaticus gut are altered by feeding on the four plant species. Nymphs (fifth-instar female) that fed on S. krylovii had the largest variation in gene expression profiles, with a total of 88 genes significantly upregulated compared with those feeding on the other three plants, mainly including nutrition digestive genes of protein, carbohydrate, and lipid digestion. GO and KEGG enrichment also showed that feeding S. krylovii could upregulate the nutrition digestion-related molecular function, biological process, and pathways. These changes in transcripts levels indicate that the physiological processes of activating nutrition digestive enzymes and metabolism pathways can well explain the high food utilization of S. krylovii by O. asiaticus. © 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.

  14. 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.

  15. Detecting treatment-subgroup interactions in clustered data with generalized linear mixed-effects model trees.

    Science.gov (United States)

    Fokkema, M; Smits, N; Zeileis, A; Hothorn, T; Kelderman, H

    2017-10-25

    Identification of subgroups of patients for whom treatment A is more effective than treatment B, and vice versa, is of key importance to the development of personalized medicine. Tree-based algorithms are helpful tools for the detection of such interactions, but none of the available algorithms allow for taking into account clustered or nested dataset structures, which are particularly common in psychological research. Therefore, we propose the generalized linear mixed-effects model tree (GLMM tree) algorithm, which allows for the detection of treatment-subgroup interactions, while accounting for the clustered structure of a dataset. The algorithm uses model-based recursive partitioning to detect treatment-subgroup interactions, and a GLMM to estimate the random-effects parameters. In a simulation study, GLMM trees show higher accuracy in recovering treatment-subgroup interactions, higher predictive accuracy, and lower type II error rates than linear-model-based recursive partitioning and mixed-effects regression trees. Also, GLMM trees show somewhat higher predictive accuracy than linear mixed-effects models with pre-specified interaction effects, on average. We illustrate the application of GLMM trees on an individual patient-level data meta-analysis on treatments for depression. We conclude that GLMM trees are a promising exploratory tool for the detection of treatment-subgroup interactions in clustered datasets.

  16. 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...

  17. Empirical analysis shows reduced cost data collection may be an efficient method in economic clinical trials.

    Science.gov (United States)

    Seidl, Hildegard; Meisinger, Christa; Wende, Rupert; Holle, Rolf

    2012-09-15

    Data collection for economic evaluation alongside clinical trials is burdensome and cost-intensive. Limiting both the frequency of data collection and recall periods can solve the problem. As a consequence, gaps in survey periods arise and must be filled appropriately. The aims of our study are to assess the validity of incomplete cost data collection and define suitable resource categories. In the randomised KORINNA study, cost data from 234 elderly patients were collected quarterly over a 1-year period. Different strategies for incomplete data collection were compared with complete data collection. The sample size calculation was modified in response to elasticity of variance. Resource categories suitable for incomplete data collection were physiotherapy, ambulatory clinic in hospital, medication, consultations, outpatient nursing service and paid household help. Cost estimation from complete and incomplete data collection showed no difference when omitting information from one quarter. When omitting information from two quarters, costs were underestimated by 3.9% to 4.6%.With respect to the observed increased standard deviation, a larger sample size would be required, increased by 3%. Nevertheless, more time was saved than extra time would be required for additional patients. Cost data can be collected efficiently by reducing the frequency of data collection. This can be achieved by incomplete data collection for shortened periods or complete data collection by extending recall windows. In our analysis, cost estimates per year for ambulatory healthcare and non-healthcare services in terms of three data collections was as valid and accurate as a four complete data collections. In contrast, data on hospitalisation, rehabilitation stays and care insurance benefits should be collected for the entire target period, using extended recall windows. When applying the method of incomplete data collection, sample size calculation has to be modified because of the increased

  18. 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.

    Science.gov (United States)

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

    2017-06-02

    Mauritius cumulated 44%. Here, among the 84 observed COI-COII haplotypes, 50 were newly described including 13 which were private to the SWIO archipelagos and Madagascar. Similarly, 24 of the 34 found ND2 haplotypes were novel which included six haplotypes particular to the SWIO populations. A new African subgroup was described in the SWIO region with mitochondrial genetic evidence that A. m. unicolor is the indigenous subspecies of the archipelagos surrounding Madagascar.

  19. 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

  20. 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.

  1. 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

  2. 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.

  3. Nonlinear Analysis of Motor Activity Shows Differences between Schizophrenia and Depression: A Study Using Fourier Analysis and Sample Entropy

    Science.gov (United States)

    Hauge, Erik R.; Berle, Jan Øystein; Oedegaard, Ketil J.; Holsten, Fred; Fasmer, Ole Bernt

    2011-01-01

    The purpose of this study has been to describe motor activity data obtained by using wrist-worn actigraphs in patients with schizophrenia and major depression by the use of linear and non-linear methods of analysis. Different time frames were investigated, i.e., activity counts measured every minute for up to five hours and activity counts made hourly for up to two weeks. The results show that motor activity was lower in the schizophrenic patients and in patients with major depression, compared to controls. Using one minute intervals the depressed patients had a higher standard deviation (SD) compared to both the schizophrenic patients and the controls. The ratio between the root mean square successive differences (RMSSD) and SD was higher in the schizophrenic patients compared to controls. The Fourier analysis of the activity counts measured every minute showed that the relation between variance in the low and the high frequency range was lower in the schizophrenic patients compared to the controls. The sample entropy was higher in the schizophrenic patients compared to controls in the time series from the activity counts made every minute. The main conclusions of the study are that schizophrenic and depressive patients have distinctly different profiles of motor activity and that the results differ according to period length analysed. PMID:21297977

  4. 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...

  5. 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

  6. Ribosomal DNA sequence analysis shows that the basidiomycete C30 belongs to the genus Trametes.

    Science.gov (United States)

    Klonowska, Agnieszka; Gaudin, Christian; Ruzzi, Maurizio; Colao, Maria Chiara; Tron, Thierry

    2003-01-01

    The basidiomycete C30 was considered as an isolate of a population of Marasmius quercophilus collected on evergreen oak litter from the Mediterranean forest. Recent phenotypic studies have clearly shown that it differs from newly characterized M. quercophilus isolates. Subsequent analysis of laccase genes revealed that C30 sequences are similar to laccase encoding sequences from organisms belonging to the polyporoid clade. Comparison of sequences of the C30 ITS regions, including 5.8S rDNA, with those found in databanks confirmed that C30 is not a Marasmius. Finally, 25S rDNA analysis revealed that C30 is closely related to the Coriolaceae and, in particular, to Trametes trogii.

  7. Analysis of competition performance in dressage and show jumping of Dutch Warmblood horses

    NARCIS (Netherlands)

    Rovere, G.; Ducro, B.J.; Arendonk, van J.A.M.; Norberg, E.; Madsen, P.

    2016-01-01

    Most Warmblood horse studbooks aim to improve the performance in dressage and show jumping. The Dutch Royal Warmblood Studbook (KWPN) includes the highest score achieved in competition by a horse to evaluate its genetic ability of performance. However, the records collected during competition are

  8. Radiographic analysis of odontogenic cysts showing displacement of the mandibular canal

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Bong Hae [Pusan National University College of Medicine, Busan (Korea, Republic of)

    2003-12-15

    To assess the radiographic findings of odontogenic cysts showing displacement of the mandibular canal using computed tomographic (CT) and panoramic images. CT and panoramic images of 63 odontogenic cysts (27 dentigerous, 16 odontogenic keratocysts, and 20 radicular cysts) were analyzed to evaluate the following parameters: the dimension and shape of the cysts, and the effect of the cysts on the mandibular canal and cortical plates. Of the 63 cysts examined in the study, 35 (55.6%) showed inferior displacement of the mandibular canal and 46 (73.0%) showed perforation of the canal. There were statistically significant differenced between CT and panoramic images in depicting displacement and perforation of the mandibular canal. Cortical expansion was seen in 46 cases (73.0%) and cortical perforation in 23 cases (36.5%). The radicular cysts showed cortical expansion and perforation less frequently than the other cyst groups. Large cysts of mandible should be evaluated by multiplanar CT images in order to detect the mandibular canal and cortical bone involvement.

  9. Economic impact and market analysis of a special event: The Great New England Air Show

    Science.gov (United States)

    Rodney B. Warnick; David C. Bojanic; Atul Sheel; Apurv Mather; Deepak. Ninan

    2010-01-01

    We conducted a post-event evaluation for the Great New England Air Show to assess its general economic impact and to refine economic estimates where possible. In addition to the standard economic impact variables, we examined travel distance, purchase decision involvement, event satisfaction, and frequency of attendance. Graphic mapping of event visitors' home ZIP...

  10. Social network analysis shows direct evidence for social transmission of tool use in wild chimpanzees.

    Directory of Open Access Journals (Sweden)

    Catherine Hobaiter

    2014-09-01

    Full Text Available Social network analysis methods have made it possible to test whether novel behaviors in animals spread through individual or social learning. To date, however, social network analysis of wild populations has been limited to static models that cannot precisely reflect the dynamics of learning, for instance, the impact of multiple observations across time. Here, we present a novel dynamic version of network analysis that is capable of capturing temporal aspects of acquisition--that is, how successive observations by an individual influence its acquisition of the novel behavior. We apply this model to studying the spread of two novel tool-use variants, "moss-sponging" and "leaf-sponge re-use," in the Sonso chimpanzee community of Budongo Forest, Uganda. Chimpanzees are widely considered the most "cultural" of all animal species, with 39 behaviors suspected as socially acquired, most of them in the domain of tool-use. The cultural hypothesis is supported by experimental data from captive chimpanzees and a range of observational data. However, for wild groups, there is still no direct experimental evidence for social learning, nor has there been any direct observation of social diffusion of behavioral innovations. Here, we tested both a static and a dynamic network model and found strong evidence that diffusion patterns of moss-sponging, but not leaf-sponge re-use, were significantly better explained by social than individual learning. The most conservative estimate of social transmission accounted for 85% of observed events, with an estimated 15-fold increase in learning rate for each time a novice observed an informed individual moss-sponging. We conclude that group-specific behavioral variants in wild chimpanzees can be socially learned, adding to the evidence that this prerequisite for culture originated in a common ancestor of great apes and humans, long before the advent of modern humans.

  11. Restriction fragment length polymorphism analysis shows that the hippuricase gene of Campylobacter jejuni is highly conserved.

    Science.gov (United States)

    Slater, E R; Owen, R J

    1997-10-01

    A 1151-bp amplicon containing the hippuricase (hipO) gene was obtained from 118 strains of Campylobacter jejuni and double-digested with AluI and DdeI to give five different PCR-RFLP patterns. Most strains had the six-banded profile predicted from sequence data. Lack of polymorphisms within the hipO gene indicated it was highly conserved amongst strains of Camp.jejuni, and the RFLP analysis provided only low discrimination as an epidemiological typing method. Detection of hipO by PCR provided a useful test for confirmatory identification of Camp. jejuni.

  12. Comparative genome analysis of the vineyard weed endophyte Pseudomonas viridiflava CDRTc14 showing selective herbicidal activity.

    Science.gov (United States)

    Samad, Abdul; Antonielli, Livio; Sessitsch, Angela; Compant, Stéphane; Trognitz, Friederike

    2017-12-11

    Microbes produce a variety of secondary metabolites to be explored for herbicidal activities. We investigated an endophyte Pseudomonas viridiflava CDRTc14, which impacted growth of its host Lepidium draba L., to better understand the possible genetic determinants for herbicidal and host-interaction traits. Inoculation tests with a variety of target plants revealed that CDRTc14 shows plant-specific effects ranging from beneficial to negative. Its herbicidal effect appeared to be dose-dependent and resembled phenotypically the germination arrest factor of Pseudomonas fluorescens WH6. CDRTc14 shares 183 genes with the herbicidal strain WH6 but the formylaminooxyvinylglycine (FVG) biosynthetic genes responsible for germination arrest of WH6 was not detected. CDRTc14 showed phosphate solubilizing ability, indole acetic acid and siderophores production in vitro and harbors genes for these functions. Moreover, genes for quorum sensing, hydrogen cyanide and ACC deaminase production were also found in this strain. Although, CDRTc14 is related to plant pathogens, we neither found a complete pathogenicity island in the genome, nor pathogenicity symptoms on susceptible plant species upon CDRTc14 inoculation. Comparison with other related genomes showed several unique genes involved in abiotic stress tolerance in CDRTc14 like genes responsible for heavy metal and herbicide resistance indicating recent adaptation to plant protection measures applied in vineyards.

  13. 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.

  14. Complete genome sequence analysis of goatpox virus isolated from China shows high variation.

    Science.gov (United States)

    Zeng, Xiancheng; Chi, Xuelin; Li, Wei; Hao, Wenbo; Li, Ming; Huang, Xiaohong; Huang, Yifan; Rock, Daniel L; Luo, Shuhong; Wang, Shihua

    2014-09-17

    Goatpox virus (GTPV), a member of the Capripoxvirus genus of the Poxviridae family, is the causative agent of variolo caprina (goatpox). GTPV can cause significant economic losses of domestic ruminants in endemic regions and can threaten breeding stocks. In this study, we report on the compilation of the complete genomic sequence of an isolated GTPV field strain FZ (GTPV_FZ). The 150,194bp GTPV genome consists of a central coding region bounded by two identical 2301bp inverted terminal repeats and contains 151 putative genes. Comparative genomic analysis reveals the apparent genetic relationships among Capripoxviruses are close, but sufficient genomic variants in the field isolate strain FZ have been identified to distinguish it from other GTPV strains and other Capripoxvirus species. Phylogenetic analysis based on the p32 and complete GTPV genome can be used to differentiate SPPVs, GTPVs and LSDVs. These data may contribute to the epidemiological study of the Chinese capripoxvirus and help to develop more specific detection methods to distinguish GTPVs, SPPVs and LSDVs. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. 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...

  16. Differential temperature Carnot heat analysis shows that computing machines are thermodynamically irreversible

    Science.gov (United States)

    Parker, Michael C.; Walker, Stuart D.

    2008-07-01

    We perform a differential temperature Carnot analysis of the changes in energy and entropy (degrees of freedom) associated with an ideal classical computing machine. Assuming that Carnot's maximum efficiency law is as equally applicable to a computing machine as to a mechanical machine, we find that useful computation is necessarily dissipative and thermodynamically irreversible. In addition, we find that copying or cloning of information is as dissipative as the original process employed to create the information (through a computation) in the first place. We prove minimum heat dissipation kT ln 2 per output calculation bit, where T is the thermodynamic temperature of unavoidable by-product bits (i.e. not the output calculation bits) rather than a generally assumed 'surrounding environment' temperature. Overall, this places computers into the same category as conventional machines, obeying the second law of thermodynamics and always operating below 100% efficiency, such that a perpetual calculating machine cannot exist.

  17. 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.

  18. Genome-wide microarray analysis of tomato roots showed defined responses to iron deficiency

    Directory of Open Access Journals (Sweden)

    Zamboni Anita

    2012-03-01

    Full Text Available Abstract Background Plants react to iron deficiency stress adopting different kind of adaptive responses. Tomato, a Strategy I plant, improves iron uptake through acidification of rhizosphere, reduction of Fe3+ to Fe2+ and transport of Fe2+ into the cells. Large-scale transcriptional analyses of roots under iron deficiency are only available for a very limited number of plant species with particular emphasis for Arabidopsis thaliana. Regarding tomato, an interesting model species for Strategy I plants and an economically important crop, physiological responses to Fe-deficiency have been thoroughly described and molecular analyses have provided evidence for genes involved in iron uptake mechanisms and their regulation. However, no detailed transcriptome analysis has been described so far. Results A genome-wide transcriptional analysis, performed with a chip that allows to monitor the expression of more than 25,000 tomato transcripts, identified 97 differentially expressed transcripts by comparing roots of Fe-deficient and Fe-sufficient tomato plants. These transcripts are related to the physiological responses of tomato roots to the nutrient stress resulting in an improved iron uptake, including regulatory aspects, translocation, root morphological modification and adaptation in primary metabolic pathways, such as glycolysis and TCA cycle. Other genes play a role in flavonoid biosynthesis and hormonal metabolism. Conclusions The transcriptional characterization confirmed the presence of the previously described mechanisms to adapt to iron starvation in tomato, but also allowed to identify other genes potentially playing a role in this process, thus opening new research perspectives to improve the knowledge on the tomato root response to the nutrient deficiency.

  19. 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.

  20. Genetic and Antigenic Analysis of Adenovirus Type 3 Strains Showing Intermediate Behavior in Standard Seroneutralization Test

    Directory of Open Access Journals (Sweden)

    Márcia TB Moraes

    1998-03-01

    Full Text Available During an epidemiological survey of acute respiratory infection in Rio de Janeiro, among 208 adenovirus isolates, we found two strains that we were not able, by a standard neutralization procedure, to distinguish between type 3 or 7. However, DNA restriction pattern for the two strains with different enzymes were analyzed and showed a typical Ad3h profile. Using a cross-neutralization test in which both Ad3p and Ad7p antisera were used in different concentration against 100 TCID50 of each adenovirus standard and both isolates, we were able to confirm that the two isolates belong to serotype 3. An hemagglutination inhibition test also corroborated the identification of both strains as adenovirus type 3. Comparing Ad3h and Ad3p genome, we observed 16 different restriction enzyme sites, three of which were located in genomic regions encoding polypeptides involved in neutralization sites

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

    Directory of Open Access Journals (Sweden)

    Ahmed HU

    2011-06-01

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

  2. Network meta-analysis shows commercialized subcutaneous and sublingual grass products have comparable efficacy.

    Science.gov (United States)

    Nelson, Harold; Cartier, Shannon; Allen-Ramey, Felicia; Lawton, Simon; Calderon, Moises A

    2015-01-01

    Subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) have been shown to effectively treat grass pollen allergies, although direct comparisons are sparse. To estimate the relative efficacy of SLIT tablets compared with SCIT and SLIT drops in commercially available products though network meta-analysis. A literature search of MEDLINE, Embase, and Cochrane Library publications. Randomized, double-blind clinical trials of SCIT, SLIT drops, and SLIT tablets for grass pollen were included. Bayesian network meta-analyses estimated the standardized mean difference (SMD) across 3 immunotherapy modalities on allergic rhinoconjunctivitis symptom and medication score data from publications or received from authors. Both fixed and random effects models were investigated. Thirty-seven studies were included in meta-analyses for symptom scores and 31 studies for medication scores. In the random effects model, SCIT and SLIT tablets were significantly different from placebo for symptom scores: SMDs (95% CI) of -0.32 (-0.45 to -0.18) and -0.32 (-0.41 to -0.23), respectively. No significant difference was identified for SLIT drops compared with placebo (SMD, -0.17; -0.37 to 0.04). For medication scores, significant differences compared with placebo were observed for SCIT (SMD, -0.33; 95% CI, -0.52 to -0.13), SLIT tablets (SMD, -0.23; 95% CI, -0.29 to -0.17), and SLIT drops (SMD, -0.44; 95% CI, -0.83 to -0.06). Network meta-analysis revealed no significant differences in SMDs (95% credible interval) for symptom scores (0.0145 [-0.19 to 0.23]) or medication scores (0.133 [-0.31 to 0.57]) between SLIT tablets and SCIT, or for symptom scores (-0.175 [-0.37 to 0.02]) and medication scores (0.188 [-0.18 to 0.56]) between SLIT tablets and SLIT drops. The comparisons for grass pollen immunotherapy products commercialized in at least 1 country indicate comparable reductions in allergic rhinoconjunctivitis symptoms and supplemental medication use for SLIT tablets

  3. A combined tract-based spatial statistics and voxel-based morphometry study of the first MRI scan after diagnosis of amyotrophic lateral sclerosis with subgroup analysis.

    Science.gov (United States)

    Alruwaili, A R; Pannek, K; Coulthard, A; Henderson, R; Kurniawan, N D; McCombe, P

    2017-08-09

    This study aims to compare the cortical and subcortical deep gray matter (GM) and white matter (WM) of ALS subjects and controls and to compare ALS subjects with (ALScog) and without (ALSnon-cog) cognitive impairment. The study was performed in 30 ALS subjects, and 19 healthy controls. Structural T1- and diffusion-weighted MRI data were analyzed using voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS). All DTI measures and GM volume differed significantly between ALS subjects and controls. Compared to controls, greater DTI changes were present in ALScog than ALSnon-cog subjects. GM results showed reduction in the caudate nucleus volume in ALScog subjects compared to ALSnon-cog. and comparing all ALS with controls, there were changes on the right side and in a small region in the left middle frontal gyrus. This combined DTI and VBM study showed changes in motor and extra-motor regions. The DTI changes were more extensive in ALScog than ALSnon-cog subjects. It is likely that the inclusion of ALS subjects with cognitive impairment in previous studies resulted in extra-motor WM abnormalities being reported in ALS subjects. Copyright © 2017. Published by Elsevier Masson SAS.

  4. Markers typed in genome-wide analysis identify regions showing deviation from Hardy-Weinberg equilibrium.

    Science.gov (United States)

    Vine, Anna E; Curtis, David

    2009-03-02

    Deviations from Hardy-Weinberg equilibrium (HWE) are commonly thought of as indicating genotyping errors, population stratification or some other artefact. However they could also arise through important biological mechanisms. In particular, genetic variants having a recessive effect on the successful fertilisation and/or development of an embryo might be manifest through such deviations in an unselected sample of "control" subjects. We investigated genotypes from 463842 autosomal markers from 1504 British subjects. We identified regions in which several neighbouring markers exhibited deviation from HWE in the same direction by considering "heterozygosity scores" in windows of 10 markers. The heterozygosity score for each marker was defined as -log(p) or log(p) according to whether the marker demonstrated increased heterozygosity or homozygosity. In each window the marker with the highest absolute score was ignored and the positive and negative scores were summed for the other nine markers. Windows were selected on the basis of this sum exceeding a given threshold, for which we used values of 50 or 15.For the threshold of 50, we identified 7 regions with increased heterozygosity and for the threshold of 15 we identified 22 regions with increased heterozygosity, 23 with increased homozygosity and 2 containing both kinds of window. The most impressive of these results came from a group of 6 markers at 17q21, each of which showed increased heterozygosity significant at p < 10(-190). The human genome contains regions which deviate markedly from HWE and these might harbour genes influencing embryonic survival.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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

  12. 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.

  13. On T-Characterized Subgroups of Compact Abelian Groups

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    Saak Gabriyelyan

    2015-06-01

    Full Text Available A sequence \\(\\{ u_n \\}_{n\\in \\omega}\\ in abstract additively-written Abelian group \\(G\\ is called a \\(T\\-sequence if there is a Hausdorff group topology on \\(G\\ relative to which \\(\\lim_n u_n =0\\. We say that a subgroup \\(H\\ of an infinite compact Abelian group \\(X\\ is \\(T\\-characterized if there is a \\(T\\-sequence \\(\\mathbf{u} =\\{ u_n \\}\\ in the dual group of \\(X\\, such that \\(H=\\{ x\\in X: \\; (u_n, x\\to 1 \\}\\. We show that a closed subgroup \\(H\\ of \\(X\\ is \\(T\\-characterized if and only if \\(H\\ is a \\(G_\\delta\\-subgroup of \\(X\\ and the annihilator of \\(H\\ admits a Hausdorff minimally almost periodic group topology. All closed subgroups of an infinite compact Abelian group \\(X\\ are \\(T\\-characterized if and only if \\(X\\ is metrizable and connected. We prove that every compact Abelian group \\(X\\ of infinite exponent has a \\(T\\-characterized subgroup, which is not an \\(F_{\\sigma}\\-subgroup of \\(X\\, that gives a negative answer to Problem 3.3 in Dikranjan and Gabriyelyan (Topol. Appl. 2013, 160, 2427–2442.

  14. Differences in pain, function and coping in Multidimensional Pain Inventory subgroups of chronic back pain: a one-group pretest-posttest study

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    Staal J Bart

    2011-06-01

    Full Text Available Abstract Background Patients with non-specific back pain are not a homogeneous group but heterogeneous with regard to their bio-psycho-social impairments. This study examined a sample of 173 highly disabled patients with chronic back pain to find out how the three subgroups based on the Multidimensional Pain Inventory (MPI differed in their response to an inpatient pain management program. Methods Subgroup classification was conducted by cluster analysis using MPI subscale scores at entry into the program. At program entry and at discharge after four weeks, participants completed the MPI, the MOS Short Form-36 (SF-36, the Hospital Anxiety and Depression Scale (HADS, and the Coping Strategies Questionnaire (CSQ. Pairwise analyses of the score changes of the mentioned outcomes of the three MPI subgroups were performed using the Mann-Whitney-U-test for significance. Results Cluster analysis identified three MPI subgroups in this highly disabled sample: a dysfunctional, interpersonally distressed and an adaptive copers subgroup. The dysfunctional subgroup (29% of the sample showed the highest level of depression in SF-36 mental health (33.4 ± 13.9, the interpersonally distressed subgroup (35% of the sample a modest level of depression (46.8 ± 20.4, and the adaptive copers subgroup (32% of the sample the lowest level of depression (57.8 ± 19.1. Significant differences in pain reduction and improvement of mental health and coping were observed across the three MPI subgroups, i.e. the effect sizes for MPI pain reduction were: 0.84 (0.44 - 1.24 for the dysfunctional subgroup, 1.22 (0.86 - 1.58 for the adaptive copers subgroup, and 0.53 (0.24 - 0.81 for the interpersonally distressed subgroup (p = 0.006 for pairwise comparison. Significant score changes between subgroups concerning activities and physical functioning could not be identified. Conclusions MPI subgroup classification showed significant differences in score changes for pain, mental health

  15. 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.

  16. 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.

  17. 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…

  18. ∗-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.

  19. Combination Therapy Showed Limited Superiority Over Monotherapy for Alzheimer Disease: A Meta-analysis of 14 Randomized Trials.

    Science.gov (United States)

    Tsoi, Kelvin K F; Chan, Joyce Y C; Leung, Nelson W Y; Hirai, Hoyee W; Wong, Samuel Y S; Kwok, Timothy C Y

    2016-09-01

    Acetylcholinesterase inhibitor (AChEI) and memantine are recognized drug treatments with limited clinical efficacy. Combination therapy for patients with Alzheimer disease (AD) was suggested, but the additional benefit of combination therapy is still controversial. To evaluate the additional benefit of combination therapy over monotherapy with either AChEI or memantine. Prospective randomized controlled trials were searched from the OVID databases. The trials were eligible if study subjects were diagnosed with AD, and were randomized to compare combination therapy with monotherapy. Any clinical assessment measured using validated scales on cognitive function, activities of daily living, behavioral problems, and global changes were the primary outcomes, and any reported adverse events were the secondary outcomes. Quality of studies and risk of bias were evaluated. Fourteen randomized trials were identified between 2004 and 2015 from the United States, Canada, Germany, Japan, China, and Korea. A total of 5019 patients with AD were randomly assigned to receive combination therapy of AChEI and memantine or monotherapy with AChEI or memantine. Combination therapy showed no significant benefit on cognitive function (mean difference [MD] of MMSE = 0.06, 95% CI -0.52 to 0.65), activities of daily living (MD of ADCS-ADL = -0.15, 95% CI -1.08 to 0.78), neuropsychiatric symptoms and behavioral problems (MD of NPI = -1.85, 95% CI -4.83 to 1.13), and global changes (MD of CIBIC-plus = 0.01, 95% CI -0.25 to 0.28). In subgroup analyses, combination therapy can improve cognitive function more than memantine alone; and it can significantly relieve neuropsychiatric symptoms and behavioral problems when concomitantly used with donepezil. No additional adverse event was reported in the combination therapy. Combination therapy only showed the benefit on neuropsychiatric symptoms and behavioral problems in moderate-to-severe AD, but no other superiority in terms of cognitive

  20. 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

  1. 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

  2. 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.

  3. 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).

  4. 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

  5. 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.

  6. Meta-Analysis of the Effects of Puppet Shows on Attitudes toward and Knowledge of Individuals with Disabilities

    Science.gov (United States)

    Dunst, Carl J.

    2014-01-01

    Findings from a meta-analysis of 26 studies investigating the effects of either the "Kids on the Block" or "Count Me In" puppet shows on changes in elementary students' attitudes toward and knowledge of individuals with disabilities are reported. The studies included 5,302 intervention group participants and 2,642…

  7. Heterogeneity in response during multisystemic therapy: Exploring subgroups and predictors

    NARCIS (Netherlands)

    Mertens, E.C.A.; Dekovic, M.; Asscher, J.J.; Manders, W.A.

    2017-01-01

    Multiple studies have shown that Multisystemic Therapy (MST) is, at group level, an effective treatment for adolescents showing serious externalizing problem behavior. The current study expands previous research on MST by, first, examining whether subgroups of participants who respond differently to

  8. Heterogeneity in response during Multisystemic Therapy : Exploring subgroups and predictors

    NARCIS (Netherlands)

    Mertens, E.C.A.; Dekovic, M.; Asscher, J.J.; Manders, W.A.

    2017-01-01

    Multiple studies have shown that Multisystemic Therapy (MST) is, at group level, an effective treatment for adolescents showing serious externalizing problem behavior. The current study expands previous research on MST by, first, examining whether subgroups of participants who respond differently to

  9. Notes on discrete subgroups of Möbius transformations

    Indian Academy of Sciences (India)

    Abstract. Jørgensen's inequality gives a necessary condition for a nonelementary two generator subgroup of SL(2, C) to be discrete. By embedding SL(2, C) into. ˆU(1, 1; H), we obtain a new type of Jørgensen's inequality, which is in terms of the coefficients of involved isometries. We provide an example to show that this ...

  10. Dietary and physical activity behaviors of New York City children from different ethnic minority subgroups.

    Science.gov (United States)

    Vangeepuram, Nita; Mervish, Nancy; Galvez, Maida P; Brenner, Barbara; Wolff, Mary S

    2012-01-01

    To examine racial/ethnic differences in diet and physical activity behaviors in ethnic minority New York City children. Cross-sectional data from a community-based study of 486 6- to 8-year-old children were used. Race/ethnicity was derived using a caregiver's report of child's race and Hispanic ancestry. Dietary intake was obtained by 24-hour diet recalls using the Nutrition Data System for Research. Physical activity was assessed with pedometers and caregiver interviews. We compared diet and activity measures across racial/ethnic subgroups using chi-square and analysis of variance tests. Multivariate analyses adjusted for age, gender, body mass index, and caregiver education (with breastfeeding history and total energy intake included in diet models). Participants (N = 486) were categorized as Mexican (29.4%), Dominican (8.4%), Puerto Rican (20.6%), other/mixed Hispanic (14.0%), or non-Hispanic black (27.6%). Obesity rates were lower in non-Hispanic blacks (18%) than in Hispanics (31%). Mexicans had the lowest obesity rates among Hispanic subgroups (25%), and Dominicans had the highest (39%). There were differences in mean daily servings of food groups, with Mexicans having healthier diets and Puerto Ricans and non-Hispanic Blacks having less healthy diets. Sedentary time was lower in Mexicans than in other groups in adjusted models. Examination of additional models, including home language, did not show significant differences in the estimates. Diet and activity behaviors varied across racial/ethnic subgroups. Specifically, Mexican children had healthier diets, the least amount of sedentary time, and the lowest rates of obesity among the Hispanic subgroups examined. Targeted interventions in ethnic subgroups may be warranted to address specific behaviors. Copyright © 2012 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

  11. The efficacy of natalizumab in patients with relapsing multiple sclerosis: subgroup analyses of AFFIRM and SENTINEL.

    LENUS (Irish Health Repository)

    Hutchinson, Michael

    2012-02-01

    The AFFIRM and SENTINEL studies showed that natalizumab was effective both as monotherapy and in combination with interferon beta (IFNbeta)-1a in patients with relapsing multiple sclerosis (MS). Further analyses of AFFIRM and SENTINEL data were conducted to determine the efficacy of natalizumab in prespecified patient subgroups according to baseline characteristics: relapse history 1 year before randomization (1, 2, > or = 3), Expanded Disability Status Scale score (< or = 3.5, > 3.5), number of T2 lesions (< 9, > or = 9), presence of gadolinium-enhancing (Gd+) lesions (0, > or = 1), age (< 40, > or = 40) and gender (male, female). A post hoc analysis was conducted to determine the efficacy of natalizumab in patients with highly active disease (i. e., > or = 2 relapses in the year before study entry and > or = 1 Gd+ lesion at study entry). In both AFFIRM and SENTINEL studies natalizumab reduced the annualized relapse rates across all subgroups (except the small subgroups with < 9 baseline T2 lesions) over 2 years. In AFFIRM, natalizumab significantly reduced the risk of sustained disability progression in most subgroups. In SENTINEL, natalizumab significantly reduced the risk of sustained disability progression in the following subgroups: > or = 9 T2 lesions at baseline, > or = 1 Gd+ lesions at baseline, female patients and patients < 40 years of age. Natalizumab reduced the risk of disability progression by 64 % and relapse rate by 81 % in treatment- naive patients with highly active disease and by 58 % and 76 %, respectively, in patients with highly active disease despite IFNbeta-1a treatment. These results indicate that natalizumab is effective in reducing disability progression and relapses in patients with relapsing MS, particularly in patients with highly active disease.

  12. 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.

  13. 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

  14. Active medulloblastoma enhancers reveal subgroup-specific cellular origins

    Science.gov (United States)

    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

  15. 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.

  16. Pain Sensitivity Subgroups in Individuals With Spine Pain: Potential Relevance to Short-Term Clinical Outcome

    Science.gov (United States)

    Bialosky, Joel E.; Robinson, Michael E.

    2014-01-01

    Background Cluster analysis can be used to identify individuals similar in profile based on response to multiple pain sensitivity measures. There are limited investigations into how empirically derived pain sensitivity subgroups influence clinical outcomes for individuals with spine pain. Objective The purposes of this study were: (1) to investigate empirically derived subgroups based on pressure and thermal pain sensitivity in individuals with spine pain and (2) to examine subgroup influence on 2-week clinical pain intensity and disability outcomes. Design A secondary analysis of data from 2 randomized trials was conducted. Methods Baseline and 2-week outcome data from 157 participants with low back pain (n=110) and neck pain (n=47) were examined. Participants completed demographic, psychological, and clinical information and were assessed using pain sensitivity protocols, including pressure (suprathreshold pressure pain) and thermal pain sensitivity (thermal heat threshold and tolerance, suprathreshold heat pain, temporal summation). A hierarchical agglomerative cluster analysis was used to create subgroups based on pain sensitivity responses. Differences in data for baseline variables, clinical pain intensity, and disability were examined. Results Three pain sensitivity cluster groups were derived: low pain sensitivity, high thermal static sensitivity, and high pressure and thermal dynamic sensitivity. There were differences in the proportion of individuals meeting a 30% change in pain intensity, where fewer individuals within the high pressure and thermal dynamic sensitivity group (adjusted odds ratio=0.3; 95% confidence interval=0.1, 0.8) achieved successful outcomes. Limitations Only 2-week outcomes are reported. Conclusions Distinct pain sensitivity cluster groups for individuals with spine pain were identified, with the high pressure and thermal dynamic sensitivity group showing worse clinical outcome for pain intensity. Future studies should aim to confirm

  17. 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.

  18. Personality does not distinguish people with fibromyalgia but identifies subgroups of patients.

    Science.gov (United States)

    Torres, Xavier; Bailles, Eva; Valdes, Manuel; Gutierrez, Fernando; Peri, Josep-Maria; Arias, Anna; Gomez, Emili; Collado, Antonio

    2013-01-01

    The objectives were to compare the personality of fibromyalgia (FM) patients with other chronic painful and nonpainful disorders considering the confusion due to psychopathology and to assess the clustering of FM patients according to their personality profile. Differences in the NEO Five-Factor Inventory between FM, non-FM chronic pain and drug-resistant epileptic patients were assessed including the confounding effect of demographics and psychopathological status by multivariate regression analysis. Clustering of FM patients was assessed by two-step cluster analysis. Differences in clinical severity and psychosocial problems between subgroups and their outcome 6 months after multidisciplinary treatment were assessed. The final sample comprised 874 patients. Once the effect of confounding variables was considered, clinically nonsignificant differences in personality were observed between groups. FM patients could, however, be grouped into two clusters. Cluster 1 was characterized by higher neuroticism and lower extraversion and showed a worse pretreatment clinical state including more psychosocial problems. In spite of having reached a wider general improvement at 6-month follow-up, Cluster 1 patients remained more anxious and depressed. Identifying personality-based subgroups of FM might allow implementing specific preventive strategies. FM treatment might be optimized by increasing medication compliance, improving therapeutic alliance and testing different therapeutic options and treatment sequencing for each personality subgroup. © 2013.

  19. 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.

  20. 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

  1. 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.

  2. Pioneer 10 and 11 orbit determination analysis shows no discrepancy with Newton-Einstein's laws of gravity

    CERN Document Server

    Modenini, Dario

    2013-01-01

    The present work describes the investigation of the navigation anomaly of Pioneer 10 and 11 probes which became known as the Pioneer Anomaly. It appeared as a linear drift in the Doppler data received by the spacecraft, which has been ascribed to an approximately constant sunward acceleration of about $8.5 \\times 10^{-13} km/s^2$. Since then, the existence of the anomaly has been confirmed independently by several groups and a large effort was devoted to find its origin. The present study consists of two main parts: thermal modeling of the spacecraft throughout its trajectory, and orbit determination analysis. Based on existing documentation and published telemetry data we built a thermal finite element model of the spacecraft, whose complexity has been constrained to a degree allowing for sensitivity analysis, leading to the computation of its formal uncertainty. The trajectory analysis and orbit determination was carried out using NASA/JPL's ODP (Orbit Determination Program) and our results show that orbita...

  3. From root to fruit: RNA-Seq analysis shows that arbuscular mycorrhizal symbiosis may affect tomato fruit metabolism.

    Science.gov (United States)

    Zouari, Inès; Salvioli, Alessandra; Chialva, Matteo; Novero, Mara; Miozzi, Laura; Tenore, Gian Carlo; Bagnaresi, Paolo; Bonfante, Paola

    2014-03-21

    Tomato (Solanum lycopersicum) establishes a beneficial symbiosis with arbuscular mycorrhizal (AM) fungi. The formation of the mycorrhizal association in the roots leads to plant-wide modulation of gene expression. To understand the systemic effect of the fungal symbiosis on the tomato fruit, we used RNA-Seq to perform global transcriptome profiling on Moneymaker tomato fruits at the turning ripening stage. Fruits were collected at 55 days after flowering, from plants colonized with Funneliformis mosseae and from control plants, which were fertilized to avoid responses related to nutrient deficiency. Transcriptome analysis identified 712 genes that are differentially expressed in fruits from mycorrhizal and control plants. Gene Ontology (GO) enrichment analysis of these genes showed 81 overrepresented functional GO classes. Up-regulated GO classes include photosynthesis, stress response, transport, amino acid synthesis and carbohydrate metabolism functions, suggesting a general impact of fungal symbiosis on primary metabolisms and, particularly, on mineral nutrition. Down-regulated GO classes include cell wall, metabolism and ethylene response pathways. Quantitative RT-PCR validated the RNA-Seq results for 12 genes out of 14 when tested at three fruit ripening stages, mature green, breaker and turning. Quantification of fruit nutraceutical and mineral contents produced values consistent with the expression changes observed by RNA-Seq analysis. This RNA-Seq profiling produced a novel data set that explores the intersection of mycorrhization and fruit development. We found that the fruits of mycorrhizal plants show two transcriptomic "signatures": genes characteristic of a climacteric fleshy fruit, and genes characteristic of mycorrhizal status, like phosphate and sulphate transporters. Moreover, mycorrhizal plants under low nutrient conditions produce fruits with a nutrient content similar to those from non-mycorrhizal plants under high nutrient conditions

  4. Systems level analysis of systemic sclerosis shows a network of immune and profibrotic pathways connected with genetic polymorphisms.

    Directory of Open Access Journals (Sweden)

    J Matthew Mahoney

    2015-01-01

    Full Text Available Systemic sclerosis (SSc is a rare systemic autoimmune disease characterized by skin and organ fibrosis. The pathogenesis of SSc and its progression are poorly understood. The SSc intrinsic gene expression subsets (inflammatory, fibroproliferative, normal-like, and limited are observed in multiple clinical cohorts of patients with SSc. Analysis of longitudinal skin biopsies suggests that a patient's subset assignment is stable over 6-12 months. Genetically, SSc is multi-factorial with many genetic risk loci for SSc generally and for specific clinical manifestations. Here we identify the genes consistently associated with the intrinsic subsets across three independent cohorts, show the relationship between these genes using a gene-gene interaction network, and place the genetic risk loci in the context of the intrinsic subsets. To identify gene expression modules common to three independent datasets from three different clinical centers, we developed a consensus clustering procedure based on mutual information of partitions, an information theory concept, and performed a meta-analysis of these genome-wide gene expression datasets. We created a gene-gene interaction network of the conserved molecular features across the intrinsic subsets and analyzed their connections with SSc-associated genetic polymorphisms. The network is composed of distinct, but interconnected, components related to interferon activation, M2 macrophages, adaptive immunity, extracellular matrix remodeling, and cell proliferation. The network shows extensive connections between the inflammatory- and fibroproliferative-specific genes. The network also shows connections between these subset-specific genes and 30 SSc-associated polymorphic genes including STAT4, BLK, IRF7, NOTCH4, PLAUR, CSK, IRAK1, and several human leukocyte antigen (HLA genes. Our analyses suggest that the gene expression changes underlying the SSc subsets may be long-lived, but mechanistically interconnected

  5. 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 ...

  6. 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 ...

  7. 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...

  8. 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

  9. Television viewing in low-income latino children: variation by ethnic subgroup and English proficiency.

    Science.gov (United States)

    Thompson, Darcy A; Matson, Pamela A; Ellen, Jonathan M

    2013-02-01

    Television viewing is associated with an increased risk for obesity in children. Latino children are at high risk for obesity and yet little is known about differences in television viewing habits within this population. The purpose of this study is to determine if hours of television viewed by young children with low-income Latina mothers differs by maternal ethnic subgroup and English language proficiency. This was a cross-sectional analysis of data from the Welfare, Children, & Families: A Three City Study. Participants were 422 low-income Latina mothers of Mexican and Puerto Rican descent with children ages 0-4 years old. The dependent variable was hours of daily television viewed by the child. The independent variable was maternal ethnic subgroup and English language proficiency. Analyses involved the use of multiple negative binomial regression models, which were adjusted for demographic variables. Multivariable regression analyses showed that compared to children with mothers of Mexican descent, children of mothers of Puerto Rican descent watch more daily television (television viewing (IRR=1.29, 95% CI 1.04, 1.61). No relationship was found for children of Puerto Rican descent. Child television viewing varies in low-income Latino children by maternal ethnic subgroup and English language proficiency. Interventionists must consider the varying sociocultural contexts of Latino children and their influence on television viewing.

  10. 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

  11. 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

  12. Linkage analysis in a Dutch population isolate shows no major gene for left-handedness or atypical language lateralization.

    Science.gov (United States)

    Somers, Metten; Ophoff, Roel A; Aukes, Maartje F; Cantor, Rita M; Boks, Marco P; Dauwan, Meenakshi; de Visser, Kees L; Kahn, René S; Sommer, Iris E

    2015-06-10

    Cerebral dominance of language function and hand preference are suggested to be heritable traits with possible shared genetic background. However, joined genetic studies of these traits have never been conducted. We performed a genetic linkage study in 37 multigenerational human pedigrees of both sexes (consisting of 355 subjects) enriched with left-handedness in which we also measured language lateralization. Hand preference was measured with the Edinburgh Handedness Inventory, and language lateralization was measured with functional transcranial Doppler during language production. The estimated heritability of left-handedness and language lateralization in these pedigrees is 0.24 and 0.31, respectively. A parametric major gene model was tested for left-handedness. Nonparametric analyses were performed for left-handedness, atypical lateralization, and degree of language lateralization. We did not observe genome-wide evidence for linkage in the parametric or nonparametric analyses for any of the phenotypes tested. However, multiple regions showed suggestive evidence of linkage. The parametric model showed suggestive linkage for left-handedness in the 22q13 region [heterogeneity logarithm of odds (HLOD) = 2.18]. Nonparametric multipoint analysis of left-handedness showed suggestive linkage in the same region [logarithm of odds (LOD) = 2.80]. Atypical language lateralization showed suggestive linkage in the 7q34 region (LODMax = 2.35). For strength of language lateralization, we observed suggestive linkage in the 6p22 (LODMax = 2.54), 7q32 (LODMax = 1.93), and 9q33 (LODMax = 2.10) regions. We did not observe any overlap of suggestive genetic signal between handedness and the extent of language lateralization. The absence of significant linkage argues against the presence of a major gene coding for both traits; rather, our results are suggestive of these traits being two independent polygenic complex traits. Copyright © 2015 the authors 0270-6474/15/358730-07$15.00/0.

  13. Single agent carboplatin for pediatric low-grade glioma: A retrospective analysis shows equivalent efficacy to multiagent chemotherapy.

    Science.gov (United States)

    Dodgshun, Andrew J; Maixner, Wirginia J; Heath, John A; Sullivan, Michael J; Hansford, Jordan R

    2016-01-15

    Pediatric low-grade gliomas (LGG) that are unresectable often require adjuvant chemotherapy such as carboplatin/vincristine. Small Phase II studies have suggested equivalent efficacy of single agent 4-weekly carboplatin. A single-institution retrospective review captured all patients aged 0 to 18 years diagnosed with LGG between 1996 and 2013 and treated with carboplatin monotherapy. The response and survival according to tumor site was compared to published results for multiagent chemotherapy. Of 268 children diagnosed with LGG diagnosed in this period, 117 received chemotherapy and 104 children received single agent carboplatin as first line chemotherapy. All patients received carboplatin at 560 mg/m(2), four-weekly for a median of 12 courses. The mean age at diagnosis was 5.8 years (range 3m-16y) and 32% had neurofibromatosis type 1. With a mean followup of 54 months, 86% of patients achieved stabilisation or better (SD/PR/CR). 3-year progression free survival (PFS) 66% (95% CI 57-76%), and 5-year PFS was 51% (95% CI 41-63%). 5-year overall survival was 97%. Multivariate analysis showed poorer PFS for those with chiasmatic/hypothalamic tumors. In this retrospective analysis single agent carboplatin shows comparable efficacy to historical multiagent chemotherapy for the treatment of patients with unresectable LGG. Equivalent outcomes are achieved with less chemotherapy, reduced side effects and fewer hospital visits. Further research is required to establish the place of this simplified regimen in the up-front treatment of unresectable LGG. © 2015 UICC.

  14. 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.

  15. Analysis of a large dataset of mycorrhiza inoculation field trials on potato shows highly significant increases in yield.

    Science.gov (United States)

    Hijri, Mohamed

    2016-04-01

    An increasing human population requires more food production in nutrient-efficient systems in order to simultaneously meet global food needs while reducing the environmental footprint of agriculture. Arbuscular mycorrhizal fungi (AMF) have the potential to enhance crop yield, but their efficiency has yet to be demonstrated in large-scale crop production systems. This study reports an analysis of a dataset consisting of 231 field trials in which the same AMF inoculant (Rhizophagus irregularis DAOM 197198) was applied to potato over a 4-year period in North America and Europe under authentic field conditions. The inoculation was performed using a liquid suspension of AMF spores that was sprayed onto potato seed pieces, yielding a calculated 71 spores per seed piece. Statistical analysis showed a highly significant increase in marketable potato yield (ANOVA, P < 0.0001) for inoculated fields (42.2 tons/ha) compared with non-inoculated controls (38.3 tons/ha), irrespective of trial year. The average yield increase was 3.9 tons/ha, representing 9.5 % of total crop yield. Inoculation was profitable with a 0.67-tons/ha increase in yield, a threshold reached in almost 79 % of all trials. This finding clearly demonstrates the benefits of mycorrhizal-based inoculation on crop yield, using potato as a case study. Further improvements of these beneficial inoculants will help compensate for crop production deficits, both now and in the future.

  16. Global morphological analysis of marine viruses shows minimal regional variation and dominance of non-tailed viruses

    Science.gov (United States)

    Brum, Jennifer R; Schenck, Ryan O; Sullivan, Matthew B

    2013-01-01

    Viruses influence oceanic ecosystems by causing mortality of microorganisms, altering nutrient and organic matter flux via lysis and auxiliary metabolic gene expression and changing the trajectory of microbial evolution through horizontal gene transfer. Limited host range and differing genetic potential of individual virus types mean that investigations into the types of viruses that exist in the ocean and their spatial distribution throughout the world's oceans are critical to understanding the global impacts of marine viruses. Here we evaluate viral morphological characteristics (morphotype, capsid diameter and tail length) using a quantitative transmission electron microscopy (qTEM) method across six of the world's oceans and seas sampled through the Tara Oceans Expedition. Extensive experimental validation of the qTEM method shows that neither sample preservation nor preparation significantly alters natural viral morphological characteristics. The global sampling analysis demonstrated that morphological characteristics did not vary consistently with depth (surface versus deep chlorophyll maximum waters) or oceanic region. Instead, temperature, salinity and oxygen concentration, but not chlorophyll a concentration, were more explanatory in evaluating differences in viral assemblage morphological characteristics. Surprisingly, given that the majority of cultivated bacterial viruses are tailed, non-tailed viruses appear to numerically dominate the upper oceans as they comprised 51–92% of the viral particles observed. Together, these results document global marine viral morphological characteristics, show that their minimal variability is more explained by environmental conditions than geography and suggest that non-tailed viruses might represent the most ecologically important targets for future research. PMID:23635867

  17. Marmosets, Raree shows and Pulcinelle: an Analysis and Edition of a Hitherto-Unpublished Carnival Play by Antonio de Zamora

    Directory of Open Access Journals (Sweden)

    Fernando Plata

    2013-05-01

    Full Text Available This paper is an analyisis, annotation and edition of the Mojiganga del mundinovo (‘The raree show, a carnival play’ by Antonio de Zamora. The play was performed in 1698 Madrid by the troupe of Carlos Vallejo, along with the sacramental one-act play El templo vivo de Dios (‘The living temple of God’. The hitherto unpublished text is based on the only two extant manuscripts, located in archives in Madrid. Despite the play’s title, my analysis argues that the novelty in this play is not so much the raree show, a contraption popularized four decades earlier in Golden Age theater, as the marmosets. The death of two marmosets and the ensuing desolation of their owner, Ms. Estupenda, both trigger the play and provide it with a plot. The marmosets, too, point to a changing mentality in late 17th-century society, regarding the possession among ladies of marmosets and other monkeys as pets.

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

    Science.gov (United States)

    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

  19. 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

  20. 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.

  1. Brain Correlates of Cognitive Remediation in Schizophrenia: Activation Likelihood Analysis Shows Preliminary Evidence of Neural Target Engagement.

    Science.gov (United States)

    Ramsay, Ian S; MacDonald, Angus W

    2015-11-01

    Cognitive remediation training (CRT) for schizophrenia has been found to improve cognitive functioning and influence neural plasticity. However, with various training approaches and mixed findings, the mechanisms driving generalization of cognitive skills from CRT are unclear. In this meta-analysis of extant imaging studies examining CRT's effects, we sought to clarify whether varying approaches to CRT suggest common neural changes and whether such mechanisms are restorative or compensatory. We conducted a literature search to identify studies appropriate for inclusion in an activation likelihood estimation (ALE) meta-analysis. Our criteria required studies to consist of training-based interventions designed to improve patients' cognitive or social functioning, including generalization to untrained circumstances. Studies were also required to examine changes in pre- vs posttraining functional activation using functional magnetic resonance imaging or positron emission tomography. The literature search identified 162 articles, 9 of which were appropriate for inclusion. ALE analyses comparing pre- and posttraining brain activation showed increased activity in the lateral and medial prefrontal cortex (PFC), parietal cortex, insula, and the caudate and thalamus. Notably, activation associated with CRT in the left PFC and thalamus partially overlapped with previous meta-analytically identified areas associated with deficits in working memory, executive control, and facial emotion processing in schizophrenia. We conclude that CRT interventions from varying theoretic modalities elicit plasticity in areas that support cognitive and socioemotional processes in this early set of studies. While preliminary, these changes appear to be both restorative and compensatory, though thalamocortical areas previously associated with dysfunction may be common sources of plasticity for cognitive remediation in schizophrenia. © The Author 2015. Published by Oxford University Press on

  2. 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.

  3. 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.

  4. Affiliative Subgroups in Preschool Classrooms: Integrating Constructs and Methods from Social Ethology and Sociometric Traditions.

    Science.gov (United States)

    Santos, António J; Daniel, João R; Fernandes, Carla; Vaughn, Brian E

    2015-01-01

    Recent studies of school-age children and adolescents have used social network analyses to characterize selection and socialization aspects of peer groups. Fewer network studies have been reported for preschool classrooms and many of those have focused on structural descriptions of peer networks, and/or, on selection processes rather than on social functions of subgroup membership. In this study we started by identifying and describing different types of affiliative subgroups (HMP- high mutual proximity, LMP- low mutual proximity, and ungrouped children) in a sample of 240 Portuguese preschool children using nearest neighbor observations. Next, we used additional behavioral observations and sociometric data to show that HMP and LMP subgroups are functionally distinct: HMP subgroups appear to reflect friendship relations, whereas LMP subgroups appear to reflect common social goals, but without strong, within-subgroup dyadic ties. Finally, we examined the longitudinal implications of subgroup membership and show that children classified as HMP in consecutive years had more reciprocated friendships than did children whose subgroup classification changed from LMP or ungrouped to HMP. These results extend previous findings reported for North American peer groups.

  5. 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.

  6. 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

  7. 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.

  8. Evolution Analysis of the Aux/IAA Gene Family in Plants Shows Dual Origins and Variable Nuclear Localization Signals

    Science.gov (United States)

    Wu, Wentao; Liu, Yaxue; Wang, Yuqian; Li, Huimin; Liu, Jiaxi; Tan, Jiaxin; He, Jiadai; Bai, Jingwen

    2017-01-01

    The plant hormone auxin plays pivotal roles in many aspects of plant growth and development. The auxin/indole-3-acetic acid (Aux/IAA) gene family encodes short-lived nuclear proteins acting on auxin perception and signaling, but the evolutionary history of this gene family remains to be elucidated. In this study, the Aux/IAA gene family in 17 plant species covering all major lineages of plants is identified and analyzed by using multiple bioinformatics methods. A total of 434 Aux/IAA genes was found among these plant species, and the gene copy number ranges from three (Physcomitrella patens) to 63 (Glycine max). The phylogenetic analysis shows that the canonical Aux/IAA proteins can be generally divided into five major clades, and the origin of Aux/IAA proteins could be traced back to the common ancestor of land plants and green algae. Many truncated Aux/IAA proteins were found, and some of these truncated Aux/IAA proteins may be generated from the C-terminal truncation of auxin response factor (ARF) proteins. Our results indicate that tandem and segmental duplications play dominant roles for the expansion of the Aux/IAA gene family mainly under purifying selection. The putative nuclear localization signals (NLSs) in Aux/IAA proteins are conservative, and two kinds of new primordial bipartite NLSs in P. patens and Selaginella moellendorffii were discovered. Our findings not only give insights into the origin and expansion of the Aux/IAA gene family, but also provide a basis for understanding their functions during the course of evolution. PMID:28991190

  9. Evolution Analysis of the Aux/IAA Gene Family in Plants Shows Dual Origins and Variable Nuclear Localization Signals.

    Science.gov (United States)

    Wu, Wentao; Liu, Yaxue; Wang, Yuqian; Li, Huimin; Liu, Jiaxi; Tan, Jiaxin; He, Jiadai; Bai, Jingwen; Ma, Haoli

    2017-10-08

    The plant hormone auxin plays pivotal roles in many aspects of plant growth and development. The auxin/indole-3-acetic acid (Aux/IAA) gene family encodes short-lived nuclear proteins acting on auxin perception and signaling, but the evolutionary history of this gene family remains to be elucidated. In this study, the Aux/IAA gene family in 17 plant species covering all major lineages of plants is identified and analyzed by using multiple bioinformatics methods. A total of 434 Aux/IAA genes was found among these plant species, and the gene copy number ranges from three (Physcomitrella patens) to 63 (Glycine max). The phylogenetic analysis shows that the canonical Aux/IAA proteins can be generally divided into five major clades, and the origin of Aux/IAA proteins could be traced back to the common ancestor of land plants and green algae. Many truncated Aux/IAA proteins were found, and some of these truncated Aux/IAA proteins may be generated from the C-terminal truncation of auxin response factor (ARF) proteins. Our results indicate that tandem and segmental duplications play dominant roles for the expansion of the Aux/IAA gene family mainly under purifying selection. The putative nuclear localization signals (NLSs) in Aux/IAA proteins are conservative, and two kinds of new primordial bipartite NLSs in P. patens and Selaginella moellendorffii were discovered. Our findings not only give insights into the origin and expansion of the Aux/IAA gene family, but also provide a basis for understanding their functions during the course of evolution.

  10. Evolution Analysis of the Aux/IAA Gene Family in Plants Shows Dual Origins and Variable Nuclear Localization Signals

    Directory of Open Access Journals (Sweden)

    Wentao Wu

    2017-10-01

    Full Text Available The plant hormone auxin plays pivotal roles in many aspects of plant growth and development. The auxin/indole-3-acetic acid (Aux/IAA gene family encodes short-lived nuclear proteins acting on auxin perception and signaling, but the evolutionary history of this gene family remains to be elucidated. In this study, the Aux/IAA gene family in 17 plant species covering all major lineages of plants is identified and analyzed by using multiple bioinformatics methods. A total of 434 Aux/IAA genes was found among these plant species, and the gene copy number ranges from three (Physcomitrella patens to 63 (Glycine max. The phylogenetic analysis shows that the canonical Aux/IAA proteins can be generally divided into five major clades, and the origin of Aux/IAA proteins could be traced back to the common ancestor of land plants and green algae. Many truncated Aux/IAA proteins were found, and some of these truncated Aux/IAA proteins may be generated from the C-terminal truncation of auxin response factor (ARF proteins. Our results indicate that tandem and segmental duplications play dominant roles for the expansion of the Aux/IAA gene family mainly under purifying selection. The putative nuclear localization signals (NLSs in Aux/IAA proteins are conservative, and two kinds of new primordial bipartite NLSs in P. patens and Selaginella moellendorffii were discovered. Our findings not only give insights into the origin and expansion of the Aux/IAA gene family, but also provide a basis for understanding their functions during the course of evolution.

  11. 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.

  12. Associations between gastric sensorimotor function, depression, somatization, and symptom-based subgroups in functional gastroduodenal disorders: are all symptoms equal?

    Science.gov (United States)

    Clauwaert, N; Jones, M P; Holvoet, L; Vandenberghe, J; Vos, R; Tack, J; Van Oudenhove, L

    2012-12-01

    Previous work indicated that psychosocial factors (depression and somatization) are more strongly associated with symptom severity and weight loss in functional dyspepsia (FD) than gastric sensorimotor function. However, there is conflicting evidence regarding the association of these etiopathogenetic factors with Rome III symptom-based subgroups in FD [epigastric pain syndrome (EPS), postprandial distress syndrome (PDS)]. We aimed to test whether gastric sensitivity and emptying, depression, and somatization are differentially associated with empirically derived functional gastroduodenal disorders (FGD) symptom factors in one comprehensive model. In 259 tertiary care FD patients, we studied gastric sensorimotor function with barostat and gastric emptying breath test. Depression, somatization, and FGD symptoms were measured using self-report questionnaires. Confirmatory factor analysis (CFA) on 7 FGD symptoms was used to determine the fit of a latent variable structure based on Rome III symptom-based subgroups. Structural equation modeling (SEM) was used to test the putative relationships of the symptom factors with gastric sensorimotor function, depression, and somatization. The results of the CFA show a good fit [C(min) /DF = 1.54, CFI(comparative fit index) = 0.97] for the three-factor solution based on Rome III subgroups. The SEM also fitted the data well (C(min) /DF = 1.24, CFI = 0.98) and demonstrated that gastric sensitivity and depression are associated with PDS and nausea and vomiting. Gastric emptying is uniquely associated with EPS and somatization is strongly associated with all three symptom factors. Confirmatory factor analysis confirms the existence of three FGD symptom factors, corresponding to Rome III symptom-based subgroups. The SEM results suggest that different psychobiological mechanisms may play a role in these subgroups. © 2012 Blackwell Publishing Ltd.

  13. Valid randomization-based p-values for partially post hoc subgroup analyses.

    Science.gov (United States)

    Lee, Joseph J; Rubin, Donald B

    2015-10-30

    By 'partially post-hoc' subgroup analyses, we mean analyses that compare existing data from a randomized experiment-from which a subgroup specification is derived-to new, subgroup-only experimental data. We describe a motivating example in which partially post hoc subgroup analyses instigated statistical debate about a medical device's efficacy. We clarify the source of such analyses' invalidity and then propose a randomization-based approach for generating valid posterior predictive p-values for such partially post hoc subgroups. Lastly, we investigate the approach's operating characteristics in a simple illustrative setting through a series of simulations, showing that it can have desirable properties under both null and alternative hypotheses. Copyright © 2015 John Wiley & Sons, Ltd.

  14. 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

  15. Sustained disease-activity-free status in patients with relapsing-remitting multiple sclerosis treated with cladribine tablets in the CLARITY study: a post-hoc and subgroup analysis

    DEFF Research Database (Denmark)

    Giovannoni, Gavin; Cook, Stuart; Rammohan, Kottil

    2011-01-01

    On the basis of various clinical and MRI measurements, the phase 3 Cladribine Tablets Treating Multiple Sclerosis Orally (CLARITY) study in patients with relapsing-remitting multiple sclerosis (RRMS) showed that short-course oral treatment with cladribine at cumulative doses of 3·5 and 5·25 mg....../kg over 96 weeks was more effective than placebo. Achieving sustained freedom from disease activity is becoming a viable treatment goal in RRMS; we therefore aimed to assess the effects of cladribine on this composite outcome measure by doing a post-hoc analysis of data from the CLARITY study....

  16. 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.

  17. Differential impact of supported housing on selected subgroups of homeless veterans with substance abuse histories.

    Science.gov (United States)

    O'Connell, Maria J; Kasprow, Wesley J; Rosenheck, Robert A

    2012-12-01

    Studies have demonstrated that supported housing is an effective intervention for individuals who are homeless and have a mental illness or substance use disorder. This study examined data from an experimental trial of the U.S. Department of Housing and Urban Development-Veterans Affairs Supported Housing (HUD-VASH) program to identify differences in the program's impact on subgroups defined by sociodemographic or clinical characteristics. Data were analyzed from 259 male homeless veterans with substance abuse problems who were randomly assigned to HUD-VASH (intensive case management [ICM] plus rent subsidy vouchers), ICM only, or treatment as usual between June 1992 and December 1995. Four subgroups were defined: African American versus Caucasian, younger versus older than 42.3 years, co-occurring diagnoses of mental illness versus diagnosis of a substance use disorder only, and active versus less active substance use upon program entry. Mixed models were used to identify significant interactions between HUD-VASH assignment and each subgroup. Compared with ICM alone, HUD-VASH was associated with more positive housing outcomes for Caucasians, veterans with co-occurring mental disorders, and veterans who were active substance users. HUD-VASH was associated with more positive socioclinical outcomes for African Americans. No differences were observed in housing or socioclinical outcomes as a function of age. Among homeless veterans with a substance use disorder, Caucasians and those with active substance use showed greater housing benefits than other veterans from HUD-VASH than from ICM alone. African Americans showed greater socioclinical benefit than Caucasians from HUD-VASH versus ICM. Interaction analysis deserves further study.

  18. 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.

  19. 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).

  20. Global gene analysis of oocytes from early stages in human folliculogenesis shows high expression of novel genes in reproduction

    DEFF Research Database (Denmark)

    Markholt, Sara; Grøndahl, M L; Ernst, Erik

    2012-01-01

    The pool of primordial follicles in humans is laid down during embryonic development and follicles can remain dormant for prolonged intervals, often decades, until individual follicles resume growth. The mechanisms that induce growth and maturation of primordial follicles are poorly understood...... but follicles once activated either continue growth or undergo atresia. We have isolated pure populations of oocytes from human primordial, intermediate and primary follicles using laser capture micro-dissection microscopy and evaluated the global gene expression profiles by whole-genome microarray analysis......) and the mitochondrial-encoded ATPase6 (ATP6). Thus, the present study provides not only a technique to capture and perform transcriptome analysis of the sparse material of human oocytes from the earliest follicle stages but further includes a comprehensive basis for our understanding of the regulatory factors...

  1. Genome sequence analysis of solanum lycopersicum showing the phylogenetic relationship based on multiple sequence alignment and conserved domain proteins.

    OpenAIRE

    Uma kumari; Ashok kumar choudhary

    2016-01-01

    Phylogenetics analysis has become essential in researching the evolutionary relationship between sequence alignment and conserved domain protein evolutionary relationship are identified from open reading frame rather than from complete sequences.A reading frame is a set of consecutive,nucleotide ,non overlapping triplets of three consecutive nucleotide .The national center for biotechnology information NCBI provide many tools for compairing database- stored nucleotide or protein sequence,i...

  2. 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.

  3. High frequency of cultivable human subgroup F adenoviruses in stool samples from a paediatric population admitted to hospital with acute gastroenteritis.

    Science.gov (United States)

    Arcangeletti, Maria-Cristina; Germini, Diego; Martorana, Davide; Rodighiero, Isabella; De Conto, Flora; Medici, Maria-Cristina; Chezzi, Carlo; Calderaro, Adriana

    2014-06-01

    The family Adenoviridae consists of five genera of which the genus Mastadenovirus includes human viruses classified into 57 serotypes clustered into seven subgroups (A-G). Serotypes 40 and 41 (subgroup F) are specifically associated with childhood gastroenteritis and are the most common cause of acute gastroenteritis in young children after rotaviruses and noroviruses. Standard methods for laboratory diagnosis of adenovirus infection include electron microscopy (EM) and conventional cell culture (CCC), although it is widely considered that adenoviruses 40 and 41 are difficult to cultivate, such that their circulation is most likely underestimated. One hundred and ten faecal specimens from paediatric patients with gastroenteritis were confirmed positive for adenovirus by EM and/or CCC at the Virology Unit of the University Hospital of Parma, Italy, during the period January 2010-December 2012. They were analysed to determine the actual prevalence of adenovirus 40 and 41 in these patients using PCR and restriction endonuclease analysis, and to evaluate their ability to be cultivated in standard cell lines. The results showed a high prevalence of subgroup F (62.7 %), with serotype 41 (89.8 %) predominating over serotype 40 (10.2 %). Surprisingly, among the 75 adenoviruses isolated by CCC, 37 (49 %) belonged to subgroup F, suggesting a higher capacity of adenovirus 40 and 41 to replicate in cell culture than previously thought. PCR and restriction enzyme techniques provide an efficient means of diagnosing enteric adenoviruses correctly, including subgroup F adenovirus strains in young children with gastroenteritis. © 2014 The Authors.

  4. De novo transcriptome analysis shows differential expression of genes in salivary glands of edible bird's nest producing swiftlets.

    Science.gov (United States)

    Looi, Q H; Amin, H; Aini, I; Zuki, M; Omar, A R

    2017-07-03

    Edible bird's nest (EBN), produced from solidified saliva secretions of specific swiftlet species during the breeding season, is one of the most valuable animal by-products in the world. The composition and medicinal benefits of EBN have been extensively studied, however, genomic and transcriptomic studies of the salivary glands of these birds have not been conducted. The study described the transcriptomes of salivary glands from three swiftlet species (28 samples) generated by RNASeq. A total of 14,835 annotated genes and 428 unmapped genes were cataloged. The current study investigated the genes and pathways that are associated with the development of salivary gland and EBN composition. Differential expression and pathway enrichment analysis indicated that the expression of CREB3L2 and several signaling pathways involved in salivary gland development, namely, the EGFR, BMP, and MAPK signaling pathways, were up-regulated in swiftlets producing white EBN (Aerodramus fuciphagus) and black EBN (Aerodramus maximus) compared with non-EBN-producing swiftlets (Apus affinis). Furthermore, MGAT, an essential gene for the biosynthesis of N-acetylneuraminic acid (sialic acid), was highly expressed in both white- and black-nest swiftlets compared to non-EBN-producing swiftlets. Interspecies comparison between Aerodramus fuciphagus and Aerodramus maximus indicated that the genes involved in N-acetylneuraminic and fatty acid synthesis were up-regulated in Aerodramus fuciphagus, while alanine and aspartate synthesis pathways were up-regulated in Aerodramus maximus. Furthermore, gender-based analysis revealed that N-glycan trimming pathway was significantly up-regulated in male Aerodramus fuciphagus from its natural habitat (cave) compared to their female counterpart. Transcriptomic analysis of salivary glands of different swiftlet species reveal differential expressions of candidate genes that are involved in salivary gland development and in the biosynthesis of various

  5. Global gene analysis of oocytes from early stages in human folliculogenesis shows high expression of novel genes in reproduction.

    Science.gov (United States)

    Markholt, S; Grøndahl, M L; Ernst, E H; Andersen, C Yding; Ernst, E; Lykke-Hartmann, K

    2012-02-01

    The pool of primordial follicles in humans is laid down during embryonic development and follicles can remain dormant for prolonged intervals, often decades, until individual follicles resume growth. The mechanisms that induce growth and maturation of primordial follicles are poorly understood but follicles once activated either continue growth or undergo atresia. We have isolated pure populations of oocytes from human primordial, intermediate and primary follicles using laser capture micro-dissection microscopy and evaluated the global gene expression profiles by whole-genome microarray analysis. The array data were confirmed by qPCR for selected genes. A total of 6301 unique genes were identified as significantly expressed representing enriched specific functional categories such as 'RNA binding', 'translation initiation' and 'structural molecule activity'. Several genes, some not previously known to be associated with early oocyte development, were identified with exceptionally high expression levels, such as the anti-proliferative transmembrane protein with an epidermal growth factor-like and two follistatin-like domains (TMEFF2), the Rho-GTPase-activating protein oligophrenin 1 (OPHN1) and the mitochondrial-encoded ATPase6 (ATP6). Thus, the present study provides not only a technique to capture and perform transcriptome analysis of the sparse material of human oocytes from the earliest follicle stages but further includes a comprehensive basis for our understanding of the regulatory factors and pathways present during early human folliculogenesis.

  6. 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.

  7. Transcriptomic and metabolomic analysis of Yukon Thellungiella plants grown in cabinets and their natural habitat show phenotypic plasticity

    Directory of Open Access Journals (Sweden)

    Guevara David R

    2012-10-01

    Full Text Available Abstract Background Thellungiella salsuginea is an important model plant due to its natural tolerance to abiotic stresses including salt, cold, and water deficits. Microarray and metabolite profiling have shown that Thellungiella undergoes stress-responsive changes in transcript and organic solute abundance when grown under controlled environmental conditions. However, few reports assess the capacity of plants to display stress-responsive traits in natural habitats where concurrent stresses are the norm. Results To determine whether stress-responsive changes observed in cabinet-grown plants are recapitulated in the field, we analyzed leaf transcript and metabolic profiles of Thellungiella growing in its native Yukon habitat during two years of contrasting meteorological conditions. We found 673 genes showing differential expression between field and unstressed, chamber-grown plants. There were comparatively few overlaps between genes expressed under field and cabinet treatment-specific conditions. Only 20 of 99 drought-responsive genes were expressed both in the field during a year of low precipitation and in plants subjected to drought treatments in cabinets. There was also a general pattern of lower abundance among metabolites found in field plants relative to control or stress-treated plants in growth cabinets. Nutrient availability may explain some of the observed differences. For example, proline accumulated to high levels in cold and salt-stressed cabinet-grown plants but proline content was, by comparison, negligible in plants at a saline Yukon field site. We show that proline accumulated in a stress-responsive manner in Thellungiella plants salinized in growth cabinets and in salt-stressed seedlings when nitrogen was provided at 1.0 mM. In seedlings grown on 0.1 mM nitrogen medium, the proline content was low while carbohydrates increased. The relatively higher content of sugar-like compounds in field plants and seedlings on low nitrogen

  8. [Wearing a pouch shows the difference between "being an "ostomized person" and "being a professional": analysis of a teaching strategy].

    Science.gov (United States)

    Santos, V L; Sawaia, B B

    2000-07-01

    This study aimed at analyzing nurses (re)construction process regarding the meanings of ostomy, ostomized patients, nursing care and the professional role after they wore an ostomy appliance. This activity is a teaching strategy applied at the Enterostomal Therapy Nursing Education Program. Two major units were identified after the analysis of students speeches: "being an ostomized person" and "being a professional". When students wore the pouches they felt as ostomized patients experiencing a violation of their identity and quality of life that promotes profound changes in daily life. These symbolic contents cause a crisis regarding the meaning of being a professional as until this experience, nursing care seemed fragmented to them. Recognizing a previous care performed as a technical action mainly directed to the ostomy and the pouch, students were able to visualize a future care, that is holistic and considers the ostomized human being, enabling them to incorporate affective, symbolic and relational dimensions.

  9. Large scale genomic analysis shows no evidence for pathogen adaptation between the blood and cerebrospinal fluid niches during bacterial meningitis

    Science.gov (United States)

    Lees, John A.; Kremer, Philip H. C.; Manso, Ana S.; Croucher, Nicholas J.; Ferwerda, Bart; Serón, Mercedes Valls; Oggioni, Marco R.; Parkhill, Julian; Brouwer, Matthijs C.; van der Ende, Arie; van de Beek, Diederik

    2017-01-01

    Recent studies have provided evidence for rapid pathogen genome diversification, some of which could potentially affect the course of disease. We have previously described such variation seen between isolates infecting the blood and cerebrospinal fluid (CSF) of a single patient during a case of bacterial meningitis. Here, we performed whole-genome sequencing of paired isolates from the blood and CSF of 869 meningitis patients to determine whether such variation frequently occurs between these two niches in cases of bacterial meningitis. Using a combination of reference-free variant calling approaches, we show that no genetic adaptation occurs in either invaded niche during bacterial meningitis for two major pathogen species, Streptococcus pneumoniae and Neisseria meningitidis. This study therefore shows that the bacteria capable of causing meningitis are already able to do this upon entering the blood, and no further sequence change is necessary to cross the blood–brain barrier. Our findings place the focus back on bacterial evolution between nasopharyngeal carriage and invasion, or diversity of the host, as likely mechanisms for determining invasiveness. PMID:28348877

  10. Large scale genomic analysis shows no evidence for pathogen adaptation between the blood and cerebrospinal fluid niches during bacterial meningitis.

    Science.gov (United States)

    Lees, John A; Kremer, Philip H C; Manso, Ana S; Croucher, Nicholas J; Ferwerda, Bart; Serón, Mercedes Valls; Oggioni, Marco R; Parkhill, Julian; Brouwer, Matthijs C; van der Ende, Arie; van de Beek, Diederik; Bentley, Stephen D

    2017-01-01

    Recent studies have provided evidence for rapid pathogen genome diversification, some of which could potentially affect the course of disease. We have previously described such variation seen between isolates infecting the blood and cerebrospinal fluid (CSF) of a single patient during a case of bacterial meningitis. Here, we performed whole-genome sequencing of paired isolates from the blood and CSF of 869 meningitis patients to determine whether such variation frequently occurs between these two niches in cases of bacterial meningitis. Using a combination of reference-free variant calling approaches, we show that no genetic adaptation occurs in either invaded niche during bacterial meningitis for two major pathogen species, Streptococcus pneumoniae and Neisseria meningitidis. This study therefore shows that the bacteria capable of causing meningitis are already able to do this upon entering the blood, and no further sequence change is necessary to cross the blood-brain barrier. Our findings place the focus back on bacterial evolution between nasopharyngeal carriage and invasion, or diversity of the host, as likely mechanisms for determining invasiveness.

  11. Mutational analysis of sclerostin shows importance of the flexible loop and the cystine-knot for Wnt-signaling inhibition.

    Directory of Open Access Journals (Sweden)

    Verena Boschert

    Full Text Available The cystine-knot containing protein Sclerostin is an important negative regulator of bone growth and therefore represents a promising therapeutic target. It exerts its biological task by inhibiting the Wnt (wingless and int1 signaling pathway, which participates in bone formation by promoting the differentiation of mesenchymal stem cells to osteoblasts. The core structure of Sclerostin consists of three loops with the first and third loop (Finger 1 and Finger 2 forming a structured β-sheet and the second loop being unstructured and highly flexible. Biochemical data showed that the flexible loop is important for binding of Sclerostin to Wnt co-receptors of the low-density lipoprotein related-protein family (LRP, by interacting with the Wnt co-receptors LRP5 or -6 it inhibits Wnt signaling. To further examine the structural requirements for Wnt inhibition, we performed an extensive mutational study within all three loops of the Sclerostin core domain involving single and multiple mutations as well as truncation of important regions. By this approach we could confirm the importance of the second loop and especially of amino acids Asn92 and Ile94 for binding to LRP6. Based on a Sclerostin variant found in a Turkish family suffering from Sclerosteosis we generated a Sclerostin mutant with cysteines 84 and 142 exchanged thereby removing the third disulfide bond of the cystine-knot. This mutant binds to LRP6 with reduced binding affinity and also exhibits a strongly reduced inhibitory activity against Wnt1 thereby showing that also elements outside the flexible loop are important for inhibition of Wnt by Sclerostin. Additionally, we examined the effect of the mutations on the inhibition of two different Wnt proteins, Wnt3a and Wnt1. We could detect clear differences in the inhibition of these proteins, suggesting that the mechanism by which Sclerostin antagonizes Wnt1 and Wnt3a is fundamentally different.

  12. Analysis of diverse regulatory networks in a hierarchical context shows consistent tendencies for collaboration in the middle levels

    Science.gov (United States)

    Bhardwaj, Nitin; Yan, Koon-Kiu; Gerstein, Mark B.

    2010-01-01

    Gene regulatory networks have been shown to share some common aspects with commonplace social governance structures. Thus, we can get some intuition into their organization by arranging them into well-known hierarchical layouts. These hierarchies, in turn, can be placed between the extremes of autocracies, with well-defined levels and clear chains of command, and democracies, without such defined levels and with more co-regulatory partnerships between regulators. In general, the presence of partnerships decreases the variation in information flow amongst nodes within a level, more evenly distributing stress. Here we study various regulatory networks (transcriptional, modification, and phosphorylation) for five diverse species, Escherichia coli to human. We specify three levels of regulators—top, middle, and bottom—which collectively govern the non-regulator targets lying in the lowest fourth level. We define quantities for nodes, levels, and entire networks that measure their degree of collaboration and autocratic vs. democratic character. We show individual regulators have a range of partnership tendencies: Some regulate their targets in combination with other regulators in local instantiations of democratic structure, whereas others regulate mostly in isolation, in more autocratic fashion. Overall, we show that in all networks studied the middle level has the highest collaborative propensity and coregulatory partnerships occur most frequently amongst midlevel regulators, an observation that has parallels in corporate settings where middle managers must interact most to ensure organizational effectiveness. There is, however, one notable difference between networks in different species: The amount of collaborative regulation and democratic character increases markedly with overall genomic complexity. PMID:20351254

  13. Microfluidic Single Cell Analysis Show Porcine Induced Pluripotent Stem Cell-Derived Endothelial Cells Improve Myocardial Function by Paracrine Activation

    Science.gov (United States)

    Gu, Mingxia; Nguyen, Patricia K.; Lee, Andrew S.; Xu, Dan; Hu, Shijun; Plews, Jordan R; Han, Leng; Huber, Bruno C.; Lee, Won Hee; Gong, Yongquan; de Almeida, Patricia E.; Lyons, Jennifer; Ikeno, Fumi; Pacharinsak, Cholawat; Connolly, Andrew J.; Gambhir, Sanjiv S.; Robbins, Robert C.; Longaker, Michael T.; Wu, Joseph C.

    2012-01-01

    Rationale Induced pluripotent stem cells (iPSCs) hold great promise for the development of patient-specific therapies for cardiovascular disease. However, clinical translation will require preclinical optimization and validation of large animal iPSC models. Objective To successfully derive endothelial cells from porcine iPSCs and demonstrate their potential utility for the treatment of myocardial ischemia. Methods and Results Porcine adipose stromal cells were reprogrammed to generate porcine iPSCs (piPSCs). Immunohistochemistry, quantitative PCR, microarray hybridization, and angiogenic assays confirmed that piPSC-derived endothelial cells (piPSC-ECs) shared similar morphological and functional properties as endothelial cells isolated from the autologous pig aorta. To demonstrate their therapeutic potential, piPSC-ECs were transplanted into mice with myocardial infarction (MI). Compared to control, animals transplanted with piPSC-ECs showed significant functional improvement measured by echocardiography (fractional shortening at week 4: 27.2±1.3% vs. 22.3±1.1%; P<0.001) and magnetic resonance imaging (ejection fraction at week 4: 45.8±1.3% vs. 42.3±0.9%; P<0.05). Quantitative protein assays and microfluidic single cell PCR profiling showed that piPSC-ECs released pro-angiogenic and anti-apoptotic factors in the ischemic microenvironment, which promoted neovascularization and cardiomyocyte survival, respectively. Release of paracrine factors varied significantly among subpopulations of transplanted cells, suggesting that transplantation of specific cell populations may result in greater functional recovery. Conclusion In summary, this is the first study to successfully differentiate piPSCs-ECs from piPSCs and demonstrate that transplantation of piPSC-ECs improved cardiac function following MI via paracrine activation. Further development of these large animal iPSC models will yield significant insights into their therapeutic potential and accelerate the

  14. Phylogenetic analysis shows that Neolithic slate plaques from the southwestern Iberian Peninsula are not genealogical recording systems.

    Science.gov (United States)

    García Rivero, Daniel; O'Brien, Michael J

    2014-01-01

    Prehistoric material culture proposed to be symbolic in nature has been the object of considerable archaeological work from diverse theoretical perspectives, yet rarely are methodological tools used to test the interpretations. The lack of testing is often justified by invoking the opinion that the slippery nature of past human symbolism cannot easily be tackled by the scientific method. One such case, from the southwestern Iberian Peninsula, involves engraved stone plaques from megalithic funerary monuments dating ca. 3,500-2,750 B.C. (calibrated age). One widely accepted proposal is that the plaques are ancient mnemonic devices that record genealogies. The analysis reported here demonstrates that this is not the case, even when the most supportive data and techniques are used. Rather, we suspect there was a common ideological background to the use of plaques that overlay the southwestern Iberian Peninsula, with little or no geographic patterning. This would entail a cultural system in which plaque design was based on a fundamental core idea, with a number of mutable and variable elements surrounding it.

  15. Phylogenetic analysis shows that Neolithic slate plaques from the southwestern Iberian Peninsula are not genealogical recording systems.

    Directory of Open Access Journals (Sweden)

    Daniel García Rivero

    Full Text Available Prehistoric material culture proposed to be symbolic in nature has been the object of considerable archaeological work from diverse theoretical perspectives, yet rarely are methodological tools used to test the interpretations. The lack of testing is often justified by invoking the opinion that the slippery nature of past human symbolism cannot easily be tackled by the scientific method. One such case, from the southwestern Iberian Peninsula, involves engraved stone plaques from megalithic funerary monuments dating ca. 3,500-2,750 B.C. (calibrated age. One widely accepted proposal is that the plaques are ancient mnemonic devices that record genealogies. The analysis reported here demonstrates that this is not the case, even when the most supportive data and techniques are used. Rather, we suspect there was a common ideological background to the use of plaques that overlay the southwestern Iberian Peninsula, with little or no geographic patterning. This would entail a cultural system in which plaque design was based on a fundamental core idea, with a number of mutable and variable elements surrounding it.

  16. Anatomical network analysis shows decoupling of modular lability and complexity in the evolution of the primate skull.

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    Borja Esteve-Altava

    Full Text Available Modularity and complexity go hand in hand in the evolution of the skull of primates. Because analyses of these two parameters often use different approaches, we do not know yet how modularity evolves within, or as a consequence of, an also-evolving complex organization. Here we use a novel network theory-based approach (Anatomical Network Analysis to assess how the organization of skull bones constrains the co-evolution of modularity and complexity among primates. We used the pattern of bone contacts modeled as networks to identify connectivity modules and quantify morphological complexity. We analyzed whether modularity and complexity evolved coordinately in the skull of primates. Specifically, we tested Herbert Simon's general theory of near-decomposability, which states that modularity promotes the evolution of complexity. We found that the skulls of extant primates divide into one conserved cranial module and up to three labile facial modules, whose composition varies among primates. Despite changes in modularity, statistical analyses reject a positive feedback between modularity and complexity. Our results suggest a decoupling of complexity and modularity that translates to varying levels of constraint on the morphological evolvability of the primate skull. This study has methodological and conceptual implications for grasping the constraints that underlie the developmental and functional integration of the skull of humans and other primates.

  17. Anatomical network analysis shows decoupling of modular lability and complexity in the evolution of the primate skull.

    Science.gov (United States)

    Esteve-Altava, Borja; Boughner, Julia C; Diogo, Rui; Villmoare, Brian A; Rasskin-Gutman, Diego

    2015-01-01

    Modularity and complexity go hand in hand in the evolution of the skull of primates. Because analyses of these two parameters often use different approaches, we do not know yet how modularity evolves within, or as a consequence of, an also-evolving complex organization. Here we use a novel network theory-based approach (Anatomical Network Analysis) to assess how the organization of skull bones constrains the co-evolution of modularity and complexity among primates. We used the pattern of bone contacts modeled as networks to identify connectivity modules and quantify morphological complexity. We analyzed whether modularity and complexity evolved coordinately in the skull of primates. Specifically, we tested Herbert Simon's general theory of near-decomposability, which states that modularity promotes the evolution of complexity. We found that the skulls of extant primates divide into one conserved cranial module and up to three labile facial modules, whose composition varies among primates. Despite changes in modularity, statistical analyses reject a positive feedback between modularity and complexity. Our results suggest a decoupling of complexity and modularity that translates to varying levels of constraint on the morphological evolvability of the primate skull. This study has methodological and conceptual implications for grasping the constraints that underlie the developmental and functional integration of the skull of humans and other primates.

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

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    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

  19. 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

  20. Comparative genomic hybridization analysis shows different epidemiology of chromosomal and plasmid-borne cpe-carrying Clostridium perfringens type A.

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    Päivi Lahti

    Full Text Available Clostridium perfringens, one of the most common causes of food poisonings, can carry the enterotoxin gene, cpe, in its chromosome or on a plasmid. C. perfringens food poisonings are more frequently caused by the chromosomal cpe-carrying strains, while the plasmid-borne cpe-positive genotypes are more commonly found in the human feces and environmental samples. Different tolerance to food processing conditions by the plasmid-borne and chromosomal cpe-carrying strains has been reported, but the reservoirs and contamination routes of enterotoxin-producing C. perfringens remain unknown. A comparative genomic hybridization (CGH analysis with a DNA microarray based on three C. perfringens type A genomes was conducted to shed light on the epidemiology of C. perfringens food poisonings caused by plasmid-borne and chromosomal cpe-carrying strains by comparing chromosomal and plasmid-borne cpe-positive and cpe-negative C. perfringens isolates from human, animal, environmental, and food samples. The chromosomal and plasmid-borne cpe-positive C. perfringens genotypes formed two distinct clusters. Variable genes were involved with myo-inositol, ethanolamine and cellobiose metabolism, suggesting a new epidemiological model for C. perfringens food poisonings. The CGH results were complemented with growth studies, which demonstrated different myo-inositol, ethanolamine, and cellobiose metabolism between the chromosomal and plasmid-borne cpe-carrying strains. These findings support a ubiquitous occurrence of the plasmid-borne cpe-positive strains and their adaptation to the mammalian intestine, whereas the chromosomal cpe-positive strains appear to have a narrow niche in environments containing degrading plant material. Thus the epidemiology of the food poisonings caused by two populations appears different, the plasmid-borne cpe-positive strains probably contaminating foods via humans and the chromosomal strains being connected to plant material.

  1. Morphometric analysis of molars in a Middle Pleistocene population shows a mosaic of 'modern' and Neanderthal features.

    Science.gov (United States)

    Martinón-Torres, María; Spěváčková, Petra; Gracia-Téllez, Ana; Martínez, Ignacio; Bruner, Emiliano; Arsuaga, Juan Luis; Bermúdez de Castro, José María

    2013-10-01

    Previous studies of upper first molar (M1) crown shape have shown significant differences between Homo sapiens and Homo neanderthalensis that were already present in the European Middle Pleistocene populations, including the large dental sample from Atapuerca-Sima de los Huesos (SH). Analysis of other M1 features such as the total crown base area, cusp proportions, cusp angles and occlusal polygon have confirmed the differences between both lineages, becoming a useful tool for the taxonomic assignment of isolated teeth from Late Pleistocene sites. However, until now the pattern of expression of these variables has not been known for the SH sample. This fossil sample, the largest collection from the European Middle Pleistocene, is generally interpreted as being from the direct ancestors of Neanderthals, and thus is a reference sample for assessing the origin of the Neanderthal morphologies. Surprisingly, our study reveals that SH M(1) s present a unique mosaic of H. neanderthalensis and H. sapiens features. Regarding the cusp angles and the relative occlusal polygon area, SH matches the H. neanderthalensis pattern. However, regarding the total crown base area and relative cusps size, SH M(1) s are similar to H. sapiens, with a small crown area, a strong hypocone reduction and a protocone enlargement, although the protocone expansion in SH is significantly larger than in any other group studied. The SH dental sample calls into question the uniqueness of some so-called modern traits. Our study also sounds a note of caution on the use of M(1) occlusal morphology for the alpha taxonomy of isolated M(1) s. © 2013 Anatomical Society.

  2. Morphometric analysis of molars in a Middle Pleistocene population shows a mosaic of ‘modern’ and Neanderthal features

    Science.gov (United States)

    Martinón-Torres, María; Spěváčková, Petra; Gracia-Téllez, Ana; Martínez, Ignacio; Bruner, Emiliano; Arsuaga, Juan Luis; Bermúdez de Castro, José María

    2013-01-01

    Previous studies of upper first molar (M1) crown shape have shown significant differences between Homo sapiens and Homo neanderthalensis that were already present in the European Middle Pleistocene populations, including the large dental sample from Atapuerca-Sima de los Huesos (SH). Analysis of other M1 features such as the total crown base area, cusp proportions, cusp angles and occlusal polygon have confirmed the differences between both lineages, becoming a useful tool for the taxonomic assignment of isolated teeth from Late Pleistocene sites. However, until now the pattern of expression of these variables has not been known for the SH sample. This fossil sample, the largest collection from the European Middle Pleistocene, is generally interpreted as being from the direct ancestors of Neanderthals, and thus is a reference sample for assessing the origin of the Neanderthal morphologies. Surprisingly, our study reveals that SH M1s present a unique mosaic of H. neanderthalensis and H. sapiens features. Regarding the cusp angles and the relative occlusal polygon area, SH matches the H. neanderthalensis pattern. However, regarding the total crown base area and relative cusps size, SH M1s are similar to H. sapiens, with a small crown area, a strong hypocone reduction and a protocone enlargement, although the protocone expansion in SH is significantly larger than in any other group studied. The SH dental sample calls into question the uniqueness of some so-called modern traits. Our study also sounds a note of caution on the use of M1 occlusal morphology for the alpha taxonomy of isolated M1s. PMID:23914934

  3. Mitochondrial DNA analysis shows a Near Eastern Neolithic origin for domestic cattle and no indication of domestication of European aurochs

    Science.gov (United States)

    Edwards, Ceiridwen J; Bollongino, Ruth; Scheu, Amelie; Chamberlain, Andrew; Tresset, Anne; Vigne, Jean-Denis; Baird, Jillian F; Larson, Greger; Ho, Simon Y.W; Heupink, Tim H; Shapiro, Beth; Freeman, Abigail R; Thomas, Mark G; Arbogast, Rose-Marie; Arndt, Betty; Bartosiewicz, László; Benecke, Norbert; Budja, Mihael; Chaix, Louis; Choyke, Alice M; Coqueugniot, Eric; Döhle, Hans-Jürgen; Göldner, Holger; Hartz, Sönke; Helmer, Daniel; Herzig, Barabara; Hongo, Hitomi; Mashkour, Marjan; Özdogan, Mehmet; Pucher, Erich; Roth, Georg; Schade-Lindig, Sabine; Schmölcke, Ulrich; Schulting, Rick J; Stephan, Elisabeth; Uerpmann, Hans-Peter; Vörös, István; Voytek, Barbara; Bradley, Daniel G; Burger, Joachim

    2007-01-01

    The extinct aurochs (Bos primigenius primigenius) was a large type of cattle that ranged over almost the whole Eurasian continent. The aurochs is the wild progenitor of modern cattle, but it is unclear whether European aurochs contributed to this process. To provide new insights into the demographic history of aurochs and domestic cattle, we have generated high-confidence mitochondrial DNA sequences from 59 archaeological skeletal finds, which were attributed to wild European cattle populations based on their chronological date and/or morphology. All pre-Neolithic aurochs belonged to the previously designated P haplogroup, indicating that this represents the Late Glacial Central European signature. We also report one new and highly divergent haplotype in a Neolithic aurochs sample from Germany, which points to greater variability during the Pleistocene. Furthermore, the Neolithic and Bronze Age samples that were classified with confidence as European aurochs using morphological criteria all carry P haplotype mitochondrial DNA, suggesting continuity of Late Glacial and Early Holocene aurochs populations in Europe. Bayesian analysis indicates that recent population growth gives a significantly better fit to our data than a constant-sized population, an observation consistent with a postglacial expansion scenario, possibly from a single European refugial population. Previous work has shown that most ancient and modern European domestic cattle carry haplotypes previously designated T. This, in combination with our new finding of a T haplotype in a very Early Neolithic site in Syria, lends persuasive support to a scenario whereby gracile Near Eastern domestic populations, carrying predominantly T haplotypes, replaced P haplotype-carrying robust autochthonous aurochs populations in Europe, from the Early Neolithic onward. During the period of coexistence, it appears that domestic cattle were kept separate from wild aurochs and introgression was extremely rare. PMID

  4. Genetic analysis shows that morphology alone cannot distinguish asian carp eggs from those of other cyprinid species

    Science.gov (United States)

    Larson, James H.; McCalla, Sunnie; Chapman, Duane C.; Rees, Christopher B.; Knights, Brent C.; Vallazza, Jon; George, Amy E.; Richardson, William B.; Amberg, Jon

    2016-01-01

    Fish eggs and embryos (hereafter collectively referred to as “eggs”) were collected in the upper Mississippi River main stem (~300 km upstream of previously reported spawning by invasive Asian carp) during summer 2013. Based on previously published morphological characteristics, the eggs were identified as belonging to Asian carp. A subsample of the eggs was subsequently analyzed by using molecular methods to determine species identity. Genetic identification using the cytochrome-c oxidase 1 gene was attempted for a total of 41 eggs. Due to the preservation technique used (formalin) and the resulting DNA degradation, sequences were recovered from only 17 individual eggs. In all 17 cases, cyprinids other than Asian carp (usually Notropis sp.) were identified as the most likely species. In previously published reports, a key characteristic that distinguished Asian carp eggs from those of other cyprinids was size: Asian carp eggs exhibited diameters ranging from 4.0 to 6.0 mm and were thought to be much larger than the otherwise similar eggs of native species. Eggs from endemic cyprinids were believed to rarely reach 3.0 mm and had not been observed to exceed 3.3 mm. However, many of the eggs that were genetically identified as originating from native cyprinids were as large as 4.0 mm in diameter (at early developmental stages) and were therefore large enough to over- lap with the lower end of the size range observed for Asian carp eggs. Researchers studying the egg stages of Asian carp and other cyprinids should plan on preserving subsets of eggs for genetic analysis to confirm morphological identifications.

  5. Comparative analysis of zygotic developmental genes in Rhodnius prolixus genome shows conserved features on the tracheal developmental pathway.

    Science.gov (United States)

    Lavore, A; Pascual, A; Salinas, F M; Esponda-Behrens, N; Martinez-Barnetche, J; Rodriguez, M; Rivera-Pomar, R

    2015-09-01

    Most of the in-depth studies on insect developmental genetic have been carried out in the fruit fly Drosophila melanogaster, an holometabolous insect, so much more still remains to be studied in hemimetabolous insects. Having Rhodnius prolixus sequenced genome available, we search for orthologue genes of zygotic signaling pathways, segmentation, and tracheogenesis in the R. prolixus genome and in three species of Triatoma genus transcriptomes, concluding that there is a high level of gene conservation. We also study the function of two genes required for tracheal system development in D. melanogaster - R. prolixus orthologues: trachealess (Rp-trh) and empty spiracles (Rp-ems). From that we see that Rp-trh is required for early tracheal development since Rp-trh RNAi shows that the primary tracheal branches fail to form. On the other hand, Rp-ems is implied in the proper formation of the posterior tracheal branches, in a similar way to D. melanogaster. These results represent the initial characterization of the genes involved in the tracheal development of an hemimetabolous insect building a bridge between the current genomic era and V. Wigglesworth's classical studies on insects' respiratory system physiology. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Comprehensive behavioral analysis of Ox1r-/- mice showed implication of orexin receptor-1 in mood, anxiety and social behavior

    Directory of Open Access Journals (Sweden)

    Md Golam Abbas

    2015-12-01

    Full Text Available Neuropeptides orexin A and orexin B, which are exclusively produced by neurons in the lateral hypothalamic area, play an important role in the regulation of a wide range of behaviors and homeostatic processes, including regulation of sleep/wakefulness states and energy homeostasis. The orexin system has close anatomical and functional relationships with systems that regulate the autonomic nervous system, emotion, mood, the reward system and sleep/wakefulness states. Recent pharmacological studies using selective antagonists have suggested that orexin receptor-1 (OX1R is involved in physiological processes that regulate emotion, the reward system and autonomic nervous system. Here, we examined Ox1r-/- mice with a comprehensive behavioral test battery to screen additional OX1R functions. Ox1r-/- mice showed increased anxiety-like behavior, altered depression-like behavior, slightly decreased spontaneous locomotor activity, reduced social interaction, increased startle response and decreased prepulse inhibition. These results suggest that OX1R plays roles in social behaviour and sensory motor gating in addition to roles in mood and anxiety.

  7. Transcriptomic analysis of inbreeding depression in cold-sensitive Drosophila melanogaster shows upregulation of the immune response.

    Science.gov (United States)

    Vermeulen, C J; Sørensen, P; Kirilova Gagalova, K; Loeschcke, V

    2013-09-01

    In sexually reproducing species, increased homozygosity often causes a decline in fitness, called inbreeding depression. Recently, researchers started describing the functional genomic changes that occur during inbreeding, both in benign conditions and under environmental stress. To further this aim, we have performed a genome-wide gene expression study of inbreeding depression, manifesting as cold sensitivity and conditional lethality. Our focus was to describe general patterns of gene expression during inbreeding depression and to identify specific processes affected in our line. There was a clear difference in gene expression between the stressful restrictive environment and the benign permissive environment in both the affected inbred line and the inbred control line. We noted a strong inbreeding-by-environment interaction, whereby virtually all transcriptional differences between lines were found in the restrictive environment. Functional annotation showed enrichment of transcripts coding for serine proteases and their inhibitors (serpins and BPTI/Kunitz family), which indicates activation of the innate immune response. These genes have previously been shown to respond transcriptionally to cold stress, suggesting the conditional lethal effect is associated with an exaggerated cold stress response. The set of differentially expressed genes significantly overlapped with those found in three other studies of inbreeding depression, demonstrating that it is possible to detect a common signature across different genetic backgrounds. © 2013 The Authors. Journal of Evolutionary Biology © 2013 European Society For Evolutionary Biology.

  8. X-ray survival characteristics and genetic analysis for nine saccharomyces deletion mutants that show altered radiation sensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Game, John C.; Williamson, Marsha S.; Baccari, Clelia

    2004-01-07

    The availability of a genome-wide set of Saccharomyces deletion mutants provides a chance to identify all the yeast genes involved in DNA repair. Using X-rays, we are screening these mutants to identify additional genes that show increased sensitivity to the lethal effects of ionizing radiation. For each mutant identified as sensitive, we are confirming that the sensitivity phenotype co-segregates with the deletion allele and are obtaining multipoint survival-versus-dose assays in at least two haploid and one homozygous diploid strains. We present data for deletion mutants involving the genes DOT1, MDM20, NAT3, SPT7, SPT20, GCN5, HFI1, DCC1 and VID21/EAF1, and discuss their potential roles in repair. Eight of these genes have a clear radiation-sensitive phenotype when deleted, but the ninth, GCN5, has at most a borderline phenotype. None of the deletions confer substantial sensitivity to ultra-violet radiation, although one or two may confer marginal sensitivity. The DOT1 gene is of interest because its only known function is to methylate one lysine residue in the core of the histone H3 protein. We find that histone H3 mutants (supplied by K. Struhl) in which this residue is replaced by other amino-acids are also X-ray sensitive, seeming to confirm that methylation of the lysine-79 residue is required for effective repair of radiation damage.

  9. Transmission electron microscopic analysis showing structural changes to bacterial cells treated with electrolyzed water and an acidic sanitizer.

    Science.gov (United States)

    Feliciano, Lizanel; Lee, Jaesung; Pascall, Melvin A

    2012-04-01

    The effects of various sanitizers on the viability and cellular injury to structures of Escherichia coli and Listeria innocua were investigated. A food grade organic acidic formulation (pH 2.5) and acidic, neutral, and basic electrolyzed water [AEW (pH 2.7, oxidation reduction potential; ORP: 1100 mV, free available chlorine; FAC: 150 ppm), NEW (pH 6.9, ORP: 840 mV, FAC: 150 ppm), BEW (pH 11.6, ORP: -810 mV)] were used to treat E. coli and L. innocua cells. After 10 min of exposure to the sanitizers, changes to the bacterial numbers and cell structures were evaluated by plate counting and transmission electron microscopy (TEM), respectively. It was concluded from the results that the sanitizers reduced the E. coli cells between 2 and 3 log CFU/mL. Except for the BEW treatment, reductions in L. innocua population were greater (>1 log CFU/mL) than that of E. coli for all treatments. Data from the TEM showed that all sanitizers caused changes to the cell envelope and cytoplasm of both organisms. However, smaller changes were observed for L. innocua cells. Decrease in the integrity of the cell envelope and aggregation of the cytoplasmic components appeared to be mainly because of exposure to the sanitizers. The organic acid formulation and AEW were the most effective sanitizers against bacterial cells, indicating that penetration of acidic substances effectively caused the cell inactivation. An understanding of the method in which E-water and an acidic sanitizer cause injury to E. coli and L. innocua would be helpful in selecting an effective chemical agent as a food safety tool. This will allow a scientist to target similar microorganisms such as food borne bacteria with structures that are vulnerable to the sanitizer. © 2012 Institute of Food Technologists®

  10. Transcriptome Analysis of Enterococcus faecalis during Mammalian Infection Shows Cells Undergo Adaptation and Exist in a Stringent Response State

    Science.gov (United States)

    Frank, Kristi L.; Colomer-Winter, Cristina; Grindle, Suzanne M.; Lemos, José A.; Schlievert, Patrick M.; Dunny, Gary M.

    2014-01-01

    As both a commensal and a major cause of healthcare-associated infections in humans, Enterococcus faecalis is a remarkably adaptable organism. We investigated how E. faecalis adapts in a mammalian host as a pathogen by characterizing changes in the transcriptome during infection in a rabbit model of subdermal abscess formation using transcriptional microarrays. The microarray experiments detected 222 and 291 differentially regulated genes in E. faecalis OG1RF at two and eight hours after subdermal chamber inoculation, respectively. The profile of significantly regulated genes at two hours post-inoculation included genes involved in stress response, metabolism, nutrient acquisition, and cell surface components, suggesting genome-wide adaptation to growth in an altered environment. At eight hours post-inoculation, 88% of the differentially expressed genes were down-regulated and matched a transcriptional profile consistent with a (p)ppGpp-mediated stringent response. Subsequent subdermal abscess infections with E. faecalis mutants lacking the (p)ppGpp synthetase/hydrolase RSH, the small synthetase RelQ, or both enzymes, suggest that intracellular (p)ppGpp levels, but not stringent response activation, influence persistence in the model. The ability of cells to synthesize (p)ppGpp was also found to be important for growth in human serum and whole blood. The data presented in this report provide the first genome-wide insights on E. faecalis in vivo gene expression and regulation measured by transcriptional profiling during infection in a mammalian host and show that (p)ppGpp levels affect viability of E. faecalis in multiple conditions relevant to mammalian infection. The subdermal abscess model can serve as a novel experimental system for studying the E. faecalis stringent response in the context of the mammalian immune system. PMID:25545155

  11. 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.

  12. Does Cognitive Behavior Therapy for Psychosis (CBTp show a sustainable effect on delusions? A meta-analysis.

    Directory of Open Access Journals (Sweden)

    Stephanie eMehl

    2015-10-01

    Full Text Available Cognitive Behavior Therapy for psychosis (CBTp is an effective treatment resulting in small to medium effect sizes with regard to changes in positive symptoms and psychopathology. As a consequence, CBTp is recommended by national guidelines for all patients with schizophrenia. However, although CBTp was originally developed as a means to improve delusions, meta-analyses have generally integrated effects for positive symptoms rather than for delusions. Thus, it is still an open question whether more broadly defined CBTp is more effective with regard to change in delusions compared to treatment as usual (TAU and to other interventions, and whether this effect remains stable over a follow-up period. Moreover, it would be interesting to explore whether newer studies that focus on specific factors involved in the formation and maintenance of delusions (causal-interventionist approach are more effective than the first generation of CBTp studies. A systematic search of the trial literature identified 19 RCTs that compared CBTp with TAU and/or other interventions and reported delusions as an outcome measure. Meta-analytic integration resulted in a significant small to medium effect size for CBTp in comparison to TAU at end-of-therapy (k=13; d ̅=0.27 and after an average follow-up period of 47 weeks (k=12; d ̅=0.25. When compared with other interventions, there was no significant effect of CBTp at end-of-therapy (k=8; d ̅=0.16 and after a follow-up period (k=5; d ̅=–0.04. Comparison between newer studies taking a causal-interventionist approach (k=4 and first-generation studies showed a difference of 0.33 in mean effect sizes in favor of newer studies at end-of-therapy. The findings suggest that CBTp is superior to TAU, but is not superior to other interventions, in bringing about a change in delusions, and that this superiority is maintained over the follow-up period. Moreover, interventions that focus on causal factors of delusions seem to be a

  13. 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.

  14. Subgrouping siblings of people with autism: Identifying the broader autism phenotype

    Science.gov (United States)

    Allison, Carrie; Smith, Paula; Watson, Peter; Auyeung, Bonnie; Ring, Howard; Baron‐Cohen, Simon

    2015-01-01

    We investigate the broader autism phenotype (BAP) in siblings of individuals with autism spectrum conditions (ASC). Autistic traits were measured in typical controls (n = 2,000), siblings (n = 496), and volunteers with ASC (n = 2,322) using the Autism‐Spectrum Quotient (AQ), both self‐report and parent‐report versions. Using cluster analysis of AQ subscale scores, two sibling subgroups were identified for both males and females: a cluster of low‐scorers and a cluster of high‐scorers. Results show that while siblings as a group have intermediate levels of autistic traits compared to control individuals and participants with ASC, when examined on a cluster level, the low‐scoring sibling group is more similar to typical controls while the high‐scoring group is more similar to the ASC clinical group. Further investigation into the underlying genetic and epigenetic characteristics of these two subgroups will be informative in understanding autistic traits, both within the general population and in relation to those with a clinical diagnosis. Autism Res 2016, 9: 658–665. © 2015 The Authors Autism Research published by Wiley Periodicals, Inc. on behalf of International Society for Autism Research PMID:26332889

  15. On the use of genetic programming for mining comprehensible rules in subgroup discovery.

    Science.gov (United States)

    Luna, José María; Romero, José Raúl; Romero, Cristóbal; Ventura, Sebastián

    2014-12-01

    This paper proposes a novel grammar-guided genetic programming algorithm for subgroup discovery. This algorithm, called comprehensible grammar-based algorithm for subgroup discovery (CGBA-SD), combines the requirements of discovering comprehensible rules with the ability to mine expressive and flexible solutions owing to the use of a context-free grammar. Each rule is represented as a derivation tree that shows a solution described using the language denoted by the grammar. The algorithm includes mechanisms to adapt the diversity of the population by self-adapting the probabilities of recombination and mutation. We compare the approach with existing evolutionary and classic subgroup discovery algorithms. CGBA-SD appears to be a very promising algorithm that discovers comprehensible subgroups and behaves better than other algorithms as measures by complexity, interest, and precision indicate. The results obtained were validated by means of a series of nonparametric tests.

  16. 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/.

  17. 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

  18. Sub-grouping and sub-functionalization of the RIFIN multi-copy protein family

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    Sonnhammer Erik L

    2008-01-01

    Full Text Available Abstract Background Parasitic protozoans possess many multicopy gene families which have central roles in parasite survival and virulence. The number and variability of members of these gene families often make it difficult to predict possible functions of the encoded proteins. The families of extra-cellular proteins that are exposed to a host immune response have been driven via immune selection to become antigenically variant, and thereby avoid immune recognition while maintaining protein function to establish a chronic infection. Results We have combined phylogenetic and function shift analyses to study the evolution of the RIFIN proteins, which are antigenically variant and are encoded by the largest multicopy gene family in Plasmodium falciparum. We show that this family can be subdivided into two major groups that we named A- and B-RIFIN proteins. This suggested sub-grouping is supported by a recently published study that showed that, despite the presence of the Plasmodium export (PEXEL motif in all RIFIN variants, proteins from each group have different cellular localizations during the intraerythrocytic life cycle of the parasite. In the present study we show that function shift analysis, a novel technique to predict functional divergence between sub-groups of a protein family, indicates that RIFINs have undergone neo- or sub-functionalization. Conclusion These results question the general trend of clustering large antigenically variant protein groups into homogenous families. Assigning functions to protein families requires their subdivision into meaningful groups such as we have shown for the RIFIN protein family. Using phylogenetic and function shift analysis methods, we identify new directions for the investigation of this broad and complex group of proteins.

  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. Pain Drawings Improve Subgrouping of Low Back Pain Patients.

    Science.gov (United States)

    Hüllemann, Philipp; Keller, Thomas; Kabelitz, Maria; Freynhagen, Rainer; Tölle, Thomas; Baron, Ralf

    2017-03-01

    Subgrouping of low back pain (LBP) patients may be improved when pain drawings are combined with the painDETECT (PD-Q) questionnaire. We hypothesized that (1) different LBP subgroups determined by their pain radiation show different clinical patterns and (2) the occurrence of neuropathic symptoms depends on pain radiation. A total of 19,263 acute ( 3 months) LBP patients were allocated prospectively into 4 groups based on the location of pain drawings on a manikin and compared regarding neuropathic pain components, functionality, depression, pain intensity, and surgical interventions. All items were investigated at baseline and follow-up visits. Group I was composed of patients with axial LBP without radiating pain; group II, LBP with radiation into the thigh; group III, LBP with radiation into the shank; and group IV, LBP with radiation into the feet. Side-dependent pain radiation was assessed additionally. Depression, functionality, and pain intensity showed no clinically relevant differences, whereas PD-Q scores and the probability to rate positive for neuropathic pain increased with more distally radiating pain. Surgery and medication intake were most frequent in group IV. Follow-up analyses showed that only axial LBP became more neuropathic, whereas pain intensity decreased over time. Radicular patterns of pain drawings in LBP patients indicate severe pain conditions with the most neuropathic components, while axial LBP has the fewest. For the categorization of LBP, pain drawings help explain the underlying mechanism of pain, which might further improve mechanism-based treatment when used in clinical routines and research. © 2016 World Institute of Pain.

  3. Resolution and Characterization of Distinct cpn60-Based Subgroups of Gardnerella vaginalis in the Vaginal Microbiota

    Science.gov (United States)

    Paramel Jayaprakash, Teenus; Schellenberg, John J.; Hill, Janet E.

    2012-01-01

    Bacterial vaginosis (BV), characterized by a shift of the vaginal microbiota from a Lactobacillus-dominated community to a dense biofilm containing a complex mixture of organisms, is an important risk factor in poor reproductive health outcomes. The Nugent score, based on Gram stain, is used to diagnose BV and Gardnerella vaginalis abundance in the sample is one factor determining Nugent score. A high Nugent score is indicative of BV but does not always correspond to the presence of clinical symptoms. G. vaginalis is recognized as a heterogeneous group of organisms, which can also be part of the normal, healthy vaginal microbiome. In addition, asymptomatic BV and non-Gardnerella types of BV are being recognized. In an attempt to resolve the heterogeneous group of G. vaginalis, a phylogenetic tree of cpn60 universal target sequences from G. vaginalis isolates was constructed that indicates the existence of four subgroups of G. vaginalis. This subdivision, supported by whole genome similarity calculation of representative strains using JSpecies, demonstrates that these subgroups may represent different species. The cpn60 subgroupings did not correspond with the Piot biotyping scheme, but did show consistency with ARDRA genotyping and sialidase gene presence. Isolates from all four subgroups produced biofilm in vitro. We also investigated the distribution of G. vaginalis subgroups in vaginal samples from Kenyan women with Nugent scores consistent with BV, Intermediate and Normal microbiota (n = 44). All subgroups of G. vaginalis were detected in these women, with a significant difference (z = −3.372, n = 39, p = 0.001) in frequency of G. vaginalis subgroup B between BV and Normal groups. Establishment of a quantifiable relationship between G. vaginalis subgroup distribution and clinical status could have significant diagnostic implications. PMID:22900080

  4. Resolution and characterization of distinct cpn60-based subgroups of Gardnerella vaginalis in the vaginal microbiota.

    Directory of Open Access Journals (Sweden)

    Teenus Paramel Jayaprakash

    Full Text Available Bacterial vaginosis (BV, characterized by a shift of the vaginal microbiota from a Lactobacillus-dominated community to a dense biofilm containing a complex mixture of organisms, is an important risk factor in poor reproductive health outcomes. The Nugent score, based on Gram stain, is used to diagnose BV and Gardnerella vaginalis abundance in the sample is one factor determining Nugent score. A high Nugent score is indicative of BV but does not always correspond to the presence of clinical symptoms. G. vaginalis is recognized as a heterogeneous group of organisms, which can also be part of the normal, healthy vaginal microbiome. In addition, asymptomatic BV and non-Gardnerella types of BV are being recognized. In an attempt to resolve the heterogeneous group of G. vaginalis, a phylogenetic tree of cpn60 universal target sequences from G. vaginalis isolates was constructed that indicates the existence of four subgroups of G. vaginalis. This subdivision, supported by whole genome similarity calculation of representative strains using JSpecies, demonstrates that these subgroups may represent different species. The cpn60 subgroupings did not correspond with the Piot biotyping scheme, but did show consistency with ARDRA genotyping and sialidase gene presence. Isolates from all four subgroups produced biofilm in vitro. We also investigated the distribution of G. vaginalis subgroups in vaginal samples from Kenyan women with Nugent scores consistent with BV, Intermediate and Normal microbiota (n = 44. All subgroups of G. vaginalis were detected in these women, with a significant difference (z = -3.372, n = 39, p = 0.001 in frequency of G. vaginalis subgroup B between BV and Normal groups. Establishment of a quantifiable relationship between G. vaginalis subgroup distribution and clinical status could have significant diagnostic implications.

  5. 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

  6. Significant changes in circulating microRNA by dietary supplementation of selenium and coenzyme Q10 in healthy elderly males. A subgroup analysis of a prospective randomized double-blind placebo-controlled trial among elderly Swedish citizens.

    Science.gov (United States)

    Alehagen, Urban; Johansson, Peter; Aaseth, Jan; Alexander, Jan; Wågsäter, Dick

    2017-01-01

    Selenium and coenzyme Q10 is essential for important cellular functions. A low selenium intake is reported from many European countries, and the endogenous coenzyme Q10 production is decreasing in the body with increasing age. Supplementation with selenium and coenzyme Q10 in elderly have shown reduced cardiovascular mortality and reduced levels of markers of inflammation. However, microRNA analyses could give important information on the mechanisms behind the clinical effects of supplementation. Out of the 443 healthy elderly participants that were given supplementation with 200 μg Se/day as organic selenium yeast tablets, and 200 mg/day of coenzyme Q10 capsules, or placebo for 4 years, 25 participants from each group were randomized and evaluated regarding levels of microRNA. Isolation of RNA from plasma samples and quantitative PCR analysis were performed. Volcano- and principal component analyses (PCA)-plots were used to illustrate the differences in microRNA expression between the intervention, and the placebo groups. Serum selenium concentrations were measured before intervention. On average 145 different microRNAs out of 172 were detected per sample. In the PCA plots two clusters could be identified indicating significant difference in microRNA expression between the two groups. The pre-treatment expression of the microRNAs did not differ between active treatment and the placebo groups. When comparing the post-treatment microRNAs in the active and the placebo groups, 70 microRNAs exhibited significant differences in expression, also after adjustment for multiple measurements. For the 20 microRNAs with the greatest difference in expression the difference was up to more than 4 fold and with a P-value that were less than 4.4e-8. Significant differences were found in expression of more than 100 different microRNAs with up to 4 fold differences as a result of the intervention of selenium and coenzyme Q10 combined. The changes in microRNA could be a part of

  7. 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...

  8. Prevalence and distribution of Gardnerella vaginalis subgroups in women with and without bacterial vaginosis.

    Science.gov (United States)

    Janulaitiene, Migle; Paliulyte, Virginija; Grinceviciene, Svitrigaile; Zakareviciene, Jolita; Vladisauskiene, Alma; Marcinkute, Agne; Pleckaityte, Milda

    2017-06-05

    Bacterial vaginosis (BV) is one of the leading causes of vaginal complaints among women of childbearing age. The role of Gardnerella vaginalis remains controversial due to its presence in healthy and BV-type vaginal microflora. The phenotypic and genotypic heterogeneity of G. vaginalis suggested the existence of strain variants linked with different health conditions. We sought to analyze prevalence and distribution of G. vaginalis subgroups (clades) in BV-positive (n = 29), partial BV (n = 27), and BV-negative (n = 53) vaginal samples from Lithuanian women. Vaginal samples were characterized by Amsel criteria and the Nugent method. Bacterial signatures characteristic of BV and concomitant infections were identified by culture and PCR. Using singleplex PCR assays, G. vaginalis subgroups were identified in 109 noncultured vaginal specimens by targeting clade-specific genes. Isolated G. vaginalis clinical strains were subtyped and the presence of the sialidase coding gene was detected by PCR. Data analysis was performed using GraphPad Prism statistical software. G. vaginalis was found in 87% of women without BV. Clade 4 was most frequently detected (79.4%), followed by clade 1 (63.7%), clade 2 (42.2%), and clade 3 (15.7%). Multi-clade G. vaginalis communities showed a positive association with Nugent score (NS) ≥ 4 (OR 3.64; 95% CI 1.48-8.91; p = 0.005). Clade 1 and clade 2 were statistically significantly more common in samples with NS 7-10 (OR 4.69; 95% CI 1.38-15.88; p = 0.01 and OR 6.26; 95% CI 2.20-17.81; p ≤ 0.001, respectively). Clade 3 and clade 4 showed no association with high NS (OR 0.88; 95% CI 0.26-3.04; p = 1.00 and OR 1.31; 95% CI 0.39-4.41; p = 0.767, respectively). The gene coding for sialidase was detected in all isolates of clade 1 and clade 2, but not in clade 4 isolates. We showed an association between the microbial state of vaginal microflora and specific subgroups of G. vaginalis, the distribution of which may determine the clinical

  9. Bortezomib before and after autologous stem cell transplantation overcomes the negative prognostic impact of renal impairment in newly diagnosed multiple myeloma: a subgroup analysis from the HOVON-65/GMMG-HD4 trial

    NARCIS (Netherlands)

    Scheid, C.; Sonneveld, P.; Schmidt-Wolf, I.G.; Holt, B. van der; Jarari, L. el; Bertsch, U.; Salwender, H.; Zweegman, S.; Blau, I.W.; Vellenga, E.; Weisel, K.; Pfreundschuh, M.; Jie, K.S.; Neben, K.; Velde, H. van der; Duehrsen, U.; Schaafsma, M.R.; Lindemann, W.; Kersten, M.J.; Peter, N.; Hanel, M.; Croockewit, S.; Martin, H.; Wittebol, S.; Bos, G.M.; Marwijk-Kooy, M. van; Wijermans, P.; Goldschmidt, H.; Lokhorst, H.M.

    2014-01-01

    Renal impairment is frequent in patients with multiple myeloma and is correlated with an inferior prognosis. This analysis evaluates the prognostic role of renal impairment in patients with myeloma treated with bortezomib before and after autologous stem cell transplantation within a prospective

  10. Bortezomib before and after autologous stem cell transplantation overcomes the negative prognostic impact of renal impairment in newly diagnosed multiple myeloma : a subgroup analysis from the HOVON-65/GMMG-HD4 trial

    NARCIS (Netherlands)

    Scheid, Christof; Sonneveld, Pieter; Schmidt-Wolf, Ingo G H; van der Holt, Bronno; el Jarari, Laila; Bertsch, Uta; Salwender, Hans; Zweegman, Sonja; Blau, Igor Wolfgang; Vellenga, Edo; Weisel, Katja; Pfreundschuh, Michael; Jie, Kon-Siong; Neben, Kai; van de Velde, Helgi; Duehrsen, Ulrich; Schaafsma, M Ron; Lindemann, Walter; Kersten, Marie José; Peter, Norma; Hänel, Mathias; Croockewit, Sandra; Martin, Hans; Wittebol, Shulamiet; Bos, Gerard Mj; van Marwijk-Kooy, Marinus; Wijermans, Pierre; Goldschmidt, Hartmut; Lokhorst, Henk M

    Renal impairment is frequent in patients with multiple myeloma and is correlated with an inferior prognosis. This analysis evaluates the prognostic role of renal impairment in patients with myeloma treated with bortezomib before and after autologous stem cell transplantation within a prospective

  11. Sustained disease-activity-free status in patients with relapsing-remitting multiple sclerosis treated with cladribine tablets in the CLARITY study: a post-hoc and subgroup analysis

    DEFF Research Database (Denmark)

    Giovannoni, Gavin; Cook, Stuart; Rammohan, Kottil

    2011-01-01

    /kg over 96 weeks was more effective than placebo. Achieving sustained freedom from disease activity is becoming a viable treatment goal in RRMS; we therefore aimed to assess the effects of cladribine on this composite outcome measure by doing a post-hoc analysis of data from the CLARITY study....

  12. Distinct Wound Healing and Quality-of-Life Outcomes in Subgroups of Patients With Venous Leg Ulcers With Different Symptom Cluster Experiences.

    Science.gov (United States)

    Finlayson, Kathleen; Miaskowski, Christine; Alexander, Kimberly; Liu, Wei-Hong; Aouizerat, Bradley; Parker, Christina; Maresco-Pennisi, Diane; Edwards, Helen

    2017-05-01

    Adults with venous leg ulcers frequently experience multiple symptoms that may influence quality of life (QOL). The objective of this study was to identify patient subgroups based on their experience with a pain-depression-fatigue-sleep disturbance symptom cluster and to identify differences in patient characteristics and wound-healing and QOL outcomes between the subgroups. Secondary data analysis from previous longitudinal studies of 247 patients with venous leg ulcers. Latent class analysis identified subgroups of patients with distinct experiences with the symptom cluster of pain, depression, fatigue, and sleep disturbance. Hierarchical regression analysis identified relationships between the subgroups and QOL outcomes. Survival analysis identified differences between the subgroups and ulcer healing. Latent class analysis found 67% of patients were in a mild symptom subgroup (i.e., experiencing no or mild pain, depressive symptoms, fatigue, or sleep disturbance). One-third of the samples were in a severe symptom subgroup, who reported moderate-to-severe levels of these symptoms. Compared with the mild subgroup, patients in the severe subgroup had poorer QOL scores (t = 8.06, P ulcer healing, decreased QOL, and membership in the severe symptom subgroup. These findings suggest that comprehensive symptom assessment is needed to identify patients at higher risk for poor outcomes and enable early intervention. Copyright © 2017 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

  13. Personalized dementia care: proven effectiveness of psychosocial interventions in subgroups

    NARCIS (Netherlands)

    van Mierlo, L.D.; van der Roest, H.G.; Meiland, F.J.M.; Dröes, R.M.

    2010-01-01

    Many psychosocial intervention studies report effects in subgroups of people with dementia. Insight into the characteristics of these subgroups is important for care practice. This study reviews personal characteristics of people with dementia (living in the community or in an institution) that are

  14. A Systematic Approach to Subgroup Classification in Intellectual Disability

    Science.gov (United States)

    Schalock, Robert L.; Luckasson, Ruth

    2015-01-01

    This article describes a systematic approach to subgroup classification based on a classification framework and sequential steps involved in the subgrouping process. The sequential steps are stating the purpose of the classification, identifying the classification elements, using relevant information, and using clearly stated and purposeful…

  15. Characteristic properties of large subgroups in primary abelian groups

    Indian Academy of Sciences (India)

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

    Invariant properties of large subgroups. We start with some extensions of totally projective p-groups, namely: 1. p-torsion A-groups. Several details on A-groups appear in [7]. For example, any p- torsion abelian A-group is an isotype subgroup of a totally projective p-group with special properties described in [7]. Theorem 1.

  16. A Data-Driven Approach to Responder Subgroup Identification after Paired Continuous Theta Burst Stimulation

    Directory of Open Access Journals (Sweden)

    Tonio Heidegger

    2017-08-01

    Full Text Available Background: Modulation of cortical excitability by transcranial magnetic stimulation (TMS is used for investigating human brain functions. A common observation is the high variability of long-term depression (LTD-like changes in human (motor cortex excitability. This study aimed at analyzing the response subgroup distribution after paired continuous theta burst stimulation (cTBS as a basis for subject selection.Methods: The effects of paired cTBS using 80% active motor threshold (AMT in 31 healthy volunteers were assessed at the primary motor cortex (M1 corresponding to the representation of the first dorsal interosseous (FDI muscle of the left hand, before and up to 50 min after plasticity induction. The changes in motor evoked potentials (MEPs were analyzed using machine-learning derived methods implemented as Gaussian mixture modeling (GMM and computed ABC analysis.Results: The probability density distribution of the MEP changes from baseline was tri-modal, showing a clear separation at 80.9%. Subjects displaying at least this degree of LTD-like changes were n = 6 responders. By contrast, n = 7 subjects displayed a paradox response with increase in MEP. Reassessment using ABC analysis as alternative approach led to the same n = 6 subjects as a distinct category.Conclusion: Depressive effects of paired cTBS using 80% AMT endure at least 50 min, however, only in a small subgroup of healthy subjects. Hence, plasticity induction by paired cTBS might not reflect a general mechanism in human motor cortex excitability. A mathematically supported criterion is proposed to select responders for enrolment in assessments of human brain functional networks using virtual brain lesions.

  17. A Data-Driven Approach to Responder Subgroup Identification after Paired Continuous Theta Burst Stimulation.

    Science.gov (United States)

    Heidegger, Tonio; Hansen-Goos, Onno; Batlaeva, Olga; Annak, Onur; Ziemann, Ulf; Lötsch, Jörn

    2017-01-01

    Background: Modulation of cortical excitability by transcranial magnetic stimulation (TMS) is used for investigating human brain functions. A common observation is the high variability of long-term depression (LTD)-like changes in human (motor) cortex excitability. This study aimed at analyzing the response subgroup distribution after paired continuous theta burst stimulation (cTBS) as a basis for subject selection. Methods: The effects of paired cTBS using 80% active motor threshold (AMT) in 31 healthy volunteers were assessed at the primary motor cortex (M1) corresponding to the representation of the first dorsal interosseous (FDI) muscle of the left hand, before and up to 50 min after plasticity induction. The changes in motor evoked potentials (MEPs) were analyzed using machine-learning derived methods implemented as Gaussian mixture modeling (GMM) and computed ABC analysis. Results: The probability density distribution of the MEP changes from baseline was tri-modal, showing a clear separation at 80.9%. Subjects displaying at least this degree of LTD-like changes were n = 6 responders. By contrast, n = 7 subjects displayed a paradox response with increase in MEP. Reassessment using ABC analysis as alternative approach led to the same n = 6 subjects as a distinct category. Conclusion: Depressive effects of paired cTBS using 80% AMT endure at least 50 min, however, only in a small subgroup of healthy subjects. Hence, plasticity induction by paired cTBS might not reflect a general mechanism in human motor cortex excitability. A mathematically supported criterion is proposed to select responders for enrolment in assessments of human brain functional networks using virtual brain lesions.

  18. Outcome of patients with diabetes and unstable angina. A subgroup analysis in the Spanish Multicentre Trial of trifusal in unstable angina. Grupo de Estudio del Trifusal en la Angina Inestable.

    Science.gov (United States)

    García-Rubira, J C; Cruz, J M; López, V; Plaza, L; Navas, J C

    1994-09-01

    We analyzed the clinical characteristics of the 58 diabetic and 218 nondiabetic patients enrolled in the Spanish multicentre trial of trifusal in unstable angina. After 6 months of follow-up, 25 suffered from myocardial infarction or death, 10 of which were diabetics (17.2%) and 15 nondiabetics (6.9%) (P = 0.0146). This difference remained significant after multivariate analysis. We conclude that diabetes is an independent predictor of adverse outcome in patients with medically treated unstable angina.

  19. Multiplicity-adjusted semiparametric benefiting subgroup identification in clinical trials.

    Science.gov (United States)

    Schnell, Patrick M; Müller, Peter; Tang, Qi; Carlin, Bradley P

    2018-02-01

    Background A recent focus in the health sciences has been the development of personalized medicine, which includes determining the population for which a given treatment is effective. Due to limited data, identifying the true benefiting population is a challenging task. To tackle this difficulty, the credible subgroups approach provides a pair of bounding subgroups for the true benefiting subgroup, constructed so that one is contained by the benefiting subgroup while the other contains the benefiting subgroup with high probability. However, the method has so far only been developed for parametric linear models. Methods In this article, we develop the details required to follow the credible subgroups approach in more realistic settings by considering nonlinear and semiparametric regression models, supported for regulatory science by conditional power simulations. We also present an improved multiple testing approach using a step-down procedure. We evaluate our approach via simulations and apply it to data from four trials of Alzheimer's disease treatments carried out by AbbVie. Results Semiparametric modeling yields credible subgroups that are more robust to violations of linear treatment effect assumptions, and careful choice of the population of interest as well as the step-down multiple testing procedure result in a higher rate of detection of benefiting types of patients. The approach allows us to identify types of patients that benefit from treatment in the Alzheimer's disease trials. Conclusion Attempts to identify benefiting subgroups of patients in clinical trials are often met with skepticism due to a lack of multiplicity control and unrealistically restrictive assumptions. Our proposed approach merges two techniques, credible subgroups, and semiparametric regression, which avoids these problems and makes benefiting subgroup identification practical and reliable.

  20. Safety and Efficacy of a Topical Sodium Channel Inhibitor (TV-45070) in Patients With Postherpetic Neuralgia (PHN): A Randomized, Controlled, Proof-of-Concept, Crossover Study, With a Subgroup Analysis of the Nav1.7 R1150W Genotype.

    Science.gov (United States)

    Price, Nicola; Namdari, Rostam; Neville, Judith; Proctor, Katie J W; Kaber, Samer; Vest, Jeffery; Fetell, Michael; Malamut, Richard; Sherrington, Robin P; Pimstone, Simon N; Goldberg, Yigal P

    2017-04-01

    The objective was to evaluate the safety and efficacy of TV-45070 ointment, as a treatment for postherpetic neuralgia, and to explore the response in patients with the Nav1.7 R1150W gain-of-function polymorphism. This was a randomized, placebo-controlled, 2-period, 2-treatment crossover trial. Patients with postherpetic neuralgia with moderate or greater pain received TV-45070 and placebo ointments, each applied twice daily for 3 weeks. The primary efficacy measure was the difference in change in mean daily pain score from baseline compared with the last week of placebo and active treatment. Secondary endpoints included responder rate analyses and a further exploratory analysis of response in carriers of the Nav1.7 R1150W polymorphism was conducted. Seventy patients were enrolled and 54 completed the study. TV-45070 was safe and well tolerated. No statistical difference was observed between treatments for the primary endpoint. However, the proportion of patients with ≥50% reduction in mean pain scores at week 3 was greater on TV-45070 than on placebo (26.8% vs. 10.7%, P=0.0039). Similarly, a greater proportion of patients on TV-45070 had a ≥30% reduction in mean pain scores at week 3 (39.3% on TV-45070 vs. 23.2% on placebo, P=0.0784). Of note, 63% of patients with the R1150W polymorphism versus 35% of wild-type carriers had a ≥30% reduction in mean pain score on TV-45070 at week 3 (no inferential analysis performed). The 50% responder analysis suggests a subpopulation may exist with a more marked analgesic response to TV-45070.The trend toward a larger proportion of responders within Nav1.7 R1150W carriers warrants further investigation.

  1. Divide and Conquer: Sub-Grouping of ASD Improves ASD Detection Based on Brain Morphometry.

    Science.gov (United States)

    Katuwal, Gajendra J; Baum, Stefi A; Cahill, Nathan D; Michael, Andrew M

    2016-01-01

    Low success (ASD) classification using brain morphometry from the large multi-site ABIDE dataset and inconsistent findings on brain morphometric abnormalities in ASD can be attributed to the ASD heterogeneity. In this study, we show that ASD brain morphometry is highly heterogeneous, and demonstrate that the heterogeneity can be mitigated and classification improved if autism severity (AS), verbal IQ (VIQ) and age are used with morphometric features. Morphometric features from structural MRIs (sMRIs) of 734 males (ASD: 361, controls: 373) of ABIDE were derived using FreeSurfer. Applying the Random Forest classifier, an AUC of 0.61 was achieved. Adding VIQ and age to morphometric features, AUC improved to 0.68. Sub-grouping the subjects by AS, VIQ and age improved the classification with the highest AUC of 0.8 in the moderate-AS sub-group (AS = 7-8). Matching subjects on age and/or VIQ in each sub-group further improved the classification with the highest AUC of 0.92 in the low AS sub-group (AS = 4-5). AUC decreased with AS and VIQ, and was the lowest in the mid-age sub-group (13-18 years). The important features were mainly from the frontal, temporal, ventricular, right hippocampal and left amygdala regions. However, they highly varied with AS, VIQ and age. The curvature and folding index features from frontal, temporal, lingual and insular regions were dominant in younger subjects suggesting their importance for early detection. When the experiments were repeated using the Gradient Boosting classifier similar results were obtained. Our findings suggest that identifying brain biomarkers in sub-groups of ASD can yield more robust and insightful results than searching across the whole spectrum. Further, it may allow identification of sub-group specific brain biomarkers that are optimized for early detection and monitoring, increasing the utility of sMRI as an important tool for early detection of ASD.

  2. A comparison of five recursive partitioning methods to find person subgroups involved in meaningful treatment-subgroup interactions

    NARCIS (Netherlands)

    Doove, L. L.; Dusseldorp, E.; Van Deun, K.; Van Mechelen, I.

    2014-01-01

    In case multiple treatment alternatives are available for some medical problem, the detection of treatment–subgroup interactions (i.e., relative treatment effectiveness varying over subgroups of persons) is of key importance for personalized medicine and the development of optimal treatment

  3. Review of a licensed dengue vaccine: Inappropriate subgroup analyses and selective reporting may cause harm in mass vaccination programs.

    Science.gov (United States)

    Dans, Antonio L; Dans, Leonila F; Lansang, Mary Ann D; Silvestre, Maria Asuncion A; Guyatt, Gordon H

    2017-11-24

    Severe life-threatening dengue fever usually occurs when a child is infected by dengue virus a 2nd time. This is caused by a phenomenon called antibody dependent enhancement or ADE. Since dengue vaccines can mimic a first infection in seronegative children (those with no previous infection), a natural infection later in life could lead to severe disease. The possibility that dengue vaccines can cause severe dengue through ADE has led to serious concern regarding the safety of mass vaccination programs. A published meta-analysis addressed this safety issue for a new vaccine against dengue fever - Dengvaxia ™. The trials in this meta-analysis have been used to campaign for mass vaccination programs in developing countries. We discuss the results of this paper and point out problems in the analyses. Reporting the findings in an Asian trial (CYD14), the authors show a 7-fold rise in one outcome - hospitalization for dengue fever in children harm for another outcome - hospitalization for severe dengue fever (as confirmed by an independent data monitoring committee): 1. in children younger than 9 years, the relative risk was 8.5 [95% CI 0.5, 146.8], and 2. in the overall study group, the relative risk was 5.5 [95% CI: 0.9, 33] The authors conduct a subgroup analysis to support claims that the vaccine is probably safe among children aged 9 years or more. This subgroup analysis has limited credibility because: 1) it was a post-hoc analysis; 2) it was one of a large number of subgroup analyses; 3) the test of interaction was not reported; but was insignificant (p=0.14); and 4) there is no biological basis for a threshold age of 9 years. The more likely explanation for the higher risk in younger children is ADE, that is, more frequent seronegativity, rather than age itself. The selective reporting and inappropriate subgroup claims mask the potential harm of dengue mass vaccination programs. Countries planning public use of the vaccine must conduct diligent post

  4. Fixed and Adaptive Parallel Subgroup-Specific Design for Survival Outcomes: Power and Sample Size

    Directory of Open Access Journals (Sweden)

    Miranta Antoniou

    2017-12-01

    Full Text Available Biomarker-guided clinical trial designs, which focus on testing the effectiveness of a biomarker-guided approach to treatment in improving patient health, have drawn considerable attention in the era of stratified medicine with many different designs being proposed in the literature. However, planning such trials to ensure they have sufficient power to test the relevant hypotheses can be challenging and the literature often lacks guidance in this regard. In this study, we focus on the parallel subgroup-specific design, which allows the evaluation of separate treatment effects in the biomarker-positive subgroup and biomarker-negative subgroup simultaneously. We also explore an adaptive version of the design, where an interim analysis is undertaken based on a fixed percentage of target events, with the option to stop each biomarker-defined subgroup early for futility or efficacy. We calculate the number of events and patients required to ensure sufficient power in each of the biomarker-defined subgroups under different scenarios when the primary outcome is time-to-event. For the adaptive version, stopping probabilities are also explored. Since multiple hypotheses are being tested simultaneously, and multiple interim analyses are undertaken, we also focus on controlling the overall type I error rate by way of multiplicity adjustment.

  5. Diversity among mandarin varieties and natural sub-groups in aroma volatiles compositions.

    Science.gov (United States)

    Goldenberg, Livnat; Yaniv, Yossi; Doron-Faigenboim, Adi; Carmi, Nir; Porat, Ron

    2016-01-15

    Mandarins constitute a large, diverse and important group within the Citrus family. Here, we analysed the aroma volatiles compositions of 13 mandarin varieties belonging to seven genetically different natural sub-groups that included common mandarin (C. reticulata Blanco), clementine (C. clementina Hort. ex. Tan), satsuma (C. unshiu Marcovitch), Mediterranean mandarin (C. deliciosa Tenore), King mandarin (C. nobilis Loureiro), and mandarin hybrids, such as tangor (C. reticulata × C. sinensis) and tangelo (C. reticulata × C. paradisi). We found that mandarin varieties among tangors ('Temple', 'Ortanique'), tangelos ('Orlando', 'Minneola') and King ('King') had more volatiles, at higher levels, and were richer in sesquiterpene and ester volatiles, than other varieties belonging to the sub-groups common mandarin ('Ora', 'Ponkan'), clementine ('Oroval', 'Caffin'), satsuma ('Okitsu', 'Owari') and Mediterranean mandarin ('Avana', 'Yusuf Efendi'). Hierarchical clustering and principal component analysis accurately differentiated between mandarin varieties and natural sub-groups according to their aroma-volatile profiles. Although we found wide differences in aroma-volatiles compositions among varieties belonging to different natural sub-groups, we detected only minor differences among varieties within any natural sub-group. These findings suggest that selecting appropriate parents would enable manipulation of aroma-volatile compositions in future mandarin breeding programmes. © 2015 Society of Chemical Industry.

  6. The Measurement of Collaborative Culture in Secondary Schools: An Informal Subgroup Approach

    Science.gov (United States)

    Meredith, Chloé; Moolenaar, Nienke M.; Struyve, Charlotte; Vandecandelaere, Machteld; Gielen, Sarah; Kyndt, Eva

    2017-01-01

    Research on teacher collaboration underlines the importance of a collaborative culture for teachers' functioning. However, while scholars usually regard collaborative culture as a school team characteristic, this study argues that subgroups may be more meaningful units of analysis to conceptualize and assess teachers' perceptions of collaborative…

  7. Are there distinct cognitive and motivational sub-groups of children with ADHD?

    DEFF Research Database (Denmark)

    Lambek, Rikke; Sonuga-Barke, Edmund; Tannock, Rosemary

    2017-01-01

    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...

  8. Evaluating simple oxidant prediction methods using complex photochemical models: cluster analysis applied to urban ozone characteristics

    Energy Technology Data Exchange (ETDEWEB)

    Hillyer, M.S.

    1981-08-01

    This report describes efforts to classify cities observing ozone levels greater than 0.12 ppm into distinct subgroups. Cluster analysis, using such factors as mixing height, wind speed, temperature, NMOC/NOx ratio and type of precursor sources, is used to identify subgroups of cities. Identification of a limited number of such subgroups could provide a means for more convincingly demonstrating the general applicability of complex photochemical models by conducting validation exercises in cities representative of each subgroup. The report indicates that the technique shows promise but, nevertheless, requires some further refinement before it can be used to identify most appropriate subgroups.

  9. Challenges in identifying asthma subgroups using unsupervised statistical learning techniques.

    Science.gov (United States)

    Prosperi, Mattia C F; Sahiner, Umit M; Belgrave, Danielle; Sackesen, Cansin; Buchan, Iain E; Simpson, Angela; Yavuz, Tolga S; Kalayci, Omer; Custovic, Adnan

    2013-12-01

    Unsupervised statistical learning techniques, such as exploratory factor analysis (EFA) and hierarchical clustering (HC), have been used to identify asthma phenotypes, with partly consistent results. Some of the inconsistency is caused by the variable selection and demographic and clinical differences among study populations. To investigate the effects of the choice of statistical method and different preparations of data on the clustering results; and to relate these to disease severity. Several variants of EFA and HC were applied and compared using various sets of variables and different encodings and transformations within a dataset of 383 children with asthma. Variables included lung function, inflammatory and allergy markers, family history, environmental exposures, and medications. Clusters and original variables were related to asthma severity (logistic regression and Bayesian network analysis). EFA identified five components (eigenvalues ≥ 1) explaining 35% of the overall variance. Variations of the HC (as linkage-distance functions) did not affect the cluster inference; however, using different variable encodings and transformations did. The derived clusters predicted asthma severity less than the original variables. Prognostic factors of severity were medication usage, current symptoms, lung function, paternal asthma, body mass index, and age of asthma onset. Bayesian networks indicated conditional dependence among variables. The use of different unsupervised statistical learning methods and different variable sets and encodings can lead to multiple and inconsistent subgroupings of asthma, not necessarily correlated with severity. The search for asthma phenotypes needs more careful selection of markers, consistent across different study populations, and more cautious interpretation of results from unsupervised learning.

  10. Subgroup Achievement and Gap Trends: Hawaii

    Science.gov (United States)

    Center on Education Policy, 2010

    2010-01-01

    Hawaii showed improvement in reading and math in grade 8 at the basic, proficient, and advanced levels for Asian and white students, low income students, and boys and girls. Gains in math tended to be larger than in reading. Trends in closing achievement gaps were mixed. Comparable data were available from 2007 through 2009. (Contains 9 tables.)…

  11. Optimizing Subgroups Formation for E-MBMS Transmissions in LTE Networks

    Science.gov (United States)

    Algharem, M.; Omar, M. H.; Stiawan, D.; Budiarto, R.

    2017-04-01

    Long Term Evolution (LTE) network provides a high throughput with low latency which make it suitable for multicast and broadcast services. In Conventional Multicast Scheme (CMS), data is transmitted according to the user with worst channel condition which results in wasting network resources. To overcome the drawback of CMS, a new subgrouping mechanism is proposed to split the multicast group into several subgroups based on users channel quality. The performance of the proposed mechanism has been evaluated using LTE simulator. The simulation results show that the proposed mechanism increase the multicast performance compared to CMS in term of goodput and spectrum efficiency, while maintain fairness index of users in an acceptable level.

  12. How does unemployment affect self-assessed health? A systematic review focusing on subgroup effects.

    Science.gov (United States)

    Norström, Fredrik; Virtanen, Pekka; Hammarström, Anne; Gustafsson, Per E; Janlert, Urban

    2014-12-22

    Almost all studies on the effect on health from unemployment have concluded that unemployment is bad for your health. However, only a few review articles have dealt with this relation in recent years, and none of them have focused on the analysis of subgroups such as age, gender, and marital status. The objective of our article is to review how unemployment relates to self-assessed health with a focus on its effect on subgroups. A search was performed in Web of Science to find articles that measured the effect on health from unemployment. The selection of articles was limited to those written in English, consisting of original data, and published in 2003 or later. Our definition of health was restricted to self-assessed health. Mortality- and morbidity-related measurements were therefore not included in our analysis. For the 41 articles included, information about health measurements, employment status definitions, other factors included in the statistical analysis, study design (including study population), and statistical method were collected with the aim of analysing the results on both the population and factor level. Most of the studies in our review showed a negative effect on health from unemployment on a population basis. Results at the factor levels were most common for gender (25 articles), age (11 articles), geographic location (8 articles), and education level (5 articles). The analysis showed that there was a health effect for gender, age, education level, household income, and geographic location. However, this effect differed between studies and no clear pattern on who benefits or suffers more among these groups could be determined. The result instead seemed to depend on the study context. The only clear patterns of association found were for socioeconomic status (manual workers suffer more), reason for unemployment (being unemployed due to health reasons is worse), and social network (a strong network is beneficial). Unemployment affects groups of

  13. Effect of Nintedanib in Subgroups of Idiopathic Pulmonary Fibrosis by Diagnostic Criteria.

    Science.gov (United States)

    Raghu, Ganesh; Wells, Athol U; Nicholson, Andrew G; Richeldi, Luca; Flaherty, Kevin R; Le Maulf, Florence; Stowasser, Susanne; Schlenker-Herceg, Rozsa; Hansell, David M

    2017-01-01

    In the absence of a surgical lung biopsy, patients diagnosed with idiopathic pulmonary fibrosis (IPF) in clinical practice could participate in the INPULSIS trials of nintedanib if they had honeycombing and/or traction bronchiectasis plus reticulation, without atypical features of usual interstitial pneumonia (UIP), on high-resolution computed tomography (HRCT). Thus, the patients in these trials represented patients with definite UIP and a large subgroup of patients with possible UIP. To investigate the potential impact of diagnostic subgroups on the progression of IPF and the effect of nintedanib. We conducted a post hoc subgroup analysis of patients with honeycombing on HRCT and/or confirmation of UIP by biopsy versus patients without either, using pooled data from the INPULSIS trials. Seven hundred twenty-three (68.1%) patients had honeycombing and/or biopsy, and 338 (31.9%) patients had no honeycombing or biopsy. In these subgroups, respectively, the adjusted annual rate of decline in FVC in patients treated with placebo was -225.7 and -221.0 ml/yr, and the nintedanib versus placebo difference in the adjusted annual rate of decline in FVC was 117.0 ml/yr (95% confidence interval, 76.3-157.8) and 98.9 ml/yr (95% confidence interval, 36.4-161.5). There was no significant treatment-by-subgroup interaction (P = 0.8139). Adverse events were similar between the subgroups. Patients with IPF diagnosed in clinical practice who had possible UIP with traction bronchiectasis on HRCT and had not undergone surgical lung biopsy had disease that progressed in a similar way, and responded similarly to nintedanib, to that of patients with honeycombing on HRCT and/or confirmation of UIP by biopsy.

  14. Cluster Analysis to Identify Possible Subgroups in Tinnitus Patients

    NARCIS (Netherlands)

    van den Berge, Minke J. C.; Free, Rolien H.; Arnold, Rosemarie; de Kleine, Emile; Hofman, Rutger; van Dijk, J. Marc C.; van Dijk, Pim

    2017-01-01

    Introduction: In tinnitus treatment, there is a tendency to shift from a "one size fits all" to a more individual, patient-tailored approach. Insight in the heterogeneity of the tinnitus spectrum might improve the management of tinnitus patients in terms of choice of treatment and identification of

  15. Identification and Characterization of Unique Subgroups of Chronic Pain Individuals with Dispositional Personality Traits

    Directory of Open Access Journals (Sweden)

    S. Mehta

    2016-01-01

    Full Text Available Objective. The current study attempted to identify and characterize distinct CP subgroups based on their level of dispositional personality traits. The secondary objective was to compare the difference among the subgroups in mood, coping, and disability. Methods. Individuals with chronic pain were assessed for demographic, psychosocial, and personality measures. A two-step cluster analysis was conducted in order to identify distinct subgroups of patients based on their level of personality traits. Differences in clinical outcomes were compared using the multivariate analysis of variance based on cluster membership. Results. In 229 participants, three clusters were formed. No significant difference was seen among the clusters on patient demographic factors including age, sex, relationship status, duration of pain, and pain intensity. Those with high levels of dispositional personality traits had greater levels of mood impairment compared to the other two groups (p<0.05. Significant difference in disability was seen between the subgroups. Conclusions. The study identified a high risk group of CP individuals whose level of personality traits significantly correlated with impaired mood and coping. Use of pharmacological treatment alone may not be successful in improving clinical outcomes among these individuals. Instead, a more comprehensive treatment involving psychological treatments may be important in managing the personality traits that interfere with recovery.

  16. Identification and Characterization of Unique Subgroups of Chronic Pain Individuals with Dispositional Personality Traits.

    Science.gov (United States)

    Mehta, S; Rice, D; McIntyre, A; Getty, H; Speechley, M; Sequeira, K; Shapiro, A P; Morley-Forster, P; Teasell, R W

    2016-01-01

    Objective. The current study attempted to identify and characterize distinct CP subgroups based on their level of dispositional personality traits. The secondary objective was to compare the difference among the subgroups in mood, coping, and disability. Methods. Individuals with chronic pain were assessed for demographic, psychosocial, and personality measures. A two-step cluster analysis was conducted in order to identify distinct subgroups of patients based on their level of personality traits. Differences in clinical outcomes were compared using the multivariate analysis of variance based on cluster membership. Results. In 229 participants, three clusters were formed. No significant difference was seen among the clusters on patient demographic factors including age, sex, relationship status, duration of pain, and pain intensity. Those with high levels of dispositional personality traits had greater levels of mood impairment compared to the other two groups (p disability was seen between the subgroups. Conclusions. The study identified a high risk group of CP individuals whose level of personality traits significantly correlated with impaired mood and coping. Use of pharmacological treatment alone may not be successful in improving clinical outcomes among these individuals. Instead, a more comprehensive treatment involving psychological treatments may be important in managing the personality traits that interfere with recovery.

  17. Radiogenomic analysis of lower grade glioma: a pilot multi-institutional study shows an association between quantitative image features and tumor genomics

    Science.gov (United States)

    Mazurowski, Maciej A.; Clark, Kal; Czarnek, Nicholas M.; Shamsesfandabadi, Parisa; Peters, Katherine B.; Saha, Ashirbani

    2017-03-01

    Recent studies showed that genomic analysis of lower grade gliomas can be very effective for stratification of patients into groups with different prognosis and proposed specific genomic classifications. In this study, we explore the association of one of those genomic classifications with imaging parameters to determine whether imaging could serve a similar role to genomics in cancer patient treatment. Specifically, we analyzed imaging and genomics data for 110 patients from 5 institutions from The Cancer Genome Atlas and The Cancer Imaging Archive datasets. The analyzed imaging data contained preoperative FLAIR sequence for each patient. The images were analyzed using the in-house algorithms which quantify 2D and 3D aspects of the tumor shape. Genomic data consisted of a cluster of clusters classification proposed in a very recent and leading publication in the field of lower grade glioma genomics. Our statistical analysis showed that there is a strong association between the tumor cluster-of-clusters subtype and two imaging features: bounding ellipsoid volume ratio and angular standard deviation. This result shows high promise for the potential use of imaging as a surrogate measure for genomics in the decision process regarding treatment of lower grade glioma patients.

  18. Meta-analysis of diffusion tensor imaging studies shows altered fractional anisotropy occurring in distinct brain areas in association with depression.

    LENUS (Irish Health Repository)

    Murphy, Melissa L

    2011-09-01

    Fractional anisotropy anomalies occurring in the white matter tracts in the brains of depressed patients may reflect microstructural changes underlying the pathophysiology of this disorder. We conducted a meta-analysis of fractional anisotropy abnormalities occurring in major depressive disorder using voxel-based diffusion tensor imaging studies. Using the Embase, PubMed and Google Scholar databases, 89 relevant data sets were identified, of which 7 (including 188 patients with major depressive disorder and 221 healthy controls) met our inclusion criteria. Authors were contacted to retrieve any additional data required. Coordinates were extracted from clusters of significant white matter fractional anisotropy differences between patients and controls. Relevant demographic, clinical and methodological variables were extracted from each study or obtained directly from authors. The meta-analysis was carried out using Signed Differential Mapping. Patients with depression showed decreased white matter fractional anisotropy values in the superior longitudinal fasciculus and increased fractional anisotropy values in the fronto-occipital fasciculus compared to controls. Using quartile and jackknife sensitivity analysis, we found that reduced fractional anisotropy in the left superior longitudinal fasciculus was very stable, with increases in the right fronto-occipital fasciculus driven by just one study. In conclusion, our meta-analysis revealed a significant reduction in fractional anisotropy values in the left superior longitudinal fasciculus, which may ultimately play an important role in the pathology of depression.

  19. Meta-analysis of diffusion tensor imaging (DTI) studies shows altered fractional anisotropy occurring in distinct brain areas in association with depression

    LENUS (Irish Health Repository)

    Murphy, Melissa L

    2011-09-27

    Abstract Fractional anisotropy anomalies occurring in the white matter tracts in the brains of depressed patients may reflect microstructural changes underlying the pathophysiology of this disorder. We conducted a meta-analysis of fractional anisotropy abnormalities occurring in major depressive disorder using voxel-based diffusion tensor imaging studies. Using the Embase, PubMed and Google Scholar databases, 89 relevant data sets were identified, of which 7 (including 188 patients with major depressive disorder and 221 healthy controls) met our inclusion criteria. Authors were contacted to retrieve any additional data required. Coordinates were extracted from clusters of significant white matter fractional anisotropy differences between patients and controls. Relevant demographic, clinical and methodological variables were extracted from each study or obtained directly from authors. The meta-analysis was carried out using Signed Differential Mapping. Patients with depression showed decreased white matter fractional anisotropy values in the superior longitudinal fasciculus and increased fractional anisotropy values in the fronto-occipital fasciculus compared to controls. Using quartile and jackknife sensitivity analysis, we found that reduced fractional anisotropy in the left superior longitudinal fasciculus was very stable, with increases in the right fronto-occipital fasciculus driven by just one study. In conclusion, our meta-analysis revealed a significant reduction in fractional anisotropy values in the left superior longitudinal fasciculus, which may ultimately play an important role in the pathology of depression.

  20. Comparative analysis of multilineage properties of mesenchymal stromal cells derived from fetal sources shows an advantage of mesenchymal stromal cells isolated from cord blood in chondrogenic differentiation potential.

    Science.gov (United States)

    Pievani, Alice; Scagliotti, Valeria; Russo, Francesca Maria; Azario, Isabella; Rambaldi, Benedetta; Sacchetti, Benedetto; Marzorati, Simona; Erba, Eugenio; Giudici, Giovanni; Riminucci, Mara; Biondi, Andrea; Vergani, Patrizia; Serafini, Marta

    2014-07-01

    Cord blood (CB) and amniotic fluid (AF) could represent new and attractive mesenchymal stromal cell (MSC) sources, but their potential therapeutic applications are still limited by lack of standardized protocols for isolation and differentiation. In particular, chondrogenic differentiation has never been deeply investigated. MSCs were obtained from CB and AF samples collected during cesarean sections at term and compared for their biological and differentiation properties, with particular interest in cartilage differentiation, in which quantitative real-time polymerase chain reaction and immunohistochemical analyses were performed to evaluate the expression of type 2 collagen, type 10 collagen, SRY-box9 and aggrecan. We were able to isolate MSCs from 12 of 30 (40%) and 5 of 20 (25%) CB and AF units, respectively. Fluorescence in situ hybridization analysis indicated the fetal origin of isolated MSC strains. Both populations expressed mesenchymal but not endothelial and hematopoietic markers, even though we observed a lower expression of human leukocyte antigen (HLA) I in CB-MSCs. No differences in proliferation rate and cell cycle analysis could be detected. After osteogenic induction, both populations showed matrix mineralization and typical marker expression. Under chondrogenic conditions, pellets derived from CB-MSCs, in contrast with AF-MSCs pellets, were significantly larger, showed cartilage-like morphology and resulted positive for chondrocyte-associated markers, such as type 2 collagen, type 10 collagen, SRY-box9 and aggrecan. Our results show that CB-MSCs and AF-MSCs collected at term differ from each other in their biological and differentiation properties. In particular, only CB-MSCs showed a clear chondrogenic potential and thus could represent an ideal candidate for cartilage-tissue engineering. Copyright © 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  1. Gene network analysis shows immune-signaling and ERK1/2 as novel genetic markers for multiple addiction phenotypes: alcohol, smoking and opioid addiction.

    Science.gov (United States)

    Reyes-Gibby, Cielito C; Yuan, Christine; Wang, Jian; Yeung, Sai-Ching J; Shete, Sanjay

    2015-06-05

    Addictions to alcohol and tobacco, known risk factors for cancer, are complex heritable disorders. Addictive behaviors have a bidirectional relationship with pain. We hypothesize that the associations between alcohol, smoking, and opioid addiction observed in cancer patients have a genetic basis. Therefore, using bioinformatics tools, we explored the underlying genetic basis and identified new candidate genes and common biological pathways for smoking, alcohol, and opioid addiction. Literature search showed 56 genes associated with alcohol, smoking and opioid addiction. Using Core Analysis function in Ingenuity Pathway Analysis software, we found that ERK1/2 was strongly interconnected across all three addiction networks. Genes involved in immune signaling pathways were shown across all three networks. Connect function from IPA My Pathway toolbox showed that DRD2 is the gene common to both the list of genetic variations associated with all three addiction phenotypes and the components of the brain neuronal signaling network involved in substance addiction. The top canonical pathways associated with the 56 genes were: 1) calcium signaling, 2) GPCR signaling, 3) cAMP-mediated signaling, 4) GABA receptor signaling, and 5) G-alpha i signaling. Cancer patients are often prescribed opioids for cancer pain thus increasing their risk for opioid abuse and addiction. Our findings provide candidate genes and biological pathways underlying addiction phenotypes, which may be future targets for treatment of addiction. Further study of the variations of the candidate genes could allow physicians to make more informed decisions when treating cancer pain with opioid analgesics.

  2. Cytogenetic analysis shows that the unusually large chromosome in the sex-limited pB silkworm (Bombyx mori) strain consists of three chromosomes.

    Science.gov (United States)

    Tanaka, N; Yokoyama, T; Abe, H; Tsuchida, K; Ninagi, O; Oshiki, T

    2000-01-01

    We have discovered an inordinately large chromosome pair at the pachytene stage in the oocyte of the sex-limited pB (black larval marking) silkworm (Bombyx mori) strain (TWPB). We have analyzed the composition and arrangement of this large chromosome. A genetic linkage analysis shows that the large chromosome is made up of the W chromosome, the second chromosome fragment (pB fragment), and the fifth chromosome (linkage group) containing at least the region from map position 0.0 to 40.8. We also observed a sex heterochromatin body (SB) that we deduced to be made up of condensed W chromosomes. The number of SBs in each female nucleus among the sucking stomach cells of the TWPB strain was variable. Evidently, the W chromosome of the TWPB strain is attached to another chromosome. The composition of the W chromosome, the second chromosome fragment, and the fifth chromosome was studied through linkage analysis for these three chromosomes. We used two strains derived from the TWPB strain, the sex-limited pM (moricaud larval marking)-like (TWPML) and the autosomal pM-like (T5PML). The results show that the TWPML strain originates through a detachment of the fifth chromosome from the large chromosome of the TWPB strain, and the T5PML strain originates through a detachment of the W chromosome from that. Accordingly, the large chromosome of the TWPB strain is arranged in the order W chromosome--second chromosome fragment--fifth chromosome.

  3. The fading affect bias shows positive outcomes at the general but not the individual level of analysis in the context of social media.

    Science.gov (United States)

    Gibbons, Jeffrey A; Horowitz, Kyle A; Dunlap, Spencer M

    2017-08-01

    Unpleasant affect fades faster than pleasant affect (e.g., Walker, Vogl, & Thompson, 1997); this effect is referred to as the Fading Affect Bias (FAB; Walker, Skowronski, Gibbons, Vogl, & Thompson, 2003a). Research shows that the FAB is consistently related to positive/healthy outcomes at a general but not at a specific level of analysis based on event types and individual differences (e.g., Gibbons et al., 2013). Based on the positive outcomes for FAB and negative outcomes for social media (Bolton et al., 2013; Huang, 2010), the current study examined FAB in the context of social media events along with related individual differences. General positive outcomes were shown in the form of robust FAB effects across social media and non-social media events, a larger FAB for non-social media events than for social media events, negative correlations of FAB with depression, anxiety, and stress as well as a positive correlation of FAB with self-esteem. However, the lack of a negative correlation between FAB and anxiety for social media events in a 3-way interaction did not show positive outcomes at a specific level of analysis. Rehearsal ratings mediated the 3-way interaction. Implications are discussed. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. APF530 versus ondansetron, each in a guideline-recommended three-drug regimen, for the prevention of chemotherapy-induced nausea and vomiting due to anthracycline plus cyclophosphamide–based highly emetogenic chemotherapy regimens: a post hoc subgroup analysis of the Phase III randomized MAGIC trial

    Directory of Open Access Journals (Sweden)

    Schnadig ID

    2017-05-01

    Full Text Available Ian D Schnadig1, Richy Agajanian2, Christopher Dakhil3, Nashat Gabrail4, Jeffrey Vacirca5, Charles Taylor6, Sharon Wilks7, Eduardo Braun8, Michael C Mosier9, Robert B Geller10, Lee Schwartzberg11, Nicholas Vogelzang12 1Compass Oncology, US Oncology Research, Tualatin, OR, 2The Oncology Institute of Hope and Innovation, Whittier, CA, 3Cancer Center of Kansas, Wichita, KS, 4Gabrail Cancer Center, Canton, OH, 5North Shore Hematology Oncology, East Setauket, NY, 6Tulsa Cancer Institute, Tulsa, OK, 7Cancer Care Centers of South Texas, San Antonio, TX, 8Michiana Hematology Oncology, Westville, IN, 9Biostatistics, EMB Statistical Solutions, LLC, Overland Park, KS, 10Medical Affairs, Heron Therapeutics, Inc., San Diego, CA, 11West Cancer Center, Germantown, TN, 12Comprehensive Cancer Centers of Nevada, Las Vegas, NV, USA Background: APF530, a novel extended-release granisetron injection, was superior to ondansetron in a guideline-recommended three-drug regimen in preventing delayed-phase chemotherapy-induced nausea and vomiting (CINV among patients receiving highly emetogenic chemotherapy (HEC in the double-blind Phase III Modified Absorption of Granisetron In the prevention of CINV (MAGIC trial.Patients and methods: This MAGIC post hoc analysis evaluated CINV prevention efficacy and safety of APF530 versus ondansetron, each with fosaprepitant and dexamethasone, in patient subgroup receiving an anthracycline plus cyclophosphamide (AC regimen. Patients were randomized 1:1 to APF530 500 mg subcutaneously (granisetron 10 mg or ondansetron 0.15 mg/kg intravenously (IV (≤16 mg; stratification was by planned cisplatin ≥50 mg/m2 (yes/no. Patients were to receive fosaprepitant 150 mg IV and dexamethasone 12 mg IV on day 1, then dexamethasone 8 mg orally once daily on day 2 and twice daily on days 3 and 4. Patients were mostly younger females (APF530 arm, mean age 54.1 years, female, 99.3%; ondansetron arm, 53.8 years, female 98.3%. The primary

  5. Local inflammation increases vanilloid receptor 1 expression within distinct subgroups of DRG neurons.

    Science.gov (United States)

    Amaya, Fumimasa; Oh-hashi, Kentaro; Naruse, Yoshihisa; Iijima, Norio; Ueda, Masashi; Shimosato, Goshun; Tominaga, Makoto; Tanaka, Yoshifumi; Tanaka, Masaki

    2003-02-14

    Vanilloid receptor 1 (VR1) is essential to the development of inflammatory hyperalgesia. We investigated whether inflammation can increase in VR1 positive neuronal profiles in rat DRG neurons using histochemical methods. We also used size frequency analysis and double staining with several neuronal markers to investigate whether or not inflammation alters VR1 expression. Inflammation induced a 1.5-fold increase in percentage of VR1-like immunoreactivity (LI) positive profiles per total neuronal profiles, suggesting that the number of heat and pH sensitive neurons increase during inflammation. Area frequency histograms showed that VR1 expression increased in small and medium-sized neurons after inflammation. Double labeling of VR1 with NF200 showed that VR1 positive neurons with NF200 positive profiles significantly increased, indicating that the medium-sized VR1 positive neurons were neurons with myelinated A-fibers. Local inflammation thus increases in VR1 protein level within distinct subgroups of DRG neurons that may participate in the development and maintenance of inflammatory hyperalgesia.

  6. Subgroup report on hard x-ray microprobes

    Energy Technology Data Exchange (ETDEWEB)

    Ice, G.E. [Oak Ridge National Lab., TN (United States); Barbee, T.; Bionta, R. [Lawrence Livermore National Lab., CA (United States); Howells, M.; Thompson, A.C. [Lawrence Berkeley Lab., CA (United States); Yun, W. [Argonne National Lab., IL (United States)

    1994-09-01

    The increasing availability of synchrotron x-ray sources has stimulated the development of advanced hard x-ray (E{>=}5 keV) microprobes. New x-ray optics have been demonstrated which show promise for achieving intense submicron hard x-ray probes. These probes will be used for extraordinary elemental detection by x-ray fluorescence/absorption and for microdiffraction to identify phase and strain. The inherent elemental and crystallographic sensitivity of an x-ray microprobe and its inherently nondestructive and penetrating nature makes the development of an advanced hard x-ray microprobe an important national goal. In this workshop state-of-the-art hard x-ray microprobe optics were described and future directions were discussed. Gene Ice, Oak Ridge National Laboratory (ORNL), presented an overview of the current status of hard x-ray microprobe optics and described the use of crystal spectrometers to improve minimum detectable limits in fluorescent microprobe experiments. Al Thompson, Lawrence Berkeley Laboratory (LBL), described work at the Center for X-ray Optics to develop a hard x-ray microprobe based on Kirkpatrick-Baez (KB) optics. Al Thompson also showed the results of some experimental measurements with their KB optics. Malcolm Howells presented a method for bending elliptical mirrors and Troy Barbee commented on the use of graded d spacings to achieve highest efficiency in KB multilayer microfocusing. Richard Bionta, Lawrence Livermore National Laboratory (LLNL), described the development of the first hard x-ray zone plates and future promise of so called {open_quotes}jelly roll{close_quotes} or sputter slice zone plates. Wenbing Yun, Argonne National Laboratory (ANL), described characterization of jelly roll and lithographically produced zone plates and described the application of zone plates to focus extremely narrow bandwidths by nuclear resonance. This report summarizes the presentations of the workshop subgroup on hard x-ray microprobes.

  7. A Content Analysis of How Sexual Behavior and Reproductive Health are Being Portrayed on Primetime Television Shows Being Watched by Teens and Young Adults.

    Science.gov (United States)

    Kinsler, Janni J; Glik, Deborah; de Castro Buffington, Sandra; Malan, Hannah; Nadjat-Haiem, Carsten; Wainwright, Nicole; Papp-Green, Melissa

    2018-02-01

    Television is a leading source of sexual education for teens and young adults, thus it is important to understand how sexual behavior and reproductive health are portrayed in popular primetime programming. This study is a media content analysis of the 19 top-rated scripted English-language primetime television shows aired between January 1, 2015 and May 31, 2015, and viewed by American youth audiences 12-24 years of age. The purpose of this study is to assess how sex/sexuality and reproductive health are being portrayed in a popular medium that reaches many adolescent and young adult audiences. Themes used for this analysis include youth pregnancy/parenting, mentoring/guidance of youth regarding sexual behavior, sex/sexuality, body image/identity, sexual violence/abuse/harassment, gender identity/sexual orientation, and reproductive health. Themes have been classified in one of the following six categories: visual cues, brief mentions, dialogue, minor storylines, major storylines, and multi-episode storylines. Our findings indicate that narratives providing educational information regarding the risks and consequences of sexual behavior were missing from the television shows we analyzed and that storylines promoting low risk sexual behavior were rare. Sexual violence and abuse, casual sex among adults, lack of contraception use, or no portrayal of consequences of risky behaviors were common. Compared to prior research, we found an emergent theme normalizing non-heterosexual gender identity and sexual orientation. Our findings have important implications as exposure to popular media shapes the perceptions and behaviors of teens and young adults. This study has the potential to shed light on the need to create stories and narratives in television shows watched by American teens and young adults with educational messages regarding the risks and consequences of sexual behavior.

  8. Patterns of alcohol use and consequences among empirically derived sexual minority subgroups.

    Science.gov (United States)

    Talley, Amelia E; Sher, Kenneth J; Steinley, Douglas; Wood, Phillip K; Littlefield, Andrew K

    2012-03-01

    The current study develops an empirically determined classification of sexual orientation developmental patterns based on participants' annual reports of self-identifications, sexual attractions, and sexual behaviors during the first 4 years of college. A secondary aim of the current work was to examine trajectories of alcohol involvement among identified subgroups. Data were drawn from a subsample of a longitudinal study of incoming first-time college students at a large, public university (n = 2,068). Longitudinal latent class analysis was used to classify sexual minority participants into empirically derived subgroups based on three self-reported facets of sexual orientation. Multivariate repeated-measures analyses were conducted to examine how trajectories of alcohol involvement varied by sexual orientation class membership. Four unique subclasses of sexual orientation developmental patterns were identified for males and females: one consistently exclusively heterosexual group and three sexual minority groups. Despite generally similar alcohol use patterns among subclasses, certain sexual minority subgroups reported elevated levels of alcohol-related negative consequences and maladaptive motivations for use throughout college compared with their exclusively heterosexual counterparts. Elevations in coping and conformity motivations for alcohol use were seen among those subgroups that also evidenced heightened negative alcohol-related consequences. Implications and limitations of the current work are discussed.

  9. Young children with language difficulties: a dimensional approach to subgrouping.

    Science.gov (United States)

    Jansen, Rianne; Ceulemans, Eva; Grauwels, Jolien; Maljaars, Jarymke; Zink, Inge; Steyaert, Jean; Noens, Ilse

    2013-11-01

    A dimensional approach was used to create bottom-up constructed subgroups that captured the behavioral heterogeneity in 36 Dutch-speaking children with language difficulties. Four subgroups were delineated based upon differences in cognitive ability, symbol understanding, joint attention and autism spectrum disorder related characteristics. Children with a different developmental disorder were found within a single cluster. Therefore, the results of this study suggest that bottom-up constructed subgroups might capture the heterogeneous behavioral profiles of young children with developmental difficulties in a more meaningful way. Furthermore, joint attention and symbol understanding seem important skills to assess in young children presenting with language difficulties. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. Differential distributions of Synechococcus subgroups across the California Current System.

    Directory of Open Access Journals (Sweden)

    Ryan William Paerl

    2011-04-01

    Full Text Available Synechococcus is an abundant marine cyanobacterial genus composed of different populations that vary physiologically. Synechococcus narB gene sequences (encoding for nitrate reductase in cyanobacteria obtained previously from isolates and the environment (e.g. North Pacific Gyre Station ALOHA, Hawaii or Monterey Bay, California were used to develop quantitative PCR (qPCR assays. These qPCR assays were used to quantify populations from specific narB phylogenetic clades across the California Current System (CCS, a region composed of dynamic zones between a coastal-upwelling zone and the oligotrophic Pacific Ocean. Targeted populations (narB subgroups had different biogeographic patterns across the CCS, which appear to be driven by environmental conditions. Subgroups C_C1, D_C1 and D_C2 were abundant in coastal-upwelling to coastal-transition zone waters with relatively high to intermediate ammonium, nitrate and chl. a concentrations. Subgroups A_C1 and F_C1 were most abundant in coastal-transition zone waters with intermediate nutrient concentrations. E_O1 and G_O1 were most abundant at different depths of oligotrophic open-ocean waters (either in the upper mixed layer or just below. E_O1, A_C1 and F_C1 distributions differed from other narB subgroups and likely possess unique ecologies enabling them to be most abundant in waters between coastal and open-ocean waters. Different CCS zones possessed distinct Synechococcus communities. Core California Current (CC water possessed low numbers of narB subgroups relative to counted Synechococcus cells, and coastal-transition waters contained high abundances of Synechococcus cells and total number of narB subgroups. The presented biogeographic data provides insight on the distributions and ecologies of Synechococcus present in an eastern boundary current system.

  11. Analysis of genetic distance between Peruvian Alpaca (Vicugna Pacos showing two distinct fleece phenotypes, Suri and Huacaya, by means of microsatellite markers

    Directory of Open Access Journals (Sweden)

    Carlo Renieri

    2011-10-01

    Full Text Available Two coat phenotypes exist in Alpaca, Huacaya and Suri. The two coats show different fleece structure, textile characteristics and prices on the market. Although present scientific knowledge suggests a simple genetic model of inheritance, there is a tendency to manage and consider the two phenotypes as two different breeds. A 13 microsatellite panel was used in this study to assess genetic distance between Suri and Huacaya alpacas in a sample of non-related animals from two phenotypically pure flocks at the Illpa-Puno experimental station in Quimsachata, Peru. The animals are part of a germplasm established approximately 20 years ago and have been bred separately according to their coat type since then. Genetic variability parameters were also calculated. The data were statistically analyzed using the software Genalex 6.3, Phylip 3.69 and Fstat 2.9.3.2. The sample was tested for Hardy-Weinberg equilibrium (HWE and after strict Bonferroni correction only one locus (LCA37 showed deviation from equilibrium (Ploci associations showed significant disequilibrium. Observed heterozygosis (Ho= 0.766; SE=0.044, expected heterozygosis (He=0.769; SE=0.033, number of alleles (Na=9.667, SE=0.772 and Fixation index (F=0.004; SE=0.036 are comparable to data from previous studies. Measures of genetic distance were 0.06 for Nei’s and 0.03 for Cavalli-Sforza’s. The analysis of molecular variance reported no existing variance between populations. Considering the origin of the animals, their post domestication evolution and the reproductive practices in place, the results do not show genetic differentiation between the two populations for the studied loci.

  12. Discrete neurocognitive subgroups in fully or partially remitted bipolar disorder

    DEFF Research Database (Denmark)

    Jensen, Johan Høy; Knorr, Ulla; Vinberg, Maj

    2016-01-01

    significance difference pairwise comparison. RESULTS: Three discrete neurocognitive subgroups were detected: one that was cognitively intact (46.1%), one that was selectively impaired with deficits in processing speed (32.6%), and one that was globally impaired across verbal learning, working memory......, and executive skills (21.2%). The globally and selectively impaired subgroups were characterized by greater perceived stress and subjective cognitive complaints, poorer work and social adjustment, and reduced quality of life compared to patients who were cognitively intact. LIMITATIONS: The study design...

  13. A propensity score analysis shows that empirical treatment with linezolid does not increase the thirty-day mortality rate in patients with Gram-negative bacteremia.

    Science.gov (United States)

    Ternavasio-de la Vega, Hugo-Guillermo; Mateos-Díaz, Ana-María; Martinez, Jose-Antonio; Almela, Manel; Cobos-Trigueros, Nazaret; Morata, Laura; De-la-Calle, Cristina; Sala, Marta; Mensa, Josep; Marcos, Miguel; Soriano, Alex

    2014-12-01

    The role of linezolid in empirical therapy of suspected bacteremia remains unclear. The aim of this study was to evaluate the influence of empirical use of linezolid or glycopeptides in addition to other antibiotics on the 30-day mortality rates in patients with Gram-negative bacteremia. For this purpose, 1,126 patients with Gram-negative bacteremia in the Hospital Clinic of Barcelona from 2000 to 2012 were included in this study. In order to compare the mortality rates between patients who received linezolid or glycopeptides, the propensity scores on baseline variables were used to balance the treatment groups, and both propensity score matching and propensity-adjusted logistic regression were used to compare the 30-day mortality rates between the groups. The overall 30-day mortality rate was 16.0% during the study period. Sixty-eight patients received empirical treatment with linezolid, and 1,058 received glycopeptides. The propensity score matching included 64 patients in each treatment group. After matching, the mortality rates were 14.1% (9/64) in patients who received glycopeptides and 21.9% (14/64) in those who received linezolid, and a nonsignificant association between empirical linezolid treatment and mortality rate (odds ratio [OR], 1.63; 95% confidence interval [CI], 0.69 to 3.82; P = 0.275, McNemar's test) was found. This association remained nonsignificant when variables that remained unbalanced after matching were included in a conditional logistic regression model. Further, the stratified propensity score analysis did not show any significant relationship between empirical linezolid treatment and the mortality rate after adjustment by propensity score quintiles or other variables potentially associated with mortality. In conclusion, the propensity score analysis showed that empirical treatment with linezolid compared with that with glycopeptides was not associated with 30-day mortality rates in patients with Gram-negative bacteremia. Copyright

  14. Large Scale Genome Analysis Shows that the Epitopes for Broadly Cross-Reactive Antibodies Are Predominant in the Pandemic 2009 Influenza Virus A H1N1 Strain

    Directory of Open Access Journals (Sweden)

    Edgar E. Lara-Ramírez

    2013-11-01

    Full Text Available The past pandemic strain H1N1 (A (H1N1pdm09 has now become a common component of current seasonal influenza viruses. It has changed the pre-existing immunity of the human population to succeeding infections. In the present study, a total of 14,210 distinct sequences downloaded from National Center for Biotechnology Information (NCBI database were used for the analysis. The epitope compositions in A (H1N1pdm09, classic seasonal strains, swine strains as well as highly virulent avian strain H5N1, identified with the aid of the Immune Epitope DataBase (IEDB, were compared at genomic level. The result showed that A (H1N1 pdm09 contains the 90% of B-cell epitopes for broadly cross-reactive antibodies (EBCA, which is in consonance with the recent reports on the experimental identification of new epitopes or antibodies for this virus and the binding tests with influenza virus protein HA of different subtypes. Our analysis supports that high proportional EBCA depends on the epitope pattern of A (H1N1pdm09 virus. This study may be helpful for better understanding of A (H1N1pdm09 and the production of new influenza vaccines.

  15. Balance Impairments in Different Subgroups of Patients With Migraine.

    Science.gov (United States)

    Carvalho, Gabriela F; Bonato, Paolo; Florencio, Lidiane L; Pinheiro, Carina F; Dach, Fabiola; Bigal, Marcelo E; Bevilaqua-Grossi, Debora

    2017-03-01

    Patients with migraine often experience balance impairments. However, the relationship between clinical features - like aura and chronicity - and the severity of balance impairments is not well established. The objective of this study was to assess balance impairments in different subgroups of migraine patients. One hundred five subjects diagnosed according to the ICHD-III were recruited in the study. They were uniformly distributed among three groups: migraine with aura, migraine without aura, and chronic migraine. Thirty-five controls were also recruited in the study. Balance impairments were assessed in all subjects via the modified Sensory Organization test and the Limits of Stability test. The results in the four groups were compared using ANCOVA tests with age, BMI, presence of dizziness, level of physical activity, time of migraine onset, and medication intake as covariates. Subjects in the migraine with aura and the chronic migraine groups showed poorer balance control than control subjects in three of the four conditions tested using the modified Sensory Organization test: FirmCE: CG: 1.5 cm2 , 95%CI 1.3 to 1.7; M: 2.1 cm2 , 95%CI 1.6 to 2.6; MA: 4.5 cm2 , 95%CI 3.2 to 5.8; CM: 4.5 cm2 , 95%CI 3.0 to 6.0; P migraine without aura group (P migraine groups were found in the reaction time, movement velocity, endpoint excursion, and maximal excursion parameters (P  .05). There is evidence of balance control impairments in subjects with all subtypes of migraine compared to control subjects. The presence of aura and frequent migraine attacks reflect negatively in the postural control performance and may have a significant clinical impact in patients with migraine that should be addressed with appropriate clinical interventions. © 2016 American Headache Society.

  16. Robotic Assisted Radical Cystectomy with Extracorporeal Urinary Diversion Does Not Show a Benefit over Open Radical Cystectomy: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

    Directory of Open Access Journals (Sweden)

    Wei Shen Tan

    Full Text Available The number of robotic assisted radical cystectomy (RARC procedures is increasing despite the lack of Level I evidence showing any advantages over open radical cystectomy (ORC. However, several systematic reviews with meta-analyses including non-randomised studies, suggest an overall benefit for RARC compared to ORC. We performed a systematic review with meta-analysis of randomised controlled trials (RCTs to evaluate the perioperative morbidity and efficacy of RARC compared to ORC in patients with bladder cancer.Literature searches of Medline/Pubmed, Embase, Web of Science and clinicaltrials.gov databases up to 10th March 2016 were performed. The inclusion criteria for eligible studies were RCTs which compared perioperative outcomes of ORC and RARC for bladder cancer. Primary objective was perioperative and histopathological outcomes of RARC versus ORC while the secondary objective was quality of life assessment (QoL, oncological outcomes and cost analysis.Four RCTs (from 5 articles met the inclusion criteria, with a total of 239 patients all with extracorporeal urinary diversion. Patient demographics and clinical characteristics of RARC and ORC patients were evenly matched. There was no significant difference between groups in perioperative morbidity, length of stay, positive surgical margin, lymph node yield and positive lymph node status. RARC group had significantly lower estimated blood loss (p<0.001 and wound complications (p = 0.03 but required significantly longer operating time (p<0.001. QoL was not measured uniformly across trials and cost analysis was reported in one RCTs. A test for heterogeneity did highlight differences across operating time of trials suggesting that surgeon experience may influence outcomes.This study does not provide evidence to support a benefit for RARC compared to ORC. These results may not have inference for RARC with intracorporeal urinary diversion. Well-designed trials with appropriate endpoints conducted

  17. An Analysis of Trafficking Receptors Shows that CD44 and P-Selectin Glycoprotein Ligand-1 Collectively Control the Migration of Activated Human T-Cells

    Directory of Open Access Journals (Sweden)

    Amal J. Ali

    2017-05-01

    Full Text Available Selectins guide the traffic of activated T-cells through the blood stream by mediating their tethering and rolling onto inflamed endothelium, in this way acting as beacons to help navigate them to sites of inflammation. Here, we present a comprehensive analysis of E-selectin ligands expressed on activated human T-cells. We identified several novel glycoproteins that function as E-selectin ligands. Specifically, we compared the role of P-selectin glycoprotein ligand-1 (PSGL-1 and CD43, known E-selectin ligands, to CD44, a ligand that has not previously been characterized as an E-selectin ligand on activated human T-cells. We showed that CD44 acts as a functional E-selectin ligand when expressed on both CD4+ and CD8+ T-cells. Moreover, the CD44 protein carries a binding epitope identifying it as hematopoietic cell E- and/or L-selectin ligand (HCELL. Furthermore, by knocking down these ligands individually or together in primary activated human T-cells, we demonstrated that CD44/HCELL, and not CD43, cooperates with PSGL-1 as a major E-selectin ligand. Additionally, we demonstrated the relevance of our findings to chronic autoimmune disease, by showing that CD44/HCELL and PSGL-1, but not CD43, from T-cells isolated from psoriasis patients, bind E-selectin.

  18. An Analysis of Trafficking Receptors Shows that CD44 and P-Selectin Glycoprotein Ligand-1 Collectively Control the Migration of Activated Human T-Cells

    KAUST Repository

    Ali, Amal J.

    2017-05-03

    Selectins guide the traffic of activated T-cells through the blood stream by mediating their tethering and rolling onto inflamed endothelium, in this way acting as beacons to help navigate them to sites of inflammation. Here, we present a comprehensive analysis of E-selectin ligands expressed on activated human T-cells. We identified several novel glycoproteins that function as E-selectin ligands. Specifically, we compared the role of P-selectin glycoprotein ligand-1 (PSGL-1) and CD43, known E-selectin ligands, to CD44, a ligand that has not previously been characterized as an E-selectin ligand on activated human T-cells. We showed that CD44 acts as a functional E-selectin ligand when expressed on both CD4+ and CD8+ T-cells. Moreover, the CD44 protein carries a binding epitope identifying it as hematopoietic cell E- and/or L-selectin ligand (HCELL). Furthermore, by knocking down these ligands individually or together in primary activated human T-cells, we demonstrated that CD44/HCELL, and not CD43, cooperates with PSGL-1 as a major E-selectin ligand. Additionally, we demonstrated the relevance of our findings to chronic autoimmune disease, by showing that CD44/HCELL and PSGL-1, but not CD43, from T-cells isolated from psoriasis patients, bind E-selectin.

  19. Proximal femoral nail shows better concordance of gait analysis between operated and uninjured limbs compared to hemiarthroplasty in intertrochanteric femoral fractures.

    Science.gov (United States)

    Güven, Melih; Kocadal, Onur; Akman, Budak; Poyanlı, Oğuz S; Kemah, Bahattin; Atay, Evren Fehmi

    2016-06-01

    The purpose of this study was to compare the results of pedobarographic gait analysis between the patients treated by proximal femoral nail or bipolar partial hemiarthroplasty due to intertrochanteric fractures. Thirty-seven patients with a minimum 1-year follow-up who had been operated for intertrochanteric fractures were evaluated clinically, radiologically and with pedobarographic gait analysis. Proximal femoral nail had been performed to 21 patients (group A), whilst 16 patients had been operated by partial bipolar hemiarthroplasty (group B). Pedobarographic analysis was performed by measuring plantar pressure, force and contact area values in both static and dynamic manner. Pedobarographic results of operated limb were compared among groups. Same data's also were compared between operated and uninjured limbs in each group to determine any asymmetry on weight-bearing. Average follow-up period in group A and group B was 36 (12-56) and 30 (12-48) months, respectively. There were no statistically significant differences among groups in terms of age, gender, body mass index, type and side of fracture, follow-up period, leg length discrepancy and postoperative hip scores. When the pedobarographic results of operated limb were compared, group B showed much more plantar force and pressure values than group A, on both static and dynamic evaluations. If the evaluation was taken into consideration to comparison of pedobarographic results between operated and uninjured limbs in each group, we found asymmetry in static load bearing, caused by higher load on uninjured limb in both groups. However, there was no statistically significant asymmetry between operated and uninjured limbs in respect to dynamic pedobarographic parameters for patients in group A. On the contrary, operated limbs in group B exposed much more plantar force and pressure values than uninjured limbs, which indicated asymmetric weight-bearing on dynamic evaluation. Assessment of pedobarographic parameters

  20. Latino Male Ethnic Subgroups: Patterns in College Enrollment and Degree Completion

    Science.gov (United States)

    Ponjuan, Luis; Palomin, Leticia; Calise, Angela

    2015-01-01

    This chapter examines Latino male ethnic subgroups and their college enrollment and degree completion patterns. The chapter also offers recommendations to improve Latino male ethnic subgroups' educational achievement.

  1. A comparison of subgroup analyses in grant applications and publications.

    NARCIS (Netherlands)

    Boonacker, C.W.; Hoes, A.W.; Liere-Visser, K. van; Schilder, A.G.M.; Rovers, M.M.

    2011-01-01

    In this paper, the authors compare subgroup analyses as outlined in grant applications and their related publications. Grants awarded by the Netherlands Organization for Health Research and Development (ZonMw) from 2001 onward that were finalized before March 1, 2010, were studied. Of the 79 grant

  2. Practical Algorithms for Subgroup Detection in Covert Networks

    DEFF Research Database (Denmark)

    Memon, Nasrullah; Wiil, Uffe Kock; Qureshi, Pir Abdul Rasool

    2010-01-01

    In this paper, we present algorithms for subgroup detection and demonstrated them with a real-time case study of USS Cole bombing terrorist network. The algorithms are demonstrated in an application by a prototype system. The system finds associations between terrorist and terrorist organisations...

  3. On approximation of Lie groups by discrete subgroups

    Indian Academy of Sciences (India)

    voila.fr; salah.suissi@yahoo.fr. MS received 11 August 2012; revised 27 January 2013. Abstract. A locally compact group G is said to be approximated by discrete sub- groups (in the sense of Tôyama) if there is a sequence of discrete subgroups ...

  4. Depression in later life : three etiologically different subgroups

    NARCIS (Netherlands)

    Van den Berg, M.D.; Oldehinkel, A.J.; Bouhuys, A.L.; Brilman, E.I.; Beekman, A.T.F.; Ormel, J.

    Background: Various studies support the notion that early onset depression and late onset depression have different etiological pathways. Late onset depression has been found to be a heterogeneous group. This study attempts to divide the late onset group in two subgroups with different aetiology and

  5. Detection of Problem Gambler Subgroups Using Recursive Partitioning

    Science.gov (United States)

    Markham, Francis; Young, Martin; Doran, Bruce

    2013-01-01

    The multivariate socio-demographic risk factors for problem gambling have been well documented. While this body of research is valuable in determining risk factors aggregated across various populations, the majority of studies tend not to specifically identify particular subgroups of problem gamblers based on the interaction between variables. The…

  6. Progressive multiple sclerosis patients show substantial lesion activity that correlates with clinical disease severity and sex: a retrospective autopsy cohort analysis.

    Science.gov (United States)

    Luchetti, Sabina; Fransen, Nina L; van Eden, Corbert G; Ramaglia, Valeria; Mason, Matthew; Huitinga, Inge

    2018-02-13

    Multiple sclerosis (MS) is a highly heterogeneous disease with large inter-individual differences in disease course. MS lesion pathology shows considerable heterogeneity in localization, cellular content and degree of demyelination between patients. In this study, we investigated pathological correlates of disease course in MS using the autopsy cohort of the Netherlands Brain Bank (NBB), containing 182 MS brain donors. Using a standardized autopsy procedure including systematic dissection from standard locations, 3188 tissue blocks containing 7562 MS lesions were dissected. Unbiased measurements of lesion load were made using the tissue from standard locations. Lesion demyelinating and innate inflammatory activity were visualized by immunohistochemistry for proteolipid protein and human leukocyte antigen. Lesions were classified into active, mixed active/inactive (also known as chronic active), inactive or remyelinated, while microglia/macrophage morphology was classified as ramified, amoeboid or foamy. The severity score was calculated from the time from first symptoms to EDSS-6. Lesion type prevalence and microglia/macrophage morphology were analyzed in relation to clinical course, disease severity, lesion load and sex, and in relation to each other. This analysis shows for the first time that (1) in progressive MS, with a mean disease duration of 28.6 ± 13.3 years (mean ± SD), there is substantial inflammatory lesion activity at time to death. 57% of all lesions were either active or mixed active/inactive and 78% of all patients had a mixed active/inactive lesion present; (2) patients that had a more severe disease course show a higher proportion of mixed active/inactive lesions (p = 6e-06) and a higher lesion load (p = 2e-04) at the time of death, (3) patients with a progressive disease course show a higher lesion load (p = 0.001), and a lower proportion of remyelinated lesions (p = 0.03) compared to patients with a relapsing disease course, (4

  7. A novel multi-variant epitope ensemble vaccine against avian leukosis virus subgroup J.

    Science.gov (United States)

    Wang, Xiaoyu; Zhou, Defang; Wang, Guihua; Huang, Libo; Zheng, Qiankun; Li, Chengui; Cheng, Ziqiang

    2017-12-04

    The hypervariable antigenicity and immunosuppressive features of avian leukosis virus subgroup J (ALV-J) has led to great challenges to develop effective vaccines. Epitope vaccine will be a perspective trend. Previously, we identified a variant antigenic neutralizing epitope in hypervariable region 1 (hr1) of ALV-J, N-LRDFIA/E/TKWKS/GDDL/HLIRPYVNQS-C. BLAST analysis showed that the mutation of A, E, T and H in this epitope cover 79% of all ALV-J strains. Base on this data, we designed a multi-variant epitope ensemble vaccine comprising the four mutation variants linked with glycine and serine. The recombinant multi-variant epitope gene was expressed in Escherichia coli BL21. The expressed protein of the variant multi-variant epitope gene can react with positive sera and monoclonal antibodies of ALV-J, while cannot react with ALV-J negative sera. The multi-variant epitope vaccine that conjugated Freund's adjuvant complete/incomplete showed high immunogenicity that reached the titer of 1:64,000 at 42 days post immunization and maintained the immune period for at least 126 days in SPF chickens. Further, we demonstrated that the antibody induced by the variant multi-variant ensemble epitope vaccine recognized and neutralized different ALV-J strains (NX0101, TA1, WS1, BZ1224 and BZ4). Protection experiment that was evaluated by clinical symptom, viral shedding, weight gain, gross and histopathology showed 100% chickens that inoculated the multi-epitope vaccine were well protected against ALV-J challenge. The result shows a promising multi-variant epitope ensemble vaccine against hypervariable viruses in animals. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Differences in Psychosocial Predictors of Obesity Among LGBT Subgroups.

    Science.gov (United States)

    Warren, Jacob C; Smalley, K Bryant; Barefoot, K Nikki

    2016-08-01

    The purpose of the current study was to examine the overall presence of and differences in rates of overweight/obesity among a large, nationally diverse sample of lesbian, gay, bisexual, transgender (LGBT)-identified individuals (i.e., cisgender lesbians, cisgender gay men, cisgender bisexual women, cisgender bisexual men, transgender women, and transgender men) and to identify specific psychosocial predictors of obesity within each of the six LGBT subgroups. A total of 2702 LGBT-identified participants participated in the online study. Participants completed a series of demographic questions (including weight and height) and the Depression Anxiety Stress Scale 21. The percentage of participants who were overweight/obese did not differ significantly across LGBT subgroups, with 61.1% of the total sample being overweight/obese. However, the percentage of participants who self-reported body mass indexes in the obese range differed significantly across the six LGBT subgroups, with the highest prevalence in transgender men (46.0%). In addition, the predictors of obesity varied by subgroup, with age a significant predictor for cisgender lesbians, cisgender gay men, and cisgender bisexual women, relationship status for cisgender bisexual women, employment status for both cisgender gay men and cisgender bisexual women, education level for cisgender lesbians, and depression, anxiety, and stress for cisgender gay men. None of the examined psychosocial factors emerged as predictors of obesity for cisgender bisexual men, transgender women, or transgender men. These findings suggest that there are substantial variations in the presence and predictors of obesity across LGBT subgroups that support the need for culturally tailored healthy weight promotion efforts within the LGBT community.

  9. Clinical implications of medulloblastoma subgroups: incidence of CSF diversion surgery.

    Science.gov (United States)

    Schneider, Christian; Ramaswamy, Vijay; Kulkarni, Abhaya V; Rutka, James T; Remke, Marc; Tabori, Uri; Hawkins, Cynthia; Bouffet, Eric; Taylor, Michael D

    2015-03-01

    While medulloblastoma was initially thought to comprise a single homogeneous entity, it is now accepted that it in fact comprises 4 discrete subgroups, each with its own distinct demographics, clinical presentation, transcriptomics, genetics, and outcome. Hydrocephalus is a common complication of medulloblastoma and not infrequently requires CSF diversion. The authors report the incidence of CSF diversion surgery in each of the subgroups of medulloblastoma (Wnt, Shh, Group 3, and Group 4). The medical and imaging records for patients who underwent surgery for medulloblastoma at The Hospital for Sick Children were retrospectively reviewed. The primary outcome was the requirement for CSF diversion surgery either before or within 60 days of tumor resection. The modified Canadian Preoperative Prediction Rule for Hydrocephalus (mCPPRH) was compared among subgroups. Of 143 medulloblastoma patients, treated from 1991 to 2013, sufficient data were available for 130 patients (15 with Wnt, 30 with Shh, 30 with Group 3, and 55 with Group 4 medulloblastomas). Of these, 28 patients (22%) ultimately underwent CSF diversion surgery: 0% with Wnt, 29% with Shh, 29% with Group 3, and 43% with Group 4 tumors. Patients in the Wnt subgroup had a lower incidence of CSF diversion than all other patients combined (p = 0.04). Wnt patients had a lower mCPPRH score (lower risk of CSF diversion, p = 0.045), were older, had smaller ventricles at diagnosis, and had no leptomeningeal metastases. The overall rate of CSF diversion surgery for Shh, Group 3, and Group 4 medulloblastomas is around 30%, but no patients in the present series with a Wnt medulloblastoma required shunting. The low incidence of hydrocephalus in patients with Wnt medulloblastoma likely reflects both host factors (age) and disease factors (lack of metastases). The absence of hydrocephalus in patients with Wnt medulloblastomas likely contributes to their excellent rate of survival and may also contribute to a higher quality

  10. The asymmetry of the entrainment range induced by the difference in intrinsic frequencies between two subgroups within the suprachiasmatic nucleus

    Science.gov (United States)

    Gu, Changgui; Yang, Huijie

    2017-06-01

    The rhythms of physiological and behavioral activities in mammals, which are regulated by the main clock suprachiasmatic nucleus (SCN) in the brain, can not be only synchronized to the natural 24 h light-dark cycle, but also to cycles with artificial periods. The range of the artificial periods that the animal can be synchronized to is called entrainment range. In the absence of the light-dark cycle, the animal can also maintain the circadian rhythm with an endogenous period close to 24 h. Experiments found that the entrainment range is not symmetrical with respect to the endogenous period. In the present study, an explanation is given for the asymmetry based on a Kuramoto model which describes the neuronal network of the SCN. Our numerical simulations and theoretical analysis show that the asymmetry results from the difference in the intrinsic frequencies between two subgroups of the SCN, as well as the entrainment range is affected by the difference.

  11. Genome-wide analysis of AP2/ERF family genes from Lotus corniculatus shows LcERF054 enhances salt tolerance.

    Science.gov (United States)

    Sun, Zhan-Min; Zhou, Mei-Liang; Xiao, Xing-Guo; Tang, Yi-Xiong; Wu, Yan-Min

    2014-09-01

    Lotus corniculatus is used in agriculture as a main forage plant. Members of the Apetala2/ethylene response factor (AP2/ERF) family play important roles in regulating gene expression in response to many forms of stress, including drought and salt. Here, starting from database of the L. corniculatus var. japonicus genome, we identified 127 AP2/ERF genes by insilico cloning method. The phylogeny, gene structures, and putative conserved motifs in L. corniculatus var. japonicus ERF proteins were analyzed. Based on the number of AP2/ERF domains and the function of the genes, 127 AP2/ERF genes from L. corniculatus var. japonicus were classified into five subfamilies named the AP2, dehydration-responsive element binding factor (DREB), ERF, RAV, and a soloist. Outside the AP2/ERF domain, many L. corniculatus var. japonicus-specific conserved motifs were detected. Expression profile analysis of AP2/ERF genes by quantitative real-time PCR revealed that 19 LcERF genes, including LcERF054 (KJ004728), were significantly induced by salt stress. The results showed that the LcERF054 gene encodes a nuclear transcription activator. Overexpression of LcERF054 in Arabidopsis enhanced the tolerances to salt stress, showed higher germination ratio of seeds, and had elevated levels of relative moisture contents, soluble sugars, proline, and lower levels of malondialdehyde under stress conditions compared to wild-type plants. The expression of hyperosmotic salinity response genes COR15A, LEA4-5, P5CS1, and RD29A was found to be elevated in the LcERF054-overexpressing Arabidopsis plants compared to wild type. These results revealed that the LcERF genes play important roles in L. corniculatus cv Leo under salt stress and that LcERFs are attractive engineering targets in applied efforts to improve abiotic stress tolerances in L. corniculatus cv Leo or other crops.

  12. Origins and biogeography of the Anolis crassulus subgroup (Squamata: Dactyloidae) in the highlands of Nuclear Central America.

    Science.gov (United States)

    Hofmann, Erich P; Townsend, Josiah H

    2017-12-21

    Recent studies have begun to reveal the complex evolutionary and biogeographic histories of mainland anoles in Central America, but the origins and relationships of many taxa remain poorly understood. One such group is the Anolis (Norops) crassulus species subgroup, which contains ten morphologically similar highland taxa, the majority of which have restricted distributions. The nominal taxon A. crassulus has a disjunct distribution from Chiapas, Mexico, through Guatemala, in the highlands of El Salvador, and in the Chortís Highlands of Honduras. We test the relationships of these species using multiple mitochondrial and nuclear loci in concatenated and multispecies coalescent frameworks, in an effort to both resolve long-standing taxonomic confusion and present new insights into the evolution and biogeography of these taxa. Sequences of multiple mitochondrial and nuclear loci were generated for eight of the ten species of the Anolis crassulus species subgroup. We analyzed phylogenetic relationships and estimated divergence times and ancestral ranges of the subgroup, recovering a monophyletic subgroup within Anolis. Within the nominal taxon Anolis crassulus, we recovered multiple genetically distinct lineages corresponding to allopatric populations, and show that the Chortís Highland lineage split from the others over 13 MYA. Additionally, distinct mitochondrial lineages are present within the taxa A. heteropholidotus and A. morazani, and importantly, samples of A. crassulus and A. sminthus previously used in major anole phylogenetic analyses are not recovered as conspecific with those taxa. We infer a Chortís Highland origin for the ancestor of this subgroup, and estimate cladogenesis of this subgroup began approximately 22 MYA. Our results provide new insights into the evolution, biogeography, and timing of diversification of the Anolis crassulus species subgroup. The disjunctly distributed Anolis crassulus sensu lato represents several morphologically

  13. Linking concepts in the ecology and evolution of invasive plants: network analysis shows what has been most studied and identifies knowledge gaps.

    Science.gov (United States)

    Vanderhoeven, Sonia; Brown, Cynthia S; Tepolt, Carolyn K; Tsutsui, Neil D; Vanparys, Valérie; Atkinson, Sheryl; Mahy, Grégory; Monty, Arnaud

    2010-03-01

    In recent decades, a growing number of studies have addressed connections between ecological and evolutionary concepts in biologic invasions. These connections may be crucial for understanding the processes underlying invaders' success. However, the extent to which scientists have worked on the integration of the ecology and evolution of invasive plants is poorly documented, as few attempts have been made to evaluate these efforts in invasion biology research. Such analysis can facilitate recognize well-documented relationships and identify gaps in our knowledge. In this study, we used a network-based method for visualizing the connections between major aspects of ecology and evolution in the primary research literature. Using the family Poaceae as an example, we show that ecological concepts were more studied and better interconnected than were evolutionary concepts. Several possible connections were not documented at all, representing knowledge gaps between ecology and evolution of invaders. Among knowledge gaps, the concepts of plasticity, gene flow, epigenetics and human influence were particularly under-connected. We discuss five possible research avenues to better understand the relationships between ecology and evolution in the success of Poaceae, and of alien plants in general.

  14. Religious subgroups influencing vaccination coverage in the Dutch Bible belt: an ecological study

    Science.gov (United States)

    2011-01-01

    Background The Netherlands has experienced epidemics of vaccine preventable diseases largely confined to the Bible belt, an area where -among others- orthodox protestant groups are living. Lacking information on the vaccination coverage in this minority, and its various subgroups, control of vaccine preventable diseases is focused on the geographical area of the Bible belt. However, the adequacy of this strategy is questionable. This study assesses the influence of presence of various orthodox protestant subgroups (orthodox protestant denominations, OPDs) on municipal vaccination coverage in the Bible belt. Methods We performed an ecological study at municipality level. Data on number of inhabitants, urbanization level, socio-economical status, immigration and vaccination coverage were obtained from national databases. As religion is not registered in the Netherlands, membership numbers of the OPDs had to be obtained from church year books and via church offices. For all municipalities in the Netherlands, the effect of presence or absence of OPDs on vaccination coverage was assessed by comparing mean vaccination coverage. For municipalities where OPDs were present, the effect of each of them (measured as membership ratio, the number of members proportional to total number of inhabitants) on vaccination coverage was assessed by bivariate correlation and multiple regression analysis in a model containing the determinants immigration, socio-economical status and urbanization as well. Results Mean vaccination coverage (93.5% ± 4.7) in municipalities with OPDs (n = 135) was significantly lower (p municipalities without OPDs (96.9% ± 2.1). Multiple regression analyses showed that in municipalities with OPDs 84% of the variance in vaccination coverage was explained by the presence of these OPDs. Immigration had a significant, but small explanatory effect as well. Membership ratios of all OPDs were negatively related to vaccination coverage; this relationship was

  15. Impact of diet on the efficacy of insulin lispro mix 25 and insulin lispro mix 50 as starter insulin in East Asian patients with type 2 diabetes: Subgroup analysis of the Comparison Between Low Mixed Insulin and Mid Mixed Insulin as Starter Insulin For Patients with Type 2 Diabetes Mellitus (CLASSIFY Study) randomized trial.

    Science.gov (United States)

    Chen, Wei; Qian, Lei; Watada, Hirotaka; Li, Peng Fei; Iwamoto, Noriyuki; Imori, Makoto; Yang, Wen Ying

    2017-01-01

    The pathophysiology of diabetes differs between Asian and Western patients in many ways, and diet is a primary contributor. The present study examined the effect of diet on the efficacy of 25% insulin lispro/75% insulin lispro protamine suspension (LM25) and 50% insulin lispro/50% insulin lispro protamine suspension (LM50) as starter insulin in Chinese and Japanese patients with type 2 diabetes and inadequate glycemic control with oral antidiabetic medication. This was a predefined subgroup analysis of a phase 4, open-label, 26-week, parallel-arm, randomized (computer-generated random sequence) trial (21 January 2013 to 22 August 2014). Nutritional intake was assessed from food records kept by participants before study drug administration. Outcomes assessed were changes from baseline in self-monitored blood glucose, 1,5-anhydroglucitol and glycated hemoglobin. In total, 328 participants were randomized to receive twice-daily LM25 (n = 168) or LM50 (n = 160). Median daily nutritional intake (by weight and percentage of total energy) was 230.8 g of carbohydrate (54%), 56.5 g of fat (31%) and 66 g of protein (15%). Improvements in self-monitored blood glucose were significantly greater (P ≤ 0.028) in the LM50 group than in the LM25 group, regardless of nutritional intake. When carbohydrate (by weight or percentage energy) or fat (by weight) intake exceeded median levels, LM50 was significantly more efficacious than LM25 (P ≤ 0.026) in improving 1,5-anhydroglucitol and glycated hemoglobin. Glycemic control improved in both LM25 and LM50 groups, but LM50 was significantly more efficacious under certain dietary conditions, particularly with increased carbohydrate intake. © 2016 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

  16. Plateau Iris Distribution Across Anterior Segment Optical Coherence Tomography Defined Subgroups of Subjects With Primary Angle Closure Glaucoma.

    Science.gov (United States)

    Verma, Sushma; Nongpiur, Monisha E; Oo, Hnin H; Atalay, Eray; Goh, David; Wong, Tina T; Perera, Shamira A; Aung, Tin

    2017-10-01

    We previously identified three distinct subgroups of patients with primary angle closure glaucoma (PACG) based on anterior segment optical coherence tomography (ASOCT) imaging. Group 1 was characterized by a large iris area with deepest anterior chambers, group 2 by a large lens vault (LV) and shallow anterior chamber depth (ACD), and group 3 displayed intermediate values across iris area, LV, and ACD. The purpose of the present study was to determine the distribution of plateau iris in these subgroups using ultrasound biomicroscopy (UBM) features. UBM images of the 210 subjects who were previously enrolled for the ASOCT subgrouping analysis and had undergone laser peripheral iridotomy were assessed and graded by a single glaucoma fellowship trained clinician. Plateau iris was defined as the presence of all the following UBM criteria in at least two quadrants: anteriorly directed ciliary body, absent ciliary sulcus, iris angulation, flat iris plane, and iridoangle touch. Of 210 subjects, 23 were excluded due to poor-quality images. Based on standardized UBM criteria, the overall prevalence of plateau iris was 36.9% (n = 187). The proportion of plateau iris was similar across the three groups (subgroup 1:35.4% (n = 29); subgroup 2:39.0% (n = 32); subgroup 3:34.8% (n = 8), P = 0.87). On multiple logistic regression analysis, iris thickness at 750 μm from the scleral spur (IT750) was the only variable associated with plateau iris (odds ratio: 1.5/100 μm increase in iris thickness [IT], P = 0.04). The proportion of plateau iris was similar across the three ASOCT-based PACG subgroups and more than one-third of subjects with PACG were diagnosed with plateau iris based on standardized UBM criteria. In addition, we noted that eyes with increased peripheral IT have an increased likelihood of plateau iris.

  17. Post-hoc analysis showing better clinical response with the loading dose of certolizumab pegol in Japanese patients with active rheumatoid arthritis.

    Science.gov (United States)

    Takeuchi, Tsutomu; Yamamoto, Kazuhiko; Yamanaka, Hisashi; Ishiguro, Naoki; Tanaka, Yoshiya; Eguchi, Katsumi; Watanabe, Akira; Origasa, Hideki; Kobayashi, Mariko; Shoji, Toshiharu; Togo, Osamu; Miyasaka, Nobuyuki; Koike, Takao

    2016-07-01

    To compare the efficacy and safety of certolizumab pegol (CZP) with and without loading dose (LD) in a post-hoc analysis of two Japanese clinical studies. Data from the double-blind trials (DBT) J-RAPID and HIKARI, and their open-label extension (OLE) studies, were used. Patients randomized to CZP 200 mg every 2 weeks (Q2W) groups starting with LD (400 mg Weeks 0/2/4; LD group; J-RAPID: n = 82, HIKARI: n = 116) and patients randomized to placebo groups who subsequently started CZP Q2W without LD in the OLEs (No-LD group; J-RAPID: n = 61, HIKARI: n = 99) were analyzed. Efficacy and pharmacokinetics were assessed during 24 weeks. Adverse events were reported from all studies. In both trials, the LD groups showed more rapid initial ACR20/50/70 kinetics, and maintained higher ACR50/70 responses until 24 weeks, compared with the No-LD groups. Anti-CZP antibody development was less frequent in the LD groups (J-RAPID: 1.2% versus 4.9%; HIKARI: 17.2% versus 27.3%). Similar safety profiles were reported between LD and No-LD groups (any AEs: 281.8 versus 315.7 [J-RAPID], 282.6 versus 321.3 [HIKARI] [incidence rate/100 patient-years]). Despite limitations, including comparing DBT and OLE studies, these results suggest that a CZP LD improves clinical response in active rheumatoid arthritis without altering the safety profile.

  18. Immunofluorescent analysis of testicular biopsies with germ cell and Sertoli cell markers shows significant MVH negative germ cell depletion with older age at orchiopexy.

    Science.gov (United States)

    Li, Ruili; Thorup, Jorgen; Sun, Cong; Cortes, Dina; Southwell, Bridget; Hutson, John

    2014-02-01

    Undescended testis is the most common defect in male newborns. This condition is associated with increased risks of infertility and testicular malignancy due to abnormal germ cell development in the testes. Early surgery may limit such risks. We analyzed germ cell development vs age at orchiopexy using a germ cell marker and a Sertoli cell marker on testicular biopsies. A total of 22 testicular biopsies at orchiopexy in 20 patients 5 to 24.5 months old were fixed and embedded in paraffin. Sections were processed and labeled with AMH antibody for Sertoli cells and MVH antibody for germ cells for immunofluorescent histochemical analysis. Confocal images were counted using ImageJ (National Institutes of Health, Bethesda, Maryland) for germ cells and testicular tubules. The data were analyzed using linear regression. Sertoli cells were clearly distinguished from MVH positive and negative germ cells located centrally or on basement membranes of tubules. Percentage of tubules with MVH negative germ cells significantly decreased with increasing age at orchiopexy (β = -0.03, p = 0.03). Total tubular numbers and "empty" tubules without germ cells significantly increased with age at orchiopexy (β = 1.15, p = 0.02 and β = 0.44, p = 0.04, respectively). AMH antibody distinguished Sertoli cells from germ cells, and MVH antibody distinguished 2 types of germ cells at different developmental stages. Biopsy at orchiopexy in older patients showed significant germ cell depletion. These results lend support to early surgery to optimize germ cell number. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  19. Transcriptomic analysis of the interaction between Helianthus annuus and its obligate parasite Plasmopara halstedii shows single nucleotide polymorphisms in CRN sequences

    Directory of Open Access Journals (Sweden)

    Gouzy Jérôme

    2011-10-01

    Full Text Available Abstract Background Downy mildew in sunflowers (Helianthus annuus L. is caused by the oomycete Plasmopara halstedii (Farl. Berlese et de Toni. Despite efforts by the international community to breed mildew-resistant varieties, downy mildew remains a major threat to the sunflower crop. Very few genomic, genetic and molecular resources are currently available to study this pathogen. Using a 454 sequencing method, expressed sequence tags (EST during the interaction between H. annuus and P. halstedii have been generated and a search was performed for sites in putative effectors to show polymorphisms between the different races of P. halstedii. Results A 454 pyrosequencing run of two infected sunflower samples (inbred lines XRQ and PSC8 infected with race 710 of P. halstedii, which exhibit incompatible and compatible interactions, respectively generated 113,720 and 172,107 useable reads. From these reads, 44,948 contigs and singletons have been produced. A bioinformatic portal, HP, was specifically created for in-depth analysis of these clusters. Using in silico filtering, 405 clusters were defined as being specific to oomycetes, and 172 were defined as non-specific oomycete clusters. A subset of these two categories was checked using PCR amplification, and 86% of the tested clusters were validated. Twenty putative RXLR and CRN effectors were detected using PSI-BLAST. Using corresponding sequences from four races (100, 304, 703 and 710, 22 SNPs were detected, providing new information on pathogen polymorphisms. Conclusions This study identified a large number of genes that are expressed during H. annuus/P. halstedii compatible or incompatible interactions. It also reveals, for the first time, that an infection mechanism exists in P. halstedii similar to that in other oomycetes associated with the presence of putative RXLR and CRN effectors. SNPs discovered in CRN effector sequences were used to determine the genetic distances between the four races

  20. Show-Bix &

    DEFF Research Database (Denmark)

    2014-01-01

    The anti-reenactment 'Show-Bix &' consists of 5 dias projectors, a dial phone, quintophonic sound, and interactive elements. A responsive interface will enable the Dias projectors to show copies of original dias slides from the Show-Bix piece ”March på Stedet”, 265 images in total. The copies...... are made from digital scans of the original dias slides located in the collection of the Museum of Contemporary Art in Roskilde. In front of the audience entering the space and placed on it’s own stand, is an original 60s style telephone with turning dial. Action begins when the audience lift the phone...... and dial a number. Any number will make the Dias change. All numbers are also assigned to specific sound documents: clips form rare interviews and the complete sound-re-enactment of the Show-Bix piece ‘Omringning’ (‘Surrounding’) in five channels (a quintophonie). This was originally produced...

  1. Show and Tell

    DEFF Research Database (Denmark)

    2013-01-01

    Fredag d. 1 november blev Kunsthal Charlottenborg indtaget af performanceprogrammet Show & Tell med et bredspektret program af danske og internationale kunstnere indenfor performance-, lyd- og installationskunst. Programmet præsenterer værker, der undersøger kroppens stadig mere symbiotiske forhold...... og studienævnet på Performance-design. Show & Tell - Performance program: kl. 16.30-19 Adresse: Kunsthal Charlottenborg, Nyhavn 2, 1051 København K...

  2. Palivizumab for immunoprophylaxis of respiratory syncytial virus (RSV) bronchiolitis in high-risk infants and young children: a systematic review and additional economic modelling of subgroup analyses.

    Science.gov (United States)

    Wang, D; Bayliss, S; Meads, C

    2011-01-01

    find any relevant studies that may have been missed. The risk factors identified from the systematic review of included studies were analysed and synthesised using stata. The base-case decision tree model developed in the original HTA journal publication [Health Technol Assess 2008;12(36)] was used to derive the cost-effectiveness of immunoprophylaxis of RSV using palivizumab in different subgroups of pre-term infants and young children who are at high risk of serious morbidity from RSV infection. Cost-effective spectra of prophylaxis with palivizumab compared with no prophylaxis for children without CLD/CHD, children with CLD, children with acyanotic CHD and children with cyanotic CHD were derived. Thirteen studies were included in this analysis. Analysis of 16,128 subgroups showed that prophylaxis with palivizumab may be cost-effective [at a willingness-to-pay threshold of £30,000/quality-adjusted life-year (QALY)] for some subgroups. For example, for children without CLD or CHD, the cost-effective subgroups included children under 6 weeks old at the start of the RSV season who had at least two other risk factors that were considered in this report and were born at 24 weeks gestational age (GA) or less, but did not include children who were > 9 months old at the start of the RSV season or had a GA of > 32 weeks. For children with CLD, the cost-effective subgroups included children 21 months old at the start of the RSV season. For children with acyanotic CHD, the cost-effective subgroups included children 21 months old at the start of the RSV season. For children with cyanotic CHD, the cost-effective subgroups included children 12 months old at the start of the RSV season. The poor quality of the studies feeding numerical results into this analysis means that the true cost-effectiveness may vary considerably from that estimated here. There is a risk that the relatively high mathematical precision of the point estimates of cost-effectiveness may be quite inaccurate

  3. Combined group ECC protection and subgroup parity protection

    Science.gov (United States)

    Gara, Alan G.; Chen, Dong; Heidelberger, Philip; Ohmacht, Martin

    2013-06-18

    A method and system are disclosed for providing combined error code protection and subgroup parity protection for a given group of n bits. The method comprises the steps of identifying a number, m, of redundant bits for said error protection; and constructing a matrix P, wherein multiplying said given group of n bits with P produces m redundant error correction code (ECC) protection bits, and two columns of P provide parity protection for subgroups of said given group of n bits. In the preferred embodiment of the invention, the matrix P is constructed by generating permutations of m bit wide vectors with three or more, but an odd number of, elements with value one and the other elements with value zero; and assigning said vectors to rows of the matrix P.

  4. Null association of maternal MTHFR A1298C polymorphism with Down syndrome pregnancy: An updated meta-analysis

    Directory of Open Access Journals (Sweden)

    Vandana Rai

    2017-01-01

    Conclusion: Subgroup and sensitivity analysis results showed that this polymorphism is a risk factor for DS pregnancy in Asian populations but not in Caucasian population as well as in overall meta-analysis.

  5. Distinguishing between Subgroups of Adolescents Who Self-Harm

    Science.gov (United States)

    Hargus, Emily; Hawton, Keith; Rodham, Karen

    2009-01-01

    The differences in factors associated with subgroups of adolescents in the continuum of deliberate self-harm (DSH) phenomena were investigated. In an anonymous self-report survey of 6,020 adolescents aged 15 and 16 years, 3.2% of adolescents (5.3% females, 1.3% males) reported DSH with intent to die, 2.8% (4.3% females; 1.5% males) reported DSH…

  6. Microscopic colitis: clinical findings, topography and persistence of histopathological subgroups.

    Science.gov (United States)

    Bjørnbak, C; Engel, P J H; Nielsen, P L; Munck, L K

    2011-11-01

    Uncertainty remains on topography and persistence of histological subgroups of microscopic colitis (MC). To assess longitudinal clinical, endoscopic, histological, and therapeutic description of MC subgroups including patients with incomplete findings of MC (MCi). Retrospective review of a consecutive cohort with MC and histological reassessment of MCi. Clinical characteristics of 168 patients with lymphocytic colitis (LC), 270 with collagenous colitis (CC) and 101 with MCi were similar. At colonoscopy 95% (95% CI: 91-98%) of CC and 98% (93-100%) of LC cases had diagnostic histopathology of MC in both left and right colon. Eight and three patients had characteristics of MC only in the left and right colon, respectively. Histology findings resembling coexistence of the other MC subtype was present in 48% (40-55%) with CC and 24% (18-31%) with LC. A first diagnosis of MC was made in 49 (30%) of 164 patients only at repeat endoscopy. Another 34 of 115 (30%) with MC in the first endoscopy did not fulfil the MC criteria at repeat endoscopy. Only seven cases had a primary endoscopy without histopathological abnormalities. Fifteen percentage of MCi were reclassified as MC. Ileal inflammation was present in 33 of 81 patients. Budesonide was efficacious in all MC subgroups irrespective of bile acid malabsorption. Clinical characteristics of microscopic colitis subgroups are indistinguishable. Biopsies from the left colon suffice to exclude microscopic colitis, and the histological diagnosis of microscopic colitis is inconsistent over time. Ileal inflammation is common. The term microscopic colitis should perhaps be considered one clinical entity and include lymphocytic colitis, collagenous colitis, and incomplete findings of microscopic colitis. © 2011 Blackwell Publishing Ltd.

  7. 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.

  8. Irreducible almost simple subgroups of classical algebraic groups

    CERN Document Server

    Burness, Timothy C; Marion, Claude; Testerman, Donna M

    2015-01-01

    Let G be a simple classical algebraic group over an algebraically closed field K of characteristic p\\geq 0 with natural module W. Let H be a closed subgroup of G and let V be a nontrivial p-restricted irreducible tensor indecomposable rational KG-module such that the restriction of V to H is irreducible. In this paper the authors classify the triples (G,H,V) of this form, where V \

  9. Mood, Disability, and Quality of Life among a Subgroup of Rheumatoid Arthritis Individuals with Experiential Avoidance and Anxiety Sensitivity

    Directory of Open Access Journals (Sweden)

    S. Mehta

    2016-01-01

    Full Text Available Objective. The current study aimed to identify and characterize distinct RA subgroups based on their level of EA and AS and compares the difference among the subgroups in mood, disability, and quality of life. Methods. Individuals with chronic pain for at least 3 months were recruited from an academic rheumatoid clinic. Participants were assessed for demographic, psychosocial, and personality measures. A two-step cluster analysis was conducted to identify distinct subgroups of patients. Differences in clinical outcomes were compared using the Multivariate ANOVA based on cluster membership. Results. From a total of 223 participants, three distinct subgroups were formed based on cluster analysis. Cluster 1 (N=78 included those with low levels of both EA and AS. Cluster 2 (N=81 consisted of individuals with moderate levels of EA and low levels AS. Cluster 3 (N=64 included those with moderate levels of EA and high AS. Compared to those in Cluster 1, those in Cluster 3 had significantly higher levels of mood impairment and disability and lower quality of life (p<0.05. Significantly lower levels of mood impairment were seen in Cluster 1 compared to Cluster 2 (p<0.05. However, no significant difference in disability or quality of life was seen between the two groups. Conclusions. The three subgroups differed significantly in levels of impairment in mood, disability, and quality of life. However, levels of EA had a greater impact on disability and quality of life than AS.

  10. Mood, Disability, and Quality of Life among a Subgroup of Rheumatoid Arthritis Individuals with Experiential Avoidance and Anxiety Sensitivity.

    Science.gov (United States)

    Mehta, S; Rice, D; Janzen, S; Pope, J E; Harth, M; Shapiro, A P; Teasell, R W

    2016-01-01

    Objective. The current study aimed to identify and characterize distinct RA subgroups based on their level of EA and AS and compares the difference among the subgroups in mood, disability, and quality of life. Methods. Individuals with chronic pain for at least 3 months were recruited from an academic rheumatoid clinic. Participants were assessed for demographic, psychosocial, and personality measures. A two-step cluster analysis was conducted to identify distinct subgroups of patients. Differences in clinical outcomes were compared using the Multivariate ANOVA based on cluster membership. Results. From a total of 223 participants, three distinct subgroups were formed based on cluster analysis. Cluster 1 (N = 78) included those with low levels of both EA and AS. Cluster 2 (N = 81) consisted of individuals with moderate levels of EA and low le