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Sample records for distinct clinical subgroups

  1. Different HLA-DRB1 allele distributions in distinct clinical subgroups of sarcoidosis patients

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    Nisell Magnus

    2010-02-01

    Full Text Available Abstract Background A strong genetic influence by the MHC class II region has been reported in sarcoidosis, however in many studies with different results. This may possibly be caused by actual differences between distinct ethnic groups, too small sample sizes, or because of lack of accurate clinical subgrouping. Subjects and methods In this study we HLA typed a large patient population (n = 754 recruited from one single centre. Patients were sub-grouped into those with Löfgren's syndrome (LS (n = 302 and those without (non-Löfgren's (n = 452, and the majority of them were clinically classified into those with recovery within two years (resolving and those with signs of disease for more than two years (non-resolving. PCR was used for determination of HLA-DRB1 alleles. Swedish healthy blood donors (n = 1366 served as controls. Results There was a dramatic difference in the distribution of HLA alleles in LS compared to non-LS patients (p = 4 × 10-36. Most notably, DRB1*01, DRB1*03 and DRB1*14, clearly differed in LS and non-LS patients. In relation to disease course, DRB1*07, DRB1*14 and DRB1*15 generally associated with, while DRB1*01 and DRB1*03 protected against, a non-resolving disease. Interestingly, the clinical influence of DRB1*03 (good prognosis dominated over that of DRB1*15 (bad prognosis. Conclusions We found several significant differences between LS and non-LS patients and we therefore suggest that genetic association studies in sarcoidosis should include a careful clinical characterisation and sub-grouping of patients, in order to reveal true genetic associations. This may be particularly accurate to do in the heterogeneous non-LS group of patients.

  2. Intergroup Leadership Across Distinct Subgroups and Identities.

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    Rast, David E; Hogg, Michael A; van Knippenberg, Daan

    2018-03-01

    Resolving intergroup conflict is a significant and often arduous leadership challenge, yet existing theory and research rarely, if ever, discuss or examine this situation. Leaders confront a significant challenge when they provide leadership across deep divisions between distinct subgroups defined by self-contained identities-The challenge is to avoid provoking subgroup identity distinctiveness threat. Drawing on intergroup leadership theory, three studies were conducted to test the core hypothesis that, where identity threat exists, leaders promoting an intergroup relational identity will be better evaluated and are more effective than leaders promoting a collective identity; in the absence of threat, leaders promoting a collective identity will prevail. Studies 1 and 2 ( N = 170; N = 120) supported this general proposition. Study 3 ( N = 136) extended these findings, showing that leaders promoting an intergroup relational identity, but not a collective identity, improved intergroup attitudes when participants experienced an identity distinctiveness threat.

  3. Clinico-Epidemiological Comparison of Delusion-Prominent and Hallucination-Prominent Clinical Subgroups of Paranoid Schizophrenia.

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    Kreinin, Anatoly; Krishtul, Vladimir; Kirsh, Zvi; Menuchin, Michael

    2015-01-01

    Though hallucinations and delusions are prominent basic impairments in schizophrenia, reports of the relationship between hallucinatory and delusional symptoms among schizophrenia patients are scant. To examine the epidemiological and clinical differences between mainly hallucinatory and mainly delusional subgroups of paranoid schizophrenia patients. One hundred schizophrenia patients, paranoid type, were recruited. In a cross-sectional study, participants were divided into Mainly Hallucinatory (H) and Mainly Delusional (D) subgroups. Demographic variables were compared and clinical characteristics were evaluated using the Scale for the Assessment of Positive Symptoms, the Scale for the Assessment of Negative Symptoms, and the Clinical Global Impression Scale. The Quality-of-Life Enjoyment and Satisfaction Questionnaire-18 was used to assess quality of life. Clinically, the H group was more heterogeneous as expressed by the broader range of scores that described the clinical picture of patients in that subgroup (in 43 of 78 variables, 55.13%) and similar ranges of scores (31 of 78 variables, 39.74%) for patients in the D group. Duration of hospitalization was significantly longer in group H than in group D (p=0.047). There was no statistically significant difference between the H and D subgroups in demographic characteristics. There are distinct epidemiological and clinical differences between the H and D subgroups, with more severe positive and negative symptoms and greater functional impairment in the H group. Paranoid schizophrenia patients with prominent hallucinations have poorer prognosis and need intensive therapeutic rehabilitation beginning with onset-of-illness. Further genetic studies and comparisons of fMRI and/or PET findings are warranted to investigate additional distinctive characteristics of these subgroups.

  4. Attacking Heterogeneity in Schizophrenia by Deriving Clinical Subgroups From Widely Available Symptom Data.

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    Dickinson, Dwight; Pratt, Danielle N; Giangrande, Evan J; Grunnagle, MeiLin; Orel, Jennifer; Weinberger, Daniel R; Callicott, Joseph H; Berman, Karen F

    2018-01-13

    Previous research has identified (1) a "deficit" subtype of schizophrenia characterized by enduring negative symptoms and diminished emotionality and (2) a "distress" subtype associated with high emotionality-including anxiety, depression, and stress sensitivity. Individuals in deficit and distress categories differ sharply in development, clinical course and behavior, and show distinct biological markers, perhaps signaling different etiologies. We tested whether deficit and distress subtypes would emerge from a simple but novel data-driven subgrouping analysis, based on Positive and Negative Syndrome Scale (PANSS) negative and distress symptom dimensions, and whether subgrouping was informative regarding other facets of behavior and brain function. PANSS data, and other assessments, were available for 549 people with schizophrenia diagnoses. Negative and distress symptom composite scores were used as indicators in 2-step cluster analyses, which divided the sample into low symptom (n = 301), distress (n = 121), and deficit (n = 127) subgroups. Relative to the low-symptom group, the deficit and distress subgroups had comparably higher total PANSS symptoms (Ps symptom, cognitive and personality variables, among others. Initial analyses of functional magnetic resonance imaging (fMRI) data from a 182-participant subset of the full sample also suggested distinct patterns of neural recruitment during working memory. The field seeks more neuroscience-based systems for classifying psychiatric conditions, but these are inescapably behavioral disorders. More effective parsing of clinical and behavioral traits could identify homogeneous target groups for further neural system and molecular studies, helping to integrate clinical and neuroscience approaches. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center 2017.

  5. Germ cell tumours in neonates and infants: a distinct subgroup?

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    Veltman, I.M.; Schepens, M.T.M.; Looijenga, L.H.J.; Strong, L.C.; Geurts van Kessel, A.H.M.

    2003-01-01

    Human germ cell tumours (GCTs) constitute a heterogeneous group of tumours that can be classified into four major subgroups. One of these subgroups encompasses (immature) teratomas and yolk sac tumours of patients under the age of 5 years. In this paper we review the various clinical, histological

  6. Subgroup analyses in confirmatory clinical trials: time to be specific about their purposes

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    Julien Tanniou

    2016-02-01

    Full Text Available Abstract Background It is well recognized that treatment effects may not be homogeneous across the study population. Subgroup analyses constitute a fundamental step in the assessment of evidence from confirmatory (Phase III clinical trials, where conclusions for the overall study population might not hold. Subgroup analyses can have different and distinct purposes, requiring specific design and analysis solutions. It is relevant to evaluate methodological developments in subgroup analyses against these purposes to guide health care professionals and regulators as well as to identify gaps in current methodology. Methods We defined four purposes for subgroup analyses: (1 Investigate the consistency of treatment effects across subgroups of clinical importance, (2 Explore the treatment effect across different subgroups within an overall non-significant trial, (3 Evaluate safety profiles limited to one or a few subgroup(s, (4 Establish efficacy in the targeted subgroup when included in a confirmatory testing strategy of a single trial. We reviewed the methodology in line with this “purpose-based” framework. The review covered papers published between January 2005 and April 2015 and aimed to classify them in none, one or more of the aforementioned purposes. Results In total 1857 potentially eligible papers were identified. Forty-eight papers were selected and 20 additional relevant papers were identified from their references, leading to 68 papers in total. Nineteen were dedicated to purpose 1, 16 to purpose 4, one to purpose 2 and none to purpose 3. Seven papers were dedicated to more than one purpose, the 25 remaining could not be classified unambiguously. Purposes of the methods were often not specifically indicated, methods for subgroup analysis for safety purposes were almost absent and a multitude of diverse methods were developed for purpose (1. Conclusions It is important that researchers developing methodology for subgroup analysis

  7. Cytogenetic prognostication within medulloblastoma subgroups.

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    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

    2014-03-20

    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. 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. 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. 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.

  8. Cluster Analysis of Clinical Data Identifies Fibromyalgia Subgroups

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

    2013-01-01

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

  9. 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.

  10. Clinically distinct trajectories of fatigue and their longitudinal relationship with the disturbance of personal goals following a cancer diagnosis

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    Müller, Fabiola; Tuinman, Marrit A.; Janse, Moniek; Almansa, Josué; Sprangers, Mirjam A. G.; Smink, Ans; Ranchor, Adelita V.; Fleer, Joke; Hagedoorn, Mariët

    Objectives. Most studies on fatigue in patients with cancer aggregate its prevalence and severity on a group level, ignoring the possibility that subgroups of patients may differ widely in their development of fatigue. This study aimed to identify subgroups of patients with clinically distinct

  11. Comprehensive profiling of DNA methylation in colorectal cancer reveals subgroups with distinct clinicopathological and molecular features

    International Nuclear Information System (INIS)

    Ang, Pei Woon; Soong, Richie; Loh, Marie; Liem, Natalia; Lim, Pei Li; Grieu, Fabienne; Vaithilingam, Aparna; Platell, Cameron; Yong, Wei Peng; Iacopetta, Barry

    2010-01-01

    Most previous studies of the CpG island methylator phenotype (CIMP) in colorectal cancer (CRC) have been conducted on a relatively small numbers of CpG sites. In the present study we performed comprehensive DNA methylation profiling of CRC with the aim of characterizing CIMP subgroups. DNA methylation at 1,505 CpG sites in 807 cancer-related genes was evaluated using the Illumina GoldenGate ® methylation array in 28 normal colonic mucosa and 91 consecutive CRC samples. Methylation data was analyzed using unsupervised hierarchical clustering. CIMP subgroups were compared for various clinicopathological and molecular features including patient age, tumor site, microsatellite instability (MSI), methylation at a consensus panel of CpG islands and mutations in BRAF and KRAS. A total of 202 CpG sites were differentially methylated between tumor and normal tissue. Unsupervised hierarchical clustering of methylation data from these sites revealed the existence of three CRC subgroups referred to as CIMP-low (CIMP-L, 21% of cases), CIMP-mid (CIMP-M, 14%) and CIMP-high (CIMP-H, 65%). In comparison to CIMP-L tumors, CIMP-H tumors were more often located in the proximal colon and showed more frequent mutation of KRAS and BRAF (P < 0.001). Comprehensive DNA methylation profiling identified three CRC subgroups with distinctive clinicopathological and molecular features. This study suggests that both KRAS and BRAF mutations are involved with the CIMP-H pathway of CRC rather than with distinct CIMP subgroups

  12. Comprehensive profiling of DNA methylation in colorectal cancer reveals subgroups with distinct clinicopathological and molecular features

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    Vaithilingam Aparna

    2010-05-01

    Full Text Available Abstract Background Most previous studies of the CpG island methylator phenotype (CIMP in colorectal cancer (CRC have been conducted on a relatively small numbers of CpG sites. In the present study we performed comprehensive DNA methylation profiling of CRC with the aim of characterizing CIMP subgroups. Methods DNA methylation at 1,505 CpG sites in 807 cancer-related genes was evaluated using the Illumina GoldenGate® methylation array in 28 normal colonic mucosa and 91 consecutive CRC samples. Methylation data was analyzed using unsupervised hierarchical clustering. CIMP subgroups were compared for various clinicopathological and molecular features including patient age, tumor site, microsatellite instability (MSI, methylation at a consensus panel of CpG islands and mutations in BRAF and KRAS. Results A total of 202 CpG sites were differentially methylated between tumor and normal tissue. Unsupervised hierarchical clustering of methylation data from these sites revealed the existence of three CRC subgroups referred to as CIMP-low (CIMP-L, 21% of cases, CIMP-mid (CIMP-M, 14% and CIMP-high (CIMP-H, 65%. In comparison to CIMP-L tumors, CIMP-H tumors were more often located in the proximal colon and showed more frequent mutation of KRAS and BRAF (P Conclusions Comprehensive DNA methylation profiling identified three CRC subgroups with distinctive clinicopathological and molecular features. This study suggests that both KRAS and BRAF mutations are involved with the CIMP-H pathway of CRC rather than with distinct CIMP subgroups.

  13. CD30 expression defines a novel subgroup of diffuse large B-cell lymphoma with favorable prognosis and distinct gene expression signature

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    Hu, Shimin; Xu-Monette, Zijun Y; Balasubramanyam, Aarthi

    2013-01-01

    CD30, originally identified as a cell-surface marker of Reed-Sternberg and Hodgkin cells of classical Hodgkin lymphoma, is also expressed by several types of non-Hodgkin lymphoma, including a subset of diffuse large B-cell lymphoma (DLBCL). However, the prognostic and biological importance of CD3...... value of CD30 as a therapeutic target for brentuximab vedotin in ongoing successful clinical trials, it seems appropriate to consider CD30(+) DLBCL as a distinct subgroup of DLBCL....

  14. Molecular subgroups of medulloblastoma

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

    2012-01-01

    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 understand...

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

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    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

  16. Intense imagery movements: a common and distinct paediatric subgroup of motor stereotypies.

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    Robinson, Sally; Woods, Martin; Cardona, Francesco; Baglioni, Valentina; Hedderly, Tammy

    2014-12-01

    The aim of this article is to describe a subgroup of children who presented with stereotyped movements in the context of episodes of intense imagery. This is of relevance to current discussions regarding the clinical usefulness of diagnosing motor stereotypies during development. The sample consisted of 10 children (nine males, one female; mean age 8y 6mo [SD 2y 5mo], range 6-15y). Referrals were from acute paediatricians, neurologists, and tertiary epilepsy services. Children were assessed by multidisciplinary teams with expertise in paediatric movement disorders. Stereotypies presented as paroxysmal complex movements involving upper and lower limbs. Imagery themes typically included computer games (60%), cartoons/films (40%), and fantasy scenes (30%). Comorbid developmental difficulties were reported for 80% of children. Brain imaging and electrophysiological investigations had been conducted for 50% of the children before referral to the clinic. The descriptive term 'intense imagery movements' (IIM) was applied if (after interview) the children reported engaging in acts of imagery while performing stereotyped movements. We believe these children may form a common and discrete stereotypy subgroup, with the concept of IIM being clinically useful to ensure the accurate diagnosis and clinical management of this paediatric movement disorder. © 2014 Mac Keith Press.

  17. Integrative genome-wide expression profiling identifies three distinct molecular subgroups of renal cell carcinoma with different patient outcome

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    Beleut Manfred

    2012-07-01

    Full Text Available Abstract Background Renal cell carcinoma (RCC is characterized by a number of diverse molecular aberrations that differ among individuals. Recent approaches to molecularly classify RCC were based on clinical, pathological as well as on single molecular parameters. As a consequence, gene expression patterns reflecting the sum of genetic aberrations in individual tumors may not have been recognized. In an attempt to uncover such molecular features in RCC, we used a novel, unbiased and integrative approach. Methods We integrated gene expression data from 97 primary RCC of different pathologic parameters, 15 RCC metastases as well as 34 cancer cell lines for two-way nonsupervised hierarchical clustering using gene groups suggested by the PANTHER Classification System. We depicted the genomic landscape of the resulted tumor groups by means of Single Nuclear Polymorphism (SNP technology. Finally, the achieved results were immunohistochemically analyzed using a tissue microarray (TMA composed of 254 RCC. Results We found robust, genome wide expression signatures, which split RCC into three distinct molecular subgroups. These groups remained stable even if randomly selected gene sets were clustered. Notably, the pattern obtained from RCC cell lines was clearly distinguishable from that of primary tumors. SNP array analysis demonstrated differing frequencies of chromosomal copy number alterations among RCC subgroups. TMA analysis with group-specific markers showed a prognostic significance of the different groups. Conclusion We propose the existence of characteristic and histologically independent genome-wide expression outputs in RCC with potential biological and clinical relevance.

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

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    Arno eVan Dam

    2016-02-01

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

  19. 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

  20. Pain modulatory phenotypes differentiate subgroups with different clinical and experimental pain sensitivity

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    Vaegter, Henrik B.; Graven-Nielsen, Thomas

    2016-01-01

    between subgroups. Cuff algometry was performed on lower legs in 400 chronic pain patients to assess pressure pain threshold (cPPT), pressure pain tolerance (cPTT), temporal summation of pain (TSP: increase in pain scores to ten repeated stimulations), and conditioned pain modulation (CPM: increase in c......PPT during cuff pain conditioning on the contralateral leg). Heat detection (HDT) and heat pain thresholds (HPT) at clinical painful and non-painful body areas were assessed. Based on TSP and CPM four distinct groups were formed: Group 1 (n=85) had impaired CPM and facilitated TSP. Group 2 (n=148) had...... impaired CPM and normal TSP. Group 3 (n=45) had normal CPM and facilitated TSP. Group 4 (n=122) had normal CPM and normal TSP. Group 1 showed more pain regions compared with the other three groups (PCPM and facilitated TSP plays an important role in widespread pain. Group 1...

  1. Histopathological subgroups in knee osteoarthritis.

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    Wyatt, L A; Moreton, B J; Mapp, P I; Wilson, D; Hill, R; Ferguson, E; Scammell, B E; Walsh, D A

    2017-01-01

    Osteoarthritis (OA) is a heterogeneous, multi-tissue disease. We hypothesised that different histopathological features characterise different stages during knee OA progression, and that discrete subgroups can be defined based on validated measures of OA histopathological features. Medial tibial plateaux and synovium were from 343 post-mortem (PM) and 143 OA arthroplasty donations. A 'chondropathy/osteophyte' group (n = 217) was classified as PM cases with osteophytes or macroscopic medial tibiofemoral chondropathy lesions ≥grade 3 to represent pre-surgical (early) OA. 'Non-arthritic' controls (n = 48) were identified from the remaining PM cases. Mankin histopathological scores were subjected to Rasch analysis and supplemented with histopathological scores for subchondral bone marrow replacement and synovitis. Item weightings were derived by principle components analysis (PCA). Histopathological subgroups were sought using latent class analysis (LCA). Chondropathy, synovitis and osteochondral pathology were each associated with OA at arthroplasty, but each was also identified in some 'non-arthritic' controls. Tidemark breaching in the chondropathy/osteophyte group was greater than in non-arthritic controls. Three histopathological subgroups were identified, characterised as 'mild OA', or 'severe OA' with mild or moderate/severe synovitis. Presence and severity of synovitis helps define distinct histopathological OA subgroups. The absence of a discrete 'normal' subgroup indicates a pathological continuum between normality and OA status. Identifying specific pathological processes and their clinical correlates in OA subgroups has potential to accelerate the development of more effective therapies. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

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

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    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

  3. Treatment implications of posterior fossa ependymoma subgroups.

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    Ramaswamy, Vijay; Taylor, Michael D

    2016-11-15

    Posterior fossa ependymoma comprises two distinct molecular entities, ependymoma_posterior fossa A (EPN_PFA) and ependymoma_posterior fossa B (EPN_PFB), with differentiable gene expression profiles. As yet, the response of the two entities to treatment is unclear. To determine the relationship between the two molecular subgroups of posterior fossa ependymoma and treatment, we studied a cohort of 820 patients with molecularly profiled, clinically annotated posterior fossa ependymomas. We found that the strongest predictor of poor outcome in patients with posterior fossa ependymoma across the entire age spectrum was molecular subgroup EPN_PFA, which was recently reported in the paper entitled "Therapeutic impact of cytoreductive surgery and irradiation of posterior fossa ependymoma in the molecular era: a retrospective multicohort analysis" in the Journal of Clinical Oncology. Patients with incompletely resected EPN_PFA tumors had a very poor outcome despite receiving adjuvant radiation therapy, whereas a substantial proportion of patients with EPN_PFB tumors can be cured with surgery alone.

  4. Post hoc subgroups in clinical trials: Anathema or analytics?

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    Weisberg, Herbert I; Pontes, Victor P

    2015-08-01

    There is currently much interest in generating more individualized estimates of treatment effects. However, traditional statistical methods are not well suited to this task. Post hoc subgroup analyses of clinical trials are fraught with methodological problems. We suggest that the alternative research paradigm of predictive analytics, widely used in many business contexts, can be adapted to help. We compare the statistical and analytics perspectives and suggest that predictive modeling should often replace subgroup analysis. We then introduce a new approach, cadit modeling, that can be useful to identify and test individualized causal effects. The cadit technique is particularly useful in the context of selecting from among a large number of potential predictors. We describe a new variable-selection algorithm that has been applied in conjunction with cadit. The cadit approach is illustrated through a reanalysis of data from the Randomized Aldactone Evaluation Study trial, which studied the efficacy of spironolactone in heart-failure patients. The trial was successful, but a serious adverse effect (hyperkalemia) was subsequently discovered. Our reanalysis suggests that it may be possible to predict the degree of hyperkalemia based on a logistic model and to identify a subgroup in which the effect is negligible. Cadit modeling is a promising alternative to subgroup analyses. Cadit regression is relatively straightforward to implement, generates results that are easy to present and explain, and can mesh straightforwardly with many variable-selection algorithms. © The Author(s) 2015.

  5. 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.

  6. Genetically meaningful phenotypic subgroups in autism spectrum disorders.

    Science.gov (United States)

    Veatch, O J; Veenstra-Vanderweele, J; Potter, M; Pericak-Vance, M A; Haines, J L

    2014-03-01

    Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with strong evidence for genetic susceptibility. However, the effect sizes for implicated chromosomal loci are small, hard to replicate and current evidence does not explain the majority of the estimated heritability. Phenotypic heterogeneity could be one phenomenon complicating identification of genetic factors. We used data from the Autism Diagnostic Interview-Revised, Autism Diagnostic Observation Schedule, Vineland Adaptive Behavior Scales, head circumferences, and ages at exams as classifying variables to identify more clinically similar subgroups of individuals with ASD. We identified two distinct subgroups of cases within the Autism Genetic Resource Exchange dataset, primarily defined by the overall severity of evaluated traits. In addition, there was significant familial clustering within subgroups (odds ratio, OR ≈ 1.38-1.42, P definition that should increase power to detect genetic factors influencing risk for ASD. © 2013 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  7. 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 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.

  8. Identification of subgroups among fibromyalgia patients.

    Science.gov (United States)

    Auvinet, B; Chaleil, D

    2012-09-28

    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.

  9. Identification of subgroups among fibromyalgia patients

    Directory of Open Access Journals (Sweden)

    D. Chaleil

    2012-09-01

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

  10. 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.

  11. Clinically distinct trajectories of fatigue and their longitudinal relationship with the disturbance of personal goals following a cancer diagnosis.

    Science.gov (United States)

    Müller, Fabiola; Tuinman, Marrit A; Janse, Moniek; Almansa, Josué; Sprangers, Mirjam A G; Smink, Ans; Ranchor, Adelita V; Fleer, Joke; Hagedoorn, Mariët

    2017-09-01

    Most studies on fatigue in patients with cancer aggregate its prevalence and severity on a group level, ignoring the possibility that subgroups of patients may differ widely in their development of fatigue. This study aimed to identify subgroups of patients with clinically distinct trajectories of fatigue from diagnosis to 18 months post-diagnosis. As fatigue might trigger goal disturbance, the study also identified trajectories of concrete and abstract goal disturbance and longitudinally examined their co-occurrence with fatigue. Prospective design with quantitative and qualitative method of data collection. Patients with colorectal cancer (n = 183) reported on their levels of fatigue and goal disturbance shortly after diagnosis (T 1 ) and at 7 months (T 2 ) and 18 months (T 3 ) post-diagnosis. Growth mixture model analyses were performed to identify trajectories of fatigue and goal disturbance. Guidelines for the clinical relevance of fatigue were applied. Four clinically distinct trajectories of fatigue were identified as follows: (1) persistent severe fatigue (25.4%), (2) moderate fatigue (56.1%), (3) no fatigue (13.8%), and (4) rapidly improving fatigue (4.7%). The majority of patients with cancer reported high disturbance of their concrete goals, while high disturbance of abstract goals was less evident. Fatigue and concrete goal disturbance co-occurred longitudinally. The fatigue and goal disturbance experienced from diagnosis to 18 months post-diagnosis differ considerably for subgroups of patients with cancer. Fatigue and concrete goal disturbance are persistent burdens in the majority of patients. Investigating symptom burden beyond average trends can guide clinicians to identify patients most in need for treatment. Targeting goal disturbance might benefit the psychological well-being in patients suffering from persistent symptoms. Statement of contribution What is already known on this subject? Fatigue is a common and distressing symptom at all

  12. Are estimates of meaningful decline in mobility performance consistent among clinically important subgroups? (Health ABC Study).

    NARCIS (Netherlands)

    Perera, S.; Studenski, S.; Newman, A.; Simonsick, E.; Harris, T.; Schwartz, A.; Visser, M.

    2014-01-01

    Background: Meaningful change criteria help determine if function has improved or declined, but their magnitudes may vary across clinically relevant subgroups. We estimate meaningful decline in four common measures of physical performance in subgroups of older adults based on initial performance,

  13. Research methods for subgrouping low back pain

    DEFF Research Database (Denmark)

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

    2010-01-01

    important distinctions in their treatment needs or prognoses. Due to a proliferation of research methods and variability in how subgrouping results are interpreted, it is timely to open discussion regarding a conceptual framework for the research designs and statistical methods available for subgrouping...... 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...... the strengths and limitations of research methods suitable for the hypothesis-setting phase of subgroup studies....

  14. Type 2 diabetes: identifying high risk Asian American subgroups in a clinical population.

    Science.gov (United States)

    Wang, Elsie J; Wong, Eric C; Dixit, Anjali A; Fortmann, Stephen P; Linde, Randolph B; Palaniappan, Latha P

    2011-08-01

    We compared the prevalence and treatment of type 2 diabetes across Asian American subgroups (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese) and Non-Hispanic Whites (NHWs) in a Northern California healthcare system. A three-year, cross-sectional sample of patient electronic health records was accessed to compare diabetes prevalence in 21,816 Asian and 73,728 NHWs aged 35+ years. Diabetes was classified through ICD-9 codes, abnormal laboratory values, or use of oral anti-diabetic medication. Multivariate adjusted prevalence rates for each Asian subgroup, and adjusted odds ratios (OR) relative to NHWs, were compared. Age-adjusted prevalence ranged from 5.8% to 18.2% (women) and 8.1 to 25.3% (men). Age-adjusted ORs of Asian subgroups ranged 1.11-3.94 (women) and 1.14-4.56 (men). The odds of diabetes were significantly higher in Asian Indians (women OR 3.44, men OR 3.54) and Filipinos (women OR 3.94, men OR 4.56), compared to NHWs. Results for Asian Indians and Filipinos were similar with age-and-BMI adjustment. Treatment rates across subgroups were 59.7-82.0% (women) and 62.9-79.4% (men). Heterogeneity exists in the prevalence of diabetes across Asian subgroups, independent of obesity prevalence. Asian Indian and Filipino subgroups had particularly high prevalence of diabetes when compared to NHWs. Future studies should explore these clinically important differences among Asian subgroups. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  15. Extended phenotype and clinical subgroups in unilateral Meniere disease: A cross-sectional study with cluster analysis.

    Science.gov (United States)

    Frejo, L; Martin-Sanz, E; Teggi, R; Trinidad, G; Soto-Varela, A; Santos-Perez, S; Manrique, R; Perez, N; Aran, I; Almeida-Branco, M S; Batuecas-Caletrio, A; Fraile, J; Espinosa-Sanchez, J M; Perez-Guillen, V; Perez-Garrigues, H; Oliva-Dominguez, M; Aleman, O; Benitez, J; Perez, P; Lopez-Escamez, J A

    2017-12-01

    To define clinical subgroups by cluster analysis in patients with unilateral Meniere disease (MD) and to compare them with the clinical subgroups found in bilateral MD. A cross-sectional study with a two-step cluster analysis. A tertiary referral multicenter study. Nine hundred and eighty-eight adult patients with unilateral MD. best predictors to define clinical subgroups with potential different aetiologies. We established five clusters in unilateral MD. Group 1 is the most frequently found, includes 53% of patients, and it is defined as the sporadic, classic MD without migraine and without autoimmune disorder (AD). Group 2 is found in 8% of patients, and it is defined by hearing loss, which antedates the vertigo episodes by months or years (delayed MD), without migraine or AD in most of cases. Group 3 involves 13% of patients, and it is considered familial MD, while group 4, which includes 15% of patients, is linked to the presence of migraine in all cases. Group 5 is found in 11% of patients and is defined by a comorbid AD. We found significant differences in the distribution of AD in clusters 3, 4 and 5 between patients with uni- and bilateral MD. Cluster analysis defines clinical subgroups in MD, and it extends the phenotype beyond audiovestibular symptoms. This classification will help to improve the phenotyping in MD and facilitate the selection of patients for randomised clinical trials. © 2017 John Wiley & Sons Ltd.

  16. Compositionally and functionally distinct sinus microbiota in chronic rhinosinusitis patients have immunological and clinically divergent consequences.

    Science.gov (United States)

    Cope, Emily K; Goldberg, Andrew N; Pletcher, Steven D; Lynch, Susan V

    2017-05-12

    Chronic rhinosinusitis (CRS) is a heterogeneous disease characterized by persistent sinonasal inflammation and sinus microbiome dysbiosis. The basis of this heterogeneity is poorly understood. We sought to address the hypothesis that a limited number of compositionally distinct pathogenic bacterial microbiota exist in CRS patients and invoke discrete immune responses and clinical phenotypes in CRS patients. Sinus brushings from patients with CRS (n = 59) and healthy individuals (n = 10) collected during endoscopic sinus surgery were analyzed using 16S rRNA gene sequencing, predicted metagenomics, and RNA profiling of the mucosal immune response. We show that CRS patients cluster into distinct sub-groups (DSI-III), each defined by specific pattern of bacterial co-colonization (permutational multivariate analysis of variance (PERMANOVA); p = 0.001, r 2  = 0.318). Each sub-group was typically dominated by a pathogenic family: Streptococcaceae (DSI), Pseudomonadaceae (DSII), Corynebacteriaceae [DSIII(a)], or Staphylococcaceae [DSIII(b)]. Each pathogenic microbiota was predicted to be functionally distinct (PERMANOVA; p = 0.005, r 2  = 0.217) and encode uniquely enriched gene pathways including ansamycin biosynthesis (DSI), tryptophan metabolism (DSII), two-component response [DSIII(b)], and the PPAR-γ signaling pathway [DSIII(a)]. Each is also associated with significantly distinct host immune responses; DSI, II, and III(b) invoked a variety of pro-inflammatory, T H 1 responses, while DSIII(a), which exhibited significantly increased incidence of nasal polyps (Fisher's exact; p = 0.034, relative risk = 2.16), primarily induced IL-5 expression (Kruskal Wallis; q = 0.045). A large proportion of CRS patient heterogeneity may be explained by the composition of their sinus bacterial microbiota and related host immune response-features which may inform strategies for tailored therapy in this patient population.

  17. Two subgroups of antipsychotic-naive, first-episode schizophrenia patients identified with a Gaussian mixture model on cognition and electrophysiology

    DEFF Research Database (Denmark)

    Bak, N.; Ebdrup, B.H.; Oranje, B

    2017-01-01

    Deficits in information processing and cognition are among the most robust findings in schizophrenia patients. Previous efforts to translate group-level deficits into clinically relevant and individualized information have, however, been non-successful, which is possibly explained by biologically...... different disease subgroups. We applied machine learning algorithms on measures of electrophysiology and cognition to identify potential subgroups of schizophrenia. Next, we explored subgroup differences regarding treatment response. Sixty-six antipsychotic-naive first-episode schizophrenia patients...... be used to classify subgroups of schizophrenia patients. The two distinct subgroups, which we identified, were psychopathologically inseparable before treatment, yet their response to dopaminergic blockade was predicted with significant accuracy. This proof of principle encourages further endeavors...

  18. 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.

  19. Molecular subgroups of medulloblastoma identification using noninvasive magnetic resonance spectroscopy.

    Science.gov (United States)

    Blüml, Stefan; Margol, Ashley S; Sposto, Richard; Kennedy, Rebekah J; Robison, Nathan J; Vali, Marzieh; Hung, Long T; Muthugounder, Sakunthala; Finlay, Jonathan L; Erdreich-Epstein, Anat; Gilles, Floyd H; Judkins, Alexander R; Krieger, Mark D; Dhall, Girish; Nelson, Marvin D; Asgharzadeh, Shahab

    2016-01-01

    Medulloblastomas in children can be categorized into 4 molecular subgroups with differing clinical characteristics, such that subgroup determination aids in prognostication and risk-adaptive treatment strategies. Magnetic resonance spectroscopy (MRS) is a widely available, noninvasive tool that is used to determine the metabolic characteristics of tumors and provide diagnostic information without the need for tumor tissue. In this study, we investigated the hypothesis that metabolite concentrations measured by MRS would differ between molecular subgroups of medulloblastoma and allow accurate subgroup determination. MRS was used to measure metabolites in medulloblastomas across molecular subgroups (SHH = 12, Groups 3/4 = 17, WNT = 1). Levels of 14 metabolites were analyzed to determine those that were the most discriminant for medulloblastoma subgroups in order to construct a multivariable classifier for distinguishing between combined Group 3/4 and SHH tumors. Medulloblastomas across molecular subgroups revealed distinct spectral features. Group 3 and Group 4 tumors demonstrated metabolic profiles with readily detectable taurine, lower levels of lipids, and high levels of creatine. SHH tumors showed prominent choline and lipid with low levels of creatine and little or no evidence of taurine. A 5-metabolite subgroup classifier inclusive of creatine, myo-inositol, taurine, aspartate, and lipid 13a was developed that could discriminate between Group 3/4 and SHH medulloblastomas with excellent accuracy (cross-validated area under the curve [AUC] = 0.88). The data show that medulloblastomas of Group 3/4 differ metabolically as measured using MRS when compared with SHH molecular subgroups. MRS is a useful and accurate tool to determine medulloblastoma molecular subgroups. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  20. Subgroup analyses in confirmatory clinical trials: time to be specific about their purposes

    NARCIS (Netherlands)

    Tanniou, J.; Tweel, I. van der; Teerenstra, S.; Roes, K.C.

    2016-01-01

    BACKGROUND: It is well recognized that treatment effects may not be homogeneous across the study population. Subgroup analyses constitute a fundamental step in the assessment of evidence from confirmatory (Phase III) clinical trials, where conclusions for the overall study population might not hold.

  1. 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

    ). 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). METHODS: 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...... classify individuals into those subgroups. CONCLUSIONS: Our subjective judgement was that Latent Gold offered the best balance of sensitivity to subgroups, ease of use and presentation of results with these datasets but we recognise that different clustering methods may suit other types of data...

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

    Science.gov (United States)

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

    2014-02-01

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

  3. 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 LBP is a complex multi-domain condition, the optimal approach when using LCA is unknown. Therefore, this paper describes the exploration of two approaches to LCA that may help improve the identification of clinically relevant and interpretable LBP subgroups. METHODS: From 928 LBP patients consulting...... of statistical performance measures, qualitative evaluation of clinical interpretability (face validity) and a subgroup membership comparison. RESULTS: For the single-stage LCA, a model solution with seven patient subgroups was preferred, and for the two-stage LCA, a nine patient subgroup model. Both approaches...

  4. Subgroups of musculoskeletal pain patients and their psychobiological patterns - the LOGIN study protocol.

    Science.gov (United States)

    Gerhardt, Andreas; Hartmann, Mechthild; Tesarz, Jonas; Janke, Susanne; Leisner, Sabine; Seidler, Günter; Eich, Wolfgang

    2012-08-03

    Pain conditions of the musculoskeletal system are very common and have tremendous socioeconomic impact. Despite its high prevalence, musculoskeletal pain remains poorly understood and predominantly non-specifically and insufficiently treated.The group of chronic musculoskeletal pain patients is supposed to be heterogeneous, due to a multitude of mechanisms involved in chronic pain. Psychological variables, psychophysiological processes, and neuroendocrine alterations are expected to be involved. Thus far, studies on musculoskeletal pain have predominantly focused on the general aspects of pain processing, thus neglecting the heterogeneity of patients with musculoskeletal pain. Consequently, there is a need for studies that comprise a multitude of mechanisms that are potentially involved in the chronicity and spread of pain. This need might foster research and facilitate a better pathophysiological understanding of the condition, thereby promoting the development of specific mechanism-based treatments for chronic pain. Therefore, the objectives of this study are as follows: 1) identify and describe subgroups of patients with musculoskeletal pain with regard to clinical manifestations (including mental co-morbidity) and 2) investigate whether distinct sensory profiles or 3) distinct plasma levels of pain-related parameters due to different underlying mechanisms can be distinguished in various subgroups of pain patients. We will examine a population-based chronic pain sample (n = 100), a clinical tertiary care sample (n = 100) and pain-free patients with depression or post-traumatic stress disorder and pain-free healthy controls (each n = 30, respectively). The samples will be pain localisation matched by sex and age to the population-based sample. Patients will undergo physical examination and thorough assessments of mental co-morbidity (including psychological trauma), perceptual and central sensitisation (quantitative sensory testing), descending

  5. Cluster subgroups based on overall pressure pain sensitivity and psychosocial factors in chronic musculoskeletal pain: Differences in clinical outcomes.

    Science.gov (United States)

    Almeida, Suzana C; George, Steven Z; Leite, Raquel D V; Oliveira, Anamaria S; Chaves, Thais C

    2018-05-17

    We aimed to empirically derive psychosocial and pain sensitivity subgroups using cluster analysis within a sample of individuals with chronic musculoskeletal pain (CMP) and to investigate derived subgroups for differences in pain and disability outcomes. Eighty female participants with CMP answered psychosocial and disability scales and were assessed for pressure pain sensitivity. A cluster analysis was used to derive subgroups, and analysis of variance (ANOVA) was used to investigate differences between subgroups. Psychosocial factors (kinesiophobia, pain catastrophizing, anxiety, and depression) and overall pressure pain threshold (PPT) were entered into the cluster analysis. Three subgroups were empirically derived: cluster 1 (high pain sensitivity and high psychosocial distress; n = 12) characterized by low overall PPT and high psychosocial scores; cluster 2 (high pain sensitivity and intermediate psychosocial distress; n = 39) characterized by low overall PPT and intermediate psychosocial scores; and cluster 3 (low pain sensitivity and low psychosocial distress; n = 29) characterized by high overall PPT and low psychosocial scores compared to the other subgroups. Cluster 1 showed higher values for mean pain intensity (F (2,77)  = 10.58, p cluster 3, and cluster 1 showed higher values for disability (F (2,77)  = 3.81, p = 0.03) compared with both clusters 2 and 3. Only cluster 1 was distinct from cluster 3 according to both pain and disability outcomes. Pain catastrophizing, depression, and anxiety were the psychosocial variables that best differentiated the subgroups. Overall, these results call attention to the importance of considering pain sensitivity and psychosocial variables to obtain a more comprehensive characterization of CMP patients' subtypes.

  6. 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

  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

    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...

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

    NARCIS (Netherlands)

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

    1993-01-01

    Objective: 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. Design: Randomized clinical trial (subgroup

  9. Distinct Evening Fatigue Profiles in Oncology Outpatients Receiving Chemotherapy

    Science.gov (United States)

    Wright, Fay; Cooper, Bruce A.; Conley, Yvette P.; Hammer, Marilyn J.; Chen, Lee-May; Paul, Steven M.; Levine, Jon D.; Miaskowski, Christine; Kober, Kord M.

    2018-01-01

    Background Fatigue is the most common and debilitating symptom experienced by oncology patients during chemotherapy (CTX). Fatigue severity demonstrates a large amount of inter-individual and diurnal variability. Purpose Study purposes were to evaluate for subgroups of patients with distinct evening fatigue profiles and evaluate how these subgroups differed on demographic, clinical, and symptom characteristics. Methods Outpatients with breast, gastrointestinal, gynecological, or lung cancer (n=1332) completed questionnaires six times over two cycles of CTX. Lee Fatigue Scale (LFS) evaluated evening fatigue severity. Latent profile analysis was used to identify distinct evening fatigue profiles. Results Four distinct evening fatigue classes (i.e., Low (14.0%), Moderate (17.2%), High (36.0%), Very High (32.8%)) were identified. Compared to the Low class, patients in the Very High evening fatigue class were: younger, female, had childcare responsibilities, had more years of education, had a lower functional status, had a higher comorbidity burden, and were diagnosed with breast cancer. Patients in the Very High class reported higher levels of depressive symptoms, sleep disturbance, and evening fatigue at enrollment. Conclusions Findings provide new insights into modifiable risk factors for higher levels of evening fatigue. Clinicians can use this information to identify higher risk patients and plan appropriate interventions. PMID:29725554

  10. Fecal metagenomic profiles in subgroups of patients with myalgic encephalomyelitis/chronic fatigue syndrome.

    Science.gov (United States)

    Nagy-Szakal, Dorottya; Williams, Brent L; Mishra, Nischay; Che, Xiaoyu; Lee, Bohyun; Bateman, Lucinda; Klimas, Nancy G; Komaroff, Anthony L; Levine, Susan; Montoya, Jose G; Peterson, Daniel L; Ramanan, Devi; Jain, Komal; Eddy, Meredith L; Hornig, Mady; Lipkin, W Ian

    2017-04-26

    Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by unexplained persistent fatigue, commonly accompanied by cognitive dysfunction, sleeping disturbances, orthostatic intolerance, fever, lymphadenopathy, and irritable bowel syndrome (IBS). The extent to which the gastrointestinal microbiome and peripheral inflammation are associated with ME/CFS remains unclear. We pursued rigorous clinical characterization, fecal bacterial metagenomics, and plasma immune molecule analyses in 50 ME/CFS patients and 50 healthy controls frequency-matched for age, sex, race/ethnicity, geographic site, and season of sampling. Topological analysis revealed associations between IBS co-morbidity, body mass index, fecal bacterial composition, and bacterial metabolic pathways but not plasma immune molecules. IBS co-morbidity was the strongest driving factor in the separation of topological networks based on bacterial profiles and metabolic pathways. Predictive selection models based on bacterial profiles supported findings from topological analyses indicating that ME/CFS subgroups, defined by IBS status, could be distinguished from control subjects with high predictive accuracy. Bacterial taxa predictive of ME/CFS patients with IBS were distinct from taxa associated with ME/CFS patients without IBS. Increased abundance of unclassified Alistipes and decreased Faecalibacterium emerged as the top biomarkers of ME/CFS with IBS; while increased unclassified Bacteroides abundance and decreased Bacteroides vulgatus were the top biomarkers of ME/CFS without IBS. Despite findings of differences in bacterial taxa and metabolic pathways defining ME/CFS subgroups, decreased metabolic pathways associated with unsaturated fatty acid biosynthesis and increased atrazine degradation pathways were independent of IBS co-morbidity. Increased vitamin B6 biosynthesis/salvage and pyrimidine ribonucleoside degradation were the top metabolic pathways in ME/CFS without IBS as well as in the

  11. Contesting the science/ethics distinction in the review of clinical research

    Science.gov (United States)

    Dawson, Angus J; Yentis, Steve M

    2007-01-01

    Recent policy in relation to clinical research proposals in the UK has distinguished between two types of review: scientific and ethical. This distinction has been formally enshrined in the recent changes to research ethics committee (REC) structure and operating procedures, introduced as the UK response to the EU Directive on clinical trials. Recent reviews and recommendations have confirmed the place of the distinction and the separate review processes. However, serious reservations can be mounted about the science/ethics distinction and the policy of separate review that has been built upon it. We argue here that, first, the science/ethics distinction is incoherent, and, second, that RECs should not only be permitted to consider a study's science, but that they have anobligation do so. PMID:17329389

  12. Subgroups of musculoskeletal pain patients and their psychobiological patterns – The LOGIN study protocol

    Directory of Open Access Journals (Sweden)

    Gerhardt Andreas

    2012-08-01

    Full Text Available Abstract Background Pain conditions of the musculoskeletal system are very common and have tremendous socioeconomic impact. Despite its high prevalence, musculoskeletal pain remains poorly understood and predominantly non-specifically and insufficiently treated. The group of chronic musculoskeletal pain patients is supposed to be heterogeneous, due to a multitude of mechanisms involved in chronic pain. Psychological variables, psychophysiological processes, and neuroendocrine alterations are expected to be involved. Thus far, studies on musculoskeletal pain have predominantly focused on the general aspects of pain processing, thus neglecting the heterogeneity of patients with musculoskeletal pain. Consequently, there is a need for studies that comprise a multitude of mechanisms that are potentially involved in the chronicity and spread of pain. This need might foster research and facilitate a better pathophysiological understanding of the condition, thereby promoting the development of specific mechanism-based treatments for chronic pain. Therefore, the objectives of this study are as follows: 1 identify and describe subgroups of patients with musculoskeletal pain with regard to clinical manifestations (including mental co-morbidity and 2 investigate whether distinct sensory profiles or 3 distinct plasma levels of pain-related parameters due to different underlying mechanisms can be distinguished in various subgroups of pain patients. Methods/Design We will examine a population-based chronic pain sample (n = 100, a clinical tertiary care sample (n = 100 and pain-free patients with depression or post-traumatic stress disorder and pain-free healthy controls (each n = 30, respectively. The samples will be pain localisation matched by sex and age to the population-based sample. Patients will undergo physical examination and thorough assessments of mental co-morbidity (including psychological trauma, perceptual and central sensitisation

  13. 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.

  14. Exhaled nitric oxide measure using multiple flows in clinically relevant subgroups of COPD

    DEFF Research Database (Denmark)

    Roberts, Nassim Bazeghi; Gerds, Thomas A; Budtz-Jørgensen, Esben

    2011-01-01

    Although there is widespread interest in fractional exhaled nitric oxide (FeNO) as a non-invasive, time and cost effective biomarker for assessing airway inflammation in chronic obstructive pulmonary disease (COPD), its usefulness is still controversial. We examined the FeNO levels in clinically...... (Caw). All patients had spirometry, assessment of symptoms with questionnaires and low-dose CT scan as well as assessment of weight and body composition. We examined the following subgroups of COPD: Patients with 1) Severe emphysema, 2) Chronic bronchitis, 3) Frequent exacerbations, 4) Loss of lean...

  15. Epigenetic subgroups of esophageal and gastric adenocarcinoma with differential GATA5 DNA methylation associated with clinical and lifestyle factors.

    Directory of Open Access Journals (Sweden)

    Xinhui Wang

    Full Text Available BACKGROUND: Adenocarcinomas located near the gastroesophageal junction have unclear etiology and are difficult to classify. We used DNA methylation analysis to identify subtype-specific markers and new subgroups of gastroesophageal adenocarcinomas, and studied their association with epidemiological risk factors and clinical outcomes. METHODOLOGY/PRINCIPAL FINDINGS: We used logistic regression models and unsupervised hierarchical cluster analysis of 74 DNA methylation markers on 45 tumor samples (44 patients of esophageal and gastric adenocarcinomas obtained from a population-based case-control study to uncover epigenetic markers and cluster groups of gastroesophageal adenocarcinomas. No distinct epigenetic differences were evident between subtypes of gastric and esophageal cancers. However, we identified two gastroesophageal adenocarcinoma subclusters based on DNA methylation profiles. Group membership was best predicted by GATA5 DNA methylation status. We analyzed the associations between these two epigenetic groups and exposure using logistic regression, and the associations with survival time using Cox regression in a larger set of 317 tumor samples (278 patients. There were more males with esophageal and gastric cardia cancers in Cluster Group 1 characterized by higher GATA5 DNA methylation values (all p<0.05. This group also showed associations of borderline statistical significance with having ever smoked (p-value = 0.07, high body mass index (p-value = 0.06, and symptoms of gastroesophageal reflux (p-value = 0.07. Subjects in cluster Group 1 showed better survival than those in Group 2 after adjusting for tumor differentiation grade, but this was not found to be independent of tumor stage. CONCLUSIONS/SIGNIFICANCE: DNA methylation profiling can be used in population-based studies to identify epigenetic subclasses of gastroesophageal adenocarcinomas and class-specific DNA methylation markers that can be linked to

  16. Finite groups in which some particular subgroups are TI-subgroups

    DEFF Research Database (Denmark)

    Shi, Jiangtao; Zhang, Cui

    2013-01-01

    We prove that G is a group in which all noncyclic subgroups are TI-subgroups if and only if all noncyclic subgroups of G are normal in G. Moreover, we classify groups in which all subgroups of even order are TI-subgroups....

  17. Real-world Clinical Outcomes Among Patients With Type 2 Diabetes Receiving Canagliflozin at a Specialty Diabetes Clinic: Subgroup Analysis by Baseline HbA1c and Age.

    Science.gov (United States)

    Johnson, June Felice; Parsa, Rahul; Bailey, Robert A

    2017-06-01

    Canagliflozin, a sodium glucose co-transporter 2 inhibitor developed for the treatment of type 2 diabetes mellitus (T2DM), has demonstrated effectiveness in patients with T2DM receiving care at a specialty diabetes clinic. We report the outcomes in these patients in subgroups classified by baseline hemoglobin A 1c (HbA 1c ) and age. This subgroup analysis was based on a review of data from the electronic health records of adults with T2DM who were prescribed canagliflozin at a specialty diabetes clinic and who returned for ≥1 follow-up office visit. Mean changes from baseline to the first and second follow-up office visits in HbA 1c , body weight, and systolic and diastolic blood pressure (BP) were calculated in each subgroup classified by baseline HbA 1c (≥7.0%, ≥8.0%, and >9.0%) and age (baseline HbA 1c ≥7.0%, ≥8.0%, and >9.0%, respectively; 396 and 66 patients were aged baseline HbA 1c and age experienced clinically and statistically significant reductions from baseline in HbA 1c , body weight, and systolic BP that were sustained over 2 office visits; diastolic BP was also reduced across baseline HbA 1c and age subgroups. Greater reductions in HbA 1c were seen among the canagliflozin-treated patients with higher baseline HbA 1c and among younger versus older patients. These findings from clinical practice demonstrate real-world effectiveness of canagliflozin in lowering HbA 1c , body weight, and systolic BP among patients with T2DM, regardless of baseline HbA 1c levels or age. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

  18. Urinary infection caused by Micrococcus subgroup 3

    Science.gov (United States)

    Kerr, Helen

    1973-01-01

    The laboratory findings and clinical presentations in urinary infections in 23 nurses, 10 caused by Micrococcus subgroup 3 and 13 by Escherichia coli, were studied, and the symptoms and possible predisposing factors compared. There were no important differences between the two groups. The infections caused by Micrococcus subgroup 3 were symptomatically severe, as were those caused by Escherichia coli. PMID:4593863

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

    Indian Academy of Sciences (India)

    Logo of the Indian Academy of Sciences. Indian Academy of Sciences ... 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 are classified.

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

    Indian Academy of Sciences (India)

    subgroup of G if there exists a subnormal subgroup T of G such that G = HT and H ∩ T is a. NE-subgroup of G. In this article, we investigate the structure of G under the assump- tion that subgroups of prime order are NE∗-subgroups of G. The finite ...

  1. Translational analysis of mouse and human placental protein and mRNA reveals distinct molecular pathologies in human preeclampsia.

    Science.gov (United States)

    Cox, Brian; Sharma, Parveen; Evangelou, Andreas I; Whiteley, Kathie; Ignatchenko, Vladimir; Ignatchenko, Alex; Baczyk, Dora; Czikk, Marie; Kingdom, John; Rossant, Janet; Gramolini, Anthony O; Adamson, S Lee; Kislinger, Thomas

    2011-12-01

    Preeclampsia (PE) adversely impacts ~5% of pregnancies. Despite extensive research, no consistent biomarkers or cures have emerged, suggesting that different molecular mechanisms may cause clinically similar disease. To address this, we undertook a proteomics study with three main goals: (1) to identify a panel of cell surface markers that distinguish the trophoblast and endothelial cells of the placenta in the mouse; (2) to translate this marker set to human via the Human Protein Atlas database; and (3) to utilize the validated human trophoblast markers to identify subgroups of human preeclampsia. To achieve these goals, plasma membrane proteins at the blood tissue interfaces were extracted from placentas using intravascular silica-bead perfusion, and then identified using shotgun proteomics. We identified 1181 plasma membrane proteins, of which 171 were enriched at the maternal blood-trophoblast interface and 192 at the fetal endothelial interface with a 70% conservation of expression in humans. Three distinct molecular subgroups of human preeclampsia were identified in existing human microarray data by using expression patterns of trophoblast-enriched proteins. Analysis of all misexpressed genes revealed divergent dysfunctions including angiogenesis (subgroup 1), MAPK signaling (subgroup 2), and hormone biosynthesis and metabolism (subgroup 3). Subgroup 2 lacked expected changes in known preeclampsia markers (sFLT1, sENG) and uniquely overexpressed GNA12. In an independent set of 40 banked placental specimens, GNA12 was overexpressed during preeclampsia when co-incident with chronic hypertension. In the current study we used a novel translational analysis to integrate mouse and human trophoblast protein expression with human microarray data. This strategy identified distinct molecular pathologies in human preeclampsia. We conclude that clinically similar preeclampsia patients exhibit divergent placental gene expression profiles thus implicating divergent

  2. Generalized Sum of Fuzzy Subgroup and α-cut Subgroup

    OpenAIRE

    Daher Waly Freh Al-Rekabi; Alia Shany Hassan

    2012-01-01

    p>In this paper we study some results of the generalized sum of a fuzzynbsp;subgroup and alpha;-cut subgroup, we define a alpha;-cut subset and alpha;-cut subgroup, and then. We study some of their properties./p>

  3. High HIV prevalence among a high-risk subgroup of women attending sexually transmitted infection clinics in Pune, India.

    Science.gov (United States)

    Mehta, Shruti H; Gupta, Amita; Sahay, Seema; Godbole, Sheela V; Joshi, Smita N; Reynolds, Steven J; Celentano, David D; Risbud, Arun; Mehendale, Sanjay M; Bollinger, Robert C

    2006-01-01

    To investigate changes over a decade in prevalence and correlates of HIV among high-risk women attending sexually transmitted infection (STI) clinics in Pune, India, who deny a history of commercial sex work (CSW). Cross-sectional. From 1993 to 2002, 2376 women attending 3 STI clinics in Pune were offered HIV screening. Women who denied CSW were included (n = 1020). Of 1020 women, 21% were HIV infected. The annual HIV prevalence increased from 14% in 1993 to 29% in 2001-2002 (P women were older, more often employed, less likely to be currently married, and more likely to report condom use. In multivariate analysis, factors independently associated with HIV were calendar period (adjusted odds ratio [AOR], 1.9 for 1997-1999 vs. 1993-1996; 95% CI, 1.2-3.0; AOR, 2.3 for 2000-2002 vs. 1993-1996; 95% CI, 1.5-3.6), lack of formal education (AOR, 2.0; 95% CI, 1.4-2.9), having been widowed (AOR, 3.1; 95% CI, 1.6-6.1), current employment (AOR, 1.8; 95% CI, 1.2-2.6), and genital ulcer disease on examination (AOR, 1.8; 95% CI, 1.2-2.7). Women attending STI clinics in India who deny a history of CSW represent a small, hidden subgroup, likely put at risk for HIV because of high-risk behavior of their male partners, generally their husbands. Educational and awareness efforts that have targeted other subgroups in India (men and CSWs) should also focus on these hard-to-reach women. Risk reduction in this subgroup of Indian women would also be expected to reduce perinatal infections in India.

  4. Clinical characteristics and distinctiveness of DSM-5 eating disorder diagnoses: findings from a large naturalistic clinical database

    Science.gov (United States)

    2013-01-01

    Background DSM-IV eating disorder (ED) diagnoses have been criticized for lack of clinical utility, diagnostic instability, and over-inclusiveness of the residual category “ED not otherwise specified” (EDNOS). Revisions made in DSM-5 attempt to generate a more scientifically valid and clinically relevant system of ED classification. The aim with the present study was to examine clinical characteristics and distinctiveness of the new DSM-5 ED diagnoses, especially concerning purging disorder (PD). Methods Using a large naturalistic Swedish ED database, 2233 adult women were diagnosed using DSM-5. Initial and 1-year follow-up psychopathology data were analyzed. Measures included the Eating Disorder Examination Questionnaire, Structural Eating Disorder Interview, Clinical Impairment Assessment, Structural Analysis of Social Behavior, Comprehensive Psychiatric Rating Scale, and Structured Clinical Interview for DSM-IV Axis I Disorders. Results Few meaningful differences emerged between anorexia nervosa binge/purge subtype (ANB/P), PD, and bulimia nervosa (BN). Unspecified Feeding and Eating Disorders (UFED) showed significantly less severity compared to other groups. Conclusions PD does not appear to constitute a distinct diagnosis, the distinction between atypical AN and PD requires clarification, and minimum inclusion criteria for UFED are needed. Further sub-classification is unlikely to improve clinical utility. Instead, better delineation of commonalities is important. PMID:24999410

  5. 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.

  6. No improvement in the reporting of clinical trial subgroup effects in high-impact general medical journals.

    Science.gov (United States)

    Gabler, Nicole B; Duan, Naihua; Raneses, Eli; Suttner, Leah; Ciarametaro, Michael; Cooney, Elizabeth; Dubois, Robert W; Halpern, Scott D; Kravitz, Richard L

    2016-07-16

    When subgroup analyses are not correctly analyzed and reported, incorrect conclusions may be drawn, and inappropriate treatments provided. Despite the increased recognition of the importance of subgroup analysis, little information exists regarding the prevalence, appropriateness, and study characteristics that influence subgroup analysis. The objective of this study is to determine (1) if the use of subgroup analyses and multivariable risk indices has increased, (2) whether statistical methodology has improved over time, and (3) which study characteristics predict subgroup analysis. We randomly selected randomized controlled trials (RCTs) from five high-impact general medical journals during three time periods. Data from these articles were abstracted in duplicate using standard forms and a standard protocol. Subgroup analysis was defined as reporting any subgroup effect. Appropriate methods for subgroup analysis included a formal test for heterogeneity or interaction across treatment-by-covariate groups. We used logistic regression to determine the variables significantly associated with any subgroup analysis or, among RCTs reporting subgroup analyses, using appropriate methodology. The final sample of 416 articles reported 437 RCTs, of which 270 (62 %) reported subgroup analysis. Among these, 185 (69 %) used appropriate methods to conduct such analyses. Subgroup analysis was reported in 62, 55, and 67 % of the articles from 2007, 2010, and 2013, respectively. The percentage using appropriate methods decreased over the three time points from 77 % in 2007 to 63 % in 2013 (p < 0.05). Significant predictors of reporting subgroup analysis included industry funding (OR 1.94 (95 % CI 1.17, 3.21)), sample size (OR 1.98 per quintile (1.64, 2.40), and a significant primary outcome (OR 0.55 (0.33, 0.92)). The use of appropriate methods to conduct subgroup analysis decreased by year (OR 0.88 (0.76, 1.00)) and was less common with industry funding (OR 0.35 (0.18, 0

  7. 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

  8. Identification of Three Distinct Eggplant Subgroups within the Solanum aethiopicum Gilo Group from Côte d’Ivoire by Morpho-Agronomic Characterization

    Directory of Open Access Journals (Sweden)

    Auguste Kouassi

    2014-10-01

    Full Text Available The Solanum aethiopicum Gilo group, described as homogeneous, shows a high diversity, at least at the morphological level. In Côte d’Ivoire, farmers distinguish three subgroups, named “N’Drowa”, “Klogbo” and “Gnangnan”, within this group. Data were obtained from 10 quantitative and 14 qualitative morpho-agronomic traits measured in 326 accessions of Gilo eggplants, at flowering and fruiting stages. Univariate and multivariate analyses allowed clearly clustering the studied accessions into the three subgroups. Fruit taste, leaf blade width, fruit diameter, leaf blade length, fruit weight, fruit color at commercial ripeness, petiole length, germination time, plant breadth, fruit position on the plant, fruit length and flowering time were, in decreasing order, the twelve most discriminating traits. Compared to the “Gnangnan” subgroup, the “N’Drowa” subgroup has smaller plant breadth and larger leaves. The fruits of this subgroup were mainly white at commercial ripeness, larger and sweeter. Most of the traits of the “Klogbo” subgroup were intermediate between those of the “N’Drowa” and “Gnangnan” subgroups. Our results could contribute to a better understanding of S. aethiopicum diversity and to the development of a core collection for African eggplant breeding.

  9. Human rotavirus subgroups and severity of associated diarrhoea in Ghana.

    Science.gov (United States)

    Armah, George E.; Hori, Hiroki; Anyanful, Akwasi; Addo, Julius A.; Commey, Joseph O.; Kamiya, Hitoshi; Nkrumah, Francis K.

    1995-11-01

    In a 12 month study of children with acute diarrhoea seeking medical care in 2 hospitals in Accra, Ghana, 16.3% were found to be infected with human rotaviruses (HRV). Vomiting and diarrhoea were the main symptoms observed. HRV infection was frequently associated with severe diarrhoea. Vomiting was however less frequent in HRV associated diarrhoea than in non HRV diarrhoea. No significant association was observed between the severity of dehydration and HRV infection. Subgroup II HRV was the predominant subgroup identified with the dominant serotypes being HRV serotypes 1 and 4. Poly-acrylamide gel electrophoresis of HRV RNAs isolated from 40 positive stool samples revealed the existence of 7 distinct electrophoretic migration patterns in the study population.

  10. Account for Clinical Heterogeneity in Assessment of Catheter-based Renal Denervation among Resistant Hypertension Patients: Subgroup Meta-analysis.

    Science.gov (United States)

    Chen, Xiao-Han; Kim, Sehee; Zeng, Xiao-Xi; Chen, Zhi-Bing; Cui, Tian-Lei; Hu, Zhang-Xue; Li, Yi; Fu, Ping

    2017-07-05

    Catheter-based renal denervation (RDN) is a novel treatment for resistant hypertension (RH). A recent meta-analysis reported that RDN did not significantly reduce blood pressure (BP) based on the pooled effects with mild to severe heterogeneity. The aim of the present study was to identify and reduce clinical sources of heterogeneity and reassess the safety and efficacy of RDN within the identified homogeneous subpopulations. This was a meta-analysis of 9 randomized clinical trials (RCTs) among patients with RH up to June 2016. Sensitivity analyses and subgroup analyses were extensively conducted by baseline systolic blood pressure (SBP) level, antihypertensive medication change rates, and coronary heart disease (CHD). In all patients with RH, no statistical differences were found in mortality, severe cardiovascular events rate, and changes in 24-h SBP and office SBP at 6 and 12 months. However, subgroup analyses showed significant differences between the RDN and control groups. In the subpopulations with baseline 24-h SBP ≥155 mmHg (1 mmHg = 0.133 kPa) and the infrequently changed medication, the use of RDN resulted in a significant reduction in 24-h SBP level at 6 months (P = 0.100 and P= 0.009, respectively). Subgrouping RCTs with a higher prevalent CHD in control showed that the control treatment was significantly better than RDN in office SBP reduction at 6 months (P < 0.001). In all patients with RH, the catheter-based RDN is not more effective in lowering ambulatory or office BP than an optimized antihypertensive drug treatment at 6 and 12 months. However, among RH patients with higher baseline SBP, RDN might be more effective in reducing SBP.

  11. A Study of the Vaginal Microbiome in Healthy Canadian Women Utilizing cpn60-Based Molecular Profiling Reveals Distinct Gardnerella Subgroup Community State Types

    Science.gov (United States)

    Wagner, Emily C.; Schellenberg, John J.; Links, Matthew G.; van Schalkwyk, Julie; Reid, Gregor; Hemmingsen, Sean M.; Hill, Janet E.; Money, Deborah

    2015-01-01

    The vaginal microbiota is important in women’s reproductive and overall health. However, the relationships between the structure, function and dynamics of this complex microbial community and health outcomes remain elusive. The objective of this study was to determine the phylogenetic range and abundance of prokaryotes in the vaginal microbiota of healthy, non-pregnant, ethnically diverse, reproductive-aged Canadian women. Socio-demographic, behavioural and clinical data were collected and vaginal swabs were analyzed from 310 women. Detailed profiles of their vaginal microbiomes were generated by pyrosequencing of the chaperonin-60 universal target. Six community state types (CST) were delineated by hierarchical clustering, including three Lactobacillus-dominated CST (L. crispatus, L. iners, L. jensenii), two Gardnerella-dominated (subgroups A and C) and an “intermediate” CST which included a small number of women with microbiomes dominated by seven other species or with no dominant species but minority populations of Streptococcus, Staphylococcus, Peptoniphilus, E. coli and various Proteobacteria in co-dominant communities. The striking correspondence between Nugent score and deep sequencing CST continues to reinforce the basic premise provided by the simpler Gram stain method, while additional analyses reveal detailed cpn60-based phylogeny and estimated abundance in microbial communities from vaginal samples. Ethnicity was the only demographic or clinical characteristic predicting CST, with differences in Asian and White women (p = 0.05). In conclusion, this study confirms previous work describing four cpn60-based subgroups of Gardnerella, revealing previously undescribed CST. The data describe the range of bacterial communities seen in Canadian women presenting with no specific vaginal health concerns, and provides an important baseline for future investigations of clinically important cohorts. PMID:26266808

  12. Could the clinical interpretability of subgroups detected using clustering methods be improved by using a novel two-stage approach?

    DEFF Research Database (Denmark)

    Kent, Peter; Stochkendahl, Mette Jensen; Wulff Christensen, Henrik

    2015-01-01

    participation, psychological factors, biomarkers and imaging. However, such ‘whole person’ research may result in data-driven subgroups that are complex, difficult to interpret and challenging to recognise clinically. This paper describes a novel approach to applying statistical clustering techniques that may...... potential benefits but requires broad testing, in multiple patient samples, to determine its clinical value. The usefulness of the approach is likely to be context-specific, depending on the characteristics of the available data and the research question being asked of it....

  13. Patients with low back pain had distinct clinical course patterns that were typically neither complete recovery nor constant pain. A latent class analysis of longitudinal data

    DEFF Research Database (Denmark)

    Kongsted, A.; Kent, P.; Hestbaek, L.

    2015-01-01

    BACKGROUND CONTEXT: The clinical presentation and outcome of patients with non-specific low back pain (LBP) are very heterogeneous and may be better understood by the recognition of reproducible subgroups. One approach to subgrouping is the identification of clinical course patterns (trajectories...

  14. Rickettsia parkeri rickettsiosis and its clinical distinction from Rocky Mountain spotted fever.

    Science.gov (United States)

    Paddock, Christopher D; Finley, Richard W; Wright, Cynthia S; Robinson, Howard N; Schrodt, Barbara J; Lane, Carole C; Ekenna, Okechukwu; Blass, Mitchell A; Tamminga, Cynthia L; Ohl, Christopher A; McLellan, Susan L F; Goddard, Jerome; Holman, Robert C; Openshaw, John J; Sumner, John W; Zaki, Sherif R; Eremeeva, Marina E

    2008-11-01

    Rickettsia parkeri rickettsiosis, a recently identified spotted fever transmitted by the Gulf Coast tick (Amblyomma maculatum), was first described in 2004. We summarize the clinical and epidemiological features of 12 patients in the United States with confirmed or probable disease attributable to R. parkeri and comment on distinctions between R. parkeri rickettsiosis and other United States rickettsioses. Clinical specimens from patients in the United States who reside within the range of A. maculatum for whom an eschar or vesicular rash was described were evaluated by > or =1 laboratory assays at the Centers for Disease Control and Prevention (Atlanta, GA) to identify probable or confirmed infection with R. parkeri. During 1998-2007, clinical samples from 12 patients with illnesses epidemiologically and clinically compatible with R. parkeri rickettsiosis were submitted for diagnostic evaluation. Using indirect immunofluorescence antibody assays, immunohistochemistry, polymerase chain reaction assays, and cell culture isolation, we identified 6 confirmed and 6 probable cases of infection with R. parkeri. The aggregate clinical characteristics of these patients revealed a disease similar to but less severe than classically described Rocky Mountain spotted fever. Closer attention to the distinct clinical features of the various spotted fever syndromes that exist in the United States and other countries of the Western hemisphere, coupled with more frequent use of specific confirmatory assays, may unveil several unique diseases that have been identified collectively as Rocky Mountain spotted fever during the past century. Accurate assessments of these distinct infections will ultimately provide a more valid description of the currently recognized distribution, incidence, and case-fatality rate of Rocky Mountain spotted fever.

  15. Inconsistent trial assessments by the National Institute for Health and Clinical Excellence and IQWiG: standards for the performance and interpretation of subgroup analyses are needed.

    Science.gov (United States)

    Hasford, J; Bramlage, P; Koch, G; Lehmacher, W; Einhäupl, K; Rothwell, P M

    2010-12-01

    The methodology for the critical assessment of medical interventions is well established. Regulatory agencies and institutions adhere, in principle, to the same standards. This consistency, however, is not always the case in practice. Using the evaluation of the CAPRIE (Clopidogrel versus Aspirin in Patients at risk of Ischemic Events) trial by the British National Institute for Health and Clinical Excellence (NICE) and the German Institute for Quality and Efficiency in Health Care (IQWiG), we illustrate that there was no consensus for the interpretation of possible heterogeneity in treatment comparisons across subgroups. The NICE concluded that CAPRIE demonstrated clinical benefit for the overall intention-to-treat (ITT) population with sufficient robustness to possible sources of heterogeneity. The IQWiG interpreted the alleged heterogeneity as implying that the clinical benefit only applied to the subgroup of patients with a statistically significant result irrespective of the results of the ITT analysis. International standards for the performance and interpretation of subgroup analyses as well as for the assessment of heterogeneity between strata are needed. Copyright © 2010 Elsevier Inc. All rights reserved.

  16. Identification of subgroups of inflammatory and degenerative MRI findings in the spine and sacroiliac joints

    DEFF Research Database (Denmark)

    Arnbak, Bodil Al-Mashhadi; Jensen, Rikke Krüger; Manniche, Claus

    and the clinical presentation of back pain. The objectives of this explorative study were: 1) Investigate subgroups of MRI findings of the spine and sacroiliac joints (SIJs) using Latent Class Analysis (LCA) and 2) Investigate whether these subgroups differ in their demographic and clinical characteristics...

  17. Distinct HbA1c trajectories in a type 2 diabetes cohort

    NARCIS (Netherlands)

    Walraven, I.; Mast, M.R.; Hoekstra, T.; Jansen, A.P.D.; van der Heijden, A.A.W.A.; Rauh, S.P.; Rutters, F.; van 't Riet, E.; Elders, P.J.M.; Moll, A.C.; Polak, B.C.P.; Dekker, J.M.; Nijpels, G.

    2015-01-01

    Aims: The aim of this study was to identify subgroups of type 2 diabetes mellitus patients with distinct hemoglobin A1c (HbA1c) trajectories. Subgroup characteristics were determined and the prevalence of microvascular complications over time was investigated. Study design and setting: Data from a

  18. The status of and future research into Myalgic Encephalomyelitis and Chronic Fatigue Syndrome: the need of accurate diagnosis, objective assessment, and acknowledging biological and clinical subgroups

    Science.gov (United States)

    Twisk, Frank N. M.

    2014-01-01

    Although Myalgic Encephalomyelitis (ME) and Chronic Fatigue Syndrome (CFS) are used interchangeably, the diagnostic criteria define two distinct clinical entities. Cognitive impairment, (muscle) weakness, circulatory disturbances, marked variability of symptoms, and, above all, post-exertional malaise: a long-lasting increase of symptoms after a minor exertion, are distinctive symptoms of ME. This latter phenomenon separates ME, a neuro-immune illness, from chronic fatigue (syndrome), other disorders and deconditioning. The introduction of the label, but more importantly the diagnostic criteria for CFS have generated much confusion, mostly because chronic fatigue is a subjective and ambiguous notion. CFS was redefined in 1994 into unexplained (persistent or relapsing) chronic fatigue, accompanied by at least four out of eight symptoms, e.g., headaches and unrefreshing sleep. Most of the research into ME and/or CFS in the last decades was based upon the multivalent CFS criteria, which define a heterogeneous patient group. Due to the fact that fatigue and other symptoms are non-discriminative, subjective experiences, research has been hampered. Various authors have questioned the physiological nature of the symptoms and qualified ME/CFS as somatization. However, various typical symptoms can be assessed objectively using standardized methods. Despite subjective and unclear criteria and measures, research has observed specific abnormalities in ME/CFS repetitively, e.g., immunological abnormalities, oxidative and nitrosative stress, neurological anomalies, circulatory deficits and mitochondrial dysfunction. However, to improve future research standards and patient care, it is crucial that patients with post-exertional malaise (ME) and patients without this odd phenomenon are acknowledged as separate clinical entities that the diagnosis of ME and CFS in research and clinical practice is based upon accurate criteria and an objective assessment of characteristic symptoms

  19. Progressive Amalgamation of Building Clusters for Map Generalization Based on Scaling Subgroups

    Directory of Open Access Journals (Sweden)

    Xianjin He

    2018-03-01

    Full Text Available Map generalization utilizes transformation operations to derive smaller-scale maps from larger-scale maps, and is a key procedure for the modelling and understanding of geographic space. Studies to date have largely applied a fixed tolerance to aggregate clustered buildings into a single object, resulting in the loss of details that meet cartographic constraints and may be of importance for users. This study aims to develop a method that amalgamates clustered buildings gradually without significant modification of geometry, while preserving the map details as much as possible under cartographic constraints. The amalgamation process consists of three key steps. First, individual buildings are grouped into distinct clusters by using the graph-based spatial clustering application with random forest (GSCARF method. Second, building clusters are decomposed into scaling subgroups according to homogeneity with regard to the mean distance of subgroups. Thus, hierarchies of building clusters can be derived based on scaling subgroups. Finally, an amalgamation operation is progressively performed from the bottom-level subgroups to the top-level subgroups using the maximum distance of each subgroup as the amalgamating tolerance instead of using a fixed tolerance. As a consequence of this step, generalized intermediate scaling results are available, which can form the multi-scale representation of buildings. The experimental results show that the proposed method can generate amalgams with correct details, statistical area balance and orthogonal shape while satisfying cartographic constraints (e.g., minimum distance and minimum area.

  20. Early- versus Late-Onset Dysthymia: A Meaningful Clinical Distinction?

    OpenAIRE

    Sansone, Randy A.; Sansone, Lori A.

    2009-01-01

    In the current Diagnostic and Statistical Manual of Mental Disorders, dysthymic disorder is categorized as either early-onset or late-onset, based upon the emergence of symptoms before or after the age of 21, respectively. Does this diagnostic distinction have any meaningful clinical implications? In this edition of The Interface, we present empirical studies that have, within a single study, compared individuals with early-versus late-onset dysthymia. In this review, we found that, compared ...

  1. Clinical outcome of Crohn's disease according to the Vienna classification: disease location is a useful predictor of disease course

    NARCIS (Netherlands)

    Oostenbrug, Liekele E.; van Dullemen, Hendrik M.; te Meerman, Gerard J.; Jansen, Peter L. M.; Kleibeuker, Jan H.

    2006-01-01

    OBJECTIVES: Crohn's disease (CD) is a complex genetic disease with multiple clinical patterns. Clinical classifications may help to identify subgroups of patients that have a distinct pattern of disease, and they are also a prerequisite for the conduction of genetic and therapeutic studies. The aim

  2. Clinical outcome of Crohn's disease according to the Vienna classification : disease location is a useful predictor of disease course

    NARCIS (Netherlands)

    Oostenbrug, Liekele E.; van Dullemen, Hendrik M.; te Meerman, Gerard J.; Jansen, Peter L. M.; Kleibeuker, Jan H.

    Objectives Crohn's disease (CD) is a complex genetic disease with multiple clinical patterns. Clinical classifications may help to identify subgroups of patients that have a distinct pattern of disease, and they are also a prerequisite for the conduction of genetic and therapeutic studies. The aim

  3. Evaluation of the zoonotic potential of multiple subgroups of clade 2.3.4.4 influenza A (H5N8) virus.

    Science.gov (United States)

    Lee, Yu-Na; Lee, Eun-Kyoung; Song, Byung-Min; Heo, Gyeong-Beom; Woo, Sang-Hee; Cheon, Sun-Ha; Lee, Youn-Jeong

    2018-03-01

    Clade 2.3.4.4 H5N8 highly pathogenic avian influenza viruses (HPAIVs) have spread worldwide. Phylogenetic analysis identified two genetic groups of the H5N8 HPAIVs in South Korea; group A evolved further into four subgroups. Here, we examined the zoonotic potential, both in vivo and in vitro, of genetically distinct subgroups of H5N8 HPAIVs isolated in South Korea. When compared with other subgroups, A/mallard/Korea/H2102/2015 (H2102) virus caused relatively severe disease in mice at high doses. In ferrets, all H5N8 viruses replicated restrictively in the respiratory tract and did not induce significant clinical signs of influenza infection. In vitro studies, all viruses displayed a hemagglutinin phenotype that was poorly adapted for infection of mammals, although the H2102 virus exhibited higher replication kinetics at 33°C than the others. Although H5N8 HPAIVs have not yet acquired all the characteristics required for adaptation to mammals, their ability to evolve continuously underscores the need for timely risk assessment. Copyright © 2018 Elsevier Inc. All rights reserved.

  4. Late-onset systemic lupus erythematosus in Latin Americans: a distinct subgroup?

    Science.gov (United States)

    Catoggio, L J; Soriano, E R; Imamura, P M; Wojdyla, D; Jacobelli, S; Massardo, L; Chacón Díaz, R; Guibert-Toledano, M; Alvarellos, A; Saurit, V; Manni, J A; Pascual-Ramos, V; Silva de Sauza, A W; Bonfa, E; Tavares Brenol, J C; Ramirez, L A; Barile-Fabris, L A; De La Torre, I Garcia; Alarcón, G S; Pons-Estel, B A

    2015-07-01

    To examine the characteristics of patients who developed late onset systemic lupus erythematosus (SLE) in the GLADEL (Grupo Latino Americano de Estudio del Lupus) cohort of patients with SLE. Patients with SLE of less than two years of disease duration, seen at 34 centers of nine Latin American countries, were included. Late-onset was defined as >50 years of age at time of first SLE-related symptom. Clinical and laboratory manifestations, activity index (SLEDAI), and damage index (SLICC/ACR- DI) were ascertained at time of entry and during the course (cumulative incidence). Features were compared between the two patient groups (lupus, adjusting for other variables. Of the 1480 patients included, 102 patients (6.9 %) had late-onset SLE, 87% of which were female. Patients with late-onset SLE had a shorter follow-up (3.6 vs. 4.4 years, p  0.05). In multivariable analysis, late onset was independently associated with higher odds of ocular (OR = 3.66, 95% CI = 2.15-6.23), pulmonary (OR = 2.04, 95% CI = 1.01-4.11), and cardiovascular (OR = 1.76, 95% CI = 1.04-2.98) involvement and lower odds of cutaneous involvement (OR = 0.41, 95% CI = 0.21-0.80), number of cumulative SLE criteria (OR = 0.79, 95% CI = 0.64-0.97), use of cyclophosphamide (OR = 0.47, 95% CI = 0.24-0.95), and anti-RNP antibodies (OR = 0.43, 95% CI = 0.20-0.91). A Cox regression model revealed a higher risk of dying in older onset than the younger-onset SLE (OR = 2.61, 95% CI = 1.2-5.6). Late-onset SLE in Latin Americans had a distinct disease expression compared to the younger-onset group. The disease seems to be mild with lower cumulative SLE criteria, reduced renal/mucocutaneous involvements, and less use of cyclophosphamide. Nevertheless, these patients have a higher risk of death and of ocular, pulmonary, and cardiovascular involvements. © The Author(s) 2014.

  5. MicroRNAs sequencing unveils distinct molecular subgroups of plasmablastic lymphoma.

    Science.gov (United States)

    Ambrosio, Maria Raffaella; Mundo, Lucia; Gazaneo, Sara; Picciolini, Matteo; Vara, Prasad Satya; Sayed, Shaheen; Ginori, Alessandro; Lo Bello, Giuseppe; Del Porro, Leonardo; Navari, Mohsen; Ascani, Stefano; Yonis, Amhed; Leoncini, Lorenzo; Piccaluga, Pier Paolo; Lazzi, Stefano

    2017-12-08

    Plasmablastic lymphoma (PBL) is an aggressive lymphoma, often arising in the context of immunodeficiency and associated with Epstein-Barr virus (EBV) infection. The most frequently detected genetic alteration is the deregulation of MYC gene through the translocation - t(8;14)(q24;q32). The diagnosis of PBL is often challenging because it has an overlap in morphology, immunophenotype, cytogenetics and virus association with other lymphomas and plasma cell neoplasms; further, its molecular basis remains elusive. In the present study we aimed to better define the possible contribution of EBV infection as well as miRNA deregulation in PBL pathogenesis. We studied 23 cases of PBL, 19 Burkitt lymphomas (BL), and 17 extra-medullary plasmacytoma (EMPC). We used qPCR and immunohistochemistry to assess EBV latency patterns, while micro-RNA (miRNA) profiling was performed by next generation sequencing (Illumina) and validated by qPCR. Our analysis revealed a non-canonical EBV latency program with the partial expression of some proteins characterizing latency II and the activation of an abortive lytic cycle. Moreover, we identified miRNA signatures discriminating PBL from BL and EMPC. Interestingly, based on the miRNA profile, PBL appeared constituted by two discrete subgroups more similar to either BL or EMPC, respectively. This pattern was confirmed in an independent set of cases studied by qPCR and corresponded to different clinico-pathological features in the two groups, including HIV infection, MYC rearrangement and disease localization. In conclusion, we uncovered for the first time 1) an atypical EBV latency program in PBL; 2) a miRNA signature distinguishing PBL from the closest malignant counterparts; 3) the molecular basis of PBL heterogeneity.

  6. Subgroups based on thermal and pressure pain thresholds in women with chronic whiplash display differences in clinical presentation – an explorative study

    Directory of Open Access Journals (Sweden)

    Börsbo B

    2012-11-01

    Full Text Available Björn Börsbo,1,2 Gunilla M Liedberg,3 Mia Wallin,1,3 Björn Gerdle1,41Department of Medicine and Health Sciences, University of Linköping, Linköping, Sweden; 2Clinical Department of Rehabilitation Medicine, County Hospital Ryhov, Jönköping, Sweden; 3Department of Social and Welfare Studies, University of Linköping, Norrköping, Sweden; 4Pain and Rehabilitation Centre, UHL, Östergötland County Council, Linköping, SwedenPurpose: To investigate the presence of subgroups in chronic whiplash-associated disorders (WAD based on pain thresholds for pressure (PPT, cold (CPT, and heat (HPT and to compare these subgroups with respect to symptomatology, disability, and health aspects. Methods: Two groups of female subjects – patients with chronic WAD (n = 28 and healthy controls (CON; n = 29 – were investigated. Quantitative sensory testing (QST for thermal thresholds and algometry for PPT at four sites in the body (over the trapezius and tibialis anterior bilaterally were determined. Habitual pain intensities, psychological strain, disability, and health aspects were registered using a questionnaire.Results: A cluster analysis based on PPT, CPT, and HPT identified two subgroups of chronic WAD: one sensitive subgroup (s-WAD; n = 21, and one less sensitive subgroup (ls-WAD; n = 6. S-WAD displayed widespread hyperalgesia, whereas ls-WAD had localized hyperalgesia in the neck area, with tendencies to supernormal values in remote areas of the body. Generally, s-WAD had a significantly worse situation than the CON with respect to symptomatology, disability, and health aspects. The ls-WAD group was intermediary between s-WAD and CON in these aspects.Conclusion: Different explanations, eg, severity of the pain condition per se, etiological factors, and pre-trauma differences in pain sensitivity, may exist for the differences in pain thresholds between the two subgroups. Future research should investigate the role of pain thresholds in the chronic

  7. Single-cell quantitative HER2 measurement identifies heterogeneity and distinct subgroups within traditionally defined HER2-positive patients.

    Science.gov (United States)

    Onsum, Matthew D; Geretti, Elena; Paragas, Violette; Kudla, Arthur J; Moulis, Sharon P; Luus, Lia; Wickham, Thomas J; McDonagh, Charlotte F; MacBeath, Gavin; Hendriks, Bart S

    2013-11-01

    Human epidermal growth factor receptor 2 (HER2) is an important biomarker for breast and gastric cancer prognosis and patient treatment decisions. HER2 positivity, as defined by IHC or fluorescent in situ hybridization testing, remains an imprecise predictor of patient response to HER2-targeted therapies. Challenges to correct HER2 assessment and patient stratification include intratumoral heterogeneity, lack of quantitative and/or objective assays, and differences between measuring HER2 amplification at the protein versus gene level. We developed a novel immunofluorescence method for quantitation of HER2 protein expression at the single-cell level on FFPE patient samples. Our assay uses automated image analysis to identify and classify tumor versus non-tumor cells, as well as quantitate the HER2 staining for each tumor cell. The HER2 staining level is converted to HER2 protein expression using a standard cell pellet array stained in parallel with the tissue sample. This approach allows assessment of HER2 expression and heterogeneity within a tissue section at the single-cell level. By using this assay, we identified distinct subgroups of HER2 heterogeneity within traditional definitions of HER2 positivity in both breast and gastric cancers. Quantitative assessment of intratumoral HER2 heterogeneity may offer an opportunity to improve the identification of patients likely to respond to HER2-targeted therapies. The broad applicability of the assay was demonstrated by measuring HER2 expression profiles on multiple tumor types, and on normal and diseased heart tissues. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  8. 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.

  9. Time-resolved magnetic resonance angiography (MRA) at 3.0 Tesla for evaluation of hemodynamic characteristics of vascular malformations: description of distinct subgroups.

    Science.gov (United States)

    Hammer, Simone; Uller, Wibke; Manger, Florentine; Fellner, Claudia; Zeman, Florian; Wohlgemuth, Walter A

    2017-01-01

    Quantitative evaluation of hemodynamic characteristics of arteriovenous and venous malformations using time-resolved magnetic resonance angiography (MRA) at 3.0 Tesla. Time-resolved MRA with interleaved stochastic trajectories (TWIST) at 3.0 Tesla was studied in 83 consecutive patients with venous malformations (VM) and arteriovenous malformations (AVM). Enhancement characteristics were calculated as percentage increase of signal intensity above baseline over time. Maximum percentage signal intensity increase (signal max ), time intervals between onset of arterial enhancement and lesion enhancement (t onset ), and time intervals between beginning of lesion enhancement and maximum percentage of lesion enhancement (t max ) were analyzed. All AVMs showed a high-flow hemodynamic pattern. Two significantly different (p 3.0 Tesla provides hemodynamic characterization of vascular malformations. VMs can be subclassified into two hemodynamic subgroups due to presence or absence of AVFs. • Time-resolved MRA at 3.0 Tesla provides quantitative hemodynamic characterization of vascular malformations. • Malformations significantly differ in time courses of enhancement and signal intensity increase. • AVMs show a distinctive high-flow hemodynamic pattern. • Two significantly different types of VMs emerged: VMs with and without AVFs.

  10. MLH1-Silenced and Non-Silenced Subgroups of Hypermutated Colorectal Carcinomas Have Distinct Mutational Landscapes

    Science.gov (United States)

    Donehower, Lawrence A.; Creighton, Chad J.; Schultz, Nikolaus; Shinbrot, Eve; Chang, Kyle; Gunaratne, Preethi H.; Muzny, Donna; Sander, Chris; Hamilton, Stanley R.; Gibbs, Richard A.; Wheeler, David

    2014-01-01

    Approximately 15% of colorectal carcinomas (CRC) exhibit a hypermutated genotype accompanied by high levels of microsatellite instability (MSI-H) and defects in DNA mismatch repair. These tumors, unlike the majority of colorectal carcinomas, are often diploid, exhibit frequent epigenetic silencing of the MLH1 DNA mismatch repair gene, and have a better clinical prognosis. As an adjunct study to The Cancer Genome Atlas consortium that recently analyzed 224 colorectal cancers by whole exome sequencing, we compared the 35 CRC (15.6%) with a hypermutated genotype to those with a non-hypermutated genotype. We found that 22 (63%) of hypermutated CRC exhibited transcriptional silencing of the MLH1 gene, a high frequency of BRAF V600E gene mutations and infrequent APC and KRAS mutations, a mutational pattern significantly different from their non-hypermutated counterparts. However, the remaining 13 (37%) hypermutated CRC lacked MLH1 silencing, contained tumors with the highest mutation rates (“ultramutated” CRC), and exhibited higher incidences of APC and KRAS mutations, but infrequent BRAF mutations. These patterns were confirmed in an independent validation set of 250 exome-sequenced CRC. Analysis of mRNA and microRNA expression signatures revealed that hypermutated CRC with MLH1 silencing had greatly reduced levels of WNT signaling and increased BRAF signaling relative non-hypermutated CRC. Our findings suggest that hypermutated CRC include one subgroup with fundamentally different pathways to malignancy than the majority of CRC. Examination of MLH1 expression status and frequencies of APC, KRAS, and BRAF mutation in CRC may provide a useful diagnostic tool that could supplement the standard microsatellite instability assays and influence therapeutic decisions. PMID:22899370

  11. Subgroup complexes

    CERN Document Server

    Smith, Stephen D

    2011-01-01

    This book is intended as an overview of a research area that combines geometries for groups (such as Tits buildings and generalizations), topological aspects of simplicial complexes from p-subgroups of a group (in the spirit of Brown, Quillen, and Webb), and combinatorics of partially ordered sets. The material is intended to serve as an advanced graduate-level text and partly as a general reference on the research area. The treatment offers optional tracks for the reader interested in buildings, geometries for sporadic simple groups, and G-equivariant equivalences and homology for subgroup complexes.

  12. 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.

  13. Clinical efficacy of BG-12 (dimethyl fumarate) in patients with relapsing-remitting multiple sclerosis: subgroup analyses of the CONFIRM study.

    LENUS (Irish Health Repository)

    Hutchinson, Michael

    2013-09-01

    In the phase 3, randomized, placebo-controlled and active reference (glatiramer acetate) comparator CONFIRM study in patients with relapsing-remitting multiple sclerosis, oral BG-12 (dimethyl fumarate) reduced the annualized relapse rate (ARR; primary endpoint), as well as the proportion of patients relapsed, magnetic resonance imaging lesion activity, and confirmed disability progression, compared with placebo. We investigated the clinical efficacy of BG-12 240 mg twice daily (BID) and three times daily (TID) in patient subgroups stratified according to baseline demographic and disease characteristics including gender, age, relapse history, McDonald criteria, treatment history, Expanded Disability Status Scale score, T2 lesion volume, and gadolinium-enhancing lesions. BG-12 treatment demonstrated generally consistent benefits on relapse-related outcomes across patient subgroups, reflecting the positive findings in the overall CONFIRM study population. Treatment with BG-12 BID and TID reduced the ARR and the proportion of patients relapsed at 2 years compared with placebo in all subgroups analyzed. Reductions in ARR with BG-12 BID versus placebo ranged from 34% [rate ratio 0.664 (95% confidence interval 0.422-1.043)] to 53% [0.466 (0.313-0.694)] and from 13% [0.870 (0.551-1.373)] to 67% [0.334 (0.226-0.493)] with BG-12 TID versus placebo. Treatment with glatiramer acetate reduced the ARR and the proportion of patients relapsed at 2 years compared with placebo in most patient subgroups. The results of these analyses indicate that treatment with BG-12 is effective on relapses across a broad range of patients with relapsing-remitting multiple sclerosis with varied demographic and disease characteristics.

  14. Different demographic, genetic, and longitudinal traits in language versus memory Alzheimer's subgroups.

    Science.gov (United States)

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

    2013-01-01

    The study's objective was to compare demographics, APOE genotypes, and rate of rise over time in functional impairment in neuropsychologically defined language, typical, and memory subgroups of clinical Alzheimer's disease (AD). 1,368 participants from the National Alzheimer's Coordinating Center database with a diagnosis of probable AD (CDR 0.5-1.0) were included. A language subgroup (n = 229) was defined as having language performance >1 SD worse than memory performance. A memory subgroup (n = 213) was defined as having memory performance >1 SD worse than language performance. A typical subgroup (n = 926) was defined as having a difference in language and memory performance of memory subgroup, the language subgroup was 3.7 years older and more frequently self-identified as African American (OR = 3.69). Under a dominant genetic model, the language subgroup had smaller odds of carrying at least one APOEε4 allele relative to the memory subgroup. While this difference was present for all ages, it was more striking at a younger age (OR = 0.19 for youngest tertile; OR = 0.52 for oldest tertile). Compared with the memory subgroup, the language subgroup rose 35% faster on the Functional Assessment Questionnaire and 44% faster on CDR sum of boxes over time. Among a subset of participants who underwent autopsy (n = 98), the language, memory, and typical subgroups were equally likely to have an AD pathologic diagnosis, suggesting that variation in non-AD pathologies across subtypes did not lead to the observed differences. The study demonstrates that a language subgroup of AD has different demographics, genetic profile, and disease course in addition to cognitive phenotype.

  15. Machine Learning Methods Improve Prognostication, Identify Clinically Distinct Phenotypes, and Detect Heterogeneity in Response to Therapy in a Large Cohort of Heart Failure Patients.

    Science.gov (United States)

    Ahmad, Tariq; Lund, Lars H; Rao, Pooja; Ghosh, Rohit; Warier, Prashant; Vaccaro, Benjamin; Dahlström, Ulf; O'Connor, Christopher M; Felker, G Michael; Desai, Nihar R

    2018-04-12

    Whereas heart failure (HF) is a complex clinical syndrome, conventional approaches to its management have treated it as a singular disease, leading to inadequate patient care and inefficient clinical trials. We hypothesized that applying advanced analytics to a large cohort of HF patients would improve prognostication of outcomes, identify distinct patient phenotypes, and detect heterogeneity in treatment response. The Swedish Heart Failure Registry is a nationwide registry collecting detailed demographic, clinical, laboratory, and medication data and linked to databases with outcome information. We applied random forest modeling to identify predictors of 1-year survival. Cluster analysis was performed and validated using serial bootstrapping. Association between clusters and survival was assessed with Cox proportional hazards modeling and interaction testing was performed to assess for heterogeneity in response to HF pharmacotherapy across propensity-matched clusters. Our study included 44 886 HF patients enrolled in the Swedish Heart Failure Registry between 2000 and 2012. Random forest modeling demonstrated excellent calibration and discrimination for survival (C-statistic=0.83) whereas left ventricular ejection fraction did not (C-statistic=0.52): there were no meaningful differences per strata of left ventricular ejection fraction (1-year survival: 80%, 81%, 83%, and 84%). Cluster analysis using the 8 highest predictive variables identified 4 clinically relevant subgroups of HF with marked differences in 1-year survival. There were significant interactions between propensity-matched clusters (across age, sex, and left ventricular ejection fraction and the following medications: diuretics, angiotensin-converting enzyme inhibitors, β-blockers, and nitrates, P <0.001, all). Machine learning algorithms accurately predicted outcomes in a large data set of HF patients. Cluster analysis identified 4 distinct phenotypes that differed significantly in outcomes and in

  16. Clinimetrics corner: choosing appropriate study designs for particular questions about treatment subgroups

    DEFF Research Database (Denmark)

    Kent, Peter; Hancock, Mark; Petersen, Ditte H.D

    2010-01-01

    that are inappropriate given the randomized controlled trial design used. The research design to choose, when developing a study protocol that investigates the effect of treatment subgroups, depends on the particular research question. Similarly, the inferences that can be drawn from an existing study will vary...... receive the same treatment?'; and (4) 'Are outcomes for a number of treatments better if those treatments are matched to patients in specific subgroups, than if the SAME treatments are randomly given to patients?'. Illustrative examples of these studies are provided. Conclusion: If the clinical usefulness......Background: Many clinicians and researchers believe that there are subgroups of people with spinal pain who respond differently to treatment and have different prognoses. There has been considerable interest in this topic recently. However, problems occur when conclusions about subgroups are made...

  17. Discrimination of multilocus sequence typing-based Campylobacter jejuni subgroups by MALDI-TOF mass spectrometry.

    Science.gov (United States)

    Zautner, Andreas Erich; Masanta, Wycliffe Omurwa; Tareen, Abdul Malik; Weig, Michael; Lugert, Raimond; Groß, Uwe; Bader, Oliver

    2013-11-07

    Campylobacter jejuni, the most common bacterial pathogen causing gastroenteritis, shows a wide genetic diversity. Previously, we demonstrated by the combination of multi locus sequence typing (MLST)-based UPGMA-clustering and analysis of 16 genetic markers that twelve different C. jejuni subgroups can be distinguished. Among these are two prominent subgroups. The first subgroup contains the majority of hyperinvasive strains and is characterized by a dimeric form of the chemotaxis-receptor Tlp7(m+c). The second has an extended amino acid metabolism and is characterized by the presence of a periplasmic asparaginase (ansB) and gamma-glutamyl-transpeptidase (ggt). Phyloproteomic principal component analysis (PCA) hierarchical clustering of MALDI-TOF based intact cell mass spectrometry (ICMS) spectra was able to group particular C. jejuni subgroups of phylogenetic related isolates in distinct clusters. Especially the aforementioned Tlp7(m+c)(+) and ansB+/ ggt+ subgroups could be discriminated by PCA. Overlay of ICMS spectra of all isolates led to the identification of characteristic biomarker ions for these specific C. jejuni subgroups. Thus, mass peak shifts can be used to identify the C. jejuni subgroup with an extended amino acid metabolism. Although the PCA hierarchical clustering of ICMS-spectra groups the tested isolates into a different order as compared to MLST-based UPGMA-clustering, the isolates of the indicator-groups form predominantly coherent clusters. These clusters reflect phenotypic aspects better than phylogenetic clustering, indicating that the genes corresponding to the biomarker ions are phylogenetically coupled to the tested marker genes. Thus, PCA clustering could be an additional tool for analyzing the relatedness of bacterial isolates.

  18. 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

  19. 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.

  20. Identifying and predicting subgroups of information needs among cancer patients: an initial study using latent class analysis.

    Science.gov (United States)

    Neumann, Melanie; Wirtz, Markus; Ernstmann, Nicole; Ommen, Oliver; Längler, Alfred; Edelhäuser, Friedrich; Scheffer, Christian; Tauschel, Diethard; Pfaff, Holger

    2011-08-01

    Understanding how the information needs of cancer patients (CaPts) vary is important because met information needs affect health outcomes and CaPts' satisfaction. The goals of the study were to identify subgroups of CaPts based on self-reported cancer- and treatment-related information needs and to determine whether subgroups could be predicted on the basis of selected sociodemographic, clinical and clinician-patient relationship variables. Three hundred twenty-three CaPts participated in a survey using the "Cancer Patients Information Needs" scale, which is a new tool for measuring cancer-related information needs. The number of information need subgroups and need profiles within each subgroup was identified using latent class analysis (LCA). Multinomial logistic regression was applied to predict class membership. LCA identified a model of five subgroups exhibiting differences in type and extent of CaPts' unmet information needs: a subgroup with "no unmet needs" (31.4% of the sample), two subgroups with "high level of psychosocial unmet information needs" (27.0% and 12.0%), a subgroup with "high level of purely medical unmet information needs" (16.0%) and a subgroup with "high level of medical and psychosocial unmet information needs" (13.6%). An assessment of sociodemographic and clinical characteristics revealed that younger CaPts and CaPts' requiring psychological support seem to belong to subgroups with a higher level of unmet information needs. However, the most significant predictor for the subgroups with unmet information needs is a good clinician-patient relationship, i.e. subjective perception of high level of trust in and caring attention from nurses together with high degree of physician empathy seems to be predictive for inclusion in the subgroup with no unmet information needs. The results of our study can be used by oncology nurses and physicians to increase their awareness of the complexity and heterogeneity of information needs among CaPts and of

  1. Schizophrenia-like symptoms in narcolepsy type 1: shared and distinctive clinical characteristics.

    Science.gov (United States)

    Plazzi, Giuseppe; Fabbri, Chiara; Pizza, Fabio; Serretti, Alessandro

    2015-01-01

    The occurrence of psychotic symptoms in narcolepsy type 1 (NT1) has been reported as responsible for delayed diagnosis due to the misdiagnosis of schizophrenia. This study aimed to identify shared and distinctive clinical characteristics between NT1 and schizophrenia, with the focus on psychotic symptoms. A total of 28 NT1 and 21 schizophrenia patients were included. Hallucination characteristics and PANSS (Positive and Negative Syndrome Scale), HRSD (Hamilton Rating Scale for Depression), DES (Dissociative Experiences Scale), and STAI (State-Trait Anxiety Inventory) scores were collected. Symptom overlap was investigated by χ(2), Fisher's or t tests and multiple logistic regression models. Hallucinations and illusions frequently occurred in both diseases. Unimodal hallucinations were more common in schizophrenia (p = 6.30e-07) and multimodal hallucinations in NT1, but no clear difference was identified in their sensory modality. Hypnagogic/hypnopompic hallucinations were typical of NT1 (p = 5.22e-07), and 25% of NT1 patients exhibited some degree of insight deficit. Hypnagogic/hypnopompic hallucinations, unimodal hallucinations and PANSS score were the most distinctive clinical characteristics. Clinical overlap was found in the dissociative and anxiety domains, while higher depressive scores were observed in schizophrenia. The overlap between NT1 and schizophrenia should be further investigated under a clinical and pathogenetic point of view to improve diagnostic and therapeutic approaches. © 2015 S. Karger AG, Basel.

  2. Identifying and Assessing Interesting Subgroups in a Heterogeneous Population.

    Science.gov (United States)

    Lee, Woojoo; Alexeyenko, Andrey; Pernemalm, Maria; Guegan, Justine; Dessen, Philippe; Lazar, Vladimir; Lehtiö, Janne; Pawitan, Yudi

    2015-01-01

    Biological heterogeneity is common in many diseases and it is often the reason for therapeutic failures. Thus, there is great interest in classifying a disease into subtypes that have clinical significance in terms of prognosis or therapy response. One of the most popular methods to uncover unrecognized subtypes is cluster analysis. However, classical clustering methods such as k-means clustering or hierarchical clustering are not guaranteed to produce clinically interesting subtypes. This could be because the main statistical variability--the basis of cluster generation--is dominated by genes not associated with the clinical phenotype of interest. Furthermore, a strong prognostic factor might be relevant for a certain subgroup but not for the whole population; thus an analysis of the whole sample may not reveal this prognostic factor. To address these problems we investigate methods to identify and assess clinically interesting subgroups in a heterogeneous population. The identification step uses a clustering algorithm and to assess significance we use a false discovery rate- (FDR-) based measure. Under the heterogeneity condition the standard FDR estimate is shown to overestimate the true FDR value, but this is remedied by an improved FDR estimation procedure. As illustrations, two real data examples from gene expression studies of lung cancer are provided.

  3. Clinical significance of determination of changes of serum IL-2, SIL-2R, TNF-α contents and T-cell subgroup distribution type in patients with psoriasis

    International Nuclear Information System (INIS)

    Mou Xudong

    2005-01-01

    Objective: To investigate the changes of serum IL-2, SIL-2R, TNF-α contents and T-cell subgroup distribution type in patients with psoriasis. Methods: Serum IL-2 and TNF-α levels were measured with RIA, SIL-2R levels was measured with ELISA and T-cell subgroup distribution type was detected with monoclonal antibody in 40 patients with psoriasis and 35 controls. Results: The serum IL-2 levels and CD 4 /CD 8 values were significantly lower in the patients than those in controls (P<0.01), while the serum SIL-2R, TNF-α levels were significantly higher (P<0.01). Conclusion: Determination of serum IL-2, SIL-2R, TNF-α contents and T-cell subgroup distribution type is clinically useful for understanding the disturbances of immuno-modulation in these patients. (authors)

  4. Co-circulation of multiple hemorrhagic fever diseases with distinct clinical characteristics in Dandong, China.

    Directory of Open Access Journals (Sweden)

    Zhi-Hai Chen

    Full Text Available Hemorrhagic fevers (HF caused by viruses and bacteria are a major public health problem in China and characterized by variable clinical manifestations, such that it is often difficult to achieve accurate diagnosis and treatment. The causes of HF in 85 patients admitted to Dandong hospital, China, between 2011-2012 were determined by serological and PCR tests. Of these, 34 patients were diagnosed with Huaiyangshan hemorrhagic fever (HYSHF, 34 with Hemorrhagic Fever with Renal Syndrome (HFRS, one with murine typhus, and one with scrub typhus. Etiologic agents could not be determined in the 15 remaining patients. Phylogenetic analyses of recovered bacterial and viral sequences revealed that the causative infectious agents were closely related to those described in other geographical regions. As these diseases have no distinctive clinical features in their early stage, only 13 patients were initially accurately diagnosed. The distinctive clinical features of HFRS and HYSHF developed during disease progression. Enlarged lymph nodes, cough, sputum, and diarrhea were more common in HYSHF patients, while more HFRS cases presented with headache, sore throat, oliguria, percussion pain kidney area, and petechiae. Additionally, HYSHF patients displayed significantly lower levels of white blood cells (WBC, higher levels of creations kinase (CK and alanine aminotransferase (ALT, while HFRS patients presented with an elevation of blood urea nitrogen (BUN and creatinine (CREA. These clinical features will assist in the accurate diagnosis of both HYSHF and HFRS. Overall, our data reveal the complexity of pathogens causing HFs in a single Chinese hospital, and highlight the need for accurate early diagnosis and a better understanding of their distinctive clinical features.

  5. A 6-gene signature identifies four molecular subgroups of neuroblastoma

    Science.gov (United States)

    2011-01-01

    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 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. PMID:21492432

  6. A single test for rejecting the null hypothesis in subgroups and in the overall sample.

    Science.gov (United States)

    Lin, Yunzhi; Zhou, Kefei; Ganju, Jitendra

    2017-01-01

    In clinical trials, some patient subgroups are likely to demonstrate larger effect sizes than other subgroups. For example, the effect size, or informally the benefit with treatment, is often greater in patients with a moderate condition of a disease than in those with a mild condition. A limitation of the usual method of analysis is that it does not incorporate this ordering of effect size by patient subgroup. We propose a test statistic which supplements the conventional test by including this information and simultaneously tests the null hypothesis in pre-specified subgroups and in the overall sample. It results in more power than the conventional test when the differences in effect sizes across subgroups are at least moderately large; otherwise it loses power. The method involves combining p-values from models fit to pre-specified subgroups and the overall sample in a manner that assigns greater weight to subgroups in which a larger effect size is expected. Results are presented for randomized trials with two and three subgroups.

  7. Identification of distinct fatigue trajectories in patients with breast cancer undergoing adjuvant chemotherapy.

    Science.gov (United States)

    Junghaenel, Doerte U; Cohen, Jules; Schneider, Stefan; Neerukonda, Anu R; Broderick, Joan E

    2015-09-01

    The goal of this study was to characterize changes in daily fatigue in women undergoing chemotherapy for breast cancer. We examined whether there are subgroups of patients with distinct fatigue trajectories and explored potential psychosocial and biomedical predictors of these subgroups. Participants were 77 women with breast cancer receiving adjuvant chemotherapy with AC-T (2-week cycle) and TC or TCH (3-week cycle) regimens. They completed 28 daily ratings online using an adapted version of the Patient-Reported Outcomes Measurement Information System (PROMIS®) fatigue instrument. Both regimens followed an "inverted-U-shaped" fatigue pattern over approximately 2 weeks. Growth mixture modeling identified three patient subgroups with distinct trajectories. Fatigue scores in the "low fatigue" group (23 %) increased following the infusion and quickly abated. The "transient fatigue" (27 %) group had a very pronounced increase. Patients in the "high fatigue" (50 %) group reported consistently elevated fatigue with a relatively small increase. Demographic and medical variables were not associated with fatigue trajectory. Patients in the "high fatigue" group reported significantly poorer physical, emotional, and social functioning, poorer general health, and more depressed mood than patients in the "low fatigue" group. The "transient fatigue" group reported significantly better physical and social functioning than the "high fatigue" group, but emotional distress and depression similar to the "high fatigue" group. The identification of patient subgroups with distinct fatigue trajectories during chemotherapy is an essential step for developing preventative strategies and tailored interventions. Our results suggest that different trajectories are associated with patients' psychosocial and general health.

  8. Recommendations for clinical staging (cTNM) of cancer of the esophagus and esophagogastric junction for the 8th edition AJCC/UICC staging manuals

    Science.gov (United States)

    Rice, Thomas W.; Ishwaran, Hemant; Blackstone, Eugene H.; Hofstetter, Wayne L.; Kelsen, David P.; Apperson-Hansen, Carolyn

    2017-01-01

    SUMMARY We report analytic and consensus processes that produced recommendations for clinical stage groups (cTNM) of esophageal and esophagogastric junction cancer for the AJCC/UICC cancer staging manuals, 8th edition. The Worldwide Esophageal Cancer Collaboration (WECC) provided data on 22,123 clinically staged patients with epithelial esophageal cancers. Risk-adjusted survival for each patient was developed using random survival forest analysis from which (1) data-driven clinical stage groups were identified wherein survival decreased monotonically and was distinctive between and homogeneous within groups and (2) data-driven anatomic clinical stage groups based only on cTNM. The AJCC Upper GI Task Force, by smoothing, simplifying, expanding, and assessing clinical applicability, produced (3) consensus clinical stage groups. Compared with pTNM, cTNM survival was “pinched,” with poorer survival for early cStage groups and better survival for advanced ones. Histologic grade was distinctive for data-driven grouping of cT2N0M0 squamous cell carcinoma (SCC) and cT1-2N0M0 adenocarcinoma, but consensus removed it. Grouping was different by histopathologic cell type. For SCC, cN0-1 was distinctive for cT3 but not cT1-2, and consensus removed cT4 subclassification and added subgroups 0, IVA, and IVB. For adenocarcinoma, N0-1 was distinctive for cT1-2 but not cT3-4a, cStage II subgrouping was necessary (T1N1M0 [IIA] and T2N0M0 [IIB]), advanced cancers cT3-4aN0-1M0 plus cT2N1M0 comprised cStage III, and consensus added subgroups 0, IVA, and IVB. Treatment decisions require accurate cStage, which differs from pStage. Understaging and overstaging are problematic, and additional factors, such as grade, may facilitate treatment decisions and prognostication until clinical staging techniques are uniformly applied and improved. PMID:27905171

  9. Recommendations for clinical staging (cTNM) of cancer of the esophagus and esophagogastric junction for the 8th edition AJCC/UICC staging manuals.

    Science.gov (United States)

    Rice, Thomas W; Ishwaran, Hemant; Blackstone, Eugene H; Hofstetter, Wayne L; Kelsen, David P; Apperson-Hansen, Carolyn

    2016-11-01

    We report analytic and consensus processes that produced recommendations for clinical stage groups (cTNM) of esophageal and esophagogastric junction cancer for the AJCC/UICC cancer staging manuals, 8th edition. The Worldwide Esophageal Cancer Collaboration (WECC) provided data on 22,123 clinically staged patients with epithelial esophageal cancers. Risk-adjusted survival for each patient was developed using random survival forest analysis from which (1) data-driven clinical stage groups were identified wherein survival decreased monotonically and was distinctive between and homogeneous within groups and (2) data-driven anatomic clinical stage groups based only on cTNM. The AJCC Upper GI Task Force, by smoothing, simplifying, expanding, and assessing clinical applicability, produced (3) consensus clinical stage groups. Compared with pTNM, cTNM survival was "pinched," with poorer survival for early cStage groups and better survival for advanced ones. Histologic grade was distinctive for data-driven grouping of cT2N0M0 squamous cell carcinoma (SCC) and cT1-2N0M0 adenocarcinoma, but consensus removed it. Grouping was different by histopathologic cell type. For SCC, cN0-1 was distinctive for cT3 but not cT1-2, and consensus removed cT4 subclassification and added subgroups 0, IVA, and IVB. For adenocarcinoma, N0-1 was distinctive for cT1-2 but not cT3-4a, cStage II subgrouping was necessary (T1N1M0 [IIA] and T2N0M0 [IIB]), advanced cancers cT3-4aN0-1M0 plus cT2N1M0 comprised cStage III, and consensus added subgroups 0, IVA, and IVB. Treatment decisions require accurate cStage, which differs from pStage. Understaging and overstaging are problematic, and additional factors, such as grade, may facilitate treatment decisions and prognostication until clinical staging techniques are uniformly applied and improved. © 2016 International Society for Diseases of the Esophagus.

  10. 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

  11. 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

  12. The interest of gait markers in the identification of subgroups among fibromyalgia patients

    Science.gov (United States)

    2011-01-01

    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 reduced SR was

  13. Predicting disease Risk by Transformation Models in the Presence of Unspecified Subgroup Membership.

    Science.gov (United States)

    Wang, Qianqian; Ma, Yanyuan; Wang, Yuanjia

    2017-10-01

    Some biomedical studies lead to mixture data. When a discrete covariate defining subgroup membership is missing for some of the subjects in a study, the distribution of the outcome follows a mixture distribution of the subgroup-specific distributions. Taking into account the uncertain distribution of the group membership and the covariates, we model the relation between the disease onset time and the covariates through transformation models in each sub-population, and develop a nonparametric maximum likelihood based estimation implemented through EM algorithm along with its inference procedure. We further propose methods to identify the covariates that have different effects or common effects in distinct populations, which enables parsimonious modeling and better understanding of the difference across populations. The methods are illustrated through extensive simulation studies and a real data example.

  14. Interpersonal Subtypes Within Social Anxiety: The Identification of Distinct Social Features.

    Science.gov (United States)

    Cooper, Danielle; Anderson, Timothy

    2017-10-05

    Although social anxiety disorder is defined by anxiety-related symptoms, little research has focused on the interpersonal features of social anxiety. Prior studies (Cain, Pincus, & Grosse Holtforth, 2010; Kachin, Newman, & Pincus, 2001) identified distinct subgroups of socially anxious individuals' interpersonal circumplex problems that were blends of agency and communion, and yet inconsistencies remain. We predicted 2 distinct interpersonal subtypes would exist for individuals with high social anxiety, and that these social anxiety subtypes would differ on empathetic concern, paranoia, received peer victimization, perspective taking, and emotional suppression. From a sample of 175 undergraduate participants, 51 participants with high social anxiety were selected as above a clinical cutoff on the social phobia scale. Cluster analyses identified 2 interpersonal subtypes of socially anxious individuals: low hostility-high submissiveness (Cluster 1) and high hostility-high submissiveness (Cluster 2). Cluster 1 reported higher levels of empathetic concern, lower paranoia, less peer victimization, and lower emotional suppression compared to Cluster 2. There were no differences between subtypes on perspective taking or cognitive reappraisal. Findings are consistent with an interpersonal conceptualization of social anxiety, and provide evidence of distinct social features between these subtypes. Findings have implications for the etiology, classification, and treatment of social anxiety.

  15. Pharmacodynamic analysis of the analgesic effect of capsaicin 8% patch (QutenzaTM in diabetic neuropathic pain patients: detection of distinct response groups

    Directory of Open Access Journals (Sweden)

    Martini C

    2012-03-01

    Full Text Available Christian Martini1,*, Ashraf Yassen2,*, Erik Olofsen1, Paul Passier2, Malcom Stoker3, Albert Dahan1 1Department of Anesthesiology, Leiden University Medical Center, Leiden, The Netherlands; 2Global Clinical Pharmacology and Exploratory Development, Astellas Pharma Global Development Europe, Leiderdorp, The Netherlands; 3Global Medical Sciences, Astellas Pharma Global Development Europe, Leiderdorp, The Netherlands*These authors contributed equally to this workAbstract: Treatment of chronic pain is associated with high variability in the response to pharmacological interventions. A mathematical pharmacodynamic model was developed to quantify the magnitude and onset/offset times of effect of a single capsaicin 8% patch application in the treatment of painful diabetic peripheral neuropathy in 91 patients. In addition, a mixture model was applied to objectively match patterns in pain-associated behavior. The model identified four distinct subgroups that responded differently to treatment: 3.3% of patients (subgroup 1 showed worsening of pain; 31% (subgroup 2 showed no change; 32% (subgroup 3 showed a quick reduction in pain that reached a nadir in week 3, followed by a slow return towards baseline (16% ± 6% pain reduction in week 12; 34% (subgroup 4 showed a quick reduction in pain that persisted (70% ± 5% reduction in week 12. The estimate of the response-onset rate constant, obtained for subgroups 1, 3, and 4, was 0.76 ± 0.12 week-1 (median ± SE, indicating that every 0.91 weeks the pain score reduces or increases by 50% relative to the score of the previous week (= t½. The response-offset rate constant could be determined for subgroup 3 only and was 0.09 ± 0.04 week-1 (t½ 7.8 weeks. The analysis allowed separation of a heterogeneous neuropathic pain population into four homogenous subgroups with distinct behaviors in response to treatment with capsaicin. It is argued that this model-based approach may have added value in analyzing

  16. Molecular characterization of subgenotype A1 (subgroup Aa) of hepatitis B virus.

    Science.gov (United States)

    Kramvis, Anna; Kew, Michael C

    2007-07-01

    Subgenotypes of hepatitis B virus (HBV) were first recognized after a unique segment of genotype A was identified when sequencing the preS2/S region of southern African HBV isolates. Originally named subgroup A', subsequently called subgroup Aa (for Africa) or subgenotype A1, this subgenotype is found in South Africa, Malawi, Uganda, Tanzania, Somalia, Yemen, India, Nepal, the Philippines and Brazil. The relatively higher mean nucleotide divergence of subgenotype A1 suggests that it has been endemic and has a long evolutionary history in the populations where it prevails. Distinctive sequence characteristics could account for the high hepatitis B e-antigen (HBeAg) negativity and low HBV DNA levels in carriers of this subgenotype. Substitutions or mutations can reduce HBeAg expression at three levels: (i) 1762T1764A atthe transcriptional level; (ii) substitutions at nt 1809-1812 at the translational level; and (iii) 1862T at the post-translational level. Co-existence of 1762T1764A and nt 1809-1812 mutations reduces HBeAg expression in an additive manner. In addition, subgenotype A1 has unique sequence alterations in the transcriptional regulatory elements and the polymerase coding region. The distinct sequence characteristics of subgenotype A1 may contribute to the 4.5-fold increased risk of heptocellular carcinoma in HBV carriers infected with genotype A, which is entirely attributable to subgenotype A1.

  17. Early antihypertensive treatment and clinical outcomes in acute ischemic stroke: subgroup analysis by baseline blood pressure.

    Science.gov (United States)

    He, William J; Zhong, Chongke; Xu, Tan; Wang, Dali; Sun, Yingxian; Bu, Xiaoqing; Chen, Chung-Shiuan; Wang, Jinchao; Ju, Zhong; Li, Qunwei; Zhang, Jintao; Geng, Deqin; Zhang, Jianhui; Li, Dong; Li, Yongqiu; Yuan, Xiaodong; Zhang, Yonghong; Kelly, Tanika N

    2018-06-01

    We studied the effect of early antihypertensive treatment on death, major disability, and vascular events among patients with acute ischemic stroke according to their baseline SBP. We randomly assigned 4071 acute ischemic stroke patients with SBP between 140 and less than 220 mmHg to receive antihypertensive treatment or to discontinue all antihypertensive medications during hospitalization. A composite primary outcome of death and major disability and secondary outcomes were compared between treatment and control stratified by baseline SBP levels of less than 160, 160-179, and at least 180 mmHg. At 24 h after randomization, differences in SBP reductions were 8.8, 8.6 and 7.8 mmHg between the antihypertensive treatment and control groups among patients with baseline SBP less than 160, 160-179, and at least 180 mmHg, respectively (P baseline SBP subgroups on death (P = 0.02): odds ratio (95% CI) of 2.42 (0.74-7.89) in patients with baseline SBP less than 60 mmHg and 0.34 (0.11-1.09) in those with baseline SBP at least 180 mmHg. At the 3-month follow-up, the primary and secondary clinical outcomes were not significantly different between the treatment and control groups by baseline SBP levels. Early antihypertensive treatment had a neutral effect on clinical outcomes among acute ischemic stroke patients with various baseline SBP levels. Future clinical trials are warranted to test BP-lowering effects in acute ischemic stroke patients by baseline SBP levels. ClinicalTrials.gov Identifier: NCT01840072.

  18. Segmental stiff skin syndrome (SSS): A distinct clinical entity.

    Science.gov (United States)

    Myers, Kathryn L; Mir, Adnan; Schaffer, Julie V; Meehan, Shane A; Orlow, Seth J; Brinster, Nooshin K

    2016-07-01

    Stiff skin syndrome (SSS) is a noninflammatory, fibrosing condition of the skin, often affecting the limb girdles. We present 4 new patients with SSS with largely unilateral, segmental distribution. To date, reported cases of SSS have been grouped based on generally accepted clinical and histopathologic findings. The purpose of this study was to analyze differences in clinical and histopathologic findings between previously reported SSS cases. This is a retrospective review of 4 new cases and 48 previously published cases of SSS obtained from PubMed search. Of 52 total cases, 18 (35%) were segmentally distributed and 34 (65%) were widespread. The average age of onset was 4.1 years versus 1.6 years for segmental versus widespread SSS, respectively. Limitation in joint mobility affected 44% of patients with segmental SSS and 97% of patients with widespread SSS. Histopathologic findings were common between the 2 groups. This was a retrospective study of previously published cases limited by the completeness and accuracy of the reviewed cases. We propose a distinct clinical entity, segmental SSS, characterized by a segmental distribution, later age of onset, and less severe functional limitation. Both segmental SSS and widespread SSS share common diagnostic histopathologic features. Copyright © 2016 American Academy of Dermatology, Inc. All rights reserved.

  19. Background-cross-section-dependent subgroup parameters

    International Nuclear Information System (INIS)

    Yamamoto, Toshihisa

    2003-01-01

    A new set of subgroup parameters was derived that can reproduce the self-shielded cross section against a wide range of background cross sections. The subgroup parameters are expressed with a rational equation which numerator and denominator are expressed as the expansion series of background cross section, so that the background cross section dependence is exactly taken into account in the parameters. The advantage of the new subgroup parameters is that they can reproduce the self-shielded effect not only by group basis but also by subgroup basis. Then an adaptive method is also proposed which uses fitting procedure to evaluate the background-cross-section-dependence of the parameters. One of the simple fitting formula was able to reproduce the self-shielded subgroup cross section by less than 1% error from the precise evaluation. (author)

  20. Pylon fractures of the ankle: A distinct clinical and radiological entity

    International Nuclear Information System (INIS)

    Mainwaring, B.L.; Daffner, R.H.; Riemer, B.L.

    1987-01-01

    Pylon fractures are a distinct clinical and radiological entity that should not be confused with trimalleolar fractures. Radiographic and clinical comparison of 20 cases of each fracture type revealed definite distinguishing features. First, pylon fractures inevitably were associated with profound comminution of the distal tibia. The trimalleolar injury was associated with fractures of the medial, lateral, and posterior malleoli without comminution. Second, in contrast to timalleolar fractures, pylon fractures had intraarticular extension of at least one tibial fracture through the dome of the plafond. Third, 60% of all pylon fractures were associated with a fractured talus; the talus was intact in all trimalleolar fractures. Fourth, the distal tibiofibular syndesmosis was constant in the pylon fractures but was separated in all trimalleolar fractures

  1. Distinct trajectories of positive and negative affect after colorectal cancer diagnosis

    NARCIS (Netherlands)

    Ciere, Yvette; Janse, Moniek; Almansa, Josué; Visser, Annemieke; Sanderman, Robbert; Sprangers, Mirjam A.G.; Ranchor, Adelita V.; Fleer, Joke

    2017-01-01

    Objective: Insight into trajectories of positive affect (PA) and negative affect (NA) across the cancer continuum may improve understanding of the nature of adjustment problems. The primary aim of this study was to identify subgroups of patients with distinct trajectories of PA and NA following

  2. Distinct Trajectories of Positive and Negative Affect After Colorectal Cancer Diagnosis

    NARCIS (Netherlands)

    Ciere, Yvette; Janse, Moniek; Almansa, Josué; Visser, Annemieke; Sanderman, Robbert; Sprangers, Mirjam A G; Ranchor, Adelita V; Fleer, Joke

    OBJECTIVE: Insight into trajectories of positive affect (PA) and negative affect (NA) across the cancer continuum may improve understanding of the nature of adjustment problems. The primary aim of this study was to identify subgroups of patients with distinct trajectories of PA and NA following

  3. Frequency and clinical impact of ETV6/RUNX1, AF4‑MLL, and BCR ...

    African Journals Online (AJOL)

    2015-05-12

    May 12, 2015 ... features of prognostic importance, which include total white blood cell count (P = 0.416) and FAB subtype (P = 0.576). Conclusion: Presence of fusion ... Frequency and clinical impact of ETV6/RUNX1, AF4‑MLL, and BCR/ABL fusion ... define distinct clinic‑pathological subgroups and have been used in risk ...

  4. Do mood symptoms subdivide the schizophrenia phenotype? : Association of the GMP6A gene with a depression subgroup

    NARCIS (Netherlands)

    Boks, Marco P M; Hoogendoorn, Mechteld; Jungerius, Bart J; Bakker, Steven C; Sommer, Iris E; Sinke, Richard J; Ophoff, Roel A; Kahn, René S

    2008-01-01

    Genetic studies of clinically defined subgroups of schizophrenia patients may reduce the phenotypic heterogeneity of schizophrenia and thus facilitate the identification of genes that confer risk to this disorder. Several latent class analyses have provided subgroups of psychotic disorders that show

  5. Model-Based Recursive Partitioning for Subgroup Analyses.

    Science.gov (United States)

    Seibold, Heidi; Zeileis, Achim; Hothorn, Torsten

    2016-05-01

    The identification of patient subgroups with differential treatment effects is the first step towards individualised treatments. A current draft guideline by the EMA discusses potentials and problems in subgroup analyses and formulated challenges to the development of appropriate statistical procedures for the data-driven identification of patient subgroups. We introduce model-based recursive partitioning as a procedure for the automated detection of patient subgroups that are identifiable by predictive factors. The method starts with a model for the overall treatment effect as defined for the primary analysis in the study protocol and uses measures for detecting parameter instabilities in this treatment effect. The procedure produces a segmented model with differential treatment parameters corresponding to each patient subgroup. The subgroups are linked to predictive factors by means of a decision tree. The method is applied to the search for subgroups of patients suffering from amyotrophic lateral sclerosis that differ with respect to their Riluzole treatment effect, the only currently approved drug for this disease.

  6. Myasthenia gravis: subgroup classification and therapeutic strategies.

    Science.gov (United States)

    Gilhus, Nils Erik; Verschuuren, Jan J

    2015-10-01

    Myasthenia gravis is an autoimmune disease that is characterised by muscle weakness and fatigue, is B-cell mediated, and is associated with antibodies directed against the acetylcholine receptor, muscle-specific kinase (MUSK), lipoprotein-related protein 4 (LRP4), or agrin in the postsynaptic membrane at the neuromuscular junction. Patients with myasthenia gravis should be classified into subgroups to help with therapeutic decisions and prognosis. Subgroups based on serum antibodies and clinical features include early-onset, late-onset, thymoma, MUSK, LRP4, antibody-negative, and ocular forms of myasthenia gravis. Agrin-associated myasthenia gravis might emerge as a new entity. The prognosis is good with optimum symptomatic, immunosuppressive, and supportive treatment. Pyridostigmine is the preferred symptomatic treatment, and for patients who do not adequately respond to symptomatic therapy, corticosteroids, azathioprine, and thymectomy are first-line immunosuppressive treatments. Additional immunomodulatory drugs are emerging, but therapeutic decisions are hampered by the scarcity of controlled studies. Long-term drug treatment is essential for most patients and must be tailored to the particular form of myasthenia gravis. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    The Driver Behavior Questionnaire and the Driver Skill Inventory are two of the most frequently used measures of self-reported driving style and driving skill. The motivation behind the present study was to identify sub-groups of drivers that potentially act dangerously in traffic (as measured...... self-reported driving skills and whether the reported skill level was reflected in the reported aberrant driving behaviors. 3908 drivers aged 18–84 participated in the survey. K-means cluster analysis revealed four distinct sub-groups that differed in driving skills and frequency of aberrant driving...... by frequency of aberrant driving behaviors and level of driving skills), as well as to test whether the sub-groups differ in characteristics such as age, gender, annual mileage and accident involvement. Furthermore, the joint analysis of the two instruments was used to test drivers’ assessment of their own...

  8. Unexpected High Response Rate to Traditional Therapy after Dendritic Cell-Based Vaccine in Advanced Melanoma: Update of Clinical Outcome and Subgroup Analysis

    Directory of Open Access Journals (Sweden)

    Laura Ridolfi

    2010-01-01

    Full Text Available We reviewed the clinical results of a dendritic cell-based phase II clinical vaccine trial in stage IV melanoma and analyzed a patient subgroup treated with standard therapies after stopping vaccination. From 2003 to 2009, 24 metastatic melanoma patients were treated with mature dendritic cells pulsed with autologous tumor lysate and keyhole limpet hemocyanin and low-dose interleukin-2. Overall response (OR to vaccination was 37.5% with a clinical benefit of 54.1%. All 14 responders showed delayed type hypersensitivity positivity. Median overall survival (OS was 15 months (95% CI, 8–33. Eleven patients underwent other treatments (3 surgery, 2 biotherapy, 2 radiotherapy, 2 chemotherapy, and 4 biochemotherapy after stopping vaccination. Of these, 2 patients had a complete response and 5 a partial response, with an OR of 63.6%. Median OS was 34 months (range 16–61. Our results suggest that therapeutic DC vaccination could favor clinical response in patients after more than one line of therapy.

  9. Unexpected high response rate to traditional therapy after dendritic cell-based vaccine in advanced melanoma: update of clinical outcome and subgroup analysis.

    Science.gov (United States)

    Ridolfi, Laura; Petrini, Massimiliano; Fiammenghi, Laura; Granato, Anna Maria; Ancarani, Valentina; Pancisi, Elena; Scarpi, Emanuela; Guidoboni, Massimo; Migliori, Giuseppe; Sanna, Stefano; Tauceri, Francesca; Verdecchia, Giorgio Maria; Riccobon, Angela; Valmorri, Linda; Ridolfi, Ruggero

    2010-01-01

    We reviewed the clinical results of a dendritic cell-based phase II clinical vaccine trial in stage IV melanoma and analyzed a patient subgroup treated with standard therapies after stopping vaccination. From 2003 to 2009, 24 metastatic melanoma patients were treated with mature dendritic cells pulsed with autologous tumor lysate and keyhole limpet hemocyanin and low-dose interleukin-2. Overall response (OR) to vaccination was 37.5% with a clinical benefit of 54.1%. All 14 responders showed delayed type hypersensitivity positivity. Median overall survival (OS) was 15 months (95% CI, 8-33). Eleven patients underwent other treatments (3 surgery, 2 biotherapy, 2 radiotherapy, 2 chemotherapy, and 4 biochemotherapy) after stopping vaccination. Of these, 2 patients had a complete response and 5 a partial response, with an OR of 63.6%. Median OS was 34 months (range 16-61). Our results suggest that therapeutic DC vaccination could favor clinical response in patients after more than one line of therapy.

  10. Model-based Recursive Partitioning for Subgroup Analyses

    OpenAIRE

    Seibold, Heidi; Zeileis, Achim; Hothorn, Torsten

    2016-01-01

    The identification of patient subgroups with differential treatment effects is the first step towards individualised treatments. A current draft guideline by the EMA discusses potentials and problems in subgroup analyses and formulated challenges to the development of appropriate statistical procedures for the data-driven identification of patient subgroups. We introduce model-based recursive partitioning as a procedure for the automated detection of patient subgroups that are identifiable by...

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    BACKGROUND: Neurocognitive impairment in remitted patients with bipolar disorder contributes to functional disabilities. However, the pattern and impact of these deficits are unclear. METHODS: We pooled data from 193 fully or partially remitted patients with bipolar disorder and 110 healthy...... controls. Hierarchical cluster analysis was conducted to determine whether there are discrete neurocognitive subgroups in bipolar disorder. The pattern of the cognitive deficits and the characteristics of patients in these neurocognitive subgroups were examined with analyses of covariance and least...... was cross-sectional which limits inferences regarding the causality of the findings. CONCLUSION: Globally and selectively impaired bipolar disorder patients displayed more functional disabilities than those who were cognitively intact. The present findings highlight a clinical need to systematically screen...

  12. Medical specialty selection criteria of Israeli medical students early in their clinical experience: subgroups.

    Science.gov (United States)

    Avidan, Alexander; Weissman, Charles; Elchalal, Uriel; Tandeter, Howard; Zisk-Rony, Rachel Yaffa

    2018-04-18

    Israeli medical school classes include a number of student subgroups. Therefore, interventions aimed at recruiting medical students to the various specialties should to be tailored to each subgroup. Questionnaires, distributed to 6 consecutive 5th-year classes of the Hebrew University - Hadassah School of Medicine, elicited information on criteria for choosing a career specialty, criteria for choosing a residency program and the importance of finding a specialty interesting and challenging when choosing a residency. Completed questionnaires were returned by 540 of 769 (70%) students. The decision processes for choosing a medical specialty and choosing a residency program were different. Family and colleagues had minimal influence on choosing a specialty, while family and their residential locality had much influence on choosing a residency, especially among women. Older age, marriage, and spousal influence were positively associated with choice of a specialty. Two-thirds of the students had completed military service, 20% were attending medical school prior to military service, 5% had completed national service and 9% had entered medical school without serving. Despite the pre-military subgroup being younger and having another 7 years of medical school, internship and military service before residency, they had begun thinking about which specialty to choose, just like the post-military students. When choosing a residency program, post-military women were more influenced by their families and family residential locality than their pre-military counterparts; differences ascribed to the older and often married post-military women having or wanting to begin families. This difference was reinforced by fewer post- than pre-military women willing to wait 2-3 years for a residency in the specialty that interested them most and were willing to begin residency immediately after internship in a specialty that interested them less. Medical school classes are composed of

  13. On the subgroups of PR groups

    International Nuclear Information System (INIS)

    Lebedenko, V.M.

    1979-01-01

    The subgroups of PR-groups are being studied, i.e., the subgroups of connected and simply connected nonabelian Lie groups, their Lie algebras being defined by the commuting relations of the type [Hsub(i), Hsub(j)] = rsub(ij)Hsub(i) (i 1 of PR-group G there exists such complementary subgroup G 2 and that group G is expanded in semidirect product G = G 1 xG 2 [ru

  14. A 6-gene signature identifies four molecular subgroups of neuroblastoma

    Directory of Open Access Journals (Sweden)

    Kogner Per

    2011-04-01

    Full Text Available 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 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 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.

  15. Prognostic value of Ki-67 index in adult medulloblastoma after accounting for molecular subgroup: a retrospective clinical and molecular analysis.

    Science.gov (United States)

    Zhao, Fu; Zhang, Jing; Li, Peng; Zhou, Qiangyi; Zhang, Shun; Zhao, Chi; Wang, Bo; Yang, Zhijun; Li, Chunde; Liu, Pinan

    2018-04-23

    Medulloblastoma (MB) is a rare primary brain tumor in adults. We previously evaluated that combining both clinical and molecular classification could improve current risk stratification for adult MB. In this study, we aimed to identify the prognostic value of Ki-67 index in adult MB. Ki-67 index of 51 primary adult MBs was reassessed using a computer-based image analysis (Image-Pro Plus). All patients were followed up ranging from 12 months up to 15 years. Gene expression profiling and immunochemistry were used to establish the molecular subgroups in adult MB. Combined risk stratification models were designed based on clinical characteristics, molecular classification and Ki-67 index, and identified by multivariable Cox proportional hazards analysis. In our cohort, the mean Ki-67 value was 30.0 ± 11.3% (range 6.56-63.55%). The average Ki-67 value was significantly higher in LC/AMB than in CMB and DNMB (P = .001). Among three molecular subgroups, Group 4-tumors had the highest average Ki-67 value compared with WNT- and SHH-tumors (P = .004). Patients with Ki-67 index large than 30% displayed poorer overall survival (OS) and progression free survival (PFS) than those with Ki-67 less than 30% (OS: P = .001; PFS: P = .006). Ki-67 index (i.e. > 30%, < 30%) was identified as an independent significant prognostic factor (OS: P = .017; PFS: P = .024) by using multivariate Cox proportional hazards model. In conclusion, Ki-67 index can be considered as a valuable independent prognostic biomarker for adult patients with MB.

  16. Expression of endogenous ALV antigens and susceptibility to subgroup E ALV in three strains of chickens (Endogenous avian C. type virus)

    International Nuclear Information System (INIS)

    Robinson, H.L.; Lamoreux, W.F.

    1976-01-01

    Cells from three strains of Kimber Farms chickens, K16, K18, and K28, have been characterized for the expression of endogenous avian C-type virus (ALV) antigens and for susceptibility to subgroup E ALV. In K16 the coordinate dominant expression of chick helper factor (chf ), the type specific antigen of endogenous subgroup E ALV, and the group specific (gs) antigen of ALV was observed. The expression of chf and gs antigen in K16 chf + gs + cells was similar to that observed in SPAFAS and H and N gs + cells. In K18 chf but not gs antigen was expressed. The expression of chf in K18 chf + gs + cells was distinct from that observed for the chf + gs + pedigrees but similar to that found in SPAFAS chf + gs - helper extremely high (h/sub E/) cells. Cells from K16 and K18 chickens were uniformly resistant to subgroup E ALV. In cells from K28 chickens, susceptibility to subgroup B virus correlated with susceptibility to subgroup E virus. The efficiency of plating of subgroup E virus on susceptible K28 cells with 10 3 --10 4 -fold lower on chf + cells than on chf - cells

  17. Autoimmune-autoinflammatory rheumatoid arthritis overlaps: a rare but potentially important subgroup of diseases.

    Science.gov (United States)

    Savic, Sinisa; Mistry, Anoop; Wilson, Anthony G; Barcenas-Morales, Gabriela; Doffinger, Rainer; Emery, Paul; McGonagle, Dennis

    2017-01-01

    At the population level, rheumatoid arthritis (RA) is generally viewed as autoimmune in nature with a small subgroup of cases having a palindromic form or systemic autoinflammatory disorder (SAID) phenotype. Herein, we describe resistant cases of classical autoantibody associated RA that had clinical, genetic and therapeutic responses indicative of coexistent autoinflammatory disease. Five patients with clinically overlapping features between RA and SAID including polysynovitis and autoantibody/shared epitope positivity, and who had abrupt severe self-limiting attacks including fevers and serositis, are described. Mutations or single nucleotide polymorphisms in recognised autoinflammatory pathways were evident. Generally, these cases responded poorly to conventional Disease-modifying anti-rheumatic drugs (DMARD) treatment with some excellent responses to colchicine or interleukin 1 pathway blockade. A subgroup of RA cases have a mixed autoimmune-autoinflammatory phenotype and genotype with therapeutic implications.

  18. Finite subgroups of SU(3)

    International Nuclear Information System (INIS)

    Bovier, A.; Lueling, M.; Wyler, D.

    1980-12-01

    We present a new class of finite subgroups of SU(3) of the form Zsub(m) s zsub(n) (semidirect product). We also apply the methods used to investigate semidirect products to the known SU(3) subgroups Δ(3n 2 ) and Δ(6n 2 ) and give analytic formulae for representations (characters) and Clebsch-Gordan coefficients. (orig.)

  19. A Note on TI-Subgroups of Finite Groups

    Indian Academy of Sciences (India)

    A subgroup of a finite group is called a TI-subgroup if H ∩ H x = 1 or for any x ∈ G . In this short note, the finite groups all of whose nonabelian subgroups are TI-subgroups are classified. Author Affiliations. Jiakuan Lu1 Linna Pang1. Department of Mathematics, Guangxi Normal University, Guangxi, Guilin 541004, ...

  20. Tephrostratigraphy and geochemical fingerprinting of the Mangaone Subgroup tephra beds, Okataina Volcanic Centre, New Zealand

    International Nuclear Information System (INIS)

    Smith, V.C.; Shane, P.; Smith, I.E.M.

    2002-01-01

    The Mangaone Subgroup is a sequence of 14 plinian tephra beds erupted from the Okataina Volcanic Centre in North Island, New Zealand, that are bracketed between the regional marker beds of Rotoehu Tephra (50-60 ka) and Oruanui Tephra (26 ka). The Mangaone Subgroup tephra beds are separated by thin paleosols in ascending stratigraphic order: unit A, unit B, unit C, Pupuwharau Tephra (new), Pongakawa Tephra (new), Maketu, Te Mahoe, Hauparu, unit G, unit H, Mangaone, Awakeri, Omataroa, and unit L. Geochemical fingerprinting of the glass and phenocryst phases allows clear subdivision of the Mangaone Subgroup into two stratigraphic intervals. Units A-G are rhyodacites and low-SiO 2 rhyolites (71-75.5 wt% SiO 2 glass; 68-71 wt% SiO 2 whole rock), clinopyroxene bearing, with calcic plagioclase (An 40-60 ) and magnesian orthopyroxene (En 60-70 ), and they display high eruption temperatures (870-940 degrees C) and oxygen fugacities (-log f O 2 11.66-10.40). Some of these units are compositionally heterogeneous in the glass phase (SiO 2 range up to 8 wt%), especially unit A, Ngamotu, Te Mahoe, and Hauparu tephra beds. Units A-G can easily be distinguished from other Taupo Volcanic Zone tephra erupted in the last c. 60 000 yr. Units H-L are high SiO 2 rhyolites (76-78 wt% SiO 2 glass; 71.5-75 wt% SiO 2 whole rock), which contain sodic plagioclase (An 30-40 ), low-Mg orthopyroxene (En 50-60 ), and display lower eruption temperatures (755-830 degrees C) and oxygen fugacities (-log f O 2 = 14.7-12.93). Compositional differences in titanomagnetite and ilmenite can also be used to distinguish them from older units. The two compositional groups also form distinct T-f O 2 trends. The shift in chemical affinity follows the large volume Hauparu eruption, and coincides with the likely geographic shift in vent location to the eastern margin of the caldera complex. Tephra beds that both predate and postdate the Mangaone Subgroup also reflect changes in magma type and vent location. The

  1. The Direct Assignment Option as a Modular Design Component: An Example for the Setting of Two Predefined Subgroups

    Directory of Open Access Journals (Sweden)

    Ming-Wen An

    2015-01-01

    Full Text Available Background. A phase II design with an option for direct assignment (stop randomization and assign all patients to experimental treatment based on interim analysis, IA for a predefined subgroup was previously proposed. Here, we illustrate the modularity of the direct assignment option by applying it to the setting of two predefined subgroups and testing for separate subgroup main effects. Methods. We power the 2-subgroup direct assignment option design with 1 IA (DAD-1 to test for separate subgroup main effects, with assessment of power to detect an interaction in a post-hoc test. Simulations assessed the statistical properties of this design compared to the 2-subgroup balanced randomized design with 1 IA, BRD-1. Different response rates for treatment/control in subgroup 1 (0.4/0.2 and in subgroup 2 (0.1/0.2, 0.4/0.2 were considered. Results. The 2-subgroup DAD-1 preserves power and type I error rate compared to the 2-subgroup BRD-1, while exhibiting reasonable power in a post-hoc test for interaction. Conclusion. The direct assignment option is a flexible design component that can be incorporated into broader design frameworks, while maintaining desirable statistical properties, clinical appeal, and logistical simplicity.

  2. Cluster analysis reveals subclinical subgroups with shared autistic and schizotypal traits.

    Science.gov (United States)

    Ford, Talitha C; Apputhurai, Pragalathan; Meyer, Denny; Crewther, David P

    2018-07-01

    Autism and schizophrenia spectrum research is typically based on coarse diagnostic classification, which overlooks individual variation within clinical groups. This method limits the identification of underlying cognitive, genetic and neural correlates of specific symptom dimensions. This study, therefore, aimed to identify homogenous subclinical subgroups of specific autistic and schizotypal traits dimensions, that may be utilised to establish more effective diagnostic and treatment practices. Latent profile analysis of subscale scores derived from an autism-schizotypy questionnaire, completed by 1678 subclinical adults aged 18-40 years (1250 females), identified a local optimum of eight population clusters: High, Moderate and Low Psychosocial Difficulties; High, Moderate and Low Autism-Schizotypy; High Psychosis-Proneness; and Moderate Schizotypy. These subgroups represent the convergent and discriminant dimensions of autism and schizotypy in the subclinical population, and highlight the importance of examining subgroups of specific symptom characteristics across these spectra in order to identify the underlying genetic and neural correlates that can be utilised to advance diagnostic and treatment practices. Copyright © 2018 Elsevier B.V. All rights reserved.

  3. Suicide Risk across Latent Class Subgroups: A Test of the Generalizability of the Interpersonal Psychological Theory of Suicide.

    Science.gov (United States)

    Ma, Jennifer S; Batterham, Philip J; Calear, Alison L; Han, Jin

    2018-01-06

    It remains unclear whether the Interpersonal Psychological Theory of Suicide (IPTS; Joiner, ) is generalizable to the population or holds more explanatory power for certain subgroups compared to others. The aim of this study was to (1) identify subgroups of individuals who endorsed suicide ideation in the past month based on a range of mental health and demographic variables, (2) compare levels of the IPTS constructs within these subgroups, and (3) test the IPTS predictions for suicide ideation and suicide attempt for each group. Latent class, negative binomial, linear, and logistic regression analyses were conducted on population-based data obtained from 1,321 adults recruited from Facebook. Among participants reporting suicide ideation, four distinct patterns of risk factors emerged based on age and severity of mental health symptoms. Groups with highly elevated mental health symptoms reported the highest levels of thwarted belongingness and perceived burdensomeness. Tests of the IPTS interactions provided partial support for the theory, primarily in young adults with elevated mental health symptoms. Lack of support found for the IPTS predictions across the subgroups and full sample in this study raise some questions around the broad applicability of the theory. © 2018 The American Association of Suicidology.

  4. Identification of subgroups of patients with tension type headache with higher widespread pressure pain hyperalgesia.

    Science.gov (United States)

    Fernández-de-Las-Peñas, César; Benito-González, Elena; Palacios-Ceña, María; Wang, Kelun; Castaldo, Matteo; Arendt-Nielsen, Lars

    2017-12-01

    Identification of subgroups of patients with different levels of sensitization and clinical features can help to identify groups at risk and the development of better therapeutic strategies. The aim of this study was to identify subgroups of patients with tension type headache (TTH) with different levels of sensitization, clinical pain features, and psychological outcomes. A total of 197 individuals with TTH participated. Headache intensity, frequency, and duration and medication intake were collected with a 4-weeks diary. Pressure pain thresholds were assessed bilaterally over the temporalis muscle, C5-C6 joint, second metacarpal and tibialis anterior muscle to determine widespread pressure pain hyperalgesia. The Hospital Anxiety and Depression Scale assessed anxiety and depression. The State-Trait Anxiety Inventory evaluated the state and trait levels of anxiety. The Headache Disability Inventory evaluated the burden of headache. Health-related quality of life was determined with the SF-36 questionnaire. Groups were considered as positive (three or more criteria) or negative (less than three criteria) on a clinical prediction rule: headache duration patients with TTH with higher sensitization, higher chronicity of headaches and worse quality of life but lower frequency and duration of headache episodes. This subgroup of individuals with TTH may need particular attention and specific therapeutic programs for avoiding potential chronification.

  5. Reporting on methods of subgroup analysis in clinical trials: a survey of four scientific journals

    Directory of Open Access Journals (Sweden)

    E.D. Moreira Jr.

    2001-11-01

    Full Text Available Results of subgroup analysis (SA reported in randomized clinical trials (RCT cannot be adequately interpreted without information about the methods used in the study design and the data analysis. Our aim was to show how often inaccurate or incomplete reports occur. First, we selected eight methodological aspects of SA on the basis of their importance to a reader in determining the confidence that should be placed in the author's conclusions regarding such analysis. Then, we reviewed the current practice of reporting these methodological aspects of SA in clinical trials in four leading journals, i.e., the New England Journal of Medicine, the Journal of the American Medical Association, the Lancet, and the American Journal of Public Health. Eight consecutive reports from each journal published after July 1, 1998 were included. Of the 32 trials surveyed, 17 (53% had at least one SA. Overall, the proportion of RCT reporting a particular methodological aspect ranged from 23 to 94%. Information on whether the SA preceded/followed the analysis was reported in only 7 (41% of the studies. Of the total possible number of items to be reported, NEJM, JAMA, Lancet and AJPH clearly mentioned 59, 67, 58 and 72%, respectively. We conclude that current reporting of SA in RCT is incomplete and inaccurate. The results of such SA may have harmful effects on treatment recommendations if accepted without judicious scrutiny. We recommend that editors improve the reporting of SA in RCT by giving authors a list of the important items to be reported.

  6. The association between subgroups of MRI findings identified with latent class analysis and low back pain in 40-year-old Danes

    DEFF Research Database (Denmark)

    Jensen, Rikke K; Kent, Peter; Jensen, Tue S

    2018-01-01

    for identifying latent classes (subgroups) of MRI findings within multivariable datasets. The purpose of this study was to investigate the association between subgroups of MRI findings and the presence of LBP in people from the general population. METHODS: To identify subgroups of lumbar MRI findings...... regression. RESULTS: Six subgroups were identified in the clinical dataset and the data from the general population cohort fitted the subgroups well, with a median posterior probability of 93%-100%. These six subgroups described two pathways of increasing degeneration on upper (L1-L3) and lower (L4-L5......) lumbar levels. An association with LBP was found for the subgroups describing severe and multiple degenerative MRI findings at the lower lumbar levels but none of the other subgroups were associated with LBP. CONCLUSION: Although MRI findings are common in asymptomatic people and the association between...

  7. ∗-supplemented subgroups of finite groups

    Indian Academy of Sciences (India)

    A subgroup H of a group G is said to be M∗-supplemented in G if ... normal subgroups and determined the structure of finite groups by using some ...... [12] Monakhov V S and Shnyparkov A V, On the p-supersolubility of a finite group with a.

  8. Atorvastatin in stroke: a review of SPARCL and subgroup analysis

    Directory of Open Access Journals (Sweden)

    Branko N Huisa

    2010-03-01

    Full Text Available Branko N Huisa, Andrew B Stemer, Justin A ZivinDepartment of Neuroscience University of California, San Diego, CA, USAAbstract: Statin therapy in patients with cardiovascular disease is associated with reduced incidence of stroke. The Stroke Prevention by Aggressive Reduction of Cholesterol Levels (SPARCL trial showed daily treatment with 80 mg of atorvastatin in patients with a recent stroke or transient ischemic attack (TIA reduced the incidence of fatal or nonfatal stroke by 16%. Several post hoc analyses of different subgroups followed the SPARCL study. They have not revealed any significant differences when patients were sorted by age, sex, presence of carotid disease or type of stroke, with the exception of intracranial hemorrhage as the entry event. Lower low-density lipoprotein cholesterol levels in addition to possible neuroprotective mechanisms due to atorvastatin treatment correlate with improved risk reduction. Although not predefined subgroups and subject to an insufficient power, these post hoc studies have generated new clinical questions. However, clinicians should avoid denying therapy based on such subgroup analysis. At this point, the best evidence powerfully demonstrates stroke and TIA patients should be prescribed high dose statin therapy for secondary stroke prevention.Keywords: statins, intracranial hemorrhage, neuroprotection, outcome, prevention, carotid stenosis, transient ischemic attack

  9. A 6-gene signature identifies four molecular subgroups of neuroblastoma

    LENUS (Irish Health Repository)

    Abel, Frida

    2011-04-14

    Abstract Background There are currently three postulated genomic subtypes of the childhood tumour neuroblastoma (NB); Type 1, Type 2A, and Type 2B. The most aggressive forms of NB are characterized by amplification of the oncogene MYCN (MNA) and low expression of the favourable marker NTRK1. Recently, mutations or high expression of the familial predisposition gene Anaplastic Lymphoma Kinase (ALK) was associated to unfavourable biology of sporadic NB. Also, various other genes have been linked to NB pathogenesis. Results The present study explores subgroup discrimination by gene expression profiling using three published microarray studies on NB (47 samples). Four distinct clusters were identified by Principal Components Analysis (PCA) in two separate data sets, which could be verified by an unsupervised hierarchical clustering in a third independent data set (101 NB samples) using a set of 74 discriminative genes. The expression signature of six NB-associated genes ALK, BIRC5, CCND1, MYCN, NTRK1, and PHOX2B, significantly discriminated the four clusters (p < 0.05, one-way ANOVA test). PCA clusters p1, p2, and p3 were found to correspond well to the postulated subtypes 1, 2A, and 2B, respectively. Remarkably, a fourth novel cluster was detected in all three independent data sets. This cluster comprised mainly 11q-deleted MNA-negative tumours with low expression of ALK, BIRC5, and PHOX2B, and was significantly associated with higher tumour stage, poor outcome and poor survival compared to the Type 1-corresponding favourable group (INSS stage 4 and\\/or dead of disease, p < 0.05, Fisher\\'s exact test). Conclusions Based on expression profiling we have identified four molecular subgroups of neuroblastoma, which can be distinguished by a 6-gene signature. The fourth subgroup has not been described elsewhere, and efforts are currently made to further investigate this group\\'s specific characteristics.

  10. Subgroups of GLn(R) for local rings R

    International Nuclear Information System (INIS)

    Kuku, A.O.; Mahdavi-Hezavehi, M.

    2002-07-01

    Let R be a local ring, with maximal ideal m, and residue class division ring R/m=D. Put A=M n (R)-n≥1, and denote by A*=GL n (R) the group of units of A. Here we investigate some algebraic structure of subnormal and maximal subgroups of A * . For instance, when D is of finite dimension over its center, it is shown that finitely generated subnormal subgroups of A* are central. It is also proved that maximal subgroups of A* are not finitely generated. Furthermore, assume that P is a nonabelian maximal subgroup of GL 1 (R) such that P contains a noncentral soluble normal subgroup of finite index, it is shown that D is a crossed product division algebra. (author)

  11. Distinct genetic difference between the Duffy binding protein (PkDBPαII) of Plasmodium knowlesi clinical isolates from North Borneo and Peninsular Malaysia.

    Science.gov (United States)

    Fong, Mun-Yik; Rashdi, Sarah A A; Yusof, Ruhani; Lau, Yee-Ling

    2015-02-21

    Plasmodium knowlesi is one of the monkey malaria parasites that can cause human malaria. The Duffy binding protein of P. knowlesi (PkDBPαII) is essential for the parasite's invasion into human and monkey erythrocytes. A previous study on P. knowlesi clinical isolates from Peninsular Malaysia reported high level of genetic diversity in the PkDBPαII. Furthermore, 36 amino acid haplotypes were identified and these haplotypes could be separated into allele group I and allele group II. In the present study, the PkDBPαII of clinical isolates from the Malaysian states of Sarawak and Sabah in North Borneo was investigated, and compared with the PkDBPαII of Peninsular Malaysia isolates. Blood samples from 28 knowlesi malaria patients were used. These samples were collected between 2011 and 2013 from hospitals in North Borneo. The PkDBPαII region of the isolates was amplified by PCR, cloned into Escherichia coli, and sequenced. The genetic diversity, natural selection and phylogenetics of PkDBPαII haplotypes were analysed using MEGA5 and DnaSP ver. 5.10.00 programmes. Forty-nine PkDBPαII sequences were obtained. Comparison at the nucleotide level against P. knowlesi strain H as reference sequence revealed 58 synonymous and 102 non-synonymous mutations. Analysis on these mutations showed that PkDBPαII was under purifying (negative) selection. At the amino acid level, 38 different PkDBPαII haplotypes were identified. Twelve of the 28 blood samples had mixed haplotype infections. Phylogenetic analysis revealed that all the haplotypes were in allele group I, but they formed a sub-group that was distinct from those of Peninsular Malaysia. Wright's FST fixation index indicated high genetic differentiation between the North Borneo and Peninsular Malaysia haplotypes. This study is the first to report the genetic diversity and natural selection of PkDBPαII of P. knowlesi from Borneo Island. The PkDBPαII haplotypes found in this study were distinct from those from

  12. Manual therapy in osteoarthritis of the hip: outcome in specific subgroups of patients.

    NARCIS (Netherlands)

    Hoeksma, H.L.; Dekker, J.; Ronday, H.K.; Breedveld, F.C.; Ende, C.H.M. van den

    2005-01-01

    OBJECTIVE: To investigate whether manual therapy has particular benefit in subgroups of patients defined on the basis of hip function, range of joint motion, pain and radiological deterioration. METHODS: The study was performed in the out-patient clinic of physical therapy of a large hospital. Data

  13. Distinct Patterns of Grey Matter Abnormality in High-Functioning Autism and Asperger's Syndrome

    Science.gov (United States)

    McAlonan, Grainne M.; Suckling, John; Wong, Naikei; Cheung, Vinci; Lienenkaemper, Nina; Cheung, Charlton; Chua, Siew E.

    2008-01-01

    Background: Autism exists across a wide spectrum and there is considerable debate as to whether children with Asperger's syndrome, who have normal language milestones, should be considered to comprise a subgroup distinct other from high-functioning children with autism (HFA), who have a history of delayed language development. Magnetic resonance…

  14. CAsubtype: An R Package to Identify Gene Sets Predictive of Cancer Subtypes and Clinical Outcomes.

    Science.gov (United States)

    Kong, Hualei; Tong, Pan; Zhao, Xiaodong; Sun, Jielin; Li, Hua

    2018-03-01

    In the past decade, molecular classification of cancer has gained high popularity owing to its high predictive power on clinical outcomes as compared with traditional methods commonly used in clinical practice. In particular, using gene expression profiles, recent studies have successfully identified a number of gene sets for the delineation of cancer subtypes that are associated with distinct prognosis. However, identification of such gene sets remains a laborious task due to the lack of tools with flexibility, integration and ease of use. To reduce the burden, we have developed an R package, CAsubtype, to efficiently identify gene sets predictive of cancer subtypes and clinical outcomes. By integrating more than 13,000 annotated gene sets, CAsubtype provides a comprehensive repertoire of candidates for new cancer subtype identification. For easy data access, CAsubtype further includes the gene expression and clinical data of more than 2000 cancer patients from TCGA. CAsubtype first employs principal component analysis to identify gene sets (from user-provided or package-integrated ones) with robust principal components representing significantly large variation between cancer samples. Based on these principal components, CAsubtype visualizes the sample distribution in low-dimensional space for better understanding of the distinction between samples and classifies samples into subgroups with prevalent clustering algorithms. Finally, CAsubtype performs survival analysis to compare the clinical outcomes between the identified subgroups, assessing their clinical value as potentially novel cancer subtypes. In conclusion, CAsubtype is a flexible and well-integrated tool in the R environment to identify gene sets for cancer subtype identification and clinical outcome prediction. Its simple R commands and comprehensive data sets enable efficient examination of the clinical value of any given gene set, thus facilitating hypothesis generating and testing in biological and

  15. 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

  16. Quality-of-Life Differences among Diagnostic Subgroups of Children Receiving Ventilating Tubes for Otitis Media

    DEFF Research Database (Denmark)

    Heidemann, Christian Hamilton; Lauridsen, Henrik Hein; Kjeldsen, Anette Drøhse

    2015-01-01

    OBJECTIVE: The pathological picture may differ considerably between diagnostic subgroups of children with otitis media receiving ventilating tubes. The aims of this study are to investigate differences in quality of life among diagnostic subgroups of children treated with ventilating tubes...... media with effusion (OME), and 38% mixed diagnosis of rAOM and OME (rAOM/OME). There were no significant differences between children diagnosed with rAOM and children diagnosed with rAOM/OME. However, these children had a significantly poorer quality of life at baseline compared with children diagnosed...... with only OME. Factors associated with clinical success included a diagnosis of rAOM, number of interrupted nights, physician visits, and canceled social activities due to OM. CONCLUSIONS: Results highlight the importance of distinguishing between diagnostic subgroups of children having ventilating tube...

  17. Clinical characteristics and long-term response to mood stabilizers in patients with bipolar disorder and different age at onset

    Science.gov (United States)

    Dell’Osso, Bernardo; Buoli, Massimiliano; Riundi, Riccardo; D’Urso, Nazario; Pozzoli, Sara; Bassetti, Roberta; Mundo, Emanuela; Altamura, A Carlo

    2009-01-01

    Introduction Bipolar disorder (BD) is a prevalent, comorbid, and impairing condition. Potential predictors of response to pharmacological treatment are object of continuous investigation in patients with BD. The present naturalistic study was aimed to assess clinical features and long-term response to mood stabilizers in a sample of bipolar subjects with different ages at onset. Methods The study sample included 108 euthymic patients, diagnosed as affected by BD, either type I or II, according to the DSM-IV-TR, who were started on mood stabilizer treatment. Patients were followed-up for 24 months and the occurrence of any mood episode collected. At the end of the follow-up, patients were divided in 3 subgroups according to the age at onset (early-onset ≤30 years, middle-onset >30–≤45 years, and late-onset >45 years, respectively) and the long-term response to mood stabilizers was compared between them along with other clinical features. Results The three subgroups showed significant differences in terms of clinical and demographic features and, with respect to long-term response to mood stabilizers, the early-onset subgroup showed a better outcome in terms of reduction of major depressive episodes during the 24-month follow-up compared to the other subgroups (one way ANOVA, F = 3.57, p = 0.032). Conclusions Even though further controlled studies are needed to clarify the relationship between age at onset and outcome in BD, the present follow-up study suggests clinical peculiarities and different patterns of response to mood stabilizers across distinct subgroups of patients with BD and different ages at onset. PMID:19649214

  18. Network analysis reveals distinct clinical syndromes underlying acute mountain sickness.

    Directory of Open Access Journals (Sweden)

    David P Hall

    Full Text Available Acute mountain sickness (AMS is a common problem among visitors at high altitude, and may progress to life-threatening pulmonary and cerebral oedema in a minority of cases. International consensus defines AMS as a constellation of subjective, non-specific symptoms. Specifically, headache, sleep disturbance, fatigue and dizziness are given equal diagnostic weighting. Different pathophysiological mechanisms are now thought to underlie headache and sleep disturbance during acute exposure to high altitude. Hence, these symptoms may not belong together as a single syndrome. Using a novel visual analogue scale (VAS, we sought to undertake a systematic exploration of the symptomatology of AMS using an unbiased, data-driven approach originally designed for analysis of gene expression. Symptom scores were collected from 292 subjects during 1110 subject-days at altitudes between 3650 m and 5200 m on Apex expeditions to Bolivia and Kilimanjaro. Three distinct patterns of symptoms were consistently identified. Although fatigue is a ubiquitous finding, sleep disturbance and headache are each commonly reported without the other. The commonest pattern of symptoms was sleep disturbance and fatigue, with little or no headache. In subjects reporting severe headache, 40% did not report sleep disturbance. Sleep disturbance correlates poorly with other symptoms of AMS (Mean Spearman correlation 0.25. These results challenge the accepted paradigm that AMS is a single disease process and describe at least two distinct syndromes following acute ascent to high altitude. This approach to analysing symptom patterns has potential utility in other clinical syndromes.

  19. European freshwater VHSV genotype Ia isolates divide into two distinct subpopulations

    DEFF Research Database (Denmark)

    Kahns, Søren; Skall, Helle Frank; Kaas, Rolf Sommer

    2012-01-01

    Viral haemorrhagic septicaemia (VHS), caused by the novirhabdovirus VHSV, often leads to significant economic losses to European rainbow trout production. The virus isolates are divided into 4 distinct genotypes with additional subgroups including sublineage Ia, isolates of which are the main...... detected in Denmark since January 2009. Full-length G-genes of all Danish VHSV isolates that were submitted for diagnostic analyses in the period 2004−2009 were sequenced and analysed. All 58 Danish isolates from rainbow trout grouped with sublineage Ia isolates. Furthermore, VHSV isolates from infected...... Danish freshwater catchments appear to have evolved into a distinct clade within sublineage Ia, herein designated clade Ia-1, whereas trout isolates originating from other continental European countries cluster in another distinct clade, designated clade Ia-2. In addition, phylogenetic analyses indicate...

  20. Myalgic Encephalomyelitis, Chronic Fatigue Syndrome, and Systemic Exertion Intolerance Disease: Three Distinct Clinical Entities

    Directory of Open Access Journals (Sweden)

    Frank N.M. Twisk

    2018-04-01

    Full Text Available Many researchers consider chronic fatigue syndrome (CFS to be a synonym of Myalgic Encephalomyelitis (ME. However, the case criteria of ME and CFS define two distinct clinical entities. Although some patients will meet both case criteria, other patients can meet the diagnosis of ME and not fulfil the case criteria for CFS, while the diagnosis of CFS is largely insufficient to be qualified as a ME patient. ME is a neuromuscular disease with distinctive muscular symptoms, including prolonged muscle weakness after exertion, and neurological signs implicating cerebral dysfunction, including cognitive impairment and sensory symptoms. The only mandatory symptom of CFS is chronic fatigue. Chronic fatigue must be accompanied by at least four out of eight nonspecific symptoms: substantial impairment in short-term memory or concentration, a sore throat, tender lymph nodes, muscle pain, multijoint pain, a new type of headaches, unrefreshing sleep, and postexertional “malaise” lasting more than 24 h. So, regardless whether the name ME is appropriate or not, ME is not synonymous to CFS. That is not a matter of opinion, but a matter of definition. Due to the definitions of ME and CFS, “ME/CFS” does not exist and cannot be replaced by a new clinical entity (SEID: Systemic Exertion Intolerance Disease, as recently suggested.

  1. Multinational comparative cross-sectional survey of views of medical students about acceptable terminology and subgroups in schizophrenia.

    Science.gov (United States)

    Rathod, Shanaya; Irfan, Muhammad; Bhargava, Rachna; Pinninti, Narsimha; Scott, Joseph; Mohammad Algahtani, Haifa; Guo, Zhihua; Gupta, Rishab; Nadkarni, Pallavi; Naeem, Farooq; Howells, Fleur; Sorsdahi, Katherine; Thorne, Kerensa; Osman-Hicks, Victoria; Pallikadavath, Sasee; Phiri, Peter; Carr, Hannah; Graves, Lizi; Kingdon, David

    2018-06-07

    The aim of this study was to inform thinking around the terminology for 'schizophrenia' in different countries. The objective of this study was to investigate: (1) whether medical students view alternative terminology (psychosis subgroups), derived from vulnerability-stress models of schizophrenia, as acceptable and less stigmatising than the term schizophrenia; (2) if there are differences in attitudes to the different terminology across countries with different cultures and (3) whether clinical training has an impact in reducing stigma. This is a cross-sectional survey that examined the attitudes of medical students towards schizophrenia and the alternative subgroups. The study was conducted across eight sites: (1) University of Southampton, UK; (2) All India Institute of Medical Science, India; (3) Rowan University, USA; (4) Peshawar Medical College, Pakistan; (5) Capital Medical University, China; (6) College of Medicine and Medical sciences, Bahrain; (7) Queens University, Kingston, Canada and (8) University of Cape Town, South Africa. This study extended an initial pilot conducted by the Royal College of Psychiatrists on the term schizophrenia and psychosis subgroups to assess whether the subgroup terminology might have an effect on the attitudes of a convenience sample of medical students from eight different countries and potentially play a role in reducing stigmatisation. 1873 medical students completed a questionnaire recording their attitudes to schizophrenia and the psychosis subgroups. A reduction in negative perceptions were found for the psychosis subgroups, especially for the stress sensitivity psychosis and anxiety psychosis subgroups. Negative perceptions were found for drug-related psychosis. Participants who had undergone clinical training had overall positive attitudes. Differences across different countries were found. The attitudes towards psychosis subgroups used in this study have shown mixed results and variation across countries. Further

  2. Health care expenditures among Asian American subgroups.

    Science.gov (United States)

    Chen, Jie; Vargas-Bustamante, Arturo; Ortega, Alexander N

    2013-06-01

    Using two nationally representative data sets, this study examined health care expenditure disparities between Caucasians and different Asian American subgroups. Multivariate analyses demonstrate that Asian Americans, as a group, have significantly lower total expenditures compared with Caucasians. Results also point to considerable heterogeneities in health care spending within Asian American subgroups. Findings suggest that language assistance programs would be effective in reducing disparities among Caucasians and Asian American subgroups with the exception of Indians and Filipinos, who tend to be more proficient in English. Results also indicate that citizenship and nativity were major factors associated with expenditure disparities. Socioeconomic status, however, could not explain expenditure disparities. Results also show that Asian Americans have lower physician and pharmaceutical costs but not emergency department or hospital expenditures. These findings suggest the need for culturally competent policies specific to Asian American subgroups and the necessity to encourage cost-effective treatments among Asian Americans.

  3. Quality-of-Life Differences among Diagnostic Subgroups of Children Receiving Ventilating Tubes for Otitis Media.

    Science.gov (United States)

    Heidemann, Christian Hamilton; Lauridsen, Henrik Hein; Kjeldsen, Anette Drøhse; Faber, Christian Emil; Johansen, Eva Charlotte Jung; Godballe, Christian

    2015-10-01

    The pathological picture may differ considerably between diagnostic subgroups of children with otitis media receiving ventilating tubes. The aims of this study are to investigate differences in quality of life among diagnostic subgroups of children treated with ventilating tubes and to investigate possible predictors for clinical success. Longitudinal observational study. Secondary care units. Four hundred ninety-one families were enrolled in the study. The Otitis Media-6 questionnaire was applied in the assessment of child quality of life. Caregivers completed questionnaires at 7 time points from before treatment to 18-month follow-up. Logistic regression analysis was used to investigate possible predictors for clinical success. Response rates ranged from 96% to 81%; diagnostic distribution: 15% recurrent acute otitis media (rAOM), 47% otitis media with effusion (OME), and 38% mixed diagnosis of rAOM and OME (rAOM/OME). There were no significant differences between children diagnosed with rAOM and children diagnosed with rAOM/OME. However, these children had a significantly poorer quality of life at baseline compared with children diagnosed with only OME. Factors associated with clinical success included a diagnosis of rAOM, number of interrupted nights, physician visits, and canceled social activities due to OM. Results highlight the importance of distinguishing between diagnostic subgroups of children having ventilating tube treatment. A diagnosis of rAOM was found to predict baseline quality of life. Children with rAOM with or without OME were found to suffer significantly more than children with only OME before treatment. Factors associated with disease severity were found to predict clinical success. © American Academy of Otolaryngology-Head and Neck Surgery Foundation 2015.

  4. Myalgic Encephalomyelitis (ME and Chronic Fatigue Syndrome (CFS: The essence of objective assessment, accurate diagnosis, and acknowledging biological and clinical subgroups.

    Directory of Open Access Journals (Sweden)

    Frank N.M. Twisk

    2014-03-01

    Full Text Available Myalgic Encephalomyelitis (ME was identified as a new clinical entity in 1959 and has been acknowledged as a disease of the central nervous system/neurological disease by the World Health Organisation since 1969. Cognitive impairment, (muscle weakness, circulatory disturbances, marked variability of symptoms, and, above all, post-exertional malaise: a long-lasting increase of symptoms after minor exertion, are distinctive symptoms of ME.Chronic Fatigue Syndrome (CFS was introduced in 1988 and was redefined into clinically evaluated, unexplained (persistent or relapsing chronic fatigue, accompanied by at least four out of a list of eight symptoms, e.g. headaches and unrefreshing sleep, in 1994.Although the labels are used interchangeably, ME and CFS define distinct diagnostic entities. Post-exertional malaise and cognitive deficits e.g. are not mandatory for the diagnosis CFS, while obligatory for the diagnosis ME. Fatigue is not obligatory for the diagnosis ME.Since fatigue and other symptoms are subjective and ambiguous, research has been hampered. Despite this and other methodological issues, research has observed specific abnormalities in ME/CFS repetitively, e.g. immunological abnormalities, oxidative and nitrosative

  5. Subgroup-Elimination Transcriptomics Identifies Signaling Proteins that Define Subclasses of TRPV1-Positive Neurons and a Novel Paracrine Circuit

    Science.gov (United States)

    Isensee, Jörg; Wenzel, Carsten; Buschow, Rene; Weissmann, Robert; Kuss, Andreas W.; Hucho, Tim

    2014-01-01

    Normal and painful stimuli are detected by specialized subgroups of peripheral sensory neurons. The understanding of the functional differences of each neuronal subgroup would be strongly enhanced by knowledge of the respective subgroup transcriptome. The separation of the subgroup of interest, however, has proven challenging as they can hardly be enriched. Instead of enriching, we now rapidly eliminated the subgroup of neurons expressing the heat-gated cation channel TRPV1 from dissociated rat sensory ganglia. Elimination was accomplished by brief treatment with TRPV1 agonists followed by the removal of compromised TRPV1(+) neurons using density centrifugation. By differential microarray and sequencing (RNA-Seq) based expression profiling we compared the transcriptome of all cells within sensory ganglia versus the same cells lacking TRPV1 expressing neurons, which revealed 240 differentially expressed genes (adj. p1.5). Corroborating the specificity of the approach, many of these genes have been reported to be involved in noxious heat or pain sensitization. Beyond the expected enrichment of ion channels, we found the TRPV1 transcriptome to be enriched for GPCRs and other signaling proteins involved in adenosine, calcium, and phosphatidylinositol signaling. Quantitative population analysis using a recent High Content Screening (HCS) microscopy approach identified substantial heterogeneity of expressed target proteins even within TRPV1-positive neurons. Signaling components defined distinct further subgroups within the population of TRPV1-positive neurons. Analysis of one such signaling system showed that the pain sensitizing prostaglandin PGD2 activates DP1 receptors expressed predominantly on TRPV1(+) neurons. In contrast, we found the PGD2 producing prostaglandin D synthase to be expressed exclusively in myelinated large-diameter neurons lacking TRPV1, which suggests a novel paracrine neuron-neuron communication. Thus, subgroup analysis based on the elimination

  6. Subgrouping of A and AB blood groups in Indian blood centres: is it required?

    Science.gov (United States)

    Hazarika, Ranjita; Basu, Sabita; Kaur, Paramjit

    2011-08-01

    Anti A1 antibody in the serum of A2 and A2B individuals is rare but when present can have laboratory and clinical significance. Routine subgrouping of all A and AB blood groups in blood centres in India is difficult due to economic constraints and has always been a point of debate. This study thus brings out the prevalence of anti A1 antibody and the clinical significance related to its presence. The results of the study showed a low prevalence of anti A1 antibody and when present, it had a low thermal amplitude and titre. Further, no blood group discrepancy or problems during compatibility testing were encountered with these (A1 antibody positive) blood units. Thus, it may be concluded that in India and other developing countries where resources are scarce, routine subgrouping of A and AB may not be really worthwhile unless there is a group discrepancy, problem during compatibility testing or history of a transfusion reaction.

  7. Symptom dimensions and subgroups in childhood-onset schizophrenia.

    Science.gov (United States)

    Craddock, Kirsten E S; Zhou, Xueping; Liu, Siyuan; Gochman, Peter; Dickinson, Dwight; Rapoport, Judith L

    2017-11-13

    This study investigated symptom dimensions and subgroups in the National Institute of Mental Health (NIMH) childhood-onset schizophrenia (COS) cohort and their similarities to adult-onset schizophrenia (AOS) literature. Scores from the Scales for the Assessment of Positive and Negative Symptoms (SAPS & SANS) from 125 COS patients were assessed for fit with previously established symptom dimensions from AOS literature using confirmatory factor analysis (CFA). K-means cluster analysis of each individual's scores on the best fitting set of dimensions was used to form patient clusters, which were then compared using demographic and clinical data. CFA showed the SAPS & SANS data was well suited to a 2-dimension solution, including positive and negative dimensions, out of five well established models. Cluster analysis identified three patient groups characterized by different dimension scores: (1) low scores on both dimensions, (2) high negative, low positive scores, and (3) high scores on both dimensions. These groups had different Full scale IQ, Children's Global Assessment Scale (CGAS) scores, ages of onset, and prevalence of some co-morbid behavior disorders (all psymptom-based subgroups within the NIMH COS cohort using an established AOS symptom structure. These findings confirm the heterogeneity of COS and were generally consistent with AOS literature. Published by Elsevier B.V.

  8. Subgroup-specific intrinsic disorder profiles of arabidopsis NAC transcription factors

    DEFF Research Database (Denmark)

    Stender, Emil G.; O'Shea, Charlotte; Skriver, Karen

    2015-01-01

    disordered but contain short, functionally important regions with structure propensities known as molecular recognition features. Here, we analyze for NAC subgroup-specific ID patterns. Some subgroups, such as the VND subgroup implicated in secondary cell wall biosynthesis, and the NAP/SHYG subgroup have...... highly conserved ID profiles. For the stress-associated ATAF1 subgroup and the CUC/ORE1 subgroup involved in development, only sub clades have similar ID patterns. For similar ID profiles, conserved molecular recognition features and sequence motifs represent likely functional determinants of e.......g. transcriptional activation and interactions. Based on our analysis, we suggest that ID profiling of regulatory proteins in general can be used to guide identification of interaction partners of network proteins....

  9. Etiological Subgroups of Small-for-Gestational-Age: Differential Neurodevelopmental Outcomes

    Science.gov (United States)

    Li, Xiuhong; Eiden, Rina D.; Epstein, Leonard H.; Shenassa, Edmond D.; Xie, Chuanbo; Wen, Xiaozhong

    2016-01-01

    Objectives It remains unclear why substantial variations in neurodevelopmental outcomes exist within small-for-gestational-age (SGA) children. We prospectively compared 5-y neurodevelopmental outcomes across SGA etiological subgroups. Methods Children born SGA (N = 1050) from U.S. Early Childhood Longitudinal Study-Birth Cohort (2001–2007) was divided into etiological subgroups by each of 7 well-established prenatal risk factors. We fit linear regression models to compare 5-y reading, math, gross motor and fine motor scores across SGA subgroups, adjusting for socio-demographic confounders. Results Compared to singleton SGA subgroup, multiple-birth SGA subgroup had lower mean reading (adjusted mean difference, -4.08 [95% confidence interval, -6.10, -2.06]) and math (-2.22 [-3.61, -0.84]) scores. These disadvantages in reading and math existed only among multiple-birth SGA subgroup without ovulation stimulation (reading, -4.50 [-6.64, -2.36]; math, -2.91 [-4.37, -1.44]), but not among those with ovulation stimulation (reading, -2.33 [-6.24, 1.57]; math 0.63 [-1.86, 3.12]). Compared to singleton SGA subgroup without maternal smoking and inadequate gestational weight gain, singleton SGA subgroup with co-occurrence of maternal smoking and inadequate gestational weight gain (GWG) had lower mean reading (-4.81 [-8.50, -1.12]) and math (-2.95 [-5.51, -0.38]) scores. These differences were not mediated by Apgar score. Conclusions Multiple-birth SGA subgroups (vs. singleton SGA) or singleton SGA subgroup with co-occurrence of smoking and inadequate GWG (vs. singleton SGA subgroup without maternal smoking and inadequate gestational weight gain) have poorer cognitive development up to 5 y. PMID:27501456

  10. Etiological Subgroups of Small-for-Gestational-Age: Differential Neurodevelopmental Outcomes.

    Directory of Open Access Journals (Sweden)

    Xiuhong Li

    Full Text Available It remains unclear why substantial variations in neurodevelopmental outcomes exist within small-for-gestational-age (SGA children. We prospectively compared 5-y neurodevelopmental outcomes across SGA etiological subgroups.Children born SGA (N = 1050 from U.S. Early Childhood Longitudinal Study-Birth Cohort (2001-2007 was divided into etiological subgroups by each of 7 well-established prenatal risk factors. We fit linear regression models to compare 5-y reading, math, gross motor and fine motor scores across SGA subgroups, adjusting for socio-demographic confounders.Compared to singleton SGA subgroup, multiple-birth SGA subgroup had lower mean reading (adjusted mean difference, -4.08 [95% confidence interval, -6.10, -2.06] and math (-2.22 [-3.61, -0.84] scores. These disadvantages in reading and math existed only among multiple-birth SGA subgroup without ovulation stimulation (reading, -4.50 [-6.64, -2.36]; math, -2.91 [-4.37, -1.44], but not among those with ovulation stimulation (reading, -2.33 [-6.24, 1.57]; math 0.63 [-1.86, 3.12]. Compared to singleton SGA subgroup without maternal smoking and inadequate gestational weight gain, singleton SGA subgroup with co-occurrence of maternal smoking and inadequate gestational weight gain (GWG had lower mean reading (-4.81 [-8.50, -1.12] and math (-2.95 [-5.51, -0.38] scores. These differences were not mediated by Apgar score.Multiple-birth SGA subgroups (vs. singleton SGA or singleton SGA subgroup with co-occurrence of smoking and inadequate GWG (vs. singleton SGA subgroup without maternal smoking and inadequate gestational weight gain have poorer cognitive development up to 5 y.

  11. Efficacy of long-term milnacipran treatment in patients meeting different thresholds of clinically relevant pain relief: subgroup analysis of a randomized, double-blind, placebo-controlled withdrawal study

    Directory of Open Access Journals (Sweden)

    Mease PJ

    2014-11-01

    Full Text Available Philip J Mease,1 Daniel J Clauw,2 Joel M Trugman,3 Robert H Palmer,3 Yong Wang3 1Swedish Medical Center and University of Washington, Seattle, WA, USA; 2Chronic Pain and Fatigue Research Center, University of Michigan Health System, Ann Arbor, MI, USA; 3Forest Research Institute, Jersey City, NJ, USA Background: Fibromyalgia patients from a long-term, open-label study of milnacipran (50–200 mg/day were eligible to participate in a 12-week, randomized, placebo-controlled withdrawal study. The withdrawal study evaluated loss of therapeutic response in patients who achieved ≥50% pain improvements after receiving up to 3.25 years of milnacipran. This post-hoc analysis investigated whether patients who met lower thresholds of pain improvement also experienced worsening of fibromyalgia symptoms upon treatment withdrawal. Method: Among patients who received milnacipran ≥100 mg/day during the long-term study, three subgroups were identified based on percentage of pain reduction at randomization: ≥50% (protocol-defined "responders"; n=150; ≥30% to <50% (patients with clinically meaningful pain improvement; n=61; and <30% (n=110. Efficacy assessments included the visual analog scale (VAS for pain, Fibromyalgia Impact Questionnaire-Revised (FIQR, 36-Item Short-Form Health Survey Physical Component Summary (SF-36 PCS, and Beck Depression Inventory (BDI. Results: In the ≥30 to <50% subgroup, significant worsening in pain was detected after treatment withdrawal. The difference between placebo and milnacipran in mean VAS score changes for this subgroup (+9.0, P<0.05 was similar to the difference in protocol-defined responders (+9.4, P<0.05. In the <30% subgroup, no worsening in pain was observed in either treatment arm. However, patients in this subgroup experienced significant worsening in FIQR scores after treatment withdrawal (placebo, +6.9; milnacipran, -2.8; P<0.001, as well as worsening in SF-36 PCS and BDI scores. Conclusion: Patients who

  12. 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.

  13. Clinical characteristics of a novel subgroup of chronic fatigue syndrome patients with postural orthostatic tachycardia syndrome.

    Science.gov (United States)

    Lewis, I; Pairman, J; Spickett, G; Newton, J L

    2013-05-01

    A significant proportion of patients with chronic fatigue syndrome (CFS) also have postural orthostatic tachycardia syndrome (POTS). We aimed to characterize these patients and differentiate them from CFS patients without POTS in terms of clinical and autonomic features. A total of 179 patients with CFS (1994 Centers for Disease Control and Prevention criteria) attending one of the largest Department of Health-funded CFS clinical services were included in this study. Outcome measures were as follows: (i) symptom assessment tools including the fatigue impact scale, Chalder fatigue scale, Epworth sleepiness scale (ESS), orthostatic grading scale (OGS) and hospital anxiety and depression scale (HADS-A and -D, respectively), (ii) autonomic function analysis including heart rate variability and (iii) haemodynamic responses including left ventricular ejection time and systolic blood pressure drop upon standing. CFS patients with POTS (13%, n = 24) were younger (29 ± 12 vs. 42 ± 13 years, P fatigued (Chalder fatigue scale, 8 ± 4 vs. 10 ± 2, P = 0.002), less depressed (HADS-D, 6 ± 4 vs. 9 ± 4, P = 0.01) and had reduced daytime hypersomnolence (ESS, 7 ± 6 vs. 10 ± 5, P = 0.02), compared with patients without POTS. In addition, they exhibited greater orthostatic intolerance (OGS, 11 ± 5; P < 0.0001) and autonomic dysfunction. A combined clinical assessment tool of ESS ≤9 and OGS ≥9 identifies accurately CFS patients with POTS with 100% positive and negative predictive values. The presence of POTS marks a distinct clinical group of CFS patents, with phenotypic features differentiating them from those without POTS. A combination of validated clinical assessment tools can determine which CFS patients have POTS with a high degree of accuracy, and thus potentially identify those who require further investigation and consideration for therapy to control heart rate. © 2013 The Association for the Publication of the Journal of Internal Medicine.

  14. Anatomic mapping of molecular subtypes in diffuse glioma.

    Science.gov (United States)

    Tang, Qisheng; Lian, Yuxi; Yu, Jinhua; Wang, Yuanyuan; Shi, Zhifeng; Chen, Liang

    2017-09-15

    Tumor location served as an important prognostic factor in glioma patients was considered to postulate molecular features according to cell origin theory. However, anatomic distribution of unique molecular subtypes was not widely investigated. The relationship between molecular phenotype and histological subgroup were also vague based on tumor location. Our group focuses on the study of glioma anatomic location of distinctive molecular subgroups and histology subtypes, and explores the possibility of their consistency based on clinical background. We retrospectively reviewed 143 cases with both molecular information (IDH1/TERT/1p19q) and MRI images diagnosed as cerebral diffuse gliomas. The anatomic distribution was analyzed between distinctive molecular subgroups and its relationship with histological subtypes. The influence of tumor location, molecular stratification and histology diagnosis on survival outcome was investigated as well. Anatomic locations of cerebral diffuse glioma indicate varied clinical outcome. Based on that, it can be stratified into five principal molecular subgroups according to IDH1/TERT/1p19q status. Triple-positive (IDH1 and TERT mutation with 1p19q codeletion) glioma tended to be oligodendroglioma present with much better clinical outcome compared to TERT mutation only group who is glioblastoma inclined (median overall survival 39 months VS 18 months). Five molecular subgroups were demonstrated with distinctive locational distribution. This kind of anatomic feature is consistent with its corresponding histological subtypes. Each molecular subgroup in glioma has unique anatomic location which indicates distinctive clinical outcome. Molecular diagnosis can be served as perfect complementary tool for the precise diagnosis. Integration of histomolecular diagnosis will be much more helpful in routine clinical practice in the future.

  15. 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

  16. Asymptomatic hyperthyroidism in older adults: is it a distinct clinical and laboratory entity?

    Science.gov (United States)

    Mooradian, Arshag D

    2008-01-01

    Hyperthyroidism is the result of increased serum free thyroid hormone levels and is associated with a well recognized set of clinical signs and symptoms. However, older patients who develop hyperthyroidism tend to have fewer hyperadrenergic signs and an increased incidence of weight loss, cardiac arrhythmias and, occasionally, apathetic mood. This article highlights the paucity of clinical signs and symptoms of hyperthyroidism in older people and reviews the potential biochemical changes in thyroid hormone physiology that may account for an altered clinical presentation in older people with hyperthyroidism. First, a brief vignette from our own clinical practice is described to highlight an unusual presentation of hyperthyroidism in an older woman. The subject is then reviewed on the basis of relevant articles identified through a MEDLINE search of the English literature, using the key words 'hyperthyroidism' and 'aging'. The available evidence indicates that the clinical syndrome of asymptomatic hyperthyroidism in older adults appears to be distinct from the more widely recognized syndromes of apathetic hyperthyroidism or thyroid hormone resistance. Age-related changes in thyroid hormone economy and reduced cellular uptake of thyroid hormone as well as changes in thyroid hormone regulation of gene expression may account for reduced manifestations of hyperthyroidism in older adults. Thus, in addition to the well known changes in thyroid gland anatomy and function with aging, there may be an age-related resistance to thyroid hormone action. Asymptomatic hyperthyroidism may well be a syndrome that is currently under-diagnosed.

  17. Clinical spectrum of anorexia nervosa in children.

    Science.gov (United States)

    Atkins, D M; Silber, T J

    1993-08-01

    A retrospective review of 21 patients ages 12 years and younger (age of onset range 7 to 12 years) with anorexia nervosa showed diagnostic delay in the youngest ones, high incidence of family psychiatric history, a remarkable severity of illness, and positive response to intensive treatment. Additional findings included significant comorbidity, a distinct subgroup with personality disorder and another with features of the "vulnerable child syndrome." This broad clinical spectrum of anorexia nervosa in children may explain the great variability in outcome. The development of anorexia nervosa in children relates to a complex combination of etiological and trigger factors. Precipitants identified in this study were physical maturation, entry into junior high, loss, or some combination thereof.

  18. Sequential formation of subgroups in OB associations

    International Nuclear Information System (INIS)

    Elmegreen, B.G.; Lada, C.J.

    1977-01-01

    We reconsider the structure and formation of OB association in view of recent radio and infrared observations of the adjacent molecular clouds. As a result of this reexamination, we propose that OB subgroups are formed in a step-by-step process which involves the propagation of ionization (I) and shock (S) fronts through a molecular cloud complex. OB stars formed at the edge of a molecular cloud drive these I-S fronts into the cloud. A layer of dense neutral material accumulates between the I and S fronts and eventually becomes gravitationally unstable. This process is analyzed in detail. Several arguments concerning the temperature and mass of this layer suggest that a new OB subgroup will form. After approximately one-half million years, these stars will emerge from and disrupt the star-forming layer. A new shock will be driven into the remaining molecular cloud and will initiate another cycle of star formation.Several observed properties of OB associations are shown to follow from a sequential star-forming mechanism. These include the spatial separation and systematic differences in age of OB subgroups in a given association, the regularity of subgroup masses, the alignment of subgroups along the galactic plane, and their physical expansion. Detailed observations of ionization fronts, masers, IR sources, and molecular clouds are also in agreement with this model. Finally, this mechanism provides a means of dissipating a molecular cloud and exposing less massive stars (e.g., T Tauri stars) which may have formed ahead of the shock as part of the original cloud collapsed and fragmented

  19. Identification of Subgroups of Women with Carpal Tunnel Syndrome with Central Sensitization.

    Science.gov (United States)

    Fernández-de-Las-Peñas, César; Fernández-Muñoz, Juan J; Navarro-Pardo, Esperanza; da-Silva-Pocinho, Ricardo F; Ambite-Quesada, Silvia; Pareja, Juan A

    2016-09-01

    Identification of subjects with different sensitization mechanisms can help to identify better therapeutic strategies for carpal tunnel syndrome (CTS). The aim of the current study was to identify subgroups of women with CTS with different levels of sensitization. A total of 223 women with CTS were recruited. Self-reported variables included pain intensity, function, disability, and depression. Pressure pain thresholds (PPT) were assessed bilaterally over median, ulnar, and radial nerves, C5-C6 joint, carpal tunnel, and tibialis anterior to assess widespread pressure pain hyperalgesia. Heat (HPT) and cold (CPT) pain thresholds were also bilaterally assessed over the carpal tunnel and the thenar eminence to determine thermal pain hyperalgesia. Pinch grip force between the thumb and the remaining fingers was calculated to determine motor assessment. Subgroups were determined according to the status on a previous clinical prediction rule: PPT over the affected C5-C6 joint 66 points. The ANOVA showed that women within group 1 (positive rule, n = 60) exhibited bilateral widespread pressure hyperalgesia (P < 0.001) and bilateral thermal thresholds (P < 0.001) than those within group 2 (negative rule, n = 162). Women in group 1 also exhibited higher depression than those in group 2 (P = 0.023). No differences in self-reported variables were observed. This study showed that a clinical prediction rule originally developed for identifying women with CTS who are likely to respond favorably to manual physical therapy was able to identify women exhibiting higher widespread pressure hyper-sensitivity and thermal hyperalgesia. This subgroup of women with CTS exhibiting higher sensitization may need specific therapeutic programs. © 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  20. 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.

  1. Phenotypic subgroups of polycystic ovary syndrome have different intra-renal resistance symptoms.

    Science.gov (United States)

    Ciftci, Ceylan F; Uckuyu, Ayla; Karadeli, Elif; Turhan, Erdem; Toprak, Erzat; Ozcimen, Emel E

    2012-12-01

    The polycystic ovary syndrome (PCOS) is known to be related with increased metabolic and cardiovascular risks. Various phenotypic subgroups of PCOS have been proven to have metabolic and endocrine disorders with varying degrees of severity However, intra-renal vascular resistance, which is an indirect indication of atherosclerosis, remains unknown in PCOS subgroups. In this study we examined whether PCOS subgroups have different intra-renal resistance symptoms. 98 PCOS patients (diagnosed according to the Rotterdam criteria) 30 controls were included in the study The diagnosis of PCOS was established in the presence of at least two of the following criteria: 1-oligo and/or amenorrhea (OM); 2-clinic and/or biochemical signs of hyperandrogenism (HA); 3-polycystic ovarian morphology (PCO) detected by transvaginal ultrasonography 37 patients (Group 1) met all three criteria (HA+OM+PCO), 29 patients (Group 2) met two of the criteria including hyperandrogenism (HA+OM or HA+PCO) and the remaining 32 patients (Group 3) had no hyperandrogenism but fulfilled the other two criteria; PCO+OM. Renal Doppler ultrasonography and hormonal/biochemical analyses were carried out. The first outcome measure was designated as the differences in the renal resistive index (RRI) values of the groups, and the second outcome measure was designated as the relation of RRI with the insulin resistance and lipid profile. In Group 1, the RRI and the homeostasis model assessment of insulin resistance (HOMA-IR) values were significantly higher than in Group 3 and controls (P PCOS subgroups have metabolic and endocrine disorders and cardiovascular risks of varying degrees of severity Moreover, we showed that there was no increase of metabolic and cardiovascular risks in PCOS patients without hyperandrogenism.

  2. Synergies and Distinctions between Computational Disciplines in Biomedical Research: Perspective from the Clinical and Translational Science Award Programs

    Science.gov (United States)

    Bernstam, Elmer V.; Hersh, William R.; Johnson, Stephen B.; Chute, Christopher G.; Nguyen, Hien; Sim, Ida; Nahm, Meredith; Weiner, Mark; Miller, Perry; DiLaura, Robert P.; Overcash, Marc; Lehmann, Harold P.; Eichmann, David; Athey, Brian D.; Scheuermann, Richard H.; Anderson, Nick; Starren, Justin B.; Harris, Paul A.; Smith, Jack W.; Barbour, Ed; Silverstein, Jonathan C.; Krusch, David A.; Nagarajan, Rakesh; Becich, Michael J.

    2010-01-01

    Clinical and translational research increasingly requires computation. Projects may involve multiple computationally-oriented groups including information technology (IT) professionals, computer scientists and biomedical informaticians. However, many biomedical researchers are not aware of the distinctions among these complementary groups, leading to confusion, delays and sub-optimal results. Although written from the perspective of clinical and translational science award (CTSA) programs within academic medical centers, the paper addresses issues that extend beyond clinical and translational research. The authors describe the complementary but distinct roles of operational IT, research IT, computer science and biomedical informatics using a clinical data warehouse as a running example. In general, IT professionals focus on technology. The authors distinguish between two types of IT groups within academic medical centers: central or administrative IT (supporting the administrative computing needs of large organizations) and research IT (supporting the computing needs of researchers). Computer scientists focus on general issues of computation such as designing faster computers or more efficient algorithms, rather than specific applications. In contrast, informaticians are concerned with data, information and knowledge. Biomedical informaticians draw on a variety of tools, including but not limited to computers, to solve information problems in health care and biomedicine. The paper concludes with recommendations regarding administrative structures that can help to maximize the benefit of computation to biomedical research within academic health centers. PMID:19550198

  3. Compositionally and functionally distinct sinus microbiota in chronic rhinosinusitis patients have immunological and clinically divergent consequences

    OpenAIRE

    Cope, Emily K.; Goldberg, Andrew N.; Pletcher, Steven D.; Lynch, Susan V.

    2017-01-01

    Background Chronic rhinosinusitis (CRS) is a heterogeneous disease characterized by persistent sinonasal inflammation and sinus microbiome dysbiosis. The basis of this heterogeneity is poorly understood. We sought to address the hypothesis that a limited number of compositionally distinct pathogenic bacterial microbiota exist in CRS patients and invoke discrete immune responses and clinical phenotypes in CRS patients. Results Sinus brushings from patients with CRS (n?=?59) and healthy individ...

  4. Functional Status, Quality of Life, and Costs Associated With Fibromyalgia Subgroups: A Latent Profile Analysis.

    Science.gov (United States)

    Luciano, Juan V; Forero, Carlos G; Cerdà-Lafont, Marta; Peñarrubia-María, María Teresa; Fernández-Vergel, Rita; Cuesta-Vargas, Antonio I; Ruíz, José M; Rozadilla-Sacanell, Antoni; Sirvent-Alierta, Elena; Santo-Panero, Pilar; García-Campayo, Javier; Serrano-Blanco, Antoni; Pérez-Aranda, Adrián; Rubio-Valera, María

    2016-10-01

    Although fibromyalgia syndrome (FM) is considered a heterogeneous condition, there is no generally accepted subgroup typology. We used hierarchical cluster analysis and latent profile analysis to replicate Giesecke's classification in Spanish FM patients. The second aim was to examine whether the subgroups differed in sociodemographic characteristics, functional status, quality of life, and in direct and indirect costs. A total of 160 FM patients completed the following measures for cluster derivation: the Center for Epidemiological Studies-Depression Scale, the Trait Anxiety Inventory, the Pain Catastrophizing Scale, and the Control over Pain subscale. Pain threshold was measured with a sphygmomanometer. In addition, the Fibromyalgia Impact Questionnaire-Revised, the EuroQoL-5D-3L, and the Client Service Receipt Inventory were administered for cluster validation. Two distinct clusters were identified using hierarchical cluster analysis ("hypersensitive" group, 69.8% and "functional" group, 30.2%). In contrast, the latent profile analysis goodness-of-fit indices supported the existence of 3 FM patient profiles: (1) a "functional" profile (28.1%) defined as moderate tenderness, distress, and pain catastrophizing; (2) a "dysfunctional" profile (45.6%) defined by elevated tenderness, distress, and pain catastrophizing; and (3) a "highly dysfunctional and distressed" profile (26.3%) characterized by elevated tenderness and extremely high distress and catastrophizing. We did not find significant differences in sociodemographic characteristics between the 2 clusters or among the 3 profiles. The functional profile was associated with less impairment, greater quality of life, and lower health care costs. We identified 3 distinct profiles which accounted for the heterogeneity of FM patients. Our findings might help to design tailored interventions for FM patients.

  5. Physiotherapy in Primary Care Triage - the effects on utilization of medical services at primary health care clinics by patients and sub-groups of patients with musculoskeletal disorders: a case-control study.

    Science.gov (United States)

    Bornhöft, Lena; Larsson, Maria E H; Thorn, Jörgen

    2015-01-01

    Primary Care Triage is a patient sorting system used in some primary health care clinics (PHCCs) in Sweden where patients with musculoskeletal disorders (MSD) are triaged directly to physiotherapists. The purpose of this study was to investigate whether sorting/triaging patients seeking a PHCC for MSD directly to physiotherapists affects their utilization of medical services at the clinic for the MSD and to determine whether the effects of the triaging system vary for different sub-groups of patients. A retrospective case-control study design was used at two PHCCs. At the intervention clinic, 656 patients with MSD were initially triaged to physiotherapists. At the control clinic, 1673 patients were initially assessed by general practitioners (GPs). The main outcome measures were the number of patients continuing to visit GPs after the initial assessment, the number of patients receiving referrals to specialists/external examinations, doctors' notes for sick-leave or prescriptions for analgesics during one year, all for the original MSD. Significantly fewer patients triaged to physiotherapists required multiple GP visits for the MSD or received MSD-related referrals to specialists/external examinations, sick-leave recommendations or prescriptions during the following year compared to the GP-assessed group. This applies to all sub-groups except for the group with lower extremity disorders, which did not reach significance for either multiple GP visits or sick-leave recommendations. The reduced utilization of medical services by patients with MSD who were triaged to physiotherapists at a PHCC is likely due to altered management of MSD with initial assessment by physiotherapists.

  6. Analysis of chronic lymphotic leukemia transcriptomic profile: differences between molecular subgroups.

    Science.gov (United States)

    Jantus Lewintre, Eloisa; Reinoso Martín, Cristina; Montaner, David; Marín, Miguel; José Terol, María; Farrás, Rosa; Benet, Isabel; Calvete, Juan J; Dopazo, Joaquín; García-Conde, Javier

    2009-01-01

    B cell chronic lymphocytic leukemia (CLL) is a lymphoproliferative disorder with a variable clinical course. Patients with unmutated IgV(H) gene show a shorter progression-free and overall survival than patients with immunoglobulin heavy chain variable regions (IgV(H)) gene mutated. In addition, BCL6 mutations identify a subgroup of patients with high risk of progression. Gene expression was analysed in 36 early-stage patients using high-density microarrays. Around 150 genes differentially expressed were found according to IgV(H) mutations, whereas no difference was found according to BCL6 mutations. Functional profiling methods allowed us to distinguish KEGG and gene ontology terms showing coordinated gene expression changes across subgroups of CLL. We validated a set of differentially expressed genes according to IgV(H) status, scoring them as putative prognostic markers in CLL. Among them, CRY1, LPL, CD82 and DUSP22 are the ones with at least equal or superior performance to ZAP70 which is actually the most used surrogate marker of IgV(H) status.

  7. Potentially three distinct roles for hypoxic cell sensitizers in the clinic

    International Nuclear Information System (INIS)

    Chapman, J.D.; Raleigh, J.A.; Pedersen, J.E.; Ngan, J.; Shum, F.Y.

    1979-01-01

    Nitroaromatic drugs have been applied to radiation therapy on the basis of their effectiveness to enhance radiation damages selectively in hypoxic mammalian cells at nontoxic concentration. Such sensitizers could improve the rate of local tumor control by conventional radiotherapy in such cases that the resistance due to hypoxia in a limiting factor. The selective cytotoxicity of the drug to hypoxic cells is the second distinct action. A third potential role for nitroaromatic drugs could involve their use for the diagnosis of the number and location of hypoxic cells within tumors. The gain in therapeutic ratio by a factor from 5 to 10 is necessary before the full clinical impact of hypoxic cell radiosensitizers can be evaluated. The drugs selected for the use as clinical radiosensitizers were originally developed as the antibacterial agents with selective activity against anaerobes. The hypoxic cells in tumors are usually resistant to chemotherapy as well as resistant to radiation, and this specific drug action of sensitizers combined with that of an agent effective against oxygenated and cycling cells could possibly produce improved tumor cures. Electron-affinitive chemicals become selectively bound to the macromolecules of hypoxic mammalian cells by radiation-induced chemical reaction. This technique was used to identify by autoradiographic procedures the location of the radioactive nitrofurazone bound to hypoxic cells within multicellular spheroids. (Yamashita, S.)

  8. Subgrouping of patients with oral lichen planus according to cytochrome P450 enzyme phenotype and genotype

    DEFF Research Database (Denmark)

    Kragelund, Camilla; Jensen, Siri Beier; Hansen, Claus

    2014-01-01

    Objective. This study aimed to determine if the activity of the environmentally influenced cytochrome P450 enzyme CYP1A2, alone or in combination with CYP2D6*4 genotype, discriminates subgroups of oral lichen planus (OLP) according to lifestyle factors and clinical manifestations. Study Design...

  9. Subgroup conflicts? Try the psychodramatic "double triad method".

    Science.gov (United States)

    Verhofstadt-Denève, Leni M F

    2012-04-01

    The present article suggests the application of a psychodramatic action method for tackling subgroup conflicts in which the direct dialogue between representatives of two opposing subgroups is prepared step by step through an indirect dialogue strategy within two triads, a strategy known as the Double Triad Method (DTM). In order to achieve integration in the group as a whole, it is important that all the members of both subgroups participate actively during the entire process. The first part of the article briefly explores the theoretical background, with a special emphasis on the Phenomenological-Dialectical Personality Model (Phe-Di PModel). In the second part, the DTM procedure is systematically described through its five action stages, each accompanied with 1) a spatial representation of the consecutive actions, 2) some illustrative statements for each stage, and 3) a theoretical interpretation of the dialectically involved personality dimensions in both protagonists. The article concludes with a discussion and suggestions for more extensive applications of the DTM method, including the question of its relationships to Agazarian's functional subgrouping, psychodrama, and sociodrama.

  10. Gene expression analyses of the spatio-temporal relationships of human medulloblastoma subgroups during early human neurogenesis.

    Directory of Open Access Journals (Sweden)

    Cornelia M Hooper

    Full Text Available Medulloblastoma is the most common form of malignant paediatric brain tumour and is the leading cause of childhood cancer related mortality. The four molecular subgroups of medulloblastoma that have been identified - WNT, SHH, Group 3 and Group 4 - have molecular and topographical characteristics suggestive of different cells of origin. Definitive identification of the cell(s of origin of the medulloblastoma subgroups, particularly the poorer prognosis Group 3 and Group 4 medulloblastoma, is critical to understand the pathogenesis of the disease, and ultimately for the development of more effective treatment options. To address this issue, the gene expression profiles of normal human neural tissues and cell types representing a broad neuro-developmental continuum, were compared to those of two independent cohorts of primary human medulloblastoma specimens. Clustering, co-expression network, and gene expression analyses revealed that WNT and SHH medulloblastoma may be derived from distinct neural stem cell populations during early embryonic development, while the transcriptional profiles of Group 3 and Group 4 medulloblastoma resemble cerebellar granule neuron precursors at weeks 10-15 and 20-30 of embryogenesis, respectively. Our data indicate that Group 3 medulloblastoma may arise through abnormal neuronal differentiation, whereas deregulation of synaptic pruning-associated apoptosis may be driving Group 4 tumorigenesis. Overall, these data provide significant new insight into the spatio-temporal relationships and molecular pathogenesis of the human medulloblastoma subgroups, and provide an important framework for the development of more refined model systems, and ultimately improved therapeutic strategies.

  11. 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.

  12. 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.

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    BACKGROUND: The aim of this study was to investigate subgroups of magnetic resonance imaging (MRI) findings for the spine and sacroiliac joints (SIJs) using latent class analysis (LCA), and to investigate whether these subgroups differ in their demographic and clinical characteristics. METHODS...

  14. Clinical characteristics in genetically distinct forms of the congenital long QT syndrome

    International Nuclear Information System (INIS)

    Kawahara, Yosuke; Sawayama, Toshitami; Samukawa, Masanobu; Nezuo, Shoso; Tanaka, Junji; Suetsuna, Ryoji; Kamiyama, Norio

    1998-01-01

    The clinical characteristics in genetically distinct forms of the congenital long QT syndrome (LQTs) were examined on the balance of bilateral sympathetic nerves, and ECG findings. The subjects (mean: 19.4 years old) were three genetically distinct forms of LQTs, including 3 patients in A-family (the high risk family with sudden death), 2 patients in B-family and 3 patients in C-family. All patients met the standard diagnostic criteria according to Schwartz. As the index of the balance of bilateral sympathetic nerves, the dissociation of Tl and MIBG uptake (D) was examined and the radioactivity ratio (the A/L ratio) of anteroseptal wall to posterolateral wall was calculated. The T-wave patterns of ECG and the situation at syncope were examined. In A-family, all 3 patients showed the lowered A/L ratio, D(+), and similar T-wave patterns in ECG. The syndrome developed at exercise, and their QTc extended at exercise. In B-family, all 2 patients showed normal A/L ratio and long T-wave at QT onset, and their QTc shortened at exercise. All patients had developed syncope at rest. In C-family, all 3 patients showed a little decrease of A/L ratio and similar T-wave patterns. Their QTc extended at exercise. These results suggest that the characteristics of the sympathetic nerve balance, ECG wave patterns and the syndrome may depend on each family. (K.H.)

  15. Distinct patterns of DNA damage response and apoptosis correlate with Jak/Stat and PI3kinase response profiles in human acute myelogenous leukemia.

    Directory of Open Access Journals (Sweden)

    David B Rosen

    Full Text Available BACKGROUND: Single cell network profiling (SCNP utilizing flow cytometry measures alterations in intracellular signaling responses. Here SCNP was used to characterize Acute Myeloid Leukemia (AML disease subtypes based on survival, DNA damage response and apoptosis pathways. METHODOLOGY AND PRINCIPAL FINDINGS: Thirty four diagnostic non-M3 AML samples from patients with known clinical outcome were treated with a panel of myeloid growth factors and cytokines, as well as with apoptosis-inducing agents. Analysis of induced Jak/Stat and PI3K pathway responses in blasts from individual patient samples identified subgroups with distinct signaling profiles that were not seen in the absence of a modulator. In vitro exposure of patient samples to etoposide, a DNA damaging agent, revealed three distinct "DNA damage response (DDR/apoptosis" profiles: 1 AML blasts with a defective DDR and failure to undergo apoptosis; 2 AML blasts with proficient DDR and failure to undergo apoptosis; 3 AML blasts with proficiency in both DDR and apoptosis pathways. Notably, AML samples from clinical responders fell within the "DDR/apoptosis" proficient profile and, as well, had low PI3K and Jak/Stat signaling responses. In contrast, samples from clinical non responders had variable signaling profiles often with in vitro apoptotic failure and elevated PI3K pathway activity. Individual patient samples often harbored multiple, distinct, leukemia-associated cell populations identifiable by their surface marker expression, functional performance of signaling pathway in the face of cytokine or growth factor stimulation, as well as their response to apoptosis-inducing agents. CONCLUSIONS AND SIGNIFICANCE: Characterizing and tracking changes in intracellular pathway profiles in cell subpopulations both at baseline and under therapeutic pressure will likely have important clinical applications, potentially informing the selection of beneficial targeted agents, used either alone or in

  16. Clinical evidence for three distinct gastric cancer subtypes: time for a new approach.

    Directory of Open Access Journals (Sweden)

    Alessandro Bittoni

    Full Text Available BACKGROUND: Recently, a new classification for gastric cancer (GC has been proposed, based on Lauren's histology and on anatomic tumour location, identifying three subtypes of disease: type 1 (proximal non diffuse GC, type 2 (diffuse GC and type 3 (distal non diffuse GC. Aim of our analysis was to compare clinical outcome according to different GC subtypes (1,2,3 in metastatic GC patients receiving first-line chemotherapy. PATIENTS AND METHODS: Advanced GC pts treated with a first-line combination chemotherapy were included in our analysis. Pts were divided in three subgroups (type 1, type 2 and type 3 as previously defined. RESULTS: A total of 248 advanced GC pts were included: 45.2% belonged to type 2, 43.6% to type 3 and 11.2% to type 1. Patients received a fluoropyrimidine-based chemotherapy doublet or three drugs regimens including a platinum derivate and a fluoropyrimidine with the addition of an anthracycline, a taxane or mytomicin C. RR was higher in type 1 pts (RR = 46.1% and type 3 (34,3% compared to type 2 (20,4%, (p = 0.015. Type 2 presented a shorter PFS, median PFS = 4.2 months, compared to type 1, mPFS = 7.2 months, and type 3, mPFS = 5.9 months (p = 0.011 and also a shorter OS (p = 0.022. CONCLUSIONS: Our analysis suggests that GC subtypes may be important predictors of benefit from chemotherapy in advanced GC patients. Future clinical trials should take in account these differences for a better stratification of patients.

  17. Isolation and characterization of a novel Betacoronavirus subgroup A coronavirus, rabbit coronavirus HKU14, from domestic rabbits.

    Science.gov (United States)

    Lau, Susanna K P; Woo, Patrick C Y; Yip, Cyril C Y; Fan, Rachel Y Y; Huang, Yi; Wang, Ming; Guo, Rongtong; Lam, Carol S F; Tsang, Alan K L; Lai, Kenneth K Y; Chan, Kwok-Hung; Che, Xiao-Yan; Zheng, Bo-Jian; Yuen, Kwok-Yung

    2012-05-01

    We describe the isolation and characterization of a novel Betacoronavirus subgroup A coronavirus, rabbit coronavirus HKU14 (RbCoV HKU14), from domestic rabbits. The virus was detected in 11 (8.1%) of 136 rabbit fecal samples by reverse transcriptase PCR (RT-PCR), with a viral load of up to 10(8) copies/ml. RbCoV HKU14 was able to replicate in HRT-18G and RK13 cells with cytopathic effects. Northern blotting confirmed the production of subgenomic mRNAs coding for the HE, S, NS5a, E, M, and N proteins. Subgenomic mRNA analysis revealed a transcription regulatory sequence, 5'-UCUAAAC-3'. Phylogenetic analysis showed that RbCoV HKU14 formed a distinct branch among Betacoronavirus subgroup A coronaviruses, being most closely related to but separate from the species Betacoronavirus 1. A comparison of the conserved replicase domains showed that RbCoV HKU14 possessed N-protein-based Western blot assay, whereas neutralizing antibody was detected in 1 of these 20 rabbits.

  18. Identities on maximal subgroups of GLn(D)

    International Nuclear Information System (INIS)

    Kiani, D.; Mahdavi-Hezavehi, M.

    2002-04-01

    Let D be a division ring with centre F. Assume that M is a maximal subgroup of GL n (D), n≥1 such that Z(M) is algebraic over F. Group identities on M and polynomial identities on the F-linear hull F[M] are investigated. It is shown that if F[M] is a PI-algebra, then [D:F] n (D) and M is a maximal subgroup of N. If M satisfies a group identity, it is shown that M is abelian-by-finite. (author)

  19. Myelodysplastic Syndrome, Unclassifiable (MDS-U) With 1% Blasts Is a Distinct Subgroup of MDS-U With a Poor Prognosis.

    Science.gov (United States)

    Margolskee, Elizabeth; Hasserjian, Robert P; Hassane, Duane; Tam, Wayne; Mathew, Susan; Ok, Chi Young; Wang, Sa A; Oak, Jean; Arber, Daniel A; Orazi, Attilio

    2017-07-01

    Three situations qualify as myelodysplastic syndrome, unclassifiable (MDS-U): (1) refractory cytopenia with dysplasia and 1% blasts in peripheral blood (BL), (2) pancytopenia with unilineage dysplasia (Pan), and (3) persistent cytopenia, less than 5% bone marrow blasts, and less than 10% dysplastic cells and presence of MDS-defining cytogenetic abnormalities (CG). We compared the clinicopathologic features and mutational profiles for these three groups. MDS-U cases were reviewed at four major academic institutions. Targeted next-generation sequencing for genes implicated in myeloid neoplasms was performed in a subset of cases. Twenty-seven patients were identified (six MDS-U BL, 13 MDS-U Pan, and eight MDS-U CG). Clonal cytogenetic abnormalities were found in six of six, seven of 13, and eight of eight cases in MDS-U BL, Pan, and CG, respectively (P > .05). Overall, four of six patients with MDS-U BL progressed to acute myeloid leukemia; no MDS-U Pan or CG patients did. The rates of progression-free survival and mortality (overall survival) were significantly higher in MDS-U BL compared with Pan and CG (P MDS-U BL is a distinct subset of MDS-U with a poor prognosis, while MDS-U Pan and CG are relatively indolent. Evaluation of peripheral blood smears in patients with MDS is essential for accurate classification and prognosis. © American Society for Clinical Pathology, 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  20. Qualitative interaction trees: A tool to identify qualitative treatment-subgroup interactions

    NARCIS (Netherlands)

    Dusseldorp, E.; Mechelen, I. van

    2014-01-01

    When two alternative treatments (A and B) are available, some subgroup of patients may display a better outcome with treatment A than with B, whereas for another subgroup, the reverse may be true. If this is the case, a qualitative (i.e., disordinal) treatment-subgroup interaction is present. Such

  1. EFFECTS OF LIRAGLUTIDE 3.0 MG ON WEIGHT AND RISK FACTORS IN HISPANIC VERSUS NON-HIPANIC POPULATIONS: SUBGROUP ANALYSIS FROM SCALE RANDOMIZED TRIALS.

    Science.gov (United States)

    O'Neil, Patrick M; Garvey, W Timothy; Gonzalez-Campoy, J Michael; Mora, Pablo; Ortiz, Rafael Violante; Guerrero, German; Claudius, Birgitte; Pi-Sunyer, Xavier

    2016-11-01

    Scarce data exist on pharmacotherapy for obesity in Hispanic individuals. This post hoc analysis of pooled data from 4 phase 3a trials compared the efficacy and safety of liraglutide 3.0 mg versus placebo, as adjunct to a reduced-calorie diet and physical activity, in Hispanic versus non-Hispanic subgroups. We conducted the double-blind randomized, placebo-controlled trials in adults with a minimum body mass index (BMI) of 27 kg/m 2 with at least 1 comorbidity, or a minimum BMI of 30 kg/m 2 , at clinical research sites worldwide. In this analysis, we investigated possible differences in treatment effects between 534 Hispanics (10.4% of the population) and 4,597 non-Hispanics (89.6%) through statistical tests of interaction between subgroups and treatment. Variables examined included mean and categorical weight change, cardiovascular risk markers, and safety data. Both subgroups achieved clinically significant mean weight loss at end-of-treatment with liraglutide 3.0 mg versus placebo: Hispanics 7.0% versus 1.5%, treatment difference -5.1% (95% CI, -6.2 to -4.0); non-Hispanics 7.5% versus 2.3%, -5.2% (95% CI, -5.5 to -4.8). More individuals in both subgroups lost ≥5%, >10%, and >15% of their baseline weight with liraglutide 3.0 mg than with placebo. Efficacy endpoints generally did not vary with ethnicity (P>.05). Adverse events were comparable between ethnic subgroups, with more gastrointestinal disorders reported with liraglutide 3.0 mg than placebo. Efficacy and safety were largely similar between Hispanic and non-Hispanic subgroups. Results support that liraglutide 3.0 mg, used with a reduced-calorie diet and physical activity, can facilitate weight loss in Hispanic individuals. A1c = glycated hemoglobin BMI = body mass index CI = confidence interval FPG = fasting plasma glucose GLP-1 = glucagon-like peptide-1 hsCRP = high-sensitivity C-reactive protein SCALE = Satiety and Clinical Adiposity - Liraglutide Evidence in individuals with and without diabetes T2DM

  2. On the growth of rank for subgroups of finitely generated groups

    International Nuclear Information System (INIS)

    Osin, D V

    1999-01-01

    In [1] and [2] the functions of rank growth were independently introduced and investigated for subgroups of a finitely generated free group. In the present paper the concept of growth of rank is extended to subgroups of an arbitrary finitely generated group G, and the dependence of the asymptotic behaviour of the above functions on the choice of a finite generating set in G is studied. For a broad class of groups (which includes, in particular, the free polynilpotent groups) estimates for the growth of rank for subgroups are obtained that generalize the wellknown Baumslag-Eidel'kind result on finitely generated normal subgroups. Some problems related to the realization of arbitrary functions as functions of rank growth for subgroups of soluble groups are treated

  3. Anatomic and Physiologic Heterogeneity of Subgroup-A Auditory Sensory Neurons in Fruit Flies.

    Science.gov (United States)

    Ishikawa, Yuki; Okamoto, Natsuki; Nakamura, Mizuki; Kim, Hyunsoo; Kamikouchi, Azusa

    2017-01-01

    The antennal ear of the fruit fly detects acoustic signals in intraspecific communication, such as the courtship song and agonistic sounds. Among the five subgroups of mechanosensory neurons in the fly ear, subgroup-A neurons respond maximally to vibrations over a wide frequency range between 100 and 1,200 Hz. The functional organization of the neural circuit comprised of subgroup-A neurons, however, remains largely unknown. In the present study, we used 11 GAL4 strains that selectively label subgroup-A neurons and explored the diversity of subgroup-A neurons by combining single-cell anatomic analysis and Ca 2+ imaging. Our findings indicate that the subgroup-A neurons that project into various combinations of subareas in the brain are more anatomically diverse than previously described. Subgroup-A neurons were also physiologically diverse, and some types were tuned to a narrow frequency range, suggesting that the response of subgroup-A neurons to sounds of a wide frequency range is due to the existence of several types of subgroup-A neurons. Further, we found that an auditory behavioral response to the courtship song of flies was attenuated when most subgroup-A neurons were silenced. Together, these findings characterize the heterogeneous functional organization of subgroup-A neurons, which might facilitate species-specific acoustic signal detection.

  4. Complex posttraumatic stress disorder: The need to consolidate a distinct clinical syndrome or to reevaluate features of psychiatric disorders following interpersonal trauma?

    Science.gov (United States)

    Giourou, Evangelia; Skokou, Maria; Andrew, Stuart P; Alexopoulou, Konstantina; Gourzis, Philippos; Jelastopulu, Eleni

    2018-03-22

    Complex posttraumatic stress disorder (Complex PTSD) has been recently proposed as a distinct clinical entity in the WHO International Classification of Diseases, 11 th version, due to be published, two decades after its first initiation. It is described as an enhanced version of the current definition of PTSD, with clinical features of PTSD plus three additional clusters of symptoms namely emotional dysregulation, negative self-cognitions and interpersonal hardship, thus resembling the clinical features commonly encountered in borderline personality disorder (BPD). Complex PTSD is related to complex trauma which is defined by its threatening and entrapping context, generally interpersonal in nature. In this manuscript, we review the current findings related to traumatic events predisposing the above-mentioned disorders as well as the biological correlates surrounding them, along with their clinical features. Furthermore, we suggest that besides the present distinct clinical diagnoses (PTSD; Complex PTSD; BPD), there is a cluster of these comorbid disorders, that follow a continuum of trauma and biological severity on a spectrum of common or similar clinical features and should be treated as such. More studies are needed to confirm or reject this hypothesis, particularly in clinical terms and how they correlate to clinical entities' biological background, endorsing a shift from the phenomenologically only classification of psychiatric disorders towards a more biologically validated classification.

  5. Irreducible geometric subgroups of classical algebraic groups

    CERN Document Server

    Burness, Timothy C; Testerman, Donna M

    2016-01-01

    Let G be a simple classical algebraic group over an algebraically closed field K of characteristic p \\ge 0 with natural module W. Let H be a closed subgroup of G and let V be a non-trivial irreducible tensor-indecomposable p-restricted 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 H is a disconnected maximal positive-dimensional closed subgroup of G preserving a natural geometric structure on W.

  6. Recombination in the evolution of enterovirus C species sub-group that contains types CVA-21, CVA-24, EV-C95, EV-C96 and EV-C99.

    Directory of Open Access Journals (Sweden)

    Teemu Smura

    Full Text Available Genetic recombination is considered to be a very frequent phenomenon among enteroviruses (Family Picornaviridae, Genus Enterovirus. However, the recombination patterns may differ between enterovirus species and between types within species. Enterovirus C (EV-C species contains 21 types. In the capsid coding P1 region, the types of EV-C species cluster further into three sub-groups (designated here as A-C. In this study, the recombination pattern of EV-C species sub-group B that contains types CVA-21, CVA-24, EV-C95, EV-C96 and EV-C99 was determined using partial 5'UTR and VP1 sequences of enterovirus strains isolated during poliovirus surveillance and previously published complete genome sequences. Several inter-typic recombination events were detected. Furthermore, the analyses suggested that inter-typic recombination events have occurred mainly within the distinct sub-groups of EV-C species. Only sporadic recombination events between EV-C species sub-group B and other EV-C sub-groups were detected. In addition, strict recombination barriers were inferred for CVA-21 genotype C and CVA-24 variant strains. These results suggest that the frequency of inter-typic recombinations, even within species, may depend on the phylogenetic position of the given viruses.

  7. Differences in MRI findings between subgroups of recent-onset childhood arthritis

    International Nuclear Information System (INIS)

    Kirkhus, Eva; Flatoe, Berit; Smith, Hans-Joergen; Riise, Oeystein; Reiseter, Tor

    2011-01-01

    MRI is sensitive for joint inflammation, but its ability to separate subgroups of arthritis in children has been questioned. Infectious arthritis (IA), postinfectious arthritis (PA), transient arthritis (TA) and juvenile idiopathic arthritis (JIA) are subgroups that may need early, different treatment. To determine whether MRI findings differ in IA, PA/TA and JIA in recent-onset childhood arthritis. Fifty-nine children from a prospective study of incidence of arthritis (n = 216) were, based on clinical and biochemical criteria, examined by MRI. Joint fluid, synovium, bone marrow, soft tissue and cartilage were scored retrospectively and analysed by Pearson chi-square test and logistic regression analysis. Fifty-nine children had MRI of one station. IA was suggested by bone marrow oedema (OR 7.46, P = 0.011) and absence of T1-weighted and T2-weighted low signal intensity synovial tissue (OR 0.06, P = 0.015). Furthermore, soft-tissue oedema and reduced contrast enhancement in the epiphyses were more frequent in children with IA. JIA correlated positively with low signal intensity synovial tissue (OR 13.30, P < 0.001) and negatively with soft-tissue oedema (OR 0.20, P = 0.018). No significant positive determinants were found for PA/TA, but bone marrow oedema, soft-tissue oedema, irregular thickened synovium and low signal intensity synovial tissue was less frequent than in IA/JIA. In children with high clinical suspicion of recent onset arthritis, there was a significant difference in the distribution of specific MRI features among the diagnostic groups. (orig.)

  8. Promoter DNA methylation pattern identifies prognostic subgroups in childhood T-cell acute lymphoblastic leukemia.

    Directory of Open Access Journals (Sweden)

    Magnus Borssén

    Full Text Available BACKGROUND: Treatment of pediatric T-cell acute lymphoblastic leukemia (T-ALL has improved, but there is a considerable fraction of patients experiencing a poor outcome. There is a need for better prognostic markers and aberrant DNA methylation is a candidate in other malignancies, but its potential prognostic significance in T-ALL is hitherto undecided. DESIGN AND METHODS: Genome wide promoter DNA methylation analysis was performed in pediatric T-ALL samples (n = 43 using arrays covering >27000 CpG sites. Clinical outcome was evaluated in relation to methylation status and compared with a contemporary T-ALL group not tested for methylation (n = 32. RESULTS: Based on CpG island methylator phenotype (CIMP, T-ALL samples were subgrouped as CIMP+ (high methylation and CIMP- (low methylation. CIMP- T-ALL patients had significantly worse overall and event free survival (p = 0.02 and p = 0.001, respectively compared to CIMP+ cases. CIMP status was an independent factor for survival in multivariate analysis including age, gender and white blood cell count. Analysis of differently methylated genes in the CIMP subgroups showed an overrepresentation of transcription factors, ligands and polycomb target genes. CONCLUSIONS: We identified global promoter methylation profiling as being of relevance for subgrouping and prognostication of pediatric T-ALL.

  9. Are there subgroups within the autistic spectrum? A cluster analysis of a group of children with autistic spectrum disorders.

    Science.gov (United States)

    Prior, M; Eisenmajer, R; Leekam, S; Wing, L; Gould, J; Ong, B; Dowe, D

    1998-09-01

    Comprehensive data on the developmental history and current behaviours of a large sample of high-functioning individuals with diagnoses of autism, Asperger's syndrome, or other related disorder were collected via parent interviews. This provided the basis for a taxonomic analysis to search for subgroups. Most participants also completed theory of mind tasks. Three clusters or subgroups were obtained; these differed on theory of mind performance and on verbal abilities. Although subgroups were identified which bore some relationship to clinical differentiation of autistic, Asperger syndrome, and Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS) cases, the nature of the differences between them appeared strongly related to ability variables. Examination of the kinds of behaviours that differentiated the groups suggested that a spectrum of autistic disorders on which children differ primarily in term of degrees of social and cognitive impairments could explain the findings.

  10. Bayesian additive decision trees of biomarker by treatment interactions for predictive biomarker detection and subgroup identification.

    Science.gov (United States)

    Zhao, Yang; Zheng, Wei; Zhuo, Daisy Y; Lu, Yuefeng; Ma, Xiwen; Liu, Hengchang; Zeng, Zhen; Laird, Glen

    2017-10-11

    Personalized medicine, or tailored therapy, has been an active and important topic in recent medical research. Many methods have been proposed in the literature for predictive biomarker detection and subgroup identification. In this article, we propose a novel decision tree-based approach applicable in randomized clinical trials. We model the prognostic effects of the biomarkers using additive regression trees and the biomarker-by-treatment effect using a single regression tree. Bayesian approach is utilized to periodically revise the split variables and the split rules of the decision trees, which provides a better overall fitting. Gibbs sampler is implemented in the MCMC procedure, which updates the prognostic trees and the interaction tree separately. We use the posterior distribution of the interaction tree to construct the predictive scores of the biomarkers and to identify the subgroup where the treatment is superior to the control. Numerical simulations show that our proposed method performs well under various settings comparing to existing methods. We also demonstrate an application of our method in a real clinical trial.

  11. 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

  12. Considerations for subgroups and phenocopies in complex disease genetics.

    Directory of Open Access Journals (Sweden)

    Ryan Ramanujam

    Full Text Available The number of identified genetic variants associated to complex disease cannot fully explain heritability. This may be partially due to more complicated patterns of predisposition than previously suspected. Diseases such as multiple sclerosis (MS may consist of multiple disease causing mechanisms, each comprised of several elements. We describe how the effect of subgroups can be calculated using the standard association measurement odds ratio, which is then manipulated to provide a formula for the true underlying association present within the subgroup. This is sensitive to the initial minor allele frequencies present in both cases and the subgroup of patients. The methodology is then extended to the χ(2 statistic, for two related scenarios. First, to determine the true χ(2 when phenocopies or disease subtypes reduce association and are reclassified as controls when calculating statistics. Here, the χ(2 is given by (1 + σ * (a + b/(c + d/(1 - σ, or (1 + σ/(1 - σ for equal numbers of cases and controls. Second, when subgroups corresponding to heterogeneity mask the true effect size, but no reclassification is made. Here, the proportion increase in total sample size required to attain the same χ(2 statistic as the subgroup is given as γ = (1 - σ/2/((1 - σ(1 - σc/(a + c(1 - σd/(b + d, and a python script to calculate and plot this value is provided at kirc.se. Practical examples show how in a study of modest size (1000 cases and 1000 controls, a non-significant SNP may exceed genome-wide significance when corresponding to a subgroup of 20% of cases, and may occur in heterozygous form in all cases. This methodology may explain the modest association found in diseases such as MS wherein heterogeneity confounds straightforward measurement of association.

  13. A method for generating subgroup parameters from resonance tables

    International Nuclear Information System (INIS)

    Devan, K.; Mohanakrishnan, P.

    1993-01-01

    A method for generating subgroup or band parameters from resonance tables is described. A computer code SPART was written using this method. This code generates the subgroup parameters for any number of bands within the specified broad groups at different temperatures by reading the required input data from the binary cross section library in the Cadarache format. The results obtained with SPART code for two bands were compared with that obtained from GROUPIE code and a good agreement was obtained. Results of the generation of subgroup parameters in four bands for sample case of 239 Pu from resonance tables of Cadarache Ver.2 library is also presented. (author). 8 refs., 2 tabs

  14. Finite Groups with Given Quantitative Non-Nilpotent Subgroups II

    DEFF Research Database (Denmark)

    Shi, Jiangtao; Zhang, Cui

    2014-01-01

    As an extension of Shi and Zhang's 2011 article [4], we prove that any finite group having at most 23 non-normal non-nilpotent proper subgroups is solvable except for G ≅ A 5 or SL(2, 5), and any finite group having at most three conjugacy classes of non-normal non-nilpotent proper subgroups is s...

  15. Adjuvant Sunitinib for High-risk Renal Cell Carcinoma After Nephrectomy: Subgroup Analyses and Updated Overall Survival Results.

    Science.gov (United States)

    Motzer, Robert J; Ravaud, Alain; Patard, Jean-Jacques; Pandha, Hardev S; George, Daniel J; Patel, Anup; Chang, Yen-Hwa; Escudier, Bernard; Donskov, Frede; Magheli, Ahmed; Carteni, Giacomo; Laguerre, Brigitte; Tomczak, Piotr; Breza, Jan; Gerletti, Paola; Lechuga, Mariajose; Lin, Xun; Casey, Michelle; Serfass, Lucile; Pantuck, Allan J; Staehler, Michael

    2018-01-01

    Adjuvant sunitinib significantly improved disease-free survival (DFS) versus placebo in patients with locoregional renal cell carcinoma (RCC) at high risk of recurrence after nephrectomy (hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.59-0.98; p=0.03). To report the relationship between baseline factors and DFS, pattern of recurrence, and updated overall survival (OS). Data for 615 patients randomized to sunitinib (n=309) or placebo (n=306) in the S-TRAC trial. Subgroup DFS analyses by baseline risk factors were conducted using a Cox proportional hazards model. Baseline risk factors included: modified University of California Los Angeles integrated staging system criteria, age, gender, Eastern Cooperative Oncology Group performance status (ECOG PS), weight, neutrophil-to-lymphocyte ratio (NLR), and Fuhrman grade. Of 615 patients, 97 and 122 in the sunitinib and placebo arms developed metastatic disease, with the most common sites of distant recurrence being lung (40 and 49), lymph node (21 and 26), and liver (11 and 14), respectively. A benefit of adjuvant sunitinib over placebo was observed across subgroups, including: higher risk (T3, no or undetermined nodal involvement, Fuhrman grade ≥2, ECOG PS ≥1, T4 and/or nodal involvement; hazard ratio [HR] 0.74, 95% confidence interval [CI] 0.55-0.99; p=0.04), NLR ≤3 (HR 0.72, 95% CI 0.54-0.95; p=0.02), and Fuhrman grade 3/4 (HR 0.73, 95% CI 0.55-0.98; p=0.04). All subgroup analyses were exploratory, and no adjustments for multiplicity were made. Median OS was not reached in either arm (HR 0.92, 95% CI 0.66-1.28; p=0.6); 67 and 74 patients died in the sunitinib and placebo arms, respectively. A benefit of adjuvant sunitinib over placebo was observed across subgroups. The results are consistent with the primary analysis, which showed a benefit for adjuvant sunitinib in patients at high risk of recurrent RCC after nephrectomy. Most subgroups of patients at high risk of recurrent renal cell carcinoma after

  16. 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

  17. Subgroup analyses in randomised controlled trials: cohort study on trial protocols and journal publications.

    Science.gov (United States)

    Kasenda, Benjamin; Schandelmaier, Stefan; Sun, Xin; von Elm, Erik; You, John; Blümle, Anette; Tomonaga, Yuki; Saccilotto, Ramon; Amstutz, Alain; Bengough, Theresa; Meerpohl, Joerg J; Stegert, Mihaela; Olu, Kelechi K; Tikkinen, Kari A O; Neumann, Ignacio; Carrasco-Labra, Alonso; Faulhaber, Markus; Mulla, Sohail M; Mertz, Dominik; Akl, Elie A; Bassler, Dirk; Busse, Jason W; Ferreira-González, Ignacio; Lamontagne, Francois; Nordmann, Alain; Gloy, Viktoria; Raatz, Heike; Moja, Lorenzo; Rosenthal, Rachel; Ebrahim, Shanil; Vandvik, Per O; Johnston, Bradley C; Walter, Martin A; Burnand, Bernard; Schwenkglenks, Matthias; Hemkens, Lars G; Bucher, Heiner C; Guyatt, Gordon H; Briel, Matthias

    2014-07-16

    To investigate the planning of subgroup analyses in protocols of randomised controlled trials and the agreement with corresponding full journal publications. Cohort of protocols of randomised controlled trial and subsequent full journal publications. Six research ethics committees in Switzerland, Germany, and Canada. 894 protocols of randomised controlled trial involving patients approved by participating research ethics committees between 2000 and 2003 and 515 subsequent full journal publications. Of 894 protocols of randomised controlled trials, 252 (28.2%) included one or more planned subgroup analyses. Of those, 17 (6.7%) provided a clear hypothesis for at least one subgroup analysis, 10 (4.0%) anticipated the direction of a subgroup effect, and 87 (34.5%) planned a statistical test for interaction. Industry sponsored trials more often planned subgroup analyses compared with investigator sponsored trials (195/551 (35.4%) v 57/343 (16.6%), P<0.001). Of 515 identified journal publications, 246 (47.8%) reported at least one subgroup analysis. In 81 (32.9%) of the 246 publications reporting subgroup analyses, authors stated that subgroup analyses were prespecified, but this was not supported by 28 (34.6%) corresponding protocols. In 86 publications, authors claimed a subgroup effect, but only 36 (41.9%) corresponding protocols reported a planned subgroup analysis. Subgroup analyses are insufficiently described in the protocols of randomised controlled trials submitted to research ethics committees, and investigators rarely specify the anticipated direction of subgroup effects. More than one third of statements in publications of randomised controlled trials about subgroup prespecification had no documentation in the corresponding protocols. Definitive judgments regarding credibility of claimed subgroup effects are not possible without access to protocols and analysis plans of randomised controlled trials. © The DISCO study group 2014.

  18. POLG1 mutations and stroke like episodes: a distinct clinical entity rather than an atypical MELAS syndrome.

    Science.gov (United States)

    Cheldi, Antonella; Ronchi, Dario; Bordoni, Andreina; Bordo, Bianca; Lanfranconi, Silvia; Bellotti, Maria Grazia; Corti, Stefania; Lucchini, Valeria; Sciacco, Monica; Moggio, Maurizio; Baron, Pierluigi; Comi, Giacomo Pietro; Colombo, Antonio; Bersano, Anna

    2013-01-15

    POLG1 mutations have been associated with MELAS-like phenotypes. However given several clinical differences it is unknown whether POLG1 mutations are possible causes of MELAS or give raise to a distinct clinical and genetic entity, named POLG1-associated encephalopathy. We describe a 74 years old man carrying POLG1 mutations presenting with strokes, myopathy and ragged red fibers with some atypical aspects for MELAS such as late onset, lack of cerebral calcification and presence of frontal and occipital MRI lesions better consistent with the POLG associated-encephalopathy spectrum. The lack of available data hampers a definite diagnosis in our patient as well as makes it difficult to compare MELAS, which is a clearly defined clinical syndrome, with POLG1-associated encephalopathy, which is so far a purely molecularly defined syndrome with a quite heterogeneous clinical picture. However, the present report contributes to expand the phenotypic spectrum of POLG1 mutations underlining the importance of searching POLG1 mutations in patients with mitochondrial signs and MELAS like phenotypes but negative for common mtDNA mutations.

  19. Effectiveness of lifestyle intervention in subgroups of obese infertile women : a subgroup analysis of a RCT

    NARCIS (Netherlands)

    van Oers, A M; Groen, H; Mutsaerts, M A Q; Burggraaff, J M; Kuchenbecker, W K H; Perquin, D A M; Koks, C A M; van Golde, R; Kaaijk, E M; Schierbeek, J M; Oosterhuis, G J E; Broekmans, F J; Vogel, N E A; Land, J A; Mol, B W J; Hoek, A

    2016-01-01

    STUDY QUESTION: Do age, ovulatory status, severity of obesity and body fat distribution affect the effectiveness of lifestyle intervention in obese infertile women? SUMMARY ANSWER: We did not identify a subgroup in which lifestyle intervention increased the healthy live birth rate however it did

  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. 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.

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

    DEFF Research Database (Denmark)

    Nielsen, Anne Mølgaard

    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......, the optimal application of the LCA method in this context is unknown and therefore, two methodological considerations were addressed during the process. Firstly, when using existing questionnaire data, whether using each single item or the summary scores would provide better subgroup information. Secondly...... the questionnaires was preferred, due to the more nuanced description available within the resulting subgroups. Therefore, the single‐item strategy was used in the subsequent single‐stage and two‐stage LCA, which identified seven and nine patient subgroups, respectively, with similar face validity and adequate...

  3. The interest of gait markers in the identification of subgroups among fibromyalgia patients

    OpenAIRE

    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

    2011-01-01

    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 characterizin...

  4. Clebsch-Gordan coefficients of discrete groups in subgroup bases

    Science.gov (United States)

    Chen, Gaoli

    2018-04-01

    We express each Clebsch-Gordan (CG) coefficient of a discrete group as a product of a CG coefficient of its subgroup and a factor, which we call an embedding factor. With an appropriate definition, such factors are fixed up to phase ambiguities. Particularly, they are invariant under basis transformations of irreducible representations of both the group and its subgroup. We then impose on the embedding factors constraints, which relate them to their counterparts under complex conjugate and therefore restrict the phases of embedding factors. In some cases, the phase ambiguities are reduced to sign ambiguities. We describe the procedure of obtaining embedding factors and then calculate CG coefficients of the group 𝒫𝒮ℒ2(7) in terms of embedding factors of its subgroups S4 and 𝒯7.

  5. Hepatocellular carcinoma displays distinct DNA methylation signatures with potential as clinical predictors.

    Directory of Open Access Journals (Sweden)

    Hector Hernandez-Vargas

    Full Text Available BACKGROUND: Hepatocellular carcinoma (HCC is characterized by late detection and fast progression, and it is believed that epigenetic disruption may be the cause of its molecular and clinicopathological heterogeneity. A better understanding of the global deregulation of methylation states and how they correlate with disease progression will aid in the design of strategies for earlier detection and better therapeutic decisions. METHODS AND FINDINGS: We characterized the changes in promoter methylation in a series of 30 HCC tumors and their respective surrounding tissue and identified methylation signatures associated with major risk factors and clinical correlates. A wide panel of cancer-related gene promoters was analyzed using Illumina bead array technology, and CpG sites were then selected according to their ability to classify clinicopathological parameters. An independent series of HCC tumors and matched surrounding tissue was used for validation of the signatures. We were able to develop and validate a signature of methylation in HCC. This signature distinguished HCC from surrounding tissue and from other tumor types, and was independent of risk factors. However, aberrant methylation of an independent subset of promoters was associated with tumor progression and etiological risk factors (HBV or HCV infection and alcohol consumption. Interestingly, distinct methylation of an independent panel of gene promoters was strongly correlated with survival after cancer therapy. CONCLUSION: Our study shows that HCC tumors exhibit specific DNA methylation signatures associated with major risk factors and tumor progression stage, with potential clinical applications in diagnosis and prognosis.

  6. Premorbid IQ subgroups in first episode non affective psychosis patients: Long-term sex differences in function and neurocognition.

    Science.gov (United States)

    Ayesa-Arriola, Rosa; Setién-Suero, Esther; Neergaard, Karl David; Belzunces, Àuria Albacete; Contreras, Fernando; van Haren, Neeltje E M; Crespo-Facorro, Benedicto

    2017-12-21

    Low IQ has been associated with schizophrenia, even to the point of being posited as a possible causal factor for psychosis. However, individuals with normal and high IQ also develop psychotic illnesses. The aim of this study was to characterize premorbid IQ subgroups at first episode of psychosis (FEP). The study sample comes from a large epidemiological, 3-year longitudinal, intervention program on psychosis containing individuals living in a catchment area in Spain. Estimated premorbid IQ (epIQ) scores were used to build low (110) epIQ subgroups in samples of FEP patients (N=292) and healthy controls (N=199). The epIQ subgroups were compared in sociodemographic, neuropsychological, clinical and premorbid characteristics. Long-term functional and cognitive outcome, with a focus on sex differences, were also explored. Low-epIQ was more frequently found in FEP patients (28.8%) than in healthy controls (14.6%). Low-epIQ patients were more likely to have worse premorbid adjustment, belong to low socioeconomic status families, have less years of education, and to be single, unemployed, and younger. They presented more severe impairments in processing speed, executive and global cognitive function. Female patients with low-epIQ showed better baseline function and more stable outcome than males. Our results indicate that low premorbid IQ is a morbid manifestation, easily detected in a subgroup of FEP patients that predicts poorer outcome particularly in males. This perspective provides important information for the tailoring of subgroup-specific early intervention programs for psychosis. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Subgrouping Poor Readers on the Basis of Individual Differences in Reading-Related Abilities

    OpenAIRE

    Catts, Hugh W.; Hogan, Tiffany; Fey, Marc E.

    2003-01-01

    The present study investigated the use of the Reading Component Model to subgroup poor readers. A large sample of poor readers was identified in second grade and subgrouped on the basis of relative strengths and weaknesses in word recognition and listening comprehension. Although homogeneous subgroups were not identified, poor readers could be classified into four subgroups that differed significantly in reading-related abilities. Further analyses showed that poor readers' strengths and weakn...

  8. CLINICAL AND IMMUNOPATHOLOGIC CHARACTERISTICS OF EARLY NEONATAL SEPSIS IN INFANTS OF DIFFERENT GESTATIONAL AGE AND CLINICAL AND ECONOMICAL EVALUATION OF IMMUNOSUPPORTIVE THERAPY EFFICACY

    Directory of Open Access Journals (Sweden)

    I.G. Soldatova

    2011-01-01

    Full Text Available Study objective — to study clinical and immunopathologic characteristics of early neonatal sepsis in infants of different gestational age and to perform clinical and economical evaluation of immunosupportive therapy with Pentaglobin efficacy in complex treatment of this disease. 79 infants diagnosed with neonatal sepsis were included into prospective study. These patients were divided into 3 subgroups in order to evaluate clinical and economical efficacy of immunosupportive therapy: subgroup A (n = 38 — patients receiving. Pentaglobin as part of basic complex treatment from 3–6 days of life; subgroup B (n = 27 — from 7–10 days of life; subgroup C  (n = 27 — patients treated without Pentaglobin. Proven high clinical and economical efficacy of immunoglobulin preparations as a part of complex treatment of neonatal sepsis allows to recommend this type of therapy for a wide application in neonatology as a part of neonatal sepsis treatment.Key words: early neonatal sepsis, prematurity, extremely low body mass, immunosupportive therapy, intravenous immunoglobines, clinical and economical analysis, neonatal sepsis. (Voprosy sovremennoi pediatrii — Current Pediatrics. — 2011; 10 (6: 52–61

  9. Demonstration of Microbial Subgroups among Normal Vaginal Microbiota Data

    OpenAIRE

    Lee, M.-L. T.

    2011-01-01

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

  10. 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

    further study.Trial registration: ClinicalTrials.gov NCT00342992.Keywords: vitamin E, pneumonia, smoking, leisure time exercise, α-tocopherol, β-carotene, subgroup analysis

  11. IMPaCT Back study protocol. Implementation of subgrouping for targeted treatment systems for low back pain patients in primary care: a prospective population-based sequential comparison

    Directory of Open Access Journals (Sweden)

    Foster Nadine E

    2010-08-01

    Full Text Available Abstract Background Prognostic assessment tools to identify subgroups of patients at risk of persistent low back pain who may benefit from targeted treatments have been developed and validated in primary care. The IMPaCT Back study is investigating the effects of introducing and supporting a subgrouping for targeted treatment system in primary care. Methods/Design A prospective, population-based, quality improvement study in one Primary Care Trust in England with a before and after design. Phases 1 and 3 collect data on current practice, attitudes and behaviour of health care practitioners, patients' outcomes and health care costs. Phase 2 introduces and supports the subgrouping for targeted treatment system, via a multi-component, quality improvement intervention that includes educational courses and outreach visits led by opinion leaders, audit/feedback, mentoring and organisational support to embed the subgrouping tools within IT and clinical management systems. We aim to recruit 1000 low back pain patients aged 18 years and over consulting 7 GP practices within one Primary Care Trust in England, UK. The study includes GPs in participating practices and physiotherapists in associated services. The primary objective is to determine the effect of the subgrouping for targeted treatment system on back pain related disability and catastrophising at 2 and 6 months, comparing data from phase 1 with phase 3. Key secondary objectives are to determine the impact on: a GPs' and physiotherapists' attitudes and behaviour regarding low back pain; b The process of care that patients receive; c The cost-effectiveness and sustainability of the new clinical system. Discussion This paper details the rationale, design, methods, planned analysis and operational aspects of the IMPaCT Back study. We aim to determine whether the new subgrouping for targeted treatment system is implemented and sustained in primary care, and evaluate its impact on clinical decision

  12. RABA Members Act in Distinct Steps of Subcellular Trafficking of the FLAGELLIN SENSING2 Receptor[W

    Science.gov (United States)

    Choi, Seung-won; Tamaki, Takayuki; Ebine, Kazuo; Uemura, Tomohiro; Ueda, Takashi; Nakano, Akihiko

    2013-01-01

    Cell surface proteins play critical roles in the perception of environmental stimuli at the plasma membrane (PM) and ensuing signal transduction. Intracellular localization of such proteins must be strictly regulated, which requires elaborate integration of exocytic and endocytic trafficking pathways. Subcellular localization of Arabidopsis thaliana FLAGELLIN SENSING2 (FLS2), a receptor that recognizes bacterial flagellin, also depends on membrane trafficking. However, our understanding about the mechanisms involved is still limited. In this study, we visualized ligand-induced endocytosis of FLS2 using green fluorescent protein (GFP)-tagged FLS2 expressed in Nicotiana benthamiana. Upon treatment with the flg22 peptide, internalized FLS2-GFP from the PM was transported to a compartment with properties intermediate between the trans-Golgi network (TGN) and the multivesicular endosome. This compartment gradually discarded the TGN characteristics as it continued along the trafficking pathway. We further found that FLS2 endocytosis involves distinct RABA/RAB11 subgroups at different steps. Moreover, we demonstrated that transport of de novo–synthesized FLS2 to the PM also involves a distinct RABA/RAB11 subgroup. Our results demonstrate the complex regulatory system for properly localizing FLS2 and functional differentiation in RABA members in endo- and exocytosis. PMID:23532067

  13. MPACT Subgroup Self-Shielding Efficiency Improvements

    International Nuclear Information System (INIS)

    Stimpson, Shane; Liu, Yuxuan; Collins, Benjamin S.; Clarno, Kevin T.

    2016-01-01

    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.

  14. FLT3 mutations in early T-cell precursor ALL characterize a stem cell like leukemia and imply the clinical use of tyrosine kinase inhibitors.

    Directory of Open Access Journals (Sweden)

    Martin Neumann

    Full Text Available Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL has been identified as high-risk subgroup of acute T-lymphoblastic leukemia (T-ALL with a high rate of FLT3-mutations in adults. To unravel the underlying pathomechanisms and the clinical course we assessed molecular alterations and clinical characteristics in a large cohort of ETP-ALL (n = 68 in comparison to non-ETP T-ALL adult patients. Interestingly, we found a high rate of FLT3-mutations in ETP-ALL samples (n = 24, 35%. Furthermore, FLT3 mutated ETP-ALL was characterized by a specific immunophenotype (CD2+/CD5-/CD13+/CD33-, a distinct gene expression pattern (aberrant expression of IGFBP7, WT1, GATA3 and mutational status (absence of NOTCH1 mutations and a low frequency, 21%, of clonal TCR rearrangements. The observed low GATA3 expression and high WT1 expression in combination with lack of NOTCH1 mutations and a low rate of TCR rearrangements point to a leukemic transformation at the pluripotent prothymocyte stage in FLT3 mutated ETP-ALL. The clinical outcome in ETP-ALL patients was poor, but encouraging in those patients with allogeneic stem cell transplantation (3-year OS: 74%. To further explore the efficacy of targeted therapies, we demonstrate that T-ALL cell lines transfected with FLT3 expression constructs were particularly sensitive to tyrosine kinase inhibitors. In conclusion, FLT3 mutated ETP-ALL defines a molecular distinct stem cell like leukemic subtype. These data warrant clinical studies with the implementation of FLT3 inhibitors in addition to early allogeneic stem cell transplantation for this high risk subgroup.

  15. QUINT : A tool to detect qualitative treatment-subgroup interactions in randomized controlled trials

    NARCIS (Netherlands)

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

    2016-01-01

    Objective: The detection of subgroups involved in qualitative treatment–subgroup interactions (i.e., for one subgroup of clients treatment A outperforms treatment B, whereas for another the reverse holds true) is crucial for personalized health. In typical Randomized Controlled Trials (RCTs), the

  16. Comparative study on cases of vertigo and dizziness in the emergency room and otorhinolaryngological clinic

    International Nuclear Information System (INIS)

    Tsujimoto, Toshiya; Kawashima, Kayoko; Hashimoto, Seiko; Imai, Takao

    2011-01-01

    We recently studied the characteristics of vertigo and dizziness in 197 patients who first visited the emergency room (ER group) and in 288 patients who first visited the otorhinolaryngological clinic of Minoh City Hospital (ENT group) between January 1 and December 31 of 2009. The ER group can be regarded as representing the hyperacute phase and the ENT group as representing the acute to chronic phase. These two groups were completely distinct. We also subdivided these groups into the high risk subgroup (H subgroup) for cases with the underlying diseases of diabetes mellitus, hypertension, cerebrovascular disease and hyperlipidemia, and the normal subgroup (N subgroup).Comparison of the two groups showed that, in the ER group, a significantly larger numbers of patients had symptoms of peripheral vestibular origin except for benign paroxysmal positional vertigo (BPPV) and Meniere's disease, and a significantly larger number of patients had symptoms of unknown origin in the ENT group. Half of this group may be accounted for by patients with symptoms of peripheral vestibular origin except for BPPV and Meniere's disease in the ER group. In 8 out of 158 patients of the ER group and 1 out of 122 patients of the ENT group, cerebral lesions were not found on CT images but were found with MRI. Careful investigation is necessary in the patients with normal CT findings. Central vestibular lesions were found in 7 out of 197 patients (3.5%) of the ER group and 5 out of 288 patients (1.7%) of the ENT group. The incidence of central lesions tended to be higher in the ER group than in the ENT group. There was no significant difference in the incidence of central lesion among the H and N subgroups of both groups. Careful investigation of the central vestibular lesion is also necessary in the N subgroup. (author)

  17. The structure of EAP-groups and self-autopermutable subgroups.

    Science.gov (United States)

    Housieni, Shima; Moghaddam, Mohammad Reza Rajabzadeh

    2014-01-01

    A subgroup H of a given group G is said to be autopermutable, if HH(α) = H(α)H for all α ∈ Aut(G). We also call H a self-autopermutable subgroup of G, when HH(α) = H(α)H implies that H(α) = H. Moreover, G is said to be EAP-group, if every subgroup of G is autopermutable. One notes that if α runs over the inner automorphisms of the group, one obtains the notions of conjugate-permutability, self-conjugate-permutability, and ECP-groups, which were studied by Foguel in 1997, Li and Meng in 2007, and Xu and Zhang in 2005, respectively. In the present paper, we determine the structure of a finite EAP-group when its centre is of index 4 in G. We also show that self-autopermutability and characteristic properties are equivalent for nilpotent groups.

  18. Patient subgroup analyses of the treatment effect of subcutaneous interferon beta-1a on development of multiple sclerosis in the randomized controlled REFLEX study

    NARCIS (Netherlands)

    Freedman, M.S.; De Stefano, N.; Barkhof, F.; Polman, C.H.; Comi, G.; Uitdehaag, B.M.J.; Casset-Semanaz, F.; Hennessy, B.; Lehr, L.; Stubinski, B.; Jack, D.L.; Kappos, L.

    2014-01-01

    The REFLEX study (NCT00404352) established that subcutaneous (sc) interferon (IFN) β-1a reduced the risks of McDonald MS (2005 criteria) and clinically definite multiple sclerosis (CDMS) in patients with a first clinical demyelinating event suggestive of MS. The aim of this subgroup analysis was to

  19. Farewell to GBM-O: Genomic and transcriptomic profiling of glioblastoma with oligodendroglioma component reveals distinct molecular subgroups.

    Science.gov (United States)

    Hinrichs, Benjamin H; Newman, Scott; Appin, Christina L; Dunn, William; Cooper, Lee; Pauly, Rini; Kowalski, Jeanne; Rossi, Michael R; Brat, Daniel J

    2016-01-13

    Glioblastoma with oligodendroglioma component (GBM-O) was recognized as a histologic pattern of glioblastoma (GBM) by the World Health Organization (WHO) in 2007 and is distinguished by the presence of oligodendroglioma-like differentiation. To better understand the genetic underpinnings of this morphologic entity, we performed a genome-wide, integrated copy number, mutational and transcriptomic analysis of eight (seven primary, primary secondary) cases. Three GBM-O samples had IDH1 (p.R132H) mutations; two of these also demonstrated 1p/19q co-deletion and had a proneural transcriptional profile, a molecular signature characteristic of oligodendroglioma. The additional IDH1 mutant tumor lacked 1p/19q co-deletion, harbored a TP53 mutation, and overall, demonstrated features most consistent with IDH mutant (secondary) GBM. Finally, five tumors were IDH wild-type (IDHwt) and had chromosome seven gains, chromosome 10 losses, and homozygous 9p deletions (CDKN2A), alterations typical of IDHwt (primary) GBM. IDHwt GBM-Os also demonstrated EGFR and PDGFRA amplifications, which correlated with classical and proneural expression subtypes, respectively. Our findings demonstrate that GBM-O is composed of three discrete molecular subgroups with characteristic mutations, copy number alterations and gene expression patterns. Despite displaying areas that morphologically resemble oligodendroglioma, the current results indicate that morphologically defined GBM-O does not correspond to a particular genetic signature, but rather represents a collection of genetically dissimilar entities. Ancillary testing, especially for IDH and 1p/19q, should be used for determining these molecular subtypes.

  20. Chemical Profiling of Primary Mesothelioma Cultures Defines Subtypes with Different Expression Profiles and Clinical Responses.

    Science.gov (United States)

    Schunselaar, Laurel M; Quispel-Janssen, Josine M M F; Kim, Yongsoo; Alifrangis, Constantine; Zwart, Wilbert; Baas, Paul; Neefjes, Jacques

    2018-04-01

    Purpose: Finding new treatment options for patients with malignant pleural mesothelioma is challenging due to the rarity and heterogeneity of this cancer type. The absence of druggable targets further complicates the development of new therapies. Current treatment options are therefore limited, and prognosis remains poor. Experimental Design: We performed drug screening on primary mesothelioma cultures to guide treatment decisions of corresponding patients that were progressive after first- or second-line treatment. Results: We observed a high concordance between in vitro results and clinical outcomes. We defined three subgroups responding differently to the anticancer drugs tested. In addition, gene expression profiling yielded distinct signatures that segregated the differently responding subgroups. These genes signatures involved various pathways, most prominently the fibroblast growth factor pathway. Conclusions: Our primary mesothelioma culture system has proved to be suitable to test novel drugs. Chemical profiling of primary mesothelioma cultures allows personalizing treatment for a group of patients with a rare tumor type where clinical trials are notoriously difficult. This personalized treatment strategy is expected to improve the poor prospects of patients with mesothelioma. Clin Cancer Res; 24(7); 1761-70. ©2017 AACR See related commentary by John and Chia, p. 1513 . ©2017 American Association for Cancer Research.

  1. Subgroup effects of occupational therapy-based intervention for people with advanced cancer.

    Science.gov (United States)

    Sampedro Pilegaard, Marc; Oestergaard, Lisa Gregersen; la Cour, Karen; Thit Johnsen, Anna; Brandt, Åse

    2018-03-23

    Many people with advanced cancer have decreased ability to perform activities of daily living (ADL). We recently performed a randomized, controlled trial (RCT) assessing the efficacy of an occupational therapy-based program, the 'Cancer Home-Life Intervention' in people with advanced cancer (N = 242) and found no overall effects on ADL ability. However, heterogeneity of treatment effect may disguise subgroup differences. To investigate whether subgroups of people with advanced cancer gain positive effects from the 'Cancer Home-Life Intervention' on ADL ability. An exploratory subgroup analysis including 191 participants from a RCT. The outcome was ADL motor ability measured by the Assessment of Motor and Process Skills (AMPS). Subgroups were defined by age, gender, years of education, type of primary tumor, functional level, and activity problems. The 'Cancer Home-Life Intervention' had no statistically significant effect in the six subgroups. Modifying effects of age (0.30 [95% CI: -0.05 to 0.64]) and gender (0.23 [95% CI: -0.11 to 0.57]) were not found. There were no subgroup effects of the 'Cancer Home-Life Intervention'on ADL motor ability. Some indications suggest greater effects for those aged below 69 years; however, this result should be interpreted with caution.

  2. Phylogeny and molecular signatures for the phylum Thermotogae and its subgroups.

    Science.gov (United States)

    Gupta, Radhey S; Bhandari, Vaibhav

    2011-06-01

    Thermotogae species are currently identified mainly on the basis of their unique toga and distinct branching in the rRNA and other phylogenetic trees. No biochemical or molecular markers are known that clearly distinguish the species from this phylum from all other bacteria. The taxonomic/evolutionary relationships within this phylum, which consists of a single family, are also unclear. We report detailed phylogenetic analyses on Thermotogae species based on concatenated sequences for many ribosomal as well as other conserved proteins that identify a number of distinct clades within this phylum. Additionally, comprehensive analyses of protein sequences from Thermotogae genomes have identified >60 Conserved Signature Indels (CSI) that are specific for the Thermotogae phylum or its different subgroups. Eighteen CSIs in important proteins such as PolI, RecA, TrpRS and ribosomal proteins L4, L7/L12, S8, S9, etc. are uniquely present in various Thermotogae species and provide molecular markers for the phylum. Many CSIs were specific for a number of Thermotogae subgroups. Twelve of these CSIs were specific for a clade consisting of various Thermotoga species except Tt. lettingae, which was separated from other Thermotoga species by a long branch in phylogenetic trees; Fourteen CSIs were specific for a clade consisting of the Fervidobacterium and Thermosipho genera and eight additional CSIs were specific for the genus Thermosipho. In addition, the existence of a clade consisting of the deep branching species Petrotoga mobilis, Kosmotoga olearia and Thermotogales bacterium mesG1 was supported by seven CSIs. The deep branching of this clade was also supported by a number of CSIs that were present in various Thermotogae species, but absent in this clade and all other bacteria. Most of these clades were strongly supported by phylogenetic analyses based on two datasets of protein sequences and they identify potential higher taxonomic grouping (viz. families) within this phylum

  3. Initial combination therapy with ambrisentan and tadalafil in connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH): subgroup analysis from the AMBITION trial.

    Science.gov (United States)

    Coghlan, John Gerry; Galiè, Nazzareno; Barberà, Joan Albert; Frost, Adaani E; Ghofrani, Hossein-Ardeschir; Hoeper, Marius M; Kuwana, Masataka; McLaughlin, Vallerie V; Peacock, Andrew J; Simonneau, Gérald; Vachiéry, Jean-Luc; Blair, Christiana; Gillies, Hunter; Miller, Karen L; Harris, Julia H N; Langley, Jonathan; Rubin, Lewis J

    2017-07-01

    Patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH), in particular systemic sclerosis (SSc), had an attenuated response compared with idiopathic PAH in most trials. Thus, there is uncertainty regarding the benefit of PAH-targeted therapy in some forms of CTD-PAH. To explore the safety and efficacy of initial combination therapy with ambrisentan and tadalafil versus ambrisentan or tadalafil monotherapy in patients with CTD-PAH and SSc-PAH enrolled in the AMBITION trial. This was a post hoc analysis of patients with CTD-PAH and SSc-PAH from AMBITION, an event-driven, double-blind trial in patients with WHO functional class II/III PAH. Treatment-naive patients were randomised 2:1:1 to once-daily initial combination therapy with ambrisentan plus tadalafil or monotherapy with ambrisentan or tadalafil, respectively. The primary endpoint was time to the first clinical failure event (first occurrence of death, hospitalisation for worsening PAH, disease progression or unsatisfactory long-term clinical response). In the primary analysis set (N=500), 187 patients had CTD-PAH, of whom 118 had SSc-PAH. Initial combination therapy reduced the risk of clinical failure versus pooled monotherapy in each subgroup: CTD-PAH (HR 0.43 (95% CI 0.24 to 0.77)) and SSc-PAH (0.44 (0.22 to 0.89)). The most common AE was peripheral oedema, which was reported more frequently with initial combination therapy than monotherapy in the two PAH subgroups. The relative frequency of adverse events between those on combination therapy versus monotherapy was similar across subgroups. This post hoc subgroup analysis provides evidence that CTD-PAH and SSc-PAH patients benefit from initial ambrisentan and tadalafil combination therapy. NCT01178073, post results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  4. The central subgroup of the nonabelian tensor square of Bieberbach ...

    African Journals Online (AJOL)

    A Bieberbach group with point group C2 xC2 is a free torsion crystallographic group. A central subgroup of a nonabelian tensor square of a group G, denoted by ∇(G) is a normal subgroup generated by generator g⊗g for all g∈G and essentially depends on the abelianization of the group. In this paper, the formula of the ...

  5. Discovering subgroups using descriptive models of adverse outcomes in medical care.

    Science.gov (United States)

    Stiglic, Gregor; Kokol, P

    2012-01-01

    Hospital discharge databases store hundreds of thousands of patients. These datasets are usually used by health insurance companies to process claims from hospitals, but they also represent a rich source of information about the patterns of medical care. The proposed subgroup discovery method aims to improve the efficiency of detecting interpretable subgroups in data. Supervised descriptive rule discovery techniques can prove inefficient in cases when target class samples represent only an extremely small amount of all available samples. Our approach aims to balance the number of samples in target and control groups prior to subgroup discovery process. Additionally, we introduce some improvements to an existing subgroup discovery algorithm enhancing the user experience and making the descriptive data mining process and visualization of rules more user friendly. Instance-based subspace subgroup discovery introduced in this paper is demonstrated on hospital discharge data with focus on medical errors. In general, the number of patients with a recorded diagnosis related to a medical error is relatively small in comparison to patients where medical errors did not occur. The ability to produce comprehensible and simple models with high degree of confidence, support, and predictive power using the proposed method is demonstrated. This paper introduces a subspace subgroup discovery process that can be applied in all settings where a large number of samples with relatively small number of target class samples are present. The proposed method is implemented in Weka machine learning environment and is available at http://ri.fzv.uni-mb.si/ssd.

  6. 1H MR spectroscopy in histopathological subgroups of mesial temporal lobe epilepsy

    International Nuclear Information System (INIS)

    Hajek, Milan; Dezortova, Monika; Krsek, Pavel; Komarek, Vladimir; Marusic, Petr; Tomasek, Martin; Krijtova, Hana; Zamecnik, Josef; Kyncl, Martin

    2009-01-01

    The aim of the study was to analyze the lateralizing value of proton magnetic resonance spectroscopy ( 1 H MRS) in histopathologically different subgroups of mesial temporal lobe epilepsies (MTLE) and to correlate results with clinical, MRI and seizure outcome data. A group of 35 patients who underwent resective epilepsy surgery was retrospectively studied. Hippocampal 1 H MR spectra were evaluated. Metabolite concentrations were obtained using LCModel and NAA/Cr, NAA/Cho, NAA/(Cr+Cho), Cho/Cr ratios and coefficients of asymmetry were calculated. MRI correctly lateralized 89% of subjects and 1 H MRS 83%. MRI together with 1 H MRS correctly lateralized 100% of patients. Nineteen subjects had ''classical'' hippocampal sclerosis (HS), whereas the remaining 16 patients had ''mild'' HS. Nineteen patients had histopathologically proven malformation of cortical development (MCD) in the temporal pole; 16 subjects had only HS. No difference in 1 H MRS findings was found between patients in different histopathological subgroups of MTLE. Our results support the hypothesis that 1 H MRS abnormalities do not directly reflect histopathological changes in MTLE patients. Subjects with non-lateralized 1 H MRS abnormalities did not have a worse postoperative seizure outcome. We found no significant impact of contralateral 1 H MRS abnormality on post-surgical seizure outcome. (orig.)

  7. Subgroup effects of occupational therapy-based intervention for people with advanced cancer

    DEFF Research Database (Denmark)

    Pilegaard, Marc Sampedro; Østergaard, Lisa Gregersen; la Cour, Karen

    2018-01-01

    cancer (N = 242) and found no overall effects on ADL ability. However, heterogeneity of treatment effect may disguise subgroup differences. Objective: To investigate whether subgroups of people with advanced cancer gain positive effects from the ‘Cancer Home-Life Intervention’ on ADL ability. Material....... Results: The ‘Cancer Home-Life Intervention’ had no statistically significant effect in the six subgroups. Modifying effects of age (0.30 [95% CI: −0.05 to 0.64]) and gender (0.23 [95% CI: −0.11 to 0.57]) were not found. Conclusion: There were no subgroup effects of the ‘Cancer Home-Life Intervention......’on ADL motor ability. Some indications suggest greater effects for those aged below 69 years; however, this result should be interpreted with caution....

  8. Hemolytic disease of the newborn caused by irregular blood subgroup (Kell, C, c, E, and e) incompatibilities: report of 106 cases at a tertiary-care centre.

    Science.gov (United States)

    Karagol, Belma Saygili; Zenciroglu, Aysegul; Okumus, Nurullah; Karadag, Nilgun; Dursun, Arzu; Hakan, Nilay

    2012-06-01

    To determine the clinical spectrum of hemolytic disease due to irregular blood subgroup incompatibility in hospitalized neonates. The medical records of the all hospitalized newborn patients diagnosed with indirect hyperbilirubinemia due to subgroup incompatibility in Kell, C, c, E, and e systems were included in the study. Data from 106 newborns with hemolytic jaundice due to irregular blood subgroups were retrospectively evaluated, and clinical and laboratory findings were compared between patients . The treatment modalities given to the patients of each subgroup types and the laboratory findings and treatment modalities of the cases according to Coombs tests results were also analyzed. Fetal affection of the hemolysis and also fetal losses due to irregular red-cell alloimmunization were not detected in prenatal course, as there was no follow-up of these pregnancies. The mean postnatal hospitalizing age was 6.1 ± 5.2 days after birth. The mean total bilirubin level and the mean hemoglobin value on hospitalization were 343.7 ± 63.3 µmol/L (=20.1 ± 3.7 mg/dL) and 14.9 ± 3.4 g/dL, respectively. Of 106 patients identified with irregular subgroup incompatibility, 40 infants (37.7%) were associated with C, 22 (20.8%) with c, 30 (28.3%) with E, 9 (8.5%) with e, and 5 (4.7%) with Kell subgroup system. Positive Coombs tests (either direct and/or indirect) occurred in 28.3% of the study cases. Hydrops fetalis was determined in 5 of 106 neonates (4.7%). Twenty-two of 106 (20.8%) patients required total exchange transfusion. Positive Coombs test in cases required total exchange transfusion was 63.6%. Our data expose the magnitude and spectrum of the potential developing severe hemolytic disease and immune hydrops due to irregular subgroup incompatibility. Minor group antibody screening is recommended both in the mother and the high-risk infants with hyperbilirubinemia and hemolytic disease of the newborn. Copyright © 2012 Thieme Medical Publishers, Inc., 333 Seventh

  9. Conditions for Effective Application of Analysis of Symmetrically-Predicted Endogenous Subgroups

    Science.gov (United States)

    Peck, Laura R.

    2015-01-01

    Several analytic strategies exist for opening up the "black box" to reveal more about what drives policy and program impacts. This article focuses on one of these strategies: the Analysis of Symmetrically-Predicted Endogenous Subgroups (ASPES). ASPES uses exogenous baseline data to identify endogenously-defined subgroups, keeping the…

  10. Stratification of type 2 diabetes based on routine clinical markers

    DEFF Research Database (Denmark)

    Safai, Narges; Ali, Ashfaq; Rossing, Peter

    2018-01-01

    AIMS: We hypothesized that patients with dysregulated type 2 diabetes may be stratified based on routine clinical markers. METHODS: In this retrospective cohort study, diabetes related clinical measures including age at onset, diabetes duration, HbA1c, BMI, HOMA2-β, HOMA2-IR and GAD65...... autoantibodies, were used for sub-grouping patients by K-means clustering and for adjusting. Probability of diabetes complications (95% confidence interval), were calculated using logistic regression. RESULTS: Based on baseline data from patients with type 2 diabetes (n=2,290), the cluster analysis suggested up....... CONCLUSIONS: Patients with type 2 diabetes cluster into clinically relevant sub-groups based on routine clinical markers. The prevalence of diabetes complications seems to be sub-group specific. Our data suggests the need for a tailored strategy for the treatment of type 2 diabetes....

  11. Extraction-differential-photometric method to determine rare earths of cerium subgroup

    International Nuclear Information System (INIS)

    Askerov, D.N.; Gusejnov, I.K.; Melikov, A.A.

    1985-01-01

    The extraction - photometric method to determine great quantities of rare earths of the cerium subgroup as a complex with antipyrine A and diphenylguanidine is developed. Isobutyl and n-butyl alcohols are used as extractants. It is established that proportional dependence between relative optical density and concentration of rare earths of the cerium subgroup in the solution takes place in the concentration interval of 10.3-14.7 μg of rare earths in 1 ml of the solution. Determination error is+-1.12%. The technique is used to determine rare earths of the cerium subgroup in rare earth oxides of a mixed composition, as well as in monozite and loparite

  12. A simple algorithm for the identification of clinical COPD phenotypes

    DEFF Research Database (Denmark)

    Burgel, Pierre-Régis; Paillasseur, Jean-Louis; Janssens, Wim

    2017-01-01

    This study aimed to identify simple rules for allocating chronic obstructive pulmonary disease (COPD) patients to clinical phenotypes identified by cluster analyses. Data from 2409 COPD patients of French/Belgian COPD cohorts were analysed using cluster analysis resulting in the identification...... of subgroups, for which clinical relevance was determined by comparing 3-year all-cause mortality. Classification and regression trees (CARTs) were used to develop an algorithm for allocating patients to these subgroups. This algorithm was tested in 3651 patients from the COPD Cohorts Collaborative...... International Assessment (3CIA) initiative. Cluster analysis identified five subgroups of COPD patients with different clinical characteristics (especially regarding severity of respiratory disease and the presence of cardiovascular comorbidities and diabetes). The CART-based algorithm indicated...

  13. Identification of distinct phenotypes of locally advanced pancreatic adenocarcinoma.

    LENUS (Irish Health Repository)

    Teo, Minyuen

    2013-03-01

    A significant number of pancreatic ductal adenocarcinoma present as locally advanced disease. Optimal treatment remains controversial. We sought to analyze the clinical course of locally advanced pancreatic adenocarcinoma (LAPC) in order to identify potential distinct clinical phenotypes.

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

    Science.gov (United States)

    Molgaard Nielsen, Anne; Hestbaek, Lise; Vach, Werner; Kent, Peter; Kongsted, Alice

    2017-08-09

    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. Previously, we developed two novel suggestions for subgrouping patients with low back pain based on Latent Class Analysis of patient baseline characteristics (patient history and physical examination), which resulted in 7 subgroups when using a single-stage analysis, and 9 subgroups when using a two-stage approach. However, their prognostic capacity was unexplored. This study (i) determined whether the subgrouping approaches were associated with the future outcomes of pain intensity, pain frequency and disability, (ii) assessed whether one of these two approaches was more strongly or more consistently associated with these outcomes, and (iii) assessed the performance of the novel subgroupings as compared to the following variables: two existing subgrouping tools (STarT Back Tool and Quebec Task Force classification), four baseline characteristics and a group of previously identified domain-specific patient categorisations (collectively, the 'comparator variables'). This was a longitudinal cohort study of 928 patients consulting for low back pain in primary care. The associations between each subgroup approach and outcomes at 2 weeks, 3 and 12 months, and with weekly SMS responses were tested in linear regression models, and their prognostic capacity (variance explained) was compared to that of the comparator variables listed above. The two previously identified subgroupings were similarly associated with all outcomes. The prognostic capacity of both subgroupings was better than that of the comparator variables, except for participants' recovery beliefs and the domain-specific categorisations, but was still limited. The explained variance ranged from 4.3%-6.9% for pain intensity and

  15. The ubiquitin-proteasome system and chromosome 17 in cerebellar granule cells and medulloblastoma subgroups.

    Science.gov (United States)

    Vriend, Jerry; Marzban, Hassan

    2017-02-01

    Chromosome 17 abnormalities are often observed in medulloblastomas (MBs), particularly those classified in the consensus Groups 3 and 4. Herein we review MB signature genes associated with chromosome 17 and the relationship of these signature genes to the ubiquitin-proteasome system. While clinical investigators have not focused on the ubiquitin-proteasome system in relation to MB, a substantial amount of data on the topic has been hidden in the form of supplemental datasets of gene expression. A supplemental dataset associated with the Thompson classification of MBs shows that a subgroup of MB with 17p deletions is characterized by reduced expression of genes for several core particle subunits of the beta ring of the proteasome (β1, β4, β5, β7). One of these genes (PSMB6, the gene for the β1 subunit) is located on chromosome 17, near the telomeric end of 17p. By comparison, in the WNT group of MBs only one core proteasome subunit, β6, associated with loss of a gene (PSMB1) on chromosome 6, was down-regulated in this dataset. The MB subgroups with the worst prognosis have a significant association with chromosome 17 abnormalities and irregularities of APC/C cyclosome genes. We conclude that the expression of proteasome subunit genes and genes for ubiquitin ligases can contribute to prognostic classification of MBs. The therapeutic value of targeting proteasome subunits and ubiquitin ligases in the various subgroups of MB remains to be determined separately for each classification of MB.

  16. Two distinct clinical courses of renal involvement in rheumatoid patients with AA amyloidosis.

    Science.gov (United States)

    Uda, Hiroshi; Yokota, Akira; Kobayashi, Kumiko; Miyake, Tadao; Fushimi, Hiroaki; Maeda, Akira; Saiki, Osamu

    2006-08-01

    We conducted a prospective study to investigate whether a correlation exists between the clinical course of renal involvement and the pathological findings of renal amyloidosis in patients with rheumatoid arthritis (RA). Patients with RA of more than 5 years' duration and who did not show renal manifestations were selected and received a duodenal biopsy for the diagnosis of amyloidosis. After the diagnosis of AA amyloidosis, patients received a renal biopsy, and patterns of amyloid deposition were examined. We followed the renal functions (serum levels of blood urea nitrogen and creatinine) of patients diagnosed with AA amyloidosis for 5 years. We diagnosed 53 patients with AA amyloidosis and monitored the renal function of 38 of them for > 5 years. The histological patterns were examined; in the 38 patients there were appreciable variations in the patterns of amyloid deposition. In 27 patients, amyloid deposits were found exclusively in the glomerulus (type 1). In the other 11 patients, however, amyloid deposits were found selectively around blood vessels and were totally absent in the glomerulus (type 2). In type 1 patients with glomerular involvement, renal function deteriorated rapidly regardless of disease state; most patients received hemodialysis. In type 2 patients with purely vascular involvement, however, renal function did not deteriorate significantly. In patients with RA and AA amyloidosis, 2 distinct clinical courses in terms of renal involvement were identified. It is suggested that renal function does not deteriorate when amyloid deposition is totally lacking in the glomerulus.

  17. Discriminative and predictive validity of the scoliosis research society-22 questionnaire in management and curve-severity subgroups of adolescents with idiopathic scoliosis.

    Science.gov (United States)

    Parent, Eric C; Hill, Doug; Mahood, Jim; Moreau, Marc; Raso, Jim; Lou, Edmond

    2009-10-15

    Prospective cross-sectional measurement study. To determine the ability of the Scoliosis Research Society (SRS)-22 questionnaire to discriminate among management and scoliosis severity subgroups and to correlate with internal and external measures of curve severity. In earlier studies of the SRS-22 discriminative ability, age was not a controlled factor. The ability of the SRS-22 to predict curve severity has not been thoroughly examined. The SRS-22 was completed by 227 females with adolescent idiopathic scoliosis. Using Analysis of covariance analyses controlling for age, the SRS-22 scores were compared among management subgroups (observation, brace, presurgery, and postsurgery) and curve-severity subgroups (in nonoperated subjects: Cobb angles of 50 degrees). A stepwise discriminant analysis was used to identify the SRS-22 domains most discriminative for curve-severity categories. Correlation between SRS-22 scores and radiographic or surface topography measurements was used to determine the predictive ability of the questionnaire. Pain was better for subjects treated with braces than for those planning surgery. Self-image was better for subjects under observation or postsurgery than for those planning surgery. Satisfaction was better for the brace and postsurgery subgroups than for the observation or presurgery subgroups. Statistically significant mean differences between subgroups were all larger than 0.5, which is within the range of minimal clinically important differences recommended for each of the 5-point SRS-22 domain scoring scales. Pain and mental health were worse for those with Cobb angles of >50 degrees than with Cobb angles of 30 degrees to 50 degrees. Self-image and total scores were worse for those with Cobb angles of >50 degrees than both other subgroups. Using discriminant analysis, self-image was the only SRS-22 domain score selected to classify subjects within curve severity subgroups. The percentage of patients accurately classified was 54

  18. Geographic Variations in Cardiovascular Disease Mortality Among Asian American Subgroups, 2003-2011.

    Science.gov (United States)

    Pu, Jia; Hastings, Katherine G; Boothroyd, Derek; Jose, Powell O; Chung, Sukyung; Shah, Janki B; Cullen, Mark R; Palaniappan, Latha P; Rehkopf, David H

    2017-07-12

    There are well-documented geographical differences in cardiovascular disease (CVD) mortality for non-Hispanic whites. However, it remains unknown whether similar geographical variation in CVD mortality exists for Asian American subgroups. This study aims to examine geographical differences in CVD mortality among Asian American subgroups living in the United States and whether they are consistent with geographical differences observed among non-Hispanic whites. Using US death records from 2003 to 2011 (n=3 897 040 CVD deaths), age-adjusted CVD mortality rates per 100 000 population and age-adjusted mortality rate ratios were calculated for the 6 largest Asian American subgroups (Asian Indian, Chinese, Filipino, Japanese, Korean, and Vietnamese) and compared with non-Hispanic whites. There were consistently lower mortality rates for all Asian American subgroups compared with non-Hispanic whites across divisions for CVD mortality and ischemic heart disease mortality. However, cerebrovascular disease mortality demonstrated substantial geographical differences by Asian American subgroup. There were a number of regional divisions where certain Asian American subgroups (Filipino and Japanese men, Korean and Vietnamese men and women) possessed no mortality advantage compared with non-Hispanic whites. The most striking geographical variation was with Filipino men (age-adjusted mortality rate ratio=1.18; 95% CI, 1.14-1.24) and Japanese men (age-adjusted mortality rate ratio=1.05; 95% CI: 1.00-1.11) in the Pacific division who had significantly higher cerebrovascular mortality than non-Hispanic whites. There was substantial geographical variation in Asian American subgroup mortality for cerebrovascular disease when compared with non-Hispanic whites. It deserves increased attention to prioritize prevention and treatment in the Pacific division where approximately 80% of Filipinos CVD deaths and 90% of Japanese CVD deaths occur in the United States. © 2017 The Authors

  19. Differential diagnosis of feline leukemia virus subgroups using pseudotype viruses expressing green fluorescent protein.

    Science.gov (United States)

    Nakamura, Megumi; Sato, Eiji; Miura, Tomoyuki; Baba, Kenji; Shimoda, Tetsuya; Miyazawa, Takayuki

    2010-06-01

    Feline leukemia virus (FeLV) is classified into three receptor interference subgroups, A, B and C. In this study, to differentiate FeLV subgroups, we developed a simple assay system using pseudotype viruses expressing green fluorescent protein (GFP). We prepared gfp pseudotype viruses, named gfp(FeLV-A), gfp(FeLV-B) and gfp(FeLV-C) harboring envelopes of FeLV-A, B and C, respectively. The gfp pseudotype viruses completely interfered with the same subgroups of FeLV reference strains on FEA cells (a feline embryonic fibroblast cell line). We also confirmed that the pseudotype viruses could differentiate FeLV subgroups in field isolates. The assay will be useful for differential diagnosis of FeLV subgroups in veterinary diagnostic laboratories in the future.

  20. Interpretation of Subgroup Effects in Published Trials

    DEFF Research Database (Denmark)

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

    2013-01-01

    With the rapidly expanding number of studies reporting on treatment subgroups come new challenges in analyzing and interpreting this sometimes complex area of the literature. This article discusses 3 important issues regarding the analysis and interpretation of existing trials or systematic revie...

  1. Automated computerized scheme for distinction between benign and malignant solitary pulmonary nodules on chest images

    International Nuclear Information System (INIS)

    Aoyama, Masahito; Li Qiang; Katsuragawa, Shigehiko; MacMahon, Heber; Doi, Kunio

    2002-01-01

    A novel automated computerized scheme has been developed to assist radiologists for their distinction between benign and malignant solitary pulmonary nodules on chest images. Our database consisted of 55 chest radiographs (33 primary lung cancers and 22 benign nodules). In this method, the location of a nodule was indicated first by a radiologist. The difference image with a nodule was produced by use of filters and then represented in a polar coordinate system. The nodule was segmented automatically by analysis of contour lines of the gray-level distribution based on the polar-coordinate representation. Two clinical parameters (age and sex) and 75 image features were determined from the outline, the image, and histogram analysis for inside and outside regions of the segmented nodule. Linear discriminant analysis (LDA) and knowledge about benign and malignant nodules were used to select initial feature combinations. Many combinations for subgroups of 77 features were evaluated as input to artificial neural networks (ANNs). The performance of ANNs with the selected 7 features by use of the round-robin test showed Az=0.872, which was greater than Az=0.854 obtained previously with the manual method (P=0.53). The performance of LDA (Az=0.886) was slightly improved compared to that of ANNs (P=0.59) and was greater than that of the manual method (Az=0.854) reported previously (P=0.40). The high level of its performance indicates the potential usefulness of this automated computerized scheme in assisting radiologists as a second opinion for distinction between benign and malignant solitary pulmonary nodules on chest images

  2. 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.

  3. Accelerated Evolution in Distinctive Species Reveals Candidate Elements for Clinically Relevant Traits, Including Mutation and Cancer Resistance.

    Science.gov (United States)

    Ferris, Elliott; Abegglen, Lisa M; Schiffman, Joshua D; Gregg, Christopher

    2018-03-06

    The identity of most functional elements in the mammalian genome and the phenotypes they impact are unclear. Here, we perform a genome-wide comparative analysis of patterns of accelerated evolution in species with highly distinctive traits to discover candidate functional elements for clinically important phenotypes. We identify accelerated regions (ARs) in the elephant, hibernating bat, orca, dolphin, naked mole rat, and thirteen-lined ground squirrel lineages in mammalian conserved regions, uncovering ∼33,000 elements that bind hundreds of different regulatory proteins in humans and mice. ARs in the elephant, the largest land mammal, are uniquely enriched near elephant DNA damage response genes. The genomic hotspot for elephant ARs is the E3 ligase subunit of the Fanconi anemia complex, a master regulator of DNA repair. Additionally, ARs in the six species are associated with specific human clinical phenotypes that have apparent concordance with overt traits in each species. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  4. Accelerated Evolution in Distinctive Species Reveals Candidate Elements for Clinically Relevant Traits, Including Mutation and Cancer Resistance

    Directory of Open Access Journals (Sweden)

    Elliott Ferris

    2018-03-01

    Full Text Available The identity of most functional elements in the mammalian genome and the phenotypes they impact are unclear. Here, we perform a genome-wide comparative analysis of patterns of accelerated evolution in species with highly distinctive traits to discover candidate functional elements for clinically important phenotypes. We identify accelerated regions (ARs in the elephant, hibernating bat, orca, dolphin, naked mole rat, and thirteen-lined ground squirrel lineages in mammalian conserved regions, uncovering ∼33,000 elements that bind hundreds of different regulatory proteins in humans and mice. ARs in the elephant, the largest land mammal, are uniquely enriched near elephant DNA damage response genes. The genomic hotspot for elephant ARs is the E3 ligase subunit of the Fanconi anemia complex, a master regulator of DNA repair. Additionally, ARs in the six species are associated with specific human clinical phenotypes that have apparent concordance with overt traits in each species.

  5. Two subgroups of antipsychotic-naive, first-episode schizophrenia patients identified with a Gaussian mixture model on cognition and electrophysiology

    DEFF Research Database (Denmark)

    Bak, N.; Ebdrup, B.H.; Oranje, B

    2017-01-01

    Deficits in information processing and cognition are among the most robust findings in schizophrenia patients. Previous efforts to translate group-level deficits into clinically relevant and individualized information have, however, been non-successful, which is possibly explained by biologically...... and sixty-five healthy controls underwent extensive electrophysiological and neurocognitive test batteries. Patients were assessed on the Positive and Negative Syndrome Scale (PANSS) before and after 6 weeks of monotherapy with the relatively selective D2 receptor antagonist, amisulpride (280.3±159 mg per...... day). A reduced principal component space based on 19 electrophysiological variables and 26 cognitive variables was used as input for a Gaussian mixture model to identify subgroups of patients. With support vector machines, we explored the relation between PANSS subscores and the identified subgroups...

  6. Life of Pizza Pie: The Implications of Sub-Group Comparisons in Education

    Science.gov (United States)

    Thomas, Tara N.

    2013-01-01

    Current educational statistics have pitted subgroups against one another without consideration of the actual population sizes of each group. This paper is intended to provided a clearer understanding of the current usage of sub-group comparisons in American education. (Contains 4 figures.)

  7. Progression-free survival results in postmenopausal Asian women: subgroup analysis from a phase III randomized trial of fulvestrant 500 mg vs anastrozole 1 mg for hormone receptor-positive advanced breast cancer (FALCON).

    Science.gov (United States)

    Noguchi, Shinzaburo; Ellis, Matthew J; Robertson, John F R; Thirlwell, Jackie; Fazal, Mehdi; Shao, Zhimin

    2018-05-01

    The international, phase III FALCON study (NCT01602380) in postmenopausal patients with hormone receptor-positive, locally advanced/metastatic breast cancer (LA/MBC) who had not received prior endocrine therapy, demonstrated statistically significant improvement in progression-free survival (PFS) for patients who received fulvestrant 500 mg vs anastrozole 1 mg. This subgroup analysis evaluated PFS in Asian (randomized in China, Japan, or Taiwan) and non-Asian patients from the FALCON study. Eligible patients (estrogen receptor- and/or progesterone receptor-positive LA/MBC; World Health Organization performance status 0-2; ≥ 1 measurable/non-measurable lesion[s]) were randomized. PFS was assessed via Response Evaluation Criteria in Solid Tumours version 1.1, surgery/radiotherapy for disease worsening, or death (any cause). Secondary endpoints included: objective response rate, clinical benefit rate, duration of response, and duration of clinical benefit. Consistency of effect across subgroups was assessed via hazard ratios and 95% confidence intervals (CIs) using a log-rank test. Adverse events (AEs) were evaluated. Of the 462 randomized patients, the Asian and non-Asian subgroups comprised 67 and 395 patients, respectively. In the Asian subgroup, median PFS was 16.6 and 15.9 months with fulvestrant and anastrozole, respectively (hazard ratio 0.81; 95% CI 0.44-1.50). In the non-Asian subgroup, median PFS was 16.5 and 13.8 months, respectively (hazard ratio 0.79; 95% CI 0.62-1.01). Secondary outcomes were numerically improved with fulvestrant vs anastrozole in both subgroups. AE profiles were generally consistent between Asian and non-Asian subgroups. Results of this subgroup analysis suggest that treatment effects in the Asian patient subgroup are broadly consistent with the non-Asian population.

  8. A Subgroup Analysis of the Impact of Vortioxetine on Functional Capacity, as Measured by UPSA, in Patients with Major Depressive Disorder and Subjective Cognitive Dysfunction.

    Science.gov (United States)

    Keefe, Richard S E; Nomikos, George; Zhong, Wei; Christensen, Michael Cronquist; Jacobson, William

    2018-05-01

    We evaluated vortioxetine's effects on functional capacity in demographic and clinical subgroups of patients with major depressive disorder. This was an exploratory analysis of the CONNECT study (NCT01564862) that evaluated changes in functional capacity using University of California San Diego Performance-based Skills Assessment data, categorized by sex, age, education, employment status, and baseline disease severity (Montgomery-Åsberg Depression Rating Scale, Clinical Global Impressions-Severity of Illness). Greater changes in University of California San Diego Performance-based Skills Assessment composite scores were observed with vortioxetine vs placebo in specific subgroups: males (∆+3.2), females (∆+2.9), 45-54 or ≥55 years (∆+5.6, ∆+3.4), working (∆+2.8), high school or greater education (∆+2.7, ∆+2.8), disease severity (Montgomery-Åsberg Depression Rating Scale, 4, ∆+3.0), major depressive episodes (≤2, >2 [∆+2.7,+3.3]), and episode duration (≤22, >22 weeks [∆+3.7,+2.4]). Our findings support the need for additional studies to assess whether vortioxetine improves functional capacity within specific patient subgroups. clinicaltrials.gov: NCT01564862.

  9. 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.

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

    Science.gov (United States)

    Hastings, Katherine G; Jose, Powell O; Kapphahn, Kristopher I; Frank, Ariel T H; Goldstein, Benjamin A; Thompson, Caroline A; Eggleston, Karen; Cullen, Mark R; Palaniappan, Latha P

    2015-01-01

    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.

  11. Identification of subgroups by risk of graft failure after paediatric renal transplantation: application of survival tree models on the ESPN/ERA-EDTA Registry

    NARCIS (Netherlands)

    Lofaro, Danilo; Jager, Kitty J.; Abu-Hanna, Ameen; Groothoff, Jaap W.; Arikoski, Pekka; Hoecker, Britta; Roussey-Kesler, Gwenaelle; Spasojević, Brankica; Verrina, Enrico; Schaefer, Franz; van Stralen, Karlijn J.; Coppo, R.; Haffner, D.; Harambat, J.; Stefanidis, C.; Shitza, D.; Kramar, R.; Oberbauer, R.; Baiko, S.; Sukalo, A.; van Hoeck, K.; Collart, F.; des Grottes, J. M.; Pokrajac, D.; Resić, H.; Prnjavorac, B.; Roussinov, D.; Batinić, D.; Lemac, M.; Slavicek, J.; Seeman, T.; Vondrak, K.; Heaf, J. G.; Toots, U.; Finne, P.; Grönhagen-Riska, C.; Couchoud, C.; Lasalle, M.; Sahpazova, E.; Gersdorf, G.; Barth, C.; Scholz, C.; Tönshoff, B.; Ioannidis, G.; Kapogiannis, A.; Papachristou, F.; Reusz, G.; Túri, S.; Szabó, L.; Szabó, T.

    2016-01-01

    Identification of patient groups by risk of renal graft loss might be helpful for accurate patient counselling and clinical decision-making. Survival tree models are an alternative statistical approach to identify subgroups, offering cut-off points for covariates and an easy-to-interpret

  12. Streptococcus pneumoniae PspC Subgroup Prevalence in Invasive Disease and Differences in Contribution to Complement Evasion.

    Science.gov (United States)

    van der Maten, Erika; van den Broek, Bryan; de Jonge, Marien I; Rensen, Kim J W; Eleveld, Marc J; Zomer, Aldert L; Cremers, Amelieke J H; Ferwerda, Gerben; de Groot, Ronald; Langereis, Jeroen D; van der Flier, Michiel

    2018-04-01

    The pneumococcal capsular serotype is an important determinant of complement resistance and invasive disease potential, but other virulence factors have also been found to contribute. Pneumococcal surface protein C (PspC), a highly variable virulence protein that binds complement factor H to evade C3 opsonization, is divided into two subgroups: choline-bound subgroup I and LPxTG-anchored subgroup II. The prevalence of different PspC subgroups in invasive pneumococcal disease (IPD) and functional differences in complement evasion are unknown. The prevalence of PspC subgroups in IPD isolates was determined in a collection of 349 sequenced strains of Streptococcus pneumoniae isolated from adult patients. pspC deletion mutants and isogenic pspC switch mutants were constructed to study differences in factor H binding and complement evasion in relation to capsule thickness. Subgroup I pspC was far more prevalent in IPD isolates than subgroup II pspC The presence of capsule was associated with a greater ability of bound factor H to reduce complement opsonization. Pneumococcal subgroup I PspC bound significantly more factor H and showed more effective complement evasion than subgroup II PspC in isogenic encapsulated pneumococci. We conclude that variation in the PspC subgroups, independent of capsule serotypes, affects pneumococcal factor H binding and its ability to evade complement deposition. Copyright © 2018 American Society for Microbiology.

  13. 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......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...... 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...

  14. A Newborn Case of “c” Subgroup Mismatch Presenting with Severe Hemolysis and Anemia

    Directory of Open Access Journals (Sweden)

    Ezgi Yangın Ergon

    2017-12-01

    Full Text Available Hemolysis and jaundice related to Rh incompatibility in the neonatal period has decreased substantially due to the widespread use of anti-D gammaglobulin in recent years. Nevertheless, the rate of subgroup mismatch in the etiology of hemolytic diseases of the newborn has increased significantly. In this article an 8-day-old newborn infant with “c” subgroup incompatibility and presenting with severe anemia, in whom hemolysis could be controlled with intravenous immunoglobulin infusion and subgroup appropriate blood transfusion, has been presented. Scientific studies have demonstrated that the hemolytic disease of patients who don’t have major blood group incompatibility but carry anti-C antibodies can be rather serious. Therefore, subgroup mismatch should always be kept in mind for newborns presenting with severe hemolytic anemia, and transfusion or if necessary exchange transfusion should be provided with subgroup matched blood products.

  15. Are Autism Spectrum Disorder and Attention-Deficit/Hyperactivity Disorder Different Manifestations of One Overarching Disorder? Cognitive and Symptom Evidence from a Clinical and Population-Based Sample

    Science.gov (United States)

    van der Meer, Jolanda M. J.; Oerlemans, Anoek M.; van Steijn, Daphne J.; Lappenschaar, Martijn G. A.; de Sonneville, Leo M. J.; Buitelaar, Jan K.; Rommelse, Nanda N. J.

    2012-01-01

    Objective: Autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD) frequently co-occur. Given the heterogeneity of both disorders, several more homogeneous ASD-ADHD comorbidity subgroups may exist. The current study examined whether such subgroups exist, and whether their overlap or distinctiveness in associated…

  16. Identification of genomic copy number variations associated with specific clinical features of head and neck cancer.

    Science.gov (United States)

    Zagradišnik, Boris; Krgović, Danijela; Herodež, Špela Stangler; Zagorac, Andreja; Ćižmarević, Bogdan; Vokač, Nadja Kokalj

    2018-01-01

    Copy number variations (CNSs) of large genomic regions are an important mechanism implicated in the development of head and neck cancer, however, for most changes their exact role is not well understood. The aim of this study was to find possible associations between gains/losses of genomic regions and clinically distinct subgroups of head and neck cancer patients. Array comparative genomic hybridization (aCGH) analysis was performed on DNA samples in 64 patients with cancer in oral cavity, oropharynx or hypopharynx. Overlapping genomic regions created from gains and losses were used for statistical analysis. Following regions were overrepresented: in tumors with stage I or II a gain of 2.98 Mb on 6p21.2-p11 and a gain of 7.4 Mb on 8q11.1-q11.23; in tumors with grade I histology a gain of 1.1 Mb on 8q24.13, a loss of a large part of p arm of chromosome 3, a loss of a 1.24 Mb on 6q14.3, and a loss of terminal 32 Mb region of 8p23.3; in cases with affected lymph nodes a gain of 0.75 Mb on 3q24, and a gain of 0.9 Mb on 3q26.32-q26.33; in cases with unaffected lymph nodes a gain of 1.1 Mb on 8q23.3, in patients not treated with surgery a gain of 12.2 Mb on 7q21.3-q22.3 and a gain of 0.33 Mb on 20q11.22. Our study identified several genomic regions of interest which appear to be associated with various clinically distinct subgroups of head and neck cancer. They represent a potentially important source of biomarkers useful for the clinical management of head and neck cancer. In particular, the PIK3CA and AGTR1 genes could be singled out to predict the lymph node involvement.

  17. The sociocommunicative deficit subgroup in anorexia nervosa: autism spectrum disorders and neurocognition in a community-based, longitudinal study

    OpenAIRE

    Anckarsäter, H.; Hofvander, B.; Billstedt, E.; Gillberg, I. C.; Gillberg, C.; Wentz, E.; Råstam, M.

    2011-01-01

    BACKGROUND: A subgroup of persons with anorexia nervosa (AN) have been proposed to have sociocommunicative problems corresponding to autism spectrum disorders [ASDs, i.e. DSM-IV pervasive developmental disorders (PDDs): autistic disorder, Asperger's disorder, PDD not otherwise specified (NOS)]. Here, clinical problems, personality traits, cognitive test results and outcome are compared across 16 subjects (32%) with teenage-onset AN who meet or have met ASD criteria (AN+ASD), 34 ASD-negati...

  18. The value of heterogeneity for cost-effectiveness subgroup analysis: conceptual framework and application.

    Science.gov (United States)

    Espinoza, Manuel A; Manca, Andrea; Claxton, Karl; Sculpher, Mark J

    2014-11-01

    This article develops a general framework to guide the use of subgroup cost-effectiveness analysis for decision making in a collectively funded health system. In doing so, it addresses 2 key policy questions, namely, the identification and selection of subgroups, while distinguishing 2 sources of potential value associated with heterogeneity. These are 1) the value of revealing the factors associated with heterogeneity in costs and outcomes using existing evidence (static value) and 2) the value of acquiring further subgroup-related evidence to resolve the uncertainty given the current understanding of heterogeneity (dynamic value). Consideration of these 2 sources of value can guide subgroup-specific treatment decisions and inform whether further research should be conducted to resolve uncertainty to explain variability in costs and outcomes. We apply the proposed methods to a cost-effectiveness analysis for the management of patients with acute coronary syndrome. This study presents the expected net benefits under current and perfect information when subgroups are defined based on the use and combination of 6 binary covariates. The results of the case study confirm the theoretical expectations. As more subgroups are considered, the marginal net benefit gains obtained under the current information show diminishing marginal returns, and the expected value of perfect information shows a decreasing trend. We present a suggested algorithm that synthesizes the results to guide policy. © The Author(s) 2014.

  19. Distinct patterns of Internet and smartphone-related problems among adolescents by gender: Latent class analysis.

    Science.gov (United States)

    Lee, Seung-Yup; Lee, Donghwan; Nam, Cho Rong; Kim, Da Yea; Park, Sera; Kwon, Jun-Gun; Kweon, Yong-Sil; Lee, Youngjo; Kim, Dai Jin; Choi, Jung-Seok

    2018-05-23

    Background and objectives The ubiquitous Internet connections by smartphones weakened the traditional boundaries between computers and mobile phones. We sought to explore whether smartphone-related problems differ from those of computer use according to gender using latent class analysis (LCA). Methods After informed consents, 555 Korean middle-school students completed surveys on gaming, Internet use, and smartphone usage patterns. They also completed various psychosocial instruments. LCA was performed for the whole group and by gender. In addition to ANOVA and χ 2 tests, post-hoc tests were conducted to examine differences among the LCA subgroups. Results In the whole group (n = 555), four subtypes were identified: dual-problem users (49.5%), problematic Internet users (7.7%), problematic smartphone users (32.1%), and "healthy" users (10.6%). Dual-problem users scored highest for addictive behaviors and other psychopathologies. The gender-stratified LCA revealed three subtypes for each gender. With dual-problem and healthy subgroup as common, problematic Internet subgroup was classified in the males, whereas problematic smartphone subgroup was classified in the females in the gender-stratified LCA. Thus, distinct patterns were observed according to gender with higher proportion of dual-problem present in males. While gaming was associated with problematic Internet use in males, aggression and impulsivity demonstrated associations with problematic smartphone use in females. Conclusions An increase in the number of digital media-related problems was associated with worse outcomes in various psychosocial scales. Gaming may play a crucial role in males solely displaying Internet-related problems. The heightened impulsivity and aggression seen in our female problematic smartphone users requires further research.

  20. Measuring the Speed of Aging across Population Subgroups

    Science.gov (United States)

    2014-01-01

    People in different subgroups age at different rates. Surveys containing biomarkers can be used to assess these subgroup differences. We illustrate this using hand-grip strength to produce an easily interpretable, physical-based measure that allows us to compare characteristic-based ages across educational subgroups in the United States. Hand-grip strength has been shown to be a good predictor of future mortality and morbidity, and therefore a useful indicator of population aging. Data from the Health and Retirement Survey (HRS) were used. Two education subgroups were distinguished, those with less than a high school diploma and those with more education. Regressions on hand-grip strength were run for each sex and race using age and education, their interactions and other covariates as independent variables. Ages of identical mean hand-grip strength across education groups were compared for people in the age range 60 to 80. The hand-grip strength of 65 year old white males with less education was the equivalent to that of 69.6 (68.2, 70.9) year old white men with more education, indicating that the more educated men had aged more slowly. This is a constant characteristic age, as defined in the Sanderson and Scherbov article “The characteristics approach to the measurement of population aging” published 2013 in Population and Development Review. Sixty-five year old white females with less education had the same average hand-grip strength as 69.4 (68.2, 70.7) year old white women with more education. African-American women at ages 60 and 65 with more education also aged more slowly than their less educated counterparts. African American men with more education aged at about the same rate as those with less education. This paper expands the toolkit of those interested in population aging by showing how survey data can be used to measure the differential extent of aging across subpopulations. PMID:24806337

  1. 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

    . Previously, we developed two novel suggestions for subgrouping patients with low back pain based on Latent Class Analysis of patient baseline characteristics (patient history and physical examination), which resulted in 7 subgroups when using a single-stage analysis, and 9 subgroups when using a two...

  2. Effects of hydroxyethyl starch in subgroups of patients with severe sepsis

    DEFF Research Database (Denmark)

    Müller, Rasmus G; Haase, Nicolai; Wetterslev, Jørn

    2013-01-01

    It has been speculated that certain subgroups of sepsis patients may benefit from treatment with hydroxyethyl starch (HES) 130/0.42, specifically in the earlier resuscitation of patients with more severely impaired circulation.......It has been speculated that certain subgroups of sepsis patients may benefit from treatment with hydroxyethyl starch (HES) 130/0.42, specifically in the earlier resuscitation of patients with more severely impaired circulation....

  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. Subgroups of class groups of algebraic quadratic function fields

    International Nuclear Information System (INIS)

    Wang Kunpeng; Zhang Xianke

    2001-09-01

    Ideal class groups H(K) of algebraic quadratic function fields K are studied, by using mainly the theory of continued fractions of algebraic functions. Properties of such continued fractions are discussed first. Then a necessary and sufficient condition is given for the class group H(K) to contain a cyclic subgroup of any order n, this criterion condition holds true for both real and imaginary fields K. Furthermore, several series of function fields K, including real, inertia imaginary, as well as ramified imaginary quadratic function fields, are given, and their class groups H(K) are proved to contain cyclic subgroups of order n. (author)

  5. 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.

  6. Assessing and reporting heterogeneity in treatment effects in clinical trials: a proposal

    Directory of Open Access Journals (Sweden)

    Kent David M

    2010-08-01

    Full Text Available Abstract Mounting evidence suggests that there is frequently considerable variation in the risk of the outcome of interest in clinical trial populations. These differences in risk will often cause clinically important heterogeneity in treatment effects (HTE across the trial population, such that the balance between treatment risks and benefits may differ substantially between large identifiable patient subgroups; the "average" benefit observed in the summary result may even be non-representative of the treatment effect for a typical patient in the trial. Conventional subgroup analyses, which examine whether specific patient characteristics modify the effects of treatment, are usually unable to detect even large variations in treatment benefit (and harm across risk groups because they do not account for the fact that patients have multiple characteristics simultaneously that affect the likelihood of treatment benefit. Based upon recent evidence on optimal statistical approaches to assessing HTE, we propose a framework that prioritizes the analysis and reporting of multivariate risk-based HTE and suggests that other subgroup analyses should be explicitly labeled either as primary subgroup analyses (well-motivated by prior evidence and intended to produce clinically actionable results or secondary (exploratory subgroup analyses (performed to inform future research. A standardized and transparent approach to HTE assessment and reporting could substantially improve clinical trial utility and interpretability.

  7. US Food and Drug Administration Pooled Analysis to Assess the Impact of Bone-Only Metastatic Breast Cancer on Clinical Trial Outcomes and Radiographic Assessments.

    Science.gov (United States)

    Wedam, Suparna B; Beaver, Julia A; Amiri-Kordestani, Laleh; Bloomquist, Erik; Tang, Shenghui; Goldberg, Kirsten B; Sridhara, Rajeshwari; Ibrahim, Amna; Kim, Geoffrey; Kluetz, Paul; McKee, Amy; Pazdur, Richard

    2018-04-20

    Purpose The outcome and proportion of patients with bone-only (BO) metastatic breast cancer (MBC) has not been well described. We sought to describe the differential outcomes of patients with BO MBC in clinical trials and explore whether there was a discrepancy in radiographic reads between investigator and blinded independent central review. Methods We pooled and analyzed data on 10,521 patients from 13 prospective trials submitted for MBC treatment in initial or supplemental New Drug or Biologics License Applications from 2005. Three subsets were evaluated: BO, bone with other metastases (BWO), and no bone metastases (NBM). Early discordance rate and late discordance rate were calculated from 3,733 and 2,813 patients subject to a blinded independent central review, respectively. Results Bone metastases were identified in 49% (range: 42% to 73%) of patients across trials. BO disease was present in 12.5% (range: 4% to 26%), dependent on subtype. Investigator-assessed progression-free survival (PFS) and overall survival (OS) for the pooled trials demonstrated improved outcomes for the BO subgroup compared with other subgroups (BO v BWO PFS hazard ratio [HR], 0.64; 95% CI, 0.591 to 0.696; BO v NBM PFS HR, 0.70; 95% CI, 0.65 to 0.76; BO v BWO OS HR, 0.56; 95% CI, 0.50 to 0.61; BO v NBM OS HR, 0.68; 95% CI, 0.61 to 0.76). The BO subgroup has a higher early discordance rate and lower late discordance rate than the BWO and NBM subgroups. Conclusion To our knowledge, this review is the largest analysis to date of the BO subgroup of MBC and suggests this subgroup may have a distinct natural history. There also seems to be a difference in how the local investigators assessed progression events in the BO subgroup when compared with the other two groups.

  8. Single-cell transcriptomics uncovers distinct molecular signatures of stem cells in chronic myeloid leukemia.

    Science.gov (United States)

    Giustacchini, Alice; Thongjuea, Supat; Barkas, Nikolaos; Woll, Petter S; Povinelli, Benjamin J; Booth, Christopher A G; Sopp, Paul; Norfo, Ruggiero; Rodriguez-Meira, Alba; Ashley, Neil; Jamieson, Lauren; Vyas, Paresh; Anderson, Kristina; Segerstolpe, Åsa; Qian, Hong; Olsson-Strömberg, Ulla; Mustjoki, Satu; Sandberg, Rickard; Jacobsen, Sten Eirik W; Mead, Adam J

    2017-06-01

    Recent advances in single-cell transcriptomics are ideally placed to unravel intratumoral heterogeneity and selective resistance of cancer stem cell (SC) subpopulations to molecularly targeted cancer therapies. However, current single-cell RNA-sequencing approaches lack the sensitivity required to reliably detect somatic mutations. We developed a method that combines high-sensitivity mutation detection with whole-transcriptome analysis of the same single cell. We applied this technique to analyze more than 2,000 SCs from patients with chronic myeloid leukemia (CML) throughout the disease course, revealing heterogeneity of CML-SCs, including the identification of a subgroup of CML-SCs with a distinct molecular signature that selectively persisted during prolonged therapy. Analysis of nonleukemic SCs from patients with CML also provided new insights into cell-extrinsic disruption of hematopoiesis in CML associated with clinical outcome. Furthermore, we used this single-cell approach to identify a blast-crisis-specific SC population, which was also present in a subclone of CML-SCs during the chronic phase in a patient who subsequently developed blast crisis. This approach, which might be broadly applied to any malignancy, illustrates how single-cell analysis can identify subpopulations of therapy-resistant SCs that are not apparent through cell-population analysis.

  9. Subgroup differences and determinants of patient-reported mental and physical health at hospital discharge among patients with ischemic heart disease

    DEFF Research Database (Denmark)

    Rasmussen, T. B.; Herning, M.; Johansen, P. P.

    2017-01-01

    Purpose: (i) To describe patient-reported outcomes (PROs) at hospital-discharge across three diagnostic IHD sub-groups; chronic ischemic heart disease/stable angina (IHD/AP), non-ST-elevation myocardial infarction/unstable angina (NSTEMI/UAP) and ST-elevation myocardial infarction (STEMI), and (i......) to examine determinants among demographic-, clinical- and self-report health behavior characteristics for PROs at hospital discharge in patients with IHD....

  10. Clonality and distribution of clinical Ureaplasma isolates recovered from male patients and infertile couples in China.

    Directory of Open Access Journals (Sweden)

    Zhi Ruan

    Full Text Available Ureaplasma spp. have gained increasing recognition as pathogens in both adult and neonatal patients with multiple clinical presentations. However, the clonality of this organism in the male population and infertile couples in China is largely unknown. In this study, 96 (53 U. parvum and 43 U. urealyticum of 103 Ureaplasma spp. strains recovered from genital specimens from male patients and 15 pairs of infertile couples were analyzed using multilocus sequence typing (MLST/expanded multilocus sequence typing (eMLST schemes. A total of 39 sequence types (STs and 53 expanded sequence types (eSTs were identified, with three predominant STs (ST1, ST9 and ST22 and eSTs (eST16, eST41 and eST82. Moreover, phylogenetic analysis revealed two distinct clusters that were highly congruent with the taxonomic differences between the two Ureaplasma species. We found significant differences in the distributions of both clusters and sub-groups between the male and female patients (P 0.80. However, this concordance was observed only for the detection of U. urealyticum within the infertile couples. In conclusion, the distributions of the clusters and sub-groups significantly differed between the male and female patients. U. urealyticum is more likely to transmit between infertile couples and be associated with clinical manifestations by the specific epidemic clonal lineages.

  11. Differences in neighborhood social cohesion and aerobic physical activity by Latino subgroup

    Directory of Open Access Journals (Sweden)

    Rosenda Murillo

    2016-12-01

    Full Text Available Previous research has examined the role of neighborhood social cohesion in physical activity outcomes; however, less is known about this relationship across Latino subgroups. The purpose of our study was to examine the association between neighborhood social cohesion and aerobic leisure-time physical activity (LTPA among Latino adults and to determine whether these associations differ by Latino subgroup. We used cross-sectional 2013–2014 National Health Interview Survey (NHIS data on Latinos originating from 5 countries/regions (i.e., Latinos of Puerto Rican, Mexican/Mexican-American, Cuban/Cuban-American, Dominican and Central or South American origin aged ≥18 years (n=11,126. Multivariable logistic regression models were used to estimate associations between self-reported neighborhood social cohesion and meeting aerobic LTPA guidelines. Models were adjusted for age, sex, education, and acculturation. We also investigated whether associations varied by Latino subgroup. In adjusted models for all Latino adults, compared with those reporting low social cohesion, individuals who reported high social cohesion (Odds Ratio [OR]: 1.33; 95% Confidence Interval [CI]: 1.17–1.52 were significantly more likely to meet the aerobic physical activity guideline. When stratified by Latino subgroups, among Mexican/Mexicans-Americans (OR: 1.39; 95% CI: 1.16, 1.66 and Cuban/Cuban Americans (OR: 1.73; 95% CI: 1.00, 2.97 high social cohesion was associated with meeting the aerobic activity guideline. Among Dominicans, those who reported medium social cohesion (OR: 0.52, 95% CI: 0.29, 0.93 were less likely to meet the aerobic activity guideline. When examining aerobic physical activity outcomes in the Latino population, the role of neighborhood social cohesion and the variability among Latino subgroups should be considered. Keywords: Neighborhood social cohesion, Physical activity, Latinos, subgroups

  12. Distinct clinical and metabolic deficits in PCA and AD are not related to amyloid distribution.

    Science.gov (United States)

    Rosenbloom, M H; Alkalay, A; Agarwal, N; Baker, S L; O'Neil, J P; Janabi, M; Yen, I V; Growdon, M; Jang, J; Madison, C; Mormino, E C; Rosen, H J; Gorno-Tempini, M L; Weiner, M W; Miller, B L; Jagust, W J; Rabinovici, G D

    2011-05-24

    Patients with posterior cortical atrophy (PCA) often have Alzheimer disease (AD) at autopsy, yet are cognitively and anatomically distinct from patients with clinical AD. We sought to compare the distribution of β-amyloid and glucose metabolism in PCA and AD in vivo using Pittsburgh compound B (PiB) and FDG-PET. Patients with PCA (n = 12, age 57.5 ± 7.4, Mini-Mental State Examination [MMSE] 22.2 ± 5.1), AD (n = 14, age 58.8 ± 9.6, MMSE 23.8 ± 6.7), and cognitively normal controls (NC, n = 30, age 73.6 ± 6.4) underwent PiB and FDG-PET. Group differences in PiB distribution volume ratios (DVR, cerebellar reference) and FDG uptake (pons-averaged) were assessed on a voxel-wise basis and by comparing binding in regions of interest (ROIs). Compared to NC, both patients with AD and patients with PCA showed diffuse PiB uptake throughout frontal, temporoparietal, and occipital cortex (p PCA and AD even after correcting for atrophy. FDG patterns in PCA and AD were distinct: while both groups showed hypometabolism compared to NC in temporoparietal cortex and precuneus/posterior cingulate, patients with PCA further showed hypometabolism in inferior occipitotemporal cortex compared to both NC and patients with AD (p PCA. Fibrillar amyloid deposition in PCA is diffuse and similar to AD, while glucose hypometabolism extends more posteriorly into occipital cortex. Further studies are needed to determine the mechanisms of selective network degeneration in focal variants of AD.

  13. Planar algebra of the subgroup-subfactor

    Indian Academy of Sciences (India)

    We think of R α G as the II1-factor (R ∪{ug: g ∈ G}) ⊂ L(L2(R)), where ug(ˆx) ..... define a global trace on P, where for 0± the trace for P0± ∼= C is the obvious identity .... function for strings is either a local maximum or a local minimum. ..... In order to understand how the inclusion tangles act on the subgroup-subfactor planar.

  14. Finite groups with the set of the number of subgroups of possible ...

    Indian Academy of Sciences (India)

    Finite group; the number of subgroups of possible order. 1. Introduction. Throughout this paper, groups mentioned are finite and p is a prime. An important topic in the group theory is to investigate the number of subgroups of possible order, and con- versely it is also an important subject to determine the structure of a finite ...

  15. Clinically distinct presentations of copper deficiency myeloneuropathy and cytopenias in a patient using excessive zinc-containing denture adhesive.

    Science.gov (United States)

    Cathcart, Sahara J; Sofronescu, Alina G

    2017-08-01

    While copper deficiency has long been known to cause cytopenias, copper deficiency myeloneuropathy is a more recently described entity. Here, we present the case of two clinically distinct presentations of acquired copper deficiency syndromes secondary to excessive use of zinc-containing denture adhesive over five years: myeloneuropathy and severe macrocytic anemia and neutropenia. Extensive laboratory testing and histologic evaluation of the liver and bone marrow, were necessary to rule out other disease processes and establish the diagnosis of copper deficiency. The initial presentation consisted of a myelopathy involving the posterior columns. Serum and urine copper were significantly decreased, and serum zinc was elevated. On second presentation (five years later), multiple hematological abnormalities were detected. Serum copper was again decreased, while serum zinc was elevated. Zinc overload is a preventable cause of copper deficiency syndromes. This rare entity presented herein highlights the importance of patient, as well as provider, education. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  16. Evaluation of a compliance device in a subgroup of adult patients receiving specific immunotherapy with grass allergen tablets (GRAZAX) in a randomized, open-label, controlled study: an a priori subgroup analysis.

    NARCIS (Netherlands)

    Jansen, A.P.H.; Andersen, K.F.; Bruning, H.

    2009-01-01

    OBJECTIVES: This a priori subgroup analysis was conducted to assess patients' experience with a compliance device for the administration of sublingual specific immunotherapy for grass pollen-induced rhinoconjunctivitis. METHODS: The present paper reports the results of a subgroup analysis of a

  17. {sup 1}H MR spectroscopy in histopathological subgroups of mesial temporal lobe epilepsy

    Energy Technology Data Exchange (ETDEWEB)

    Hajek, Milan; Dezortova, Monika [Institute for Clinical and Experimental Medicine, MR Unit, Department of Diagnostic and Interventional Radiology, Prague (Czech Republic); Krsek, Pavel; Komarek, Vladimir [Charles University, Department of Pediatric Neurology, Prague 5 (Czech Republic); Marusic, Petr; Tomasek, Martin; Krijtova, Hana [Charles University, Department of Neurology, Prague (Czech Republic); Zamecnik, Josef [Charles University, Department of Pathology and Molecular Medicine, Prague (Czech Republic); Kyncl, Martin [Charles University, Department of Radiology, Prague (Czech Republic)

    2009-02-15

    The aim of the study was to analyze the lateralizing value of proton magnetic resonance spectroscopy ({sup 1}H MRS) in histopathologically different subgroups of mesial temporal lobe epilepsies (MTLE) and to correlate results with clinical, MRI and seizure outcome data. A group of 35 patients who underwent resective epilepsy surgery was retrospectively studied. Hippocampal {sup 1}H MR spectra were evaluated. Metabolite concentrations were obtained using LCModel and NAA/Cr, NAA/Cho, NAA/(Cr+Cho), Cho/Cr ratios and coefficients of asymmetry were calculated. MRI correctly lateralized 89% of subjects and {sup 1}H MRS 83%. MRI together with {sup 1}H MRS correctly lateralized 100% of patients. Nineteen subjects had 'classical' hippocampal sclerosis (HS), whereas the remaining 16 patients had 'mild' HS. Nineteen patients had histopathologically proven malformation of cortical development (MCD) in the temporal pole; 16 subjects had only HS. No difference in {sup 1}H MRS findings was found between patients in different histopathological subgroups of MTLE. Our results support the hypothesis that {sup 1}H MRS abnormalities do not directly reflect histopathological changes in MTLE patients. Subjects with non-lateralized {sup 1}H MRS abnormalities did not have a worse postoperative seizure outcome. We found no significant impact of contralateral {sup 1}H MRS abnormality on post-surgical seizure outcome. (orig.)

  18. Identification of subgroups by risk of graft failure after paediatric renal transplantation: application of survival tree models on the ESPN/ERA-EDTA Registry.

    Science.gov (United States)

    Lofaro, Danilo; Jager, Kitty J; Abu-Hanna, Ameen; Groothoff, Jaap W; Arikoski, Pekka; Hoecker, Britta; Roussey-Kesler, Gwenaelle; Spasojević, Brankica; Verrina, Enrico; Schaefer, Franz; van Stralen, Karlijn J

    2016-02-01

    Identification of patient groups by risk of renal graft loss might be helpful for accurate patient counselling and clinical decision-making. Survival tree models are an alternative statistical approach to identify subgroups, offering cut-off points for covariates and an easy-to-interpret representation. Within the European Society of Pediatric Nephrology/European Renal Association-European Dialysis and Transplant Association (ESPN/ERA-EDTA) Registry data we identified paediatric patient groups with specific profiles for 5-year renal graft survival. Two analyses were performed, including (i) parameters known at time of transplantation and (ii) additional clinical measurements obtained early after transplantation. The identified subgroups were added as covariates in two survival models. The prognostic performance of the models was tested and compared with conventional Cox regression analyses. The first analysis included 5275 paediatric renal transplants. The best 5-year graft survival (90.4%) was found among patients who received a renal graft as a pre-emptive transplantation or after short-term dialysis (2.2 years). The Cox model including both pre-transplant factors and tree subgroups had a significantly better predictive performance than conventional Cox regression (P 30 mL/min/1.73 m(2) and dialysis 20 months). Also in this case combining tree findings and clinical factors improved the predictive performance as compared with conventional Cox model models (P tree model to be an accurate and attractive tool to predict graft failure for patients with specific characteristics. This may aid the evaluation of individual graft prognosis and thereby the design of measures to improve graft survival in the poor prognosis groups. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  19. On the same side of the faultline: Inclusion in the leader’s subgroup and employee performance

    NARCIS (Netherlands)

    Meyer, B.; Shemla, M.; Li, J.; Wegge, J.

    Extending theory on faultlines and subgroups, we argue that faultlines splitting a team into homogeneous subgroups can have different effects on team members' individual performance, depending on different intra-subgroup processes. Specifically, we propose that the effect of faultline strength on

  20. Discovering biomarkers from gene expression data for predicting cancer subgroups using neural networks and relational fuzzy clustering

    Directory of Open Access Journals (Sweden)

    Sharma Animesh

    2007-01-01

    Full Text Available Abstract Background The four heterogeneous childhood cancers, neuroblastoma, non-Hodgkin lymphoma, rhabdomyosarcoma, and Ewing sarcoma present a similar histology of small round blue cell tumor (SRBCT and thus often leads to misdiagnosis. Identification of biomarkers for distinguishing these cancers is a well studied problem. Existing methods typically evaluate each gene separately and do not take into account the nonlinear interaction between genes and the tools that are used to design the diagnostic prediction system. Consequently, more genes are usually identified as necessary for prediction. We propose a general scheme for finding a small set of biomarkers to design a diagnostic system for accurate classification of the cancer subgroups. We use multilayer networks with online gene selection ability and relational fuzzy clustering to identify a small set of biomarkers for accurate classification of the training and blind test cases of a well studied data set. Results Our method discerned just seven biomarkers that precisely categorized the four subgroups of cancer both in training and blind samples. For the same problem, others suggested 19–94 genes. These seven biomarkers include three novel genes (NAB2, LSP1 and EHD1 – not identified by others with distinct class-specific signatures and important role in cancer biology, including cellular proliferation, transendothelial migration and trafficking of MHC class antigens. Interestingly, NAB2 is downregulated in other tumors including Non-Hodgkin lymphoma and Neuroblastoma but we observed moderate to high upregulation in a few cases of Ewing sarcoma and Rabhdomyosarcoma, suggesting that NAB2 might be mutated in these tumors. These genes can discover the subgroups correctly with unsupervised learning, can differentiate non-SRBCT samples and they perform equally well with other machine learning tools including support vector machines. These biomarkers lead to four simple human interpretable

  1. Overlap Between Autism Spectrum Disorders and Attention Deficit Hyperactivity Disorder: Searching for Distinctive/Common Clinical Features.

    Science.gov (United States)

    Craig, Francesco; Lamanna, Anna Linda; Margari, Francesco; Matera, Emilia; Simone, Marta; Margari, Lucia

    2015-06-01

    Recent studies support several overlapping traits between autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD), assuming the existence of a combined phenotype. The aim of our study was to evaluate the common or distinctive clinical features between ASD and ADHD in order to identify possible different phenotypes that could have a clinical value. We enrolled 181 subjects divided into four diagnostic groups: ADHD group, ASD group, ASD+ADHD group (that met diagnostic criteria for both ASD and ADHD), and control group. Intelligent quotient (IQ), emotional and behavior problems, ADHD symptoms, ASD symptoms, and adaptive behaviors were investigated through the following test: Wechsler Intelligence Scale for Children, Wechsler Preschool and Primary Scale of Intelligence or Leiter International Performances Scale Revised, Child Behavior Checklist, Conners' Rating Scales-Revised, SNAP-IV Rating Scale, the Social Communication Questionnaire, Vineland Adaptive Behavior Scales. The ASD+ADHD group differs from ADHD or ASD in some domains such as lower IQ mean level and a higher autistic symptoms severity. However, the ASD+ADHD group shares inattention and hyperactivity deficit and some emotional and behavior problems with the ADHD group, while it shares adaptive behavior impairment with ASD group. These findings provide a new understanding of clinical manifestation of ASD+ADHD phenotype, they may also inform a novel treatment target. © 2015 The Authors Autism Research published by Wiley Periodicals, Inc. on behalf of International Society for Autism Research.

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

    Science.gov (United States)

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

    2010-03-31

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

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

    Science.gov (United States)

    2010-01-01

    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 comprises four subgroups: two

  4. On approximation of Lie groups by discrete subgroups

    Indian Academy of Sciences (India)

    1Department of Mathematics, Faculty of Sciences at Sfax, University of Sfax,. Route Soukra ... Let S (G) denote the space of discrete co-compact subgroup of a Lie group G. We ..... For example, it suffices to apply the following fact: The mapping.

  5. Development of emergency medicine as academic and distinct clinical discipline in Bosnia & Herzegovina.

    Science.gov (United States)

    Salihefendic, Nizama; Zildzic, Muharem; Masic, Izet; Hadziahmetovic, Zoran; Vasic, Dusko

    2011-01-01

    Emergency medicine is a new academic discipline, as well as a recent independent clinical specialization with the specific principles of practice, education and research. It is also a very important segment of the overall health care and health system. Emergency medicine as a distinct specialty was introduced in the U.S. in 1970. Ten years later and relatively quickly emergency medicine was introduced in the health system in Bosnia and Herzegovina as a specialty with a special education program for specialist and a final exam. Compare the development of emergency medicine in Bosnia and Herzegovina with the trends of development of this discipline in the world as a specialization and an academic discipline. Identify specific problems and possible solutions and learn lessons from other countries. Reviewed are the literature data on the development of emergency medicine in the world, programs of undergraduate and postgraduate teaching, the organizational scheme of emergency centers and residency. This is then compared with data of the current status of emergency medicine as an academic discipline and a recognized specialization, in Bosnia and Herzegovina. There are substantial differences in the development of emergency medicine in the United States, European Union and Bosnia and Herzegovina. Although Bosnia and Herzegovina relatively early recognized specialty of emergency medicine in academia, it failed to mach the academic progress with the practical implementation. A&E departments in the Community Health Centers failed to meet the desired objectives even though they were led by specialists in emergency medicine. The main reason being the lack of space and equipment as well as staff needed to meet set standards of good clinical practice, education and research. Furthermore the Curriculum of undergraduate education and specialization does not match modern concept of educational programs that meet the principles set out in emergency medicine and learning through

  6. How to Diagnose and Classify Tattoo Complications in the Clinic: A System of Distinctive Patterns.

    Science.gov (United States)

    Serup, Jørgen

    2017-01-01

    Tattoo complications represent a broad spectrum of clinical entities and disease mechanisms. Infections are known, but chronic inflammatory reactions have hitherto been inconsistently reported and given many interpretations and terms. A clinical classification system of distinct patterns with emphasis on inflammatory tattoo reactions is introduced. Allergic reactions prevalent in red tattoos and often associated with azo pigments are manifested as the 'plaque elevation', 'excessive hyperkeratosis', and 'ulceronecrotic' patterns. The allergen is a hapten. Nonallergic reactions prevalent in black tattoos and associated with carbon black are manifested as the 'papulonodular' pattern. Carbon black nanoparticles agglomerate in the dermis over time forming foreign bodies that elicit reactions. Many black tattoos even develop sarcoid granuloma, and the 'papulonodular' pattern is strongly associated with sarcoidosis affecting other organs. Tattoo complications include a large group of less frequent but nevertheless specific entities, i.e. irritant and toxic local events, photosensitivity, urticaria, eczematous rash due to soluble allergen, neurosensitivity and pain syndrome, lymphopathies, pigment diffusion or fan, scars, and other sequels of tattooing or tattoo removal. Keratoacanthoma occurs in tattoos. Carcinoma and melanoma are rare and occur by coincidence only. Different tattoo complications require different therapeutic approaches, and precise diagnosis is thus important as a key to therapy. The proposed new classification with characteristic patterns relies on simple tools, namely patient history, objective findings, and supplementary punch biopsy. By virtue of simplicity and broad access, these methods make the proposed classification widely applicable in clinics and hospitals. The system is reported to the 11th revision of the WHO diagnosis classification used as international standard. © 2017 S. Karger AG, Basel.

  7. Prognostic factors associated with the success rates of posterior orthodontic miniscrew implants: A subgroup meta-analysis.

    Science.gov (United States)

    Hong, Sung-Bin; Kusnoto, Budi; Kim, Eun-Jeong; BeGole, Ellen A; Hwang, Hyeon-Shik; Lim, Hoi-Jeong

    2016-03-01

    To systematically review previous studies and to assess, via a subgroup meta-analysis, the combined odds ratio (OR) of prognostic factors affecting the success of miniscrew implants (MIs) inserted into the buccal posterior region. Three electronic searches that were limited to articles on clinical human studies using MIs that were published in English prior to March 2015 were conducted. The outcome measure was the success of MIs. Patient factors included age, sex, and jaw of insertion (maxilla vs. mandible), while the MI factors included length and diameter. A meta-analysis was performed on 17 individual studies. The quality of each study was assessed for non-randomized studies and quantified using the Newcastle-Ottawa Scale. The meta-analysis outcome was a combined OR. Subgroup and sensitivity analyses based on the study design, study quality, and sample size of miniscrews implanted were performed. Significantly higher success rates were revealed for MIs inserted in the maxilla, for patients ≥ 20 years of age, and for long MIs (≥ 8 mm) and MIs with a large diameter (> 1.4 mm). All subgroups acquired homogeneity, and the combined OR of the prospective studies (OR, 3.67; 95% confidence interval [CI], 2.10-6.44) was significantly higher in the maxilla than that in the retrospective studies (OR, 2.10; 95% CI, 1.60-2.74). When a treatment plan is made, these risk factors, i.e. jaw of insertion, age, MI length, and MI diameter, should be taken into account, while sex is not critical to the success of MIs.

  8. Subgroup analyses on return to work in sick-listed employees with low back pain in a randomised trial comparing brief and multidisciplinary intervention

    Directory of Open Access Journals (Sweden)

    Petersen Karin D

    2011-05-01

    Full Text Available Abstract Background Multidisciplinary intervention is recommended for rehabilitation of employees sick-listed for 4-12 weeks due to low back pain (LBP. However, comparison of a brief and a multidisciplinary intervention in a randomised comparative trial of sick-listed employees showed similar return to work (RTW rates in the two groups. The aim of the present study was to identify subgroups, primarily defined by work-related baseline factors that would benefit more from the multidisciplinary intervention than from the brief intervention. Methods A total of 351 employees sick-listed for 3-16 weeks due to LBP were recruited from their general practitioners. They received a brief or a multidisciplinary intervention. Both interventions comprised clinical examination and advice by a rehabilitation doctor and a physiotherapist. The multidisciplinary intervention also comprised assignment of a case manager, who made a rehabilitation plan in collaboration with the patient and a multidisciplinary team. Using data from a national database, we defined RTW as no sickness compensation benefit disbursement for four consecutive weeks within the first year after the intervention. At the first interview in the clinic, it was ensured that sick leave was primarily due to low back problems.Questionnaires were used to obtain data on health, disability, demographic and workplace-related factors. Cox hazard regression analyses were used with RTW as outcome measure and hazard rate ratios (HRR = HRmultidisciplinary/HRbrief were adjusted for demographic and health-related variables. An interaction term consisting of a baseline variable*intervention group was added to the multivariable regression model to analyse whether the effects of the interventions were moderated by the baseline factor. Subsequently, a new study was performed that included 120 patients who followed the same protocol. This group was analyzed in the same way to verify the findings from the original

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

    Directory of Open Access Journals (Sweden)

    Wang Jun

    2010-03-01

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

  10. Prediction of an excessive response in in vitro fertilization from patient characteristics and ovarian reserve tests and comparison in subgroups: an individual patient data meta-analysis

    NARCIS (Netherlands)

    Broer, Simone L.; Dólleman, Madeleine; van Disseldorp, Jeroen; Broeze, Kimiko A.; Opmeer, Brent C.; Bossuyt, Patrick M. M.; Eijkemans, Martinus J. C.; Mol, Ben Willem; Broekmans, Frank J. M.; Broer, S. L.; Dólleman, M.; van Disseldorp, J.; Eijkemans, M. J. C.; Broekmans, F. J. M.; Aflatoonian, A.; Anderson, R. A.; Ashrafi, M.; Bancsi, L.; Caroppo, E.; Copperman, A. B.; Ebner, T.; Eldar-Geva, T.; Erdem, M.; Freour, T.; Gnoth, C.; Greenblatt, E. M.; Jayaprakasan, K.; Raine-Fenning, N.; Klinkert, E.; Kwee, J.; La Marca, A.; Lambalk, C. B.; McIlveen, M.; Mohiyiddeen, L.; Merce, L. T.; Muttukrishna, S.; Nardo, L. G.; Nelson, S. M.; Ng, H. Y.; Popovic-Todorovic, B.; Smeenk, J. M. J.; Tomás, C.; van der Linden, P. J. Q.; van Rooij, I. A.; Vladimirov, I. K.

    2013-01-01

    To evaluate whether ovarian reserve tests (ORTs) add prognostic value to patient characteristics, such as female age, in the prediction of excessive response to ovarian hyperstimulation in patients undergoing IVF, and whether their performance differs across clinical subgroups. Authors of studies

  11. Maintaining a Distinction Between Possible and Impossible Topics of Conversation in the Outpatient Respiratory Medical Clinic.

    Science.gov (United States)

    Jensen, Lone Birgitte Skov; Larsen, Kristian; Konradsen, Hanne

    2016-01-01

    The aim of this study is to generate a grounded theory explaining patterns of behavior among health care professionals (HCPs) during interactions with patients in outpatient respiratory medical clinics. The findings suggest that the HCPs managed contradictory expectations to the interaction by maintaining a distinction between possible and impossible topics to counseling. Three subcategories explaining the effort that maintain the impossible and possible topics separated were identified: (a) an effort to maintain the diseased lungs as the main task in counseling, (b) navigating interactions to avoid strong emotions of suffering in patients to reveal, (c) avoiding the appearance of the non-alterable life circumstances of the patients. The HCPs' attitudes toward what patients could be offered generated a distance and a difficulty during counseling and created further suffering in the patients but likewise a discomfort and frustration among the HCPs.

  12. NSAID gastropathy and enteropathy: distinct pathogenesis likely necessitates distinct prevention strategies.

    Science.gov (United States)

    Wallace, John L

    2012-01-01

    The mechanisms underlying the ability of nonsteroidal anti-inflammatory drugs (NSAIDs) to cause ulceration in the stomach and proximal duodenum are well understood, and this injury can largely be prevented through suppression of gastric acid secretion (mainly with proton pump inhibitors). In contrast, the pathogenesis of small intestinal injury induced by NSAIDs is less well understood, involving more complex mechanisms than those in the stomach and proximal duodenum. There is clear evidence for important contributions to NSAID enteropathy of enteric bacteria, bile and enterohepatic recirculation of the NSAID. There is no evidence that suppression of gastric acid secretion will reduce the incidence or severity of NSAID enteropathy. Indeed, clinical data suggest little, if any, benefit. Animal studies suggest a significant exacerbation of NSAID enteropathy when proton pump inhibitors are co-administered with the NSAID. This worsening of damage appears to be linked to changes in the number and types of bacteria in the small intestine during proton pump inhibitor therapy. The distinct mechanisms of NSAID-induced injury in the stomach/proximal duodenum versus the more distal small intestine likely dictate distinct strategies for prevention. © 2011 The Author. British Journal of Pharmacology © 2011 The British Pharmacological Society.

  13. A method for generating subgroup parameters from resonance tables and the SPART code

    International Nuclear Information System (INIS)

    Devan, K.; Mohanakrishnan, P.

    1995-01-01

    A method for generating subgroup or band parameters from resonance tables is described. A computer code SPART was written using this method. This code generates the subgroup parameters for any number of bands within the specified broad groups at different temperatures by reading the required input data from the binary cross section library in the Cadarache format. The results obtained with SPART code for two bands were compared with that obtained from GROUPIE code and a good agreement was obtained. Results of the generation of subgroup parameters in four bands for sample case of 239 Pu from resonance tables of Cadarache Ver.2 library is also presented. 6 refs, 2 tabs

  14. Some topics on permutable subgroups in infinite groups

    OpenAIRE

    Ialenti, Roberto

    2017-01-01

    The aim of this thesis is to study permutability in different aspects of the theory of infinite groups. In particular, it will be studied the structure of groups in which all the members of a relevant system of subgroups satisfy a suitable generalized condition of permutability.

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

    Science.gov (United States)

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

    2016-11-01

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

  16. Subgroups of some Fuchsian groups defined by two linear congruences

    Science.gov (United States)

    Yayenie, Omer

    In this article we define a new family of subgroups of Fuchsian groups H(√{m}) , for a squarefree positive integer m , and calculate their index in H(√{m}) and their parabolic class number. Moreover, we will show that the index of these subgroups is closely related to the solvability of a quadratic congruence x2≡ m(mod n) and the number of inequivalent solutions of a quadratic congruence x2≡ 1(mod n) . Finally, we will show that the results obtained by Yilmaz and Keskin [Acta Math. Sin 25 (2005), 215-222] are immediate corollaries of one of the main theorems of this article.

  17. Avian metapneumovirus subgroup C infection in chickens, China.

    Science.gov (United States)

    Wei, Li; Zhu, Shanshan; Yan, Xv; Wang, Jing; Zhang, Chunyan; Liu, Shuhang; She, Ruiping; Hu, Fengjiao; Quan, Rong; Liu, Jue

    2013-07-01

    Avian metapneumovirus causes acute respiratory tract infection and reductions in egg production in various avian species. We isolated and characterized an increasingly prevalent avian metapneumovirus subgroup C strain from meat-type commercial chickens with severe respiratory signs in China. Culling of infected flocks could lead to economic consequences.

  18. Avian Metapneumovirus Subgroup C Infection in Chickens, China

    OpenAIRE

    Wei, Li; Zhu, Shanshan; Yan, Xv; Wang, Jing; Zhang, Chunyan; Liu, Shuhang; She, Ruiping; Hu, Fengjiao; Quan, Rong; Liu, Jue

    2013-01-01

    Avian metapneumovirus causes acute respiratory tract infection and reductions in egg production in various avian species. We isolated and characterized an increasingly prevalent avian metapneumovirus subgroup C strain from meat-type commercial chickens with severe respiratory signs in China. Culling of infected flocks could lead to economic consequences.

  19. Functional heartburn: the stimulus, the pain, and the brain

    Science.gov (United States)

    Fass, R; Tougas, G

    2002-01-01

    Functional heartburn is a common disorder and appears to be composed of several distinct subgroups. Identifying the different subgroups based on clinical history only is not achievable at present. The mechanisms responsible for pain, clinical characteristics, and the optimal therapeutic approach remain poorly understood. Response to potent antireflux treatment is relatively limited. Current and future treatment strategies for functional heartburn patients who have failed standard dose proton pump inhibitors (PPIs) include increased PPI dose in some, as well as addition of pain modulators in others. PMID:12427796

  20. Seronegative necrolytic acral erythema: A distinct clinical subset?

    Directory of Open Access Journals (Sweden)

    Panda S

    2010-01-01

    Full Text Available A patient was referred to us with asymptomatic, erythematous, nonitchy, scaly lesions present bilaterally on the dorsa of his feet and toes since the last 2 months. Both the legs had pitting edema as well. There were hyperkeratosis, focal parakeratosis, acanthosis and scattered spongiosis in the epidermis, and proliferation of capillaries with perivascular infiltration of lymphomononuclear cells in the dermis. There was no serological evidence of hepatitis C virus. Laboratory investigations revealed hypoalbuminemia and low-normal serum zinc. On clinicopathological correlation, we made a diagnosis of necrolytic acral erythema (NAE. The lesions responded dramatically to oral zinc sulfate and topical clobetasol propionate within 3 weeks with disappearance of edema and scaling and only a minimal residual erythema. This is the first reported case of NAE from Eastern India. NAE with negative serology for hepatitis C may be viewed as a distinct subset of the condition that had been originally described.

  1. 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.

  2. Objectives and tasks for sub-group B: Plutonium management and recycle

    International Nuclear Information System (INIS)

    1978-01-01

    The paper restates the prime objectives of Working Group 4 and explains that in order to accomplish their objectives two sub-groups (A and B) have been established. The Co-Chairmen suggested that sub group B take as their terms of reference those tasks remitted to them by Working Group 4 as a whole. The paper identifies and comments on 11 tasks into which the work of the sub-group is divided. The paper also includes a number of annexes giving the guidelines for data input to each task

  3. Genome-scale analysis of aberrant DNA methylation in colorectal cancer

    Science.gov (United States)

    Hinoue, Toshinori; Weisenberger, Daniel J.; Lange, Christopher P.E.; Shen, Hui; Byun, Hyang-Min; Van Den Berg, David; Malik, Simeen; Pan, Fei; Noushmehr, Houtan; van Dijk, Cornelis M.; Tollenaar, Rob A.E.M.; Laird, Peter W.

    2012-01-01

    Colorectal cancer (CRC) is a heterogeneous disease in which unique subtypes are characterized by distinct genetic and epigenetic alterations. Here we performed comprehensive genome-scale DNA methylation profiling of 125 colorectal tumors and 29 adjacent normal tissues. We identified four DNA methylation–based subgroups of CRC using model-based cluster analyses. Each subtype shows characteristic genetic and clinical features, indicating that they represent biologically distinct subgroups. A CIMP-high (CIMP-H) subgroup, which exhibits an exceptionally high frequency of cancer-specific DNA hypermethylation, is strongly associated with MLH1 DNA hypermethylation and the BRAFV600E mutation. A CIMP-low (CIMP-L) subgroup is enriched for KRAS mutations and characterized by DNA hypermethylation of a subset of CIMP-H-associated markers rather than a unique group of CpG islands. Non-CIMP tumors are separated into two distinct clusters. One non-CIMP subgroup is distinguished by a significantly higher frequency of TP53 mutations and frequent occurrence in the distal colon, while the tumors that belong to the fourth group exhibit a low frequency of both cancer-specific DNA hypermethylation and gene mutations and are significantly enriched for rectal tumors. Furthermore, we identified 112 genes that were down-regulated more than twofold in CIMP-H tumors together with promoter DNA hypermethylation. These represent ∼7% of genes that acquired promoter DNA methylation in CIMP-H tumors. Intriguingly, 48/112 genes were also transcriptionally down-regulated in non-CIMP subgroups, but this was not attributable to promoter DNA hypermethylation. Together, we identified four distinct DNA methylation subgroups of CRC and provided novel insight regarding the role of CIMP-specific DNA hypermethylation in gene silencing. PMID:21659424

  4. The home health workforce: a distinction between worker categories.

    Science.gov (United States)

    Stone, Robyn; Sutton, Janet P; Bryant, Natasha; Adams, Annelise; Squillace, Marie

    2013-01-01

    The demand for home health aides is expected to rise, despite concerns about the sustainability of this workforce. Home health workers receive low wages and little training and have high turnover. It is difficult to recruit and retain workers to improve clinical outcomes. This study presents national estimates to examine how home health workers and the subgroup of workers differ in terms of sociodemographic characteristics, compensation, benefits, satisfaction, and retention. Hospice aides fare better than other categories of workers and are less likely to leave their job. Policymakers should consider strategies to increase the quality and stability of this workforce.

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

    Science.gov (United States)

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

    2017-10-01

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

  6. Objective and quantitative equilibriometric evaluation of individual locomotor behaviour in schizophrenia: Translational and clinical implications.

    Science.gov (United States)

    Haralanov, Svetlozar; Haralanova, Evelina; Milushev, Emil; Shkodrova, Diana; Claussen, Claus-Frenz

    2018-04-17

    Psychiatry is the only medical specialty that lacks clinically applicable biomarkers for objective evaluation of the existing pathology at a single-patient level. On the basis of an original translational equilibriometric method for evaluation of movement patterns, we have introduced in the everyday clinical practice of psychiatry an easy-to-perform computerized objective quantification of the individual locomotor behaviour during execution of the Unterberger stepping test. For the last 20 years, we have gradually collected a large database of more than 1000 schizophrenic patients, their relatives, and matched psychiatric, neurological, and healthy controls via cross-sectional and longitudinal investigations. Comparative analyses revealed transdiagnostic locomotor similarities among schizophrenic patients, high-risk schizotaxic individuals, and neurological patients with multiple sclerosis and cerebellar ataxia, thus suggesting common underlying brain mechanisms. In parallel, intradiagnostic dissimilarities were revealed, which allow to separate out subclinical locomotor subgroups within the diagnostic categories. Prototypical qualitative (dysmetric and ataxic) locomotor abnormalities in schizophrenic patients were differentiated from 2 atypical quantitative ones, manifested as either hypolocomotion or hyperlocomotion. Theoretical analyses suggested that these 3 subtypes of locomotor abnormalities could be conceived as objectively measurable biomarkers of 3 schizophrenic subgroups with dissimilar brain mechanisms, which require different treatment strategies. Analogies with the prominent role of locomotor measures in some well-known animal models of mental disorders advocate for a promising objective translational research in the so far over-subjective field of psychiatry. Distinctions among prototypical, atypical, and diagnostic biomarkers, as well as between neuromotor and psychomotor locomotor abnormalities, are discussed. Conclusions are drawn about the

  7. Reports of MC and A system design workshop subgroups

    International Nuclear Information System (INIS)

    Hatcher, C.R.

    1984-01-01

    A summary of subgroup reports from the workshop on design of a materials control and accounting system for a low-enrichment fuel fabrication facility is presented. Responses to a MC and A design system questionnaire are also summarized

  8. Clonality and distribution of clinical Ureaplasma isolates recovered from male patients and infertile couples in China.

    Science.gov (United States)

    Ruan, Zhi; Yang, Ting; Shi, Xinyan; Kong, Yingying; Xie, Xinyou; Zhang, Jun

    2017-01-01

    Ureaplasma spp. have gained increasing recognition as pathogens in both adult and neonatal patients with multiple clinical presentations. However, the clonality of this organism in the male population and infertile couples in China is largely unknown. In this study, 96 (53 U. parvum and 43 U. urealyticum) of 103 Ureaplasma spp. strains recovered from genital specimens from male patients and 15 pairs of infertile couples were analyzed using multilocus sequence typing (MLST)/expanded multilocus sequence typing (eMLST) schemes. A total of 39 sequence types (STs) and 53 expanded sequence types (eSTs) were identified, with three predominant STs (ST1, ST9 and ST22) and eSTs (eST16, eST41 and eST82). Moreover, phylogenetic analysis revealed two distinct clusters that were highly congruent with the taxonomic differences between the two Ureaplasma species. We found significant differences in the distributions of both clusters and sub-groups between the male and female patients (P Ureaplasma spp. The present study also attained excellent agreement of the identification of both Ureaplasma species between paired urine and semen specimens from the male partners (k > 0.80). However, this concordance was observed only for the detection of U. urealyticum within the infertile couples. In conclusion, the distributions of the clusters and sub-groups significantly differed between the male and female patients. U. urealyticum is more likely to transmit between infertile couples and be associated with clinical manifestations by the specific epidemic clonal lineages.

  9. 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.

  10. Identification of Two Subgroups of Type I IFNs in Perciforme Fish Large Yellow Croaker Larimichthys crocea Provides Novel Insights into Function and Regulation of Fish Type I IFNs

    Directory of Open Access Journals (Sweden)

    Yang Ding

    2016-09-01

    Full Text Available Like mammals, fish possess an interferon regulatory factor 3 (IRF3/IRF7-dependent type I IFN responses, but the exact mechanism by which IRF3/IRF7 regulate the type I IFNs remains largely unknown. In this study, we identified two type I IFNs in the Perciforme fish large yellow croaker Larimichthys crocea, one of which belongs to the fish IFNd subgroup, and the other is assigned to a novel subgroup of group I IFNs in fish, tentatively termed IFNh. The two IFN genes are constitutively expressed in all examined tissues, but with varied expression levels. Both IFN genes can be rapidly induced in head kidney and spleen tissues by polyinosinic-polycytidylic acid. The recombinant IFNh was shown to be more potent to trigger a rapid induction of the antiviral genes MxA and PKR than the IFNd, suggesting that they may play distinct roles in regulating early antiviral immunity. Strikingly, IFNd, but not IFNh, could induce the gene expression of itself and IFNh through a positive feedback loop mediated by the IFNd-dependent activation of IRF3 and IRF7. Furthermore, our data demonstrate that the induction of IFNd can be enhanced by the dimeric formation of IRF3 and IRF7, while the IFNh expression mainly involves IRF3. Taken together, our findings demonstrate that the IFN responses are diverse in fish and are likely to be regulated by distinct mechanisms.

  11. Verification of a Subgroup Generation Method for Thorium Fuel Assemblies

    International Nuclear Information System (INIS)

    Sim, Ohsung; Kim, Myunghyun

    2013-01-01

    Resonance parameter consists of subgroup level and weight. The subgroup weight is obtained by solving the ultrafine slowing down equation and fixed source problem. That means this cross section library procedure considers conservation of the shielded cross section for pin-cell in order to obtain subgroup parameters. There are some isotopes to be concerned for research such as actinides and thorium. Minor actinides(MA) are existing with very small amount in a spent fuel, but effect is not negligible in a high burnup fuel assemblies. Some MAs have high fission cross sections under thermal neutron spectrum. Thorium isotopes was not investigated as much as uranium, but it has high potential for future application. In this study, a new cross section library to be replaced with HELIOS library was generated and compared for the assembly calculation, specially for assembly with thorium. An average capture cross section value at a certain fuel pin and multiplication factor of assembly were compared with nTRACER calculation with HELIOS library and Monte Carlo calculation of MCNP with ENDF-B/II. The accuracy of library data generated for thorium isotope in nTRACER calculation was tested for WASB model. There was a great improvement in K-eff and capture cross section for this assembly compared with old library, HELIOS library

  12. Giant serpentine intracranial aneurysm: a case report

    International Nuclear Information System (INIS)

    Park, Jae Seong; Lee, Myeong Sub; Kim, Myung Soon; Kim, Dong Jin; Park, Joong Wha; Whang, Kum

    2001-01-01

    The authors present a case of giant serpentine aneurysm (a partially thrombosed aneurysm containing tortuous vascular channels with a separate entrance and outflow pathway). Giant serpentine aneurysms form a subgroup of giant intracranial aneurysms, distinct from saccular and fusiform varieties, and in this case, too, the clinical presentation and radiographic features of CT, MR imaging and angiography were distinct

  13. 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

    2018-04-01

    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) 2018 APA, all rights reserved).

  14. The subgroups in the special linear group over a skew field that contain the group of diagonal matrices

    International Nuclear Information System (INIS)

    Bui Xuan Hai.

    1990-05-01

    For an arbitrary skew field T we study the lattice of subgroups of the special linear group Γ=SL(n,T) that contain the subgroup Δ-SD(n,T) of diagonal matrices with Dieudonne's determinant equal to 1. We show that the description of these subgroups is standard in the following sense: For any subgroup H,Δ≤H≤Γ there exists a unique unital net such that Γ(σ) ≤H≤N(σ), where Γ(σ) is the net subgroup that corresponds to the net σ and N(σ) is the normalizer of Γ(σ) in Γ. (author). 11 refs

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

    Science.gov (United States)

    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. PMID:27065101

  16. Ethnic Identity and Major Depression in Asian American Subgroups Nationwide: Differential Findings in Relation to Subcultural Contexts.

    Science.gov (United States)

    Ai, Amy L; Nicdao, Ethel G; Appel, Hoa B; Lee, Daniel Hyung Jik

    2015-12-01

    Asian Americans (AA) are the fastest growing minority population in the United States. Leading AA scholars have highlighted the unmet service needs and the necessity to investigate subgroup variations in the mental health of AAs. This study addressed a research gap of whether racial and ethnic identity (REI) in three AA subgroups (Chinese, Filipino, and Vietnamese) consistently protects against major depressive disorder (MDD), counteracting the deleterious role of discrimination. Using the National Latino and Asian American Study (NLAAS), we explored the varying and incremental predictive values of REI, above and beyond the effects of known demographic and acculturation predictors, alongside other potentially protective factors. In three sets of two-step logistic regressions, REI had an inverse relationship with MDD in the Filipino subgroup only but a positive association in the Chinese subgroup. The damaging role of negative REI moderated the effect of discrimination. The longest stay in the United States and discrimination predicted a higher likelihood of a MDD diagnosis in the Filipino subgroup. Social support contributed to the lower odds of MDD in Chinese and Vietnamese subgroups, had lower odds of having MDD, and religious attendance may act as a protective factor in the Vietnamese subgroup. Our findings do not reinforce uniform protection of REI but lend partial support for two underlying rationales. Based on cultural psychologists' framework, inconsistent findings are interpreted within the sociocultural contexts of the 3 subgroups. © 2015 Wiley Periodicals, Inc.

  17. Distinctive skeletal dysplasia in Cockayne syndrome

    International Nuclear Information System (INIS)

    Silengo, M.C.; Franceschini, P.; Bianco, R.; Biagioli, M.; Pastorin, L.; Vista, N.; Baldassar, A.; Benso, L.

    1986-01-01

    Cockayne syndrom is a well-known autosomal recessive form of dwarfism with senile-like appearance. Skeletal changes such as flattening of vertebral bodies, ivory epiphyses and thickening of cranial vault, have been observed in some patients with this condition. We describe here a 5.5-year-old girl with the typical clinical signs of Cockayne syndrome and a distinctive form of bone dysplasia with major involvment of the spine. (orig.)

  18. Distinctive skeletal dysplasia in Cockayne syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Silengo, M.C.; Franceschini, P.; Bianco, R.; Biagioli, M.; Pastorin, L.; Vista, N.; Baldassar, A.; Benso, L.

    1986-03-01

    Cockayne syndrome is a well-known autosomal recessive form of dwarfism with senile-like appearance. Skeletal changes such as flattening of vertebral bodies, ivory epiphyses and thickening of cranial vault, have been observed in some patients with this condition. We describe here a 5.5-year-old girl with the typical clinical signs of Cockayne syndrome and a distinctive form of bone dysplasia with major involvement of the spine.

  19. electropherotypes and subgroups of group a rotaviruses circulating ...

    African Journals Online (AJOL)

    Emmanuel Ameh

    diarrhea caused by rotaviruses. The virus is a double stranded RNA (dsRNA) virus with 11 segments. Group A rotaviruses show a characteristic 4-2-3-2 pattern following electrophoresis. The VP6 subgroups, I and II exist. This work was carried out to study the prevalence of rotavirus infection among children 0-5 years with ...

  20. A Low-Complexity Subgroup Formation with QoS-Aware for Enhancing Multicast Services in LTE Networks

    Science.gov (United States)

    Algharem, M.; Omar, M. H.; Rahmat, R. F.; Budiarto, R.

    2018-03-01

    The high demand of Multimedia services on in Long Term Evolution (LTE) and beyond networks forces the networks operators to find a solution that can handle the huge traffic. Along with this, subgroup formation techniques are introduced to overcome the limitations of the Conventional Multicast Scheme (CMS) by splitting the multicast users into several subgroups based on the users’ channels quality signal. However, finding the best subgroup configuration with low complexity is need more investigations. In this paper, an efficient and simple subgroup formation mechanisms are proposed. The proposed mechanisms take the transmitter MAC queue in account. The effectiveness of the proposed mechanisms is evaluated and compared with CMS in terms of throughput, fairness, delay, Block Error Rate (BLER).

  1. Clinical Benefits of Memantine Treatment for Alzheimer's Disease in the Okayama Memantine Study II (OMS II).

    Science.gov (United States)

    Matsuzono, Kosuke; Yamashita, Toru; Ohta, Yasuyuki; Hishikawa, Nozomi; Koike, Makoto; Sato, Kota; Kono, Syoichiro; Deguchi, Kentaro; Nakano, Yumiko; Abe, Koji

    2015-01-01

    The clinical benefits of memantine, depending on the baseline cognitive and affective conditions in real world dementia clinics, have not been completely examined. We performed the "Okayama Memantine Study II (OMS II)" to retrospectively evaluate the clinical effects of memantine monotherapy (n = 38) in Alzheimer's disease (AD) patients using seven batteries to assess dementia at the baseline, at 3, 6, and 12 months. Additionally, we divided 163 AD patients treated with memantine into two subgroups depending on the baseline cognitive score of the Mini-Mental State Examination (MMSE): the MMSE OMS II showed that memantine monotherapy improved BPSD until 12 months. The higher baseline cognitive subgroup (MMSE ≥15) and the worse baseline BPSD subgroup were expected to show better effects with memantine.

  2. Trajectories of personal control in cancer patients receiving psychological care

    NARCIS (Netherlands)

    Zhu, Lei; Schroevers, Maya J.; van der Lee, Marije; Garssen, Bert; Stewart, Roy E.; Sanderman, Robbert; Ranchor, Adelita V.

    Objective: This study aimed to (1) identify subgroups of cancer patients with distinct personal control trajectories during psychological care, (2) examine whether socio-demographic, clinical, and psychological care characteristics could distinguish trajectories, and (3) examine differential

  3. Piracetam and piracetam-like drugs: from basic science to novel clinical applications to CNS disorders.

    Science.gov (United States)

    Malykh, Andrei G; Sadaie, M Reza

    2010-02-12

    There is an increasing interest in nootropic drugs for the treatment of CNS disorders. Since the last meta-analysis of the clinical efficacy of piracetam, more information has accumulated. The primary objective of this systematic survey is to evaluate the clinical outcomes as well as the scientific literature relating to the pharmacology, pharmacokinetics/pharmacodynamics, mechanism of action, dosing, toxicology and adverse effects of marketed and investigational drugs. The major focus of the literature search was on articles demonstrating evidence-based clinical investigations during the past 10 years for the following therapeutic categories of CNS disorders: (i) cognition/memory; (ii) epilepsy and seizure; (iii) neurodegenerative diseases; (iv) stroke/ischaemia; and (v) stress and anxiety. In this article, piracetam-like compounds are divided into three subgroups based on their chemical structures, known efficacy and intended clinical uses. Subgroup 1 drugs include piracetam, oxiracetam, aniracetam, pramiracetam and phenylpiracetam, which have been used in humans and some of which are available as dietary supplements. Of these, oxiracetam and aniracetam are no longer in clinical use. Pramiracetam reportedly improved cognitive deficits associated with traumatic brain injuries. Although piracetam exhibited no long-term benefits for the treatment of mild cognitive impairments, recent studies demonstrated its neuroprotective effect when used during coronary bypass surgery. It was also effective in the treatment of cognitive disorders of cerebrovascular and traumatic origins; however, its overall effect on lowering depression and anxiety was higher than improving memory. As add-on therapy, it appears to benefit individuals with myoclonus epilepsy and tardive dyskinesia. Phenylpiracetam is more potent than piracetam and is used for a wider range of indications. In combination with a vasodilator drug, piracetam appeared to have an additive beneficial effect on various

  4. Trajectories of personal control in cancer patients receiving psychological care

    NARCIS (Netherlands)

    Zhu, Lei; Schroevers, Maya J.; van der Lee, Marije; Garssen, Bert; Stewart, Roy E.; Sanderman, Robbert; Ranchor, A.V.

    2015-01-01

    Objective This study aimed to (1) identify subgroups of cancer patients with distinct personal control trajectories during psychological care, (2) examine whether socio-demographic, clinical, and psychological care characteristics could distinguish trajectories, and (3) examine differential patterns

  5. On approximation of Lie groups by discrete subgroups

    Indian Academy of Sciences (India)

    2016-08-26

    Aug 26, 2016 ... The notion of approximation of Lie groups by discrete subgroups was introduced by Tôyama in Kodai Math. Sem. Rep. 1 (1949) 36–37 and investigated in detail by Kuranishi in Nagoya Math. J. 2 (1951) 63–71. It is known as a theorem of Tôyama that any connected Lie group approximated by discrete ...

  6. 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 ...

  7. Non-meagre subgroups of reals disjoint with meagre sets

    Czech Academy of Sciences Publication Activity Database

    Kostana, Ziemowit

    2018-01-01

    Roč. 241, June (2018), s. 11-19 ISSN 0166-8641 Institutional support: RVO:67985840 Keywords : algebraic sum * Baire property * non-meaurable subgroup Subject RIV: BA - General Mathematics OBOR OECD: Pure mathematics Impact factor: 0.377, year: 2016 https://www.sciencedirect.com/science/ article /pii/S0166864118300567

  8. Three-dimensional Cervical Movement Characteristics in Healthy Subjects and Subgroups of Chronic Neck Pain Patients Based on Their Pain Location.

    Science.gov (United States)

    Waeyaert, Patirck; Jansen, Daniel; Bastiaansen, Marco; Scafoglieri, Aldo; Buyl, Ronald; Schmitt, Maarten; Cattrysse, Erik

    2016-08-01

    A cross-sectional observational study of three-dimensional (3D) cervical kinematics in 41 chronic neck pain (CNPs) patients and 156 asymptomatic controls. The objective was to investigate 3D cervical kinematics by analyzing and comparing quantitative and qualitative parameters in healthy subjects and CNPs. Furthermore, subgroups were formed to explore the influence of pain-location on cervical kinematics. The possible correlation of kinematic parameters with the degree of functional disability was examined as well. In patients with chronic neck pain, a clear pathological cause is frequently not identifiable. Therefore, the need to assess neck pain with a broader view than structure or anatomical-based divergences is desirable. Movements of the cervical spine were registered using an electromagnetic tracking system. Quantitative and qualitative kinematics were analyzed for active axial rotation, lateral bending, and flexion-extension motion components. During lateral bending, the range of the main motion demonstrated significant higher values (P = 0.001) in the controls (mean: 68.67° ± 15.17°) than patients (mean: 59.28° ± 15.41°). Significant differences were demonstrated between subgroups for several kinematic parameters (P pain group, some parameters also distinguished subgroups from controls. On average, the symmetrical group showed significant less harmonic movement patterns, expressed by qualitative parameters, in comparison with the "asymmetrical" group and controls. Furthermore, the "asymmetrical" group showed significant lower scores on quantitative parameters than the "symmetrical" group and controls. The degree of functional disability correlated moderately with changes in qualitative parameters. In this study, chronic neck pain patients with a symmetrical pain pattern showed significant poorer quality of movement, while those with asymmetrical pain showed a significant reduction in quantitative measures. Subgrouping of neck patients

  9. Differences in feedforward trunk muscle activity in subgroups of patients with mechanical low back pain.

    Science.gov (United States)

    Silfies, Sheri P; Mehta, Rupal; Smith, Sue S; Karduna, Andrew R

    2009-07-01

    To investigate alterations in trunk muscle timing patterns in subgroups of patients with mechanical low back pain (MLBP). Our hypothesis was that subjects with MLBP would demonstrate delayed muscle onset and have fewer muscles functioning in a feedforward manner than the control group. We further hypothesized that we would find differences between subgroups of our patients with MLBP, grouped according to diagnosis (segmental instability and noninstability). Case-control. Laboratory. Forty-three patients with chronic MLBP (25 instability, 18 noninstability) and 39 asymptomatic controls. Not applicable. Surface electromyography was used to measure onset time of 10 trunk muscles during a self-perturbation task. Trunk muscle onset latency relative to the anterior deltoid was calculated and the number of muscles functioning in feedforward determined. Activation timing patterns (Pfeedforward (P=.02; eta=.30; 1-beta=.83) were statistically different between patients with MLBP and controls. The control group activated the external oblique, lumbar multifidus, and erector spinae muscles in a feedforward manner. The heterogeneous MLBP group did not activate the trunk musculature in feedforward, but responded with significantly delayed activations. MLBP subgroups demonstrated significantly different timing patterns. The noninstability MLBP subgroup activated trunk extensors in a feedforward manner, similar to the control group, but significantly earlier than the instability subgroup. Lack of feedforward activation of selected trunk musculature in patients with MLBP may result in a period of inefficient muscular stabilization. Activation timing was more impaired in the instability than the noninstability MLBP subgroup. Training specifically for recruitment timing may be an important component of the rehabilitation program.

  10. Data on subgroup specific baseline characteristics and serum sphingosine-1-phosphate concentrations in the Study of Health in Pomerania

    Directory of Open Access Journals (Sweden)

    Eileen Moritz

    2017-06-01

    Full Text Available In this data article, we provide subgroup specific baseline characteristics and serum sphingosine-1-phosphate (S1P concentrations for healthy individuals within the Study of Health in Pomerania (SHIP-TREND cohort. After exclusion of subjects with cardiovascular disease, diabetes mellitus, hypertension, metabolic syndrome, elevated liver enzymes and/or chronic kidney disease stadium III or IV, four subgroups were defined according to different limits for body mass index (BMI, alterations in blood lipid levels and smoking status. Tables show respective clinical and laboratory parameters stratified by gender. Serum S1P concentrations are also stratified by age groups. The data presented herein is related to the research article entitled “Reference intervals for serum sphingosine-1-phosphate in the population-based Study of Health in Pomerania” (E. Moritz, D. Wegner, S. Groß, M. Bahls, M. Dörr, S.B. Felix, T. Ittermann, S. Oswald, M. Nauck, N. Friedrich, R.H. Böger, G. Daum, E. Schwedhelm, B.H. Rauch, Clin Chim Acta. 468 (2017 25–31 [1].

  11. Emergence of multiple clade 2.3.2.1 influenza A (H5N1) virus subgroups in Vietnam and detection of novel reassortants.

    Science.gov (United States)

    Creanga, Adrian; Thi Nguyen, Diep; Gerloff, Nancy; Thi Do, Hoa; Balish, Amanda; Dang Nguyen, Hoang; Jang, Yunho; Thi Dam, Vui; Thor, Sharmi; Jones, Joyce; Simpson, Natosha; Shu, Bo; Emery, Shannon; Berman, LaShondra; Nguyen, Ha T; Bryant, Juliet E; Lindstrom, Steve; Klimov, Alexander; Donis, Ruben O; Davis, C Todd; Nguyen, Tung

    2013-09-01

    Phylogenetic analyses of 169 influenza A(H5N1) virus genomes were conducted for samples collected through active surveillance and outbreak responses in Vietnam between September 2010 and September 2012. While clade 1.1 viruses persisted in southern regions, three genetically distinct subgroups of clade 2.3.2.1 were found in northern and central Vietnam. The identification of each subgroup corresponded with detection of novel reassortants, likely due to their overlapping circulation throughout the country. While the previously identified clade 1.1 and A/Hubei/1/2010-like 2.3.2.1 genotypes remained the predominant viruses detected, four viruses were found to be reassortants between A/Hubei/1/2010-like (HA, NA, PB2, PB1, PA, NP) and A/duck/Vietnam/NCVD-885/2010-like (M, NS) viruses and one virus was identified as having A/duck/Vietnam/NCVD-885/2010-like HA, NA, PB1, and NP with A/Hubei/1/2010-like PB2 and PA genes. Additionally, clade 2.3.2.1 A/Hong Kong/6841/2010-like viruses, first detected in mid-2012, were identified as reassortants comprised of A/Hubei/1/2010-like PB2 and PA and A/duck/Vietnam/NCVD-885/2010-like PB1, NP, NA, M, NS genes. Published by Elsevier Inc.

  12. Conclusions from the engineering subgroup of the SSC liquid argon calorimeter working group

    International Nuclear Information System (INIS)

    Bederede, D.; Cooper, W.; Mulholland, G.; Kroon, P.; Guryn, W.; Lobkowicz, F.; Mason, I.; Pohlen, J.; Schindler, R.H.; Scholle, E.A.; Watanabe, Y.; Watt, R.

    1990-01-01

    The SSC Calorimeter Workshop was organized to explore the feasibility of each calorimeter technology for use in a 4π detector at the SSC. The Liquid Argon Calorimeter group further subdivided into four subgroups; Hermeticity, Engineering, Module Details, and Electronics. This is the report of the Engineering Subgroup whose charge was to evaluate the cost, schedule, manpower, safety, and facilities requirements for the construction of a large liquid argon calorimeter for the SSC

  13. Distinct trajectories of positive and negative affect after colorectal cancer diagnosis.

    Science.gov (United States)

    Ciere, Yvette; Janse, Moniek; Almansa, Josué; Visser, Annemieke; Sanderman, Robbert; Sprangers, Mirjam A G; Ranchor, Adelita V; Fleer, Joke

    2017-06-01

    Insight into trajectories of positive affect (PA) and negative affect (NA) across the cancer continuum may improve understanding of the nature of adjustment problems. The primary aim of this study was to identify subgroups of patients with distinct trajectories of PA and NA following diagnosis of colorectal cancer (CRC). Secondary to this aim, the co-occurrence between trajectories and their association with goal-related processes was explored. CRC patients (n = 186) completed questionnaires within 1 month, 7 months, and 18 months after diagnosis. Multilevel models were used to study the trajectory of PA and NA, as measured with the Positive and Negative Affect Schedule (PANAS). Four classes with distinct PA trajectories were identified: low (18.8%), increasing (6.7%), moderate (68.2%), and high (6.3%); 2 trajectories of NA emerged: low (36.3%) and moderate (63.7%). There was no significant association between PA and NA trajectory class probabilities. The average trajectory of PA covaried with levels of goal disturbance and goal reengagement over time, while the average NA trajectory covaried with goal disturbance and goal disengagement. Compared with the general population, our sample of cancer patients suffered from a lack of positive emotions, but not a high presence of negative emotions. About one fifth of patients reported low PA up to 18 months after diagnosis and may benefit from supportive care. Furthermore, the trajectory of PA was independent of that of NA and related with a distinct goal adjustment process (i.e., goal disengagement vs. goal reengagement). This finding indicates the need to tailor psychological care to the nature of the adjustment problem. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  14. Presidential address: distinction or extinction.

    Science.gov (United States)

    Pressman, Barry D

    2008-10-01

    Despite its continuing scientific successes in imaging, radiology as a specialty is faced with a very difficult and competitive environment. Nonradiologists are more and more interested in vertically integrating imaging into their practices, while teleradiology and picture archiving and communication systems are resulting in the greater isolation of radiologists. Commoditization is a realistic and devastating threat to the survival and professionalism of the specialty. To remain viable as a specialty, radiologists must elevate their practice by subspecializing, becoming more involved with clinical care, and actively interacting with patients and referring clinicians. Distinction will prevent extinction.

  15. Identifying Changes in Youth's Subgroup Membership over Time Based on Their Targeted Communication about Substance Use with Parents and Friends

    Science.gov (United States)

    Kam, Jennifer A.

    2011-01-01

    Using latent class/transition analyses, this study: (a) identified subgroups of youth based on their targeted communication about substance use with parents and friends, (b) examined subgroup differences in substance use, and (c) considered changes in subgroup membership over four years. Among 5,874 youth, five subgroups emerged, with parents-only…

  16. The Immunohistochemical Analysis of SOCS3 Protein Identifies a Subgroup of Prostatic Cancer Biopsies With Aggressive Behavior.

    Science.gov (United States)

    Pierconti, Francesco; Martini, Maurizio; Cenci, Tonia; Larocca, Luigi M

    Recently, we demonstrated that hypermethylation of SOCS3 determines a significant reduction of its mRNA and protein expression and identifies a subgroup of prostate cancer with aggressive behavior. In this paper, our objective was to investigate whether the immunohistochemical expression of the SOCS3 protein could represent an alternative method to molecular analysis for the individualization of aggressive prostate carcinoma. We analyzed the SOCS3 immunohistochemical expression in 65 patients undergoing biopsies at the Institute of Urology of our hospital between September 2011 and October 2011 (median age, 66.4 y; range, 50 to 73 y), and in 35 cases, a subset of 65 cases originally used for the immunohistochemical study, we studied the methylation status of the SOCS3 promoter. We found that the percentage of cases with SOCS3 negativity (-) or with SOCS3 weak staining in <50% of the neoplastic glands (+/-) correlated to the worst prognosis in terms of the Gleason score (P=0.0001; Fisher's exact test), the pT stage (P=0.012; Fisher's exact test), and progression-free survival (P=0.0334; hazard ratio, 0.34; and 95% confidence interval, from 0.1261 to 0.9188). Moreover, some cases with an SOCS3 unmethylated pattern showed SOCS3-negative immunostaining (-) or SOCS3-negative glands with weak cytoplasmatic staining in <50% of the neoplastic glands (+/-). Our data suggest that in prostatic cancer biopsies, the immunohistochemical analysis of SOCS3 protein expression may provide a method that is less expensive and easier to apply than SOCS3 methylation analysis for the distinction of a subgroup of prostate cancer with a more aggressive behavior.

  17. [Subgroup Analysis of the Non-interventional REASON Study: PFS and OS According to Age, Smoking History, Gender, and Histology in NSCLC Patients Treated with Gefitinib or Chemotherapy].

    Science.gov (United States)

    Schuette, W; Eberhardt, W E E; Waller, C; Schirmacher, P; Dietel, M; Zirrgiebel, U; Radke, S; Thomas, M

    2016-09-01

    Assessment of several clinical factors on progression-free (PFS) and overall survival (OS) in NSCLC patients (pts.) (stage IV) with mutated epidermal growth factor receptor (EGFRm+) treated with gefitinib (gef) or with chemotherapy (CT) under real-world conditions. 285 EGFRm+ pts. of the non-interventional REASON study treated with gef (n = 206) or CT (n = 79) as first-line therapy or with gef (n = 213) or CT (n = 61) in any line throughout the course of therapy were analyzed according to age, gender, smoking history and histology. Compared with CT, patients treated with gef showed prolongation of PFS and OS in all subgroups. PFS was significantly increased in women and non-smokers. OS was significantly increased in women, non-smokers, (ex)-smokers, patients with adenocarcinoma and elderly patients when treated with gef compared to CT. Female gender turned out to be an independent positive predictive factor for OS in patients treated with gef (HRmale: 1.74, p = 0.0009). A clinical benefit of gef was shown for all analyzed clinical subgroups of EGFRm+ pts. This was confirmed for the female gender in a multivariate analysis. © Georg Thieme Verlag KG Stuttgart · New York.

  18. Profiles in fibromyalgia: algometry, auditory evoked potentials and clinical characterization of different subtypes.

    Science.gov (United States)

    Triñanes, Yolanda; González-Villar, Alberto; Gómez-Perretta, Claudio; Carrillo-de-la-Peña, María T

    2014-11-01

    The heterogeneity found in fibromyalgia (FM) patients has led to the investigation of disease subgroups, mainly based on clinical features. The aim of this study was to test the hypothesis that clinical FM subgroups are associated with different underlying pathophysiological mechanisms. Sixty-three FM patients were classified in type I or type II, according to the Fibromyalgia Impact Questionnaire (FIQ), and in mild/moderate versus severe FM, according to the severity of three cardinal symptoms considered in the American College of Rheumatology (ACR) 2010 criteria (unrefreshed sleep, cognitive problems and fatigue). To validate the subgroups obtained by these two classifications, we calculated the area under the receiver operating characteristic curves for various clinical variables and for two potential biomarkers of FM: Response to experimental pressure pain (algometry) and the amplitude/intensity slopes of the auditory evoked potentials (AEPs) obtained to stimuli of increasing intensity. The variables that best discriminated type I versus type II were those related to depression, while the indices of clinical or experimental pain (threshold or tolerance) did not significantly differ between them. The variables that best discriminated the mild/moderate versus severe subgroups were those related to the algometry. The AEPs did not allow discrimination among the generated subsets. The FIQ-based classification allows the identification of subgroups that differ in psychological distress, while the index based on the ACR 2010 criteria seems to be useful to characterize the severity of FM mainly based on hyperalgesia. The incorporation of potential biomarkers to generate or validate classification criteria is crucial to advance in the knowledge of FM and in the understanding of pathophysiological pathways.

  19. Non-meagre subgroups of reals disjoint with meagre sets

    Czech Academy of Sciences Publication Activity Database

    Kostana, Ziemowit

    2018-01-01

    Roč. 241, June (2018), s. 11-19 ISSN 0166-8641 Institutional support: RVO:67985840 Keywords : algebraic sum * Baire property * non-meaurable subgroup Subject RIV: BA - General Mathematics OBOR OECD: Pure mathematics Impact factor: 0.377, year: 2016 https://www. science direct.com/ science /article/pii/S0166864118300567

  20. Cohesive subgroup formation : enabling and constraining effects of social capital in strategic technology alliance networks

    NARCIS (Netherlands)

    Duysters, G.M.; Lemmens, C.E.A.V.

    2002-01-01

    In this paper we will examine the role of embeddedness and social capital in the process of cohesive subgroup formation in strategic technology alliance networks. More in particular, we will investigate the social mechanisms that enable and enforce cohesive subgroup formation. We will argue that the

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

    International Nuclear Information System (INIS)

    Jakobi, Annika; Bandurska-Luque, Anna; Stützer, Kristin; Haase, Robert; Löck, Steffen; Wack, Linda-Jacqueline; Mönnich, David; Thorwarth, Daniela

    2015-01-01

    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

  2. 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.

  3. Personalized medicine enrichment design for DHA supplementation clinical trial

    Directory of Open Access Journals (Sweden)

    Yang Lei

    2017-03-01

    Full Text Available Personalized medicine aims to match patient subpopulation to the most beneficial treatment. The purpose of this study is to design a prospective clinical trial in which we hope to achieve the highest level of confirmation in identifying and making treatment recommendations for subgroups, when the risk levels in the control arm can be ordered. This study was motivated by our goal to identify subgroups in a DHA (docosahexaenoic acid supplementation trial to reduce preterm birth (gestational age<37 weeks rate. We performed a meta-analysis to obtain informative prior distributions and simulated operating characteristics to ensure that overall Type I error rate was close to 0.05 in designs with three different models: independent, hierarchical, and dynamic linear models. We performed simulations and sensitivity analysis to examine the subgroup power of models and compared results to a chi-square test. We performed simulations under two hypotheses: a large overall treatment effect and a small overall treatment effect. Within each hypothesis, we designed three different subgroup effects scenarios where resulting subgroup rates are linear, flat, or nonlinear. When the resulting subgroup rates are linear or flat, dynamic linear model appeared to be the most powerful method to identify the subgroups with a treatment effect. It also outperformed other methods when resulting subgroup rates are nonlinear and the overall treatment effect is big. When the resulting subgroup rates are nonlinear and the overall treatment effect is small, hierarchical model and chi-square test did better. Compared to independent and hierarchical models, dynamic linear model tends to be relatively robust and powerful when the control arm has ordinal risk subgroups.

  4. Personalized Medicine Enrichment Design for DHA Supplementation Clinical Trial.

    Science.gov (United States)

    Lei, Yang; Mayo, Matthew S; Carlson, Susan E; Gajewski, Byron J

    2017-03-01

    Personalized medicine aims to match patient subpopulation to the most beneficial treatment. The purpose of this study is to design a prospective clinical trial in which we hope to achieve the highest level of confirmation in identifying and making treatment recommendations for subgroups, when the risk levels in the control arm can be ordered. This study was motivated by our goal to identify subgroups in a DHA (docosahexaenoic acid) supplementation trial to reduce preterm birth (gestational agerate. We performed a meta-analysis to obtain informative prior distributions and simulated operating characteristics to ensure that overall Type I error rate was close to 0.05 in designs with three different models: independent, hierarchical, and dynamic linear models. We performed simulations and sensitivity analysis to examine the subgroup power of models and compared results to a chi-square test. We performed simulations under two hypotheses: a large overall treatment effect and a small overall treatment effect. Within each hypothesis, we designed three different subgroup effects scenarios where resulting subgroup rates are linear, flat, or nonlinear. When the resulting subgroup rates are linear or flat, dynamic linear model appeared to be the most powerful method to identify the subgroups with a treatment effect. It also outperformed other methods when resulting subgroup rates are nonlinear and the overall treatment effect is big. When the resulting subgroup rates are nonlinear and the overall treatment effect is small, hierarchical model and chi-square test did better. Compared to independent and hierarchical models, dynamic linear model tends to be relatively robust and powerful when the control arm has ordinal risk subgroups.

  5. Single-Phase Mail Survey Design for Rare Population Subgroups

    Science.gov (United States)

    Brick, J. Michael; Andrews, William R.; Mathiowetz, Nancy A.

    2016-01-01

    Although using random digit dialing (RDD) telephone samples was the preferred method for conducting surveys of households for many years, declining response and coverage rates have led researchers to explore alternative approaches. The use of address-based sampling (ABS) has been examined for sampling the general population and subgroups, most…

  6. 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

  7. Mineralogy and Petrography of MIL 090001, a Highly Altered CV Chondrite from the Reduced Sub-Group

    Science.gov (United States)

    Keller, Lindsay P.

    2011-01-01

    MIL 090001 is a large (greater than 6 kg) CV chondrite from the reduced subgroup (CV(sub red)) that was recovered during the 2009-2010 ANSMET field season [1]. The CV(sub red) subgroup meteorites retain primitive characteristics and have escaped the Na and Fe meta-somatism that affected the oxidized (CV(sub ox)) subgroups. MIL 090001 is, however, reported to be altered [1], and thus a major objective of this study is to characterize its mineralogy and petrography and the extent of the alteration.

  8. Petrography and geochemistry of iron formations of the Paleoproterozoic Koegas Subgroup, Transvaal Supergroup, Griqualand West, South Africa

    OpenAIRE

    2013-01-01

    M.Sc. (Geology) Nel, B.P. (2013). Petrography and geochemistry of iron formations of the Paleoproterozoic Koegas Subgroup, Transvaal Supergroup, Griqualand West, South Africa. MSc thesis (unpublished), University of Johannesburg, Aucklandpark, pp. 133. The Early Paleoproterozoic Koegas Subgroup comprises a succession of siltstone, mudstone, iron-­‐formation, chert and carbonate rocks that overlies the iron-­‐formations of the Asbestos Hills Subgroup with sharp contact. It is overlain with ...

  9. Distinct characteristics of mandibular bone collagen relative to long bone collagen: relevance to clinical dentistry.

    Science.gov (United States)

    Matsuura, Takashi; Tokutomi, Kentaro; Sasaki, Michiko; Katafuchi, Michitsuna; Mizumachi, Emiri; Sato, Hironobu

    2014-01-01

    Bone undergoes constant remodeling throughout life. The cellular and biochemical mechanisms of bone remodeling vary in a region-specific manner. There are a number of notable differences between the mandible and long bones, including developmental origin, osteogenic potential of mesenchymal stem cells, and the rate of bone turnover. Collagen, the most abundant matrix protein in bone, is responsible for determining the relative strength of particular bones. Posttranslational modifications of collagen, such as intermolecular crosslinking and lysine hydroxylation, are the most essential determinants of bone strength, although the amount of collagen is also important. In comparison to long bones, the mandible has greater collagen content, a lower amount of mature crosslinks, and a lower extent of lysine hydroxylation. The great abundance of immature crosslinks in mandibular collagen suggests that there is a lower rate of cross-link maturation. This means that mandibular collagen is relatively immature and thus more readily undergoes degradation and turnover. The greater rate of remodeling in mandibular collagen likely renders more flexibility to the bone and leaves it more suited to constant exercise. As reviewed here, it is important in clinical dentistry to understand the distinctive features of the bones of the jaw.

  10. Distinct Characteristics of Mandibular Bone Collagen Relative to Long Bone Collagen: Relevance to Clinical Dentistry

    Directory of Open Access Journals (Sweden)

    Takashi Matsuura

    2014-01-01

    Full Text Available Bone undergoes constant remodeling throughout life. The cellular and biochemical mechanisms of bone remodeling vary in a region-specific manner. There are a number of notable differences between the mandible and long bones, including developmental origin, osteogenic potential of mesenchymal stem cells, and the rate of bone turnover. Collagen, the most abundant matrix protein in bone, is responsible for determining the relative strength of particular bones. Posttranslational modifications of collagen, such as intermolecular crosslinking and lysine hydroxylation, are the most essential determinants of bone strength, although the amount of collagen is also important. In comparison to long bones, the mandible has greater collagen content, a lower amount of mature crosslinks, and a lower extent of lysine hydroxylation. The great abundance of immature crosslinks in mandibular collagen suggests that there is a lower rate of cross-link maturation. This means that mandibular collagen is relatively immature and thus more readily undergoes degradation and turnover. The greater rate of remodeling in mandibular collagen likely renders more flexibility to the bone and leaves it more suited to constant exercise. As reviewed here, it is important in clinical dentistry to understand the distinctive features of the bones of the jaw.

  11. Empirically derived pain-patient MMPI subgroups: prediction of treatment outcome.

    Science.gov (United States)

    Moore, J E; Armentrout, D P; Parker, J C; Kivlahan, D R

    1986-02-01

    Fifty-seven male chronic pain patients admitted to an inpatient multimodal pain treatment program at a Midwestern Veterans Administration hospital completed the MMPI, Profile of Mood States (POMS), Tennessee Self-Concept Scale (TSCS), Rathus Assertiveness Schedule (RAS), activity diaries, and an extensive pain questionnaire. All patients were assessed both before and after treatment, and most also were assessed 2-5 months prior to treatment. No significant changes occurred during the baseline period, but significant improvements were evident at posttreatment on most variables: MMPI, POMS, TSCS, RAS, pain severity, sexual functioning, and activity diaries. MMPI subgroup membership, based on a hierarchical cluster analysis in a larger sample, was not predictive of differential treatment outcome. Possible reasons for comparable treatment gains among these subgroups, which previously have been shown to differ on many psychological and behavioral factors, are discussed.

  12. The Florida manatee (Trichechus manatus latirostris) T cell receptor loci exhibit V subgroup synteny and chain-specific evolution

    Science.gov (United States)

    Breaux, Breanna; Hunter, Margaret; Cruz-Schneider, Maria Paula; Sena, Leonardo; Bonde, Robert K.; Criscitiello, Michael F.

    2018-01-01

    The Florida manatee (Trichechus manatus latirostris) has limited diversity in the immunoglobulin heavy chain. We therefore investigated the antigen receptor loci of the other arm of the adaptive immune system: the T cell receptor. Manatees are the first species from Afrotheria, a basal eutherian superorder, to have an in-depth characterization of all T cell receptor loci. By annotating the genome and expressed transcripts, we found that each chain has distinct features that correlates to their individual functions. The genomic organization also plays a role in modulating sequence conservation between species. There were extensive V subgroup synteny blocks in the TRA and TRB loci between T. m. latirostrisand human. Increased genomic locus complexity correlated to increased locus synteny. We also identified evidence for a VHD pseudogene for the first time in a eutherian mammal. These findings emphasize the value of including species within this basal eutherian radiation in comparative studies.

  13. Density character of subgroups of topological groups

    OpenAIRE

    Leiderman, Arkady; Morris, Sidney A.; Tkachenko, Mikhail G.

    2015-01-01

    A subspace Y of a separable metrizable space X is separable, but without X metrizable this is not true even If Y is a closed linear subspace of a topological vector space X. K.H. Hofmann and S.A. Morris introduced the class of pro-Lie groups which consists of projective limits of finite-dimensional Lie groups and proved that it contains all compact groups, locally compact abelian groups and connected locally compact groups and is closed under products and closed subgroups. A topological group...

  14. A note on TI-subgroups of finite groups

    Indian Academy of Sciences (India)

    A kernel and a complement of a quasi-Frobenius group G are the preimages of a kernel and a complement of the Frobenius group G/Z(G), respectively. Lemma 1.2 [1]. A group G is quasi-Frobenius if and only if G possesses a noncentral subgroup H such that H ∩ Hg ≤ Z(G) for all g ∈ G − H. In this case, H is a comple-.

  15. 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 \

  16. Study of Clinical and Genetic Risk Factors for Aspirin-induced Gastric Mucosal Injury

    Directory of Open Access Journals (Sweden)

    Yun Wu

    2016-01-01

    Full Text Available Background: Current knowledge about clinical and genetic risk factors for aspirin-induced gastric mucosal injury is not sufficient to prevent these gastric mucosal lesions. Methods: We recruited aspirin takers as the exposed group and healthy volunteers as the control group. The exposed group was categorized into two subgroups such as subgroup A as gastric mucosal injury diagnosed by gastroscopy, including erosion, ulcer or bleeding of the esophagus, stomach, or duodenum; subgroup B as no injury of the gastric mucosa was detected by gastroscopy. Clinical information was collected, and 53 single nucleotide polymorphisms were evaluated. Results: Among 385 participants, 234 were in the aspirin-exposed group. According to gastroscopy, 82 belonged to subgroup A, 91 belonged to subgroup B, and gastroscopic results of 61 participants were not available. Using the Chi-square test and logistic regression, we found that peptic ulcer history (odds ratio [OR] = 5.924, 95% confidence intervals [CI]: 2.115-16.592, dual anti-platelet medication (OR = 3.443, 95% CI: 1.154-10.271, current Helicobacter pylori infection (OR = 2.242, 95% CI: 1.032-4.870, male gender (OR = 2.211, 95% CI: 1.027-4.760, GG genotype of rs2243086 (OR = 4.516, 95% CI: 1.180-17.278, and AA genotype of rs1330344 (OR = 2.178, 95% CI: 1.016-4.669 were more frequent in subgroup A than subgroup B. In aspirin users who suffered from upper gastrointestinal bleeding, the frequency of the TT genotype of rs2238631 and TT genotype of rs2243100 was higher than in those without upper gastrointestinal bleeding. Conclusions: Peptic ulcer history, dual anti-platelet medication, H. pylori current infection, and male gender were possible clinical risk factors for aspirin-induced gastric mucosal injury. GG genotype of rs2243086 and AA genotype of rs1330344 were possible genetic risk factors. TT genotype of rs2238631 and TT genotype of rs2243100 may be risk factors for upper gastrointestinal bleeding in

  17. Comparison of the effectiveness of three manual physical therapy techniques in a subgroup of patients with low back pain who satisfy a clinical prediction rule: Study protocol of a randomized clinical trial [NCT00257998

    Directory of Open Access Journals (Sweden)

    Childs John D

    2006-02-01

    Full Text Available Abstract Background Recently a clinical prediction rule (CPR has been developed and validated that accurately identifies patients with low back pain (LBP that are likely to benefit from a lumbo-pelvic thrust manipulation. The studies that developed and validated the rule used the identical manipulation procedure. However, recent evidence suggests that different manual therapy techniques may result similar outcomes. The purpose of this study is to investigate the effectiveness of three different manual therapy techniques in a subgroup of patient with low back pain that satisfy the CPR. Methods/Design Consecutive patients with LBP referred to physical therapy clinics in one of four geographical locations who satisfy the CPR will be invited to participate in this randomized clinical trial. Subjects who agree to participate will undergo a standard evaluation and complete a number of patient self-report questionnaires including the Oswestry Disability Index (OSW, which will serve as the primary outcome measure. Following the baseline examination patients will be randomly assigned to receive the lumbopelvic manipulation used in the development of the CPR, an alternative lumbar manipulation technique, or non-thrust lumbar mobilization technique for the first 2 visits. Beginning on visit 3, all 3 groups will receive an identical standard exercise program for 3 visits (visits 3,4,5. Outcomes of interest will be captured by a therapist blind to group assignment at 1 week (3rd visit, 4 weeks (6th visit and at a 6-month follow-up. The primary aim of the study will be tested with analysis of variance (ANOVA using the change in OSW score from baseline to 4-weeks (OSWBaseline – OSW4-weeks as the dependent variable. The independent variable will be treatment with three levels (lumbo-pelvic manipulation, alternative lumbar manipulation, lumbar mobilization. Discussion This trial will be the first to investigate the effectiveness of various manual therapy

  18. International collaboration including patients is essential to develop new therapies for patients with myositis.

    Science.gov (United States)

    Lundberg, Ingrid E; Vencovsky, Jiri

    2017-05-01

    To discuss the needs for international collaborations between investigators in different disciplines working with myositis and with patients with myositis. Recent advances in detection of several myositis-specific autoantibodies that are associated with distinct clinical phenotypes, will enable studies in new well defined clinically homogenous subgroups of myositis This is likely to lead to development of new information on molecular pathogenesis that might be different in different myositis subgroups. Subgrouping patients according to autoantibody profile may also be important to assess outcome, to identify prognostic biomarkers and in clinical trials. As these are rare disorders international collaboration is essential to enrol large enough cohorts of the subgroups. To facilitate such collaboration we have developed a web-based international myositis register, www.euromyositis.eu, which includes validated outcome measures and patient reported outcome measures. This register is to support research but also to support decision-making in the clinic. We welcome investigators to join the Euromyositis register. Myositis is a heterogeneous disorder with varying treatment response and outcome. There is a high unmet need for new therapies which can only be achieved by increased knowledge on molecular disease mechanisms. Subgrouping patients according to autoantibody profile may be a new way forward to get a better understanding on disease mechanisms and to develop novel therapies.

  19. Electroencephalographic characterization of subgroups of children with learning disorders.

    Directory of Open Access Journals (Sweden)

    Milene Roca-Stappung

    Full Text Available Electroencephalographic alterations have been reported in subjects with learning disorders, but there is no consensus on what characterizes their electroencephalogram findings. Our objective was to determine if there were subgroups within a group of scholars with not otherwise specified learning disorders and if they had specific electroencephalographic patterns. Eighty-five subjects (31 female, 8-11 years who scored low in at least two subscales -reading, writing and arithmetic- of the Infant Neuropsychological Evaluation were included. Electroencephalograms were recorded in 19 leads during rest with eyes closed; absolute power was obtained every 0.39 Hz. Three subgroups were formed according to children's performance: Group 1 (G1, higher scores than Group 2 in reading speed and reading and writing accuracy, Group 2 (G2, better performance than G1 in composition and Group 3 (G3, lower scores than Groups 1 and 2 in the three subscales. G3 had higher absolute power in frequencies in the delta and theta range at left frontotemporal sites than G1 and G2. G2 had higher absolute power within alpha frequencies than G3 and G1 at the left occipital site. G3 had higher absolute power in frequencies in the beta range than G1 in parietotemporal areas and than G2 in left frontopolar and temporal sites. G1 had higher absolute power within beta frequencies than G2 in the left frontopolar site. G3 had lower gamma absolute power values than the other groups in the left hemisphere, and gamma activity was higher in G1 than in G2 in frontopolar and temporal areas. This group of children with learning disorders is very heterogeneous. Three subgroups were found with different cognitive profiles, as well as a different electroencephalographic pattern. It is important to consider these differences when planning interventions for children with learning disorders.

  20. Burnside structures of finite subgroups

    International Nuclear Information System (INIS)

    Lysenok, I G

    2007-01-01

    We establish conditions guaranteeing that a group B possesses the following property: there is a number l such that if elements w, x -1 wx,...,x -l+1 wx l-1 of B generate a finite subgroup G then x lies in the normalizer of G. These conditions are of a quite special form. They hold for groups with relations of the form x n =1 which appear as approximating groups for the free Burnside groups B(m,n) of sufficiently large even exponent n. We extract an algebraic assertion which plays an important role in all known approaches to substantial results on the groups B(m,n) of large even exponent, in particular, to proving their infiniteness. The main theorem asserts that when n is divisible by 16, B has the above property with l=6

  1. Time-resolved magnetic resonance angiography (MRA) at 3.0 Tesla for evaluation of hemodynamic characteristics of vascular malformations: description of distinct subgroups

    Energy Technology Data Exchange (ETDEWEB)

    Hammer, Simone; Fellner, Claudia; Wohlgemuth, Walter A. [University Hospital Regensburg, Department of Radiology, Regensburg (Germany); Uller, Wibke [Boston Children' s Hospital and Harvard Medical School, Division of Vascular and Interventional Radiology, Boston, MA (United States); University Hospital Regensburg, Department of Radiology, Regensburg (Germany); Manger, Florentine [University Hospital Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany); Zeman, Florian [University Hospital Regensburg, Center for Clinical Trials, Regensburg (Germany)

    2017-01-15

    Quantitative evaluation of hemodynamic characteristics of arteriovenous and venous malformations using time-resolved magnetic resonance angiography (MRA) at 3.0 Tesla. Time-resolved MRA with interleaved stochastic trajectories (TWIST) at 3.0 Tesla was studied in 83 consecutive patients with venous malformations (VM) and arteriovenous malformations (AVM). Enhancement characteristics were calculated as percentage increase of signal intensity above baseline over time. Maximum percentage signal intensity increase (signal{sub max}), time intervals between onset of arterial enhancement and lesion enhancement (t{sub onset}), and time intervals between beginning of lesion enhancement and maximum percentage of lesion enhancement (t{sub max}) were analyzed. All AVMs showed a high-flow hemodynamic pattern. Two significantly different (p < 0.001) types of venous malformations emerged: VMs with arteriovenous fistulas (AVF) (median signal{sub max} 737 %, IQR [interquartile range] = 511 - 1182 %; median t{sub onset} 5 s, IQR = 5 - 10 s; median t{sub max} 35 s, IQR = 26 - 40 s) and without AVFs (median signal{sub max} 284 %, IQR = 177-432 %; median t{sub onset} 23 s, IQR = 15 - 30 s; median t{sub max} 60 s, IQR = 55 - 75 s). Quantitative evaluation of time-resolved MRA at 3.0 Tesla provides hemodynamic characterization of vascular malformations. VMs can be subclassified into two hemodynamic subgroups due to presence or absence of AVFs. (orig.)

  2. How FDG-PET helps making decision for surgery in various difficult subgroups of temporal lobe epilepsy?

    Energy Technology Data Exchange (ETDEWEB)

    Tepmongkol, S [Division of Nuclear Medicine, Department of Radiology and Division of Neurology, Department of Internal Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok (Thailand); Locharernkul, C [Division of Neurology, Department of Internal Medicine, Faculty of Medicine, Chulalongkorn University and Chulalongkorn Comprehensive Epilepsy Program under the patronage of Professor Doctor HRH Princess Chulabhorn, Bangkok (Thailand); Chaiwatanarat, T; Kingpetch, K; Sirisalipoch, S [Division of Nuclear Medicine, Department of Radiology, Faculty of Medicine, Chulalongkorn University, Bangkok (Thailand); Limotai, C; Loplumlert, J [Chulalongkorn Comprehensive Epilepsy Program under the patronage of Professor Doctor HRH Princess Chulabhorn, Bangkok (Thailand)

    2007-07-01

    Concordant pre-surgical data are the important predictors of good surgical outcome in patients with localization-related epilepsy. Medically intractable temporal lobe epilepsy with hippocampal sclerosis (HS) and concordant pre-surgical data is straightforward and may not need functional imaging. However, in other instances for example, HS with discordant data (HSD), bilateral HS with discordant data (BHSD), temporal lobe epilepsy with dual pathology (DP), non-lesional temporal lobe epilepsy (NL) are the difficult subgroups. In these groups, functional imaging eg. brain perfusion SPECT or brain PET may play a major role for surgical decision making. To our knowledge, there was no previous data in using FDG-PET in different subgroups as mentioned. Only some previous studies in single subgroup without analyzing impact of PET findings on decision-making have been reported. We thus aim to evaluate the usefulness of FDG-PET in these 4 subgroups.

  3. Subgroups of Paediatric Acute Lymphoblastic Leukaemia Might Differ Significantly in Genetic Predisposition to Asparaginase Hypersensitivity.

    Directory of Open Access Journals (Sweden)

    Nóra Kutszegi

    Full Text Available L-asparaginase (ASP is a key element in the treatment of paediatric acute lymphoblastic leukaemia (ALL. However, hypersensitivity reactions (HSRs to ASP are major challenges in paediatric patients. Our aim was to investigate genetic variants that may influence the risk to Escherichia coli-derived ASP hypersensitivity. Sample and clinical data collection was carried out from 576 paediatric ALL patients who were treated according to protocols from the Berlin-Frankfurt-Münster Study Group. A total of 20 single nucleotide polymorphisms (SNPs in GRIA1 and GALNT10 genes were genotyped. Patients with GRIA1 rs4958351 AA/AG genotype showed significantly reduced risk to ASP hypersensitivity compared to patients with GG genotype in the T-cell ALL subgroup (OR = 0.05 (0.01-0.26; p = 4.70E-04, while no such association was found in pre-B-cell ALL. In the medium risk group two SNPs of GRIA1 (rs2055083 and rs707176 were associated significantly with the occurrence of ASP hypersensitivity (OR = 0.21 (0.09-0.53; p = 8.48E-04 and OR = 3.02 (1.36-6.73; p = 6.76E-03, respectively. Evaluating the genders separately, however, the association of rs707176 with ASP HSRs was confined only to females. Our results suggest that genetic variants of GRIA1 might influence the risk to ASP hypersensitivity, but subgroups of patients can differ significantly in this respect.

  4. Gestational weight gain and perinatal outcomes of subgroups of Asian-American women, Texas, 2009.

    Science.gov (United States)

    Cheng, Hsiu-Rong; Walker, Lorraine O; Brown, Adama; Lee, Ju-Young

    2015-01-01

    Asian-American subgroups are heterogeneous, but few studies had addressed differences on gestational weight gain (GWG) and perinatal outcomes related to GWG among this growing and diverse population. The purposes of this study were to examine whether Asian-American women are at higher risk of inadequate or excessive GWG and adverse perinatal outcomes than non-Hispanic White (NH-White) women, and to compare those risks among Asian-American subgroups. This retrospective study included all singleton births to NH-Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnam, and NH-White women documented in 2009 Texas birth certificate data (N = 150,674). Data were analyzed using the χ(2) test, t test, multinomial logistic regression, and binary logistic regression. Chinese women were the reference group in the comparisons among Asian subgroups. Asian women had a higher risk of inadequate GWG and gestational diabetes mellitus (GDM) than NH-White women. No difference in the odds of excessive GWG was found among Asian subgroups, although Japanese women had the highest risk of inadequate GWG. After adjusting for confounders, Korean women had the lowest risk of GDM (adjusted odds ratio [AOR], 0.49), whereas Filipino women and Asian Indian had the highest risks of gestational hypertension (AOR, 2.01 and 1.61), cesarean birth (AOR, 1.44 and 1.39), and low birth weight (AOR, 1.94 and 2.51) compared with Chinese women. These results support the heterogeneity of GWG and perinatal outcomes among Asian-American subgroups. The risks of adverse perinatal outcomes should be carefully evaluated separately among Asian-American subpopulations. Copyright © 2015 Jacobs Institute of Women's Health. Published by Elsevier Inc. All rights reserved.

  5. 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.

  6. Subgroup analyses of the effectiveness of oral glucosamine for knee and hip osteoarthritis: a systematic review and individual patient data meta-analysis from the OA trial bank.

    Science.gov (United States)

    Runhaar, Jos; Rozendaal, Rianne M; van Middelkoop, Marienke; Bijlsma, Hans J W; Doherty, Michael; Dziedzic, Krysia S; Lohmander, L Stefan; McAlindon, Timothy; Zhang, Weiya; Bierma Zeinstra, Sita

    2017-11-01

    To evaluate the effectiveness of oral glucosamine in subgroups of people with hip or knee osteoarthritis (OA) based on baseline pain severity, body mass index (BMI), sex, structural abnormalities and presence of inflammation using individual patient data. After a systematic search of the literature and clinical trial registries, all randomised controlled trials (RCTs) evaluating the effect of any oral glucosamine substance in patients with clinically or radiographically defined hip or knee OA were contacted. As a minimum, pain, age, sex and BMI at baseline and pain as an outcome measure needed to be assessed. Of 21 eligible studies, six (n=1663) shared their trial data with the OA Trial Bank. Five trials (all independent of industry, n=1625) compared glucosamine with placebo, representing 55% of the total number of participants in all published placebo-controlled RCTs. Glucosamine was no better than placebo for pain or function at short (3 months) and long-term (24 months) follow-up. Glucosamine was also no better than placebo among the predefined subgroups. Stratification for knee OA and type of glucosamine did not alter these results. Although proposed and debated for several years, open trial data are not widely made available for studies of glucosamine for OA, especially those sponsored by industry. Currently, there is no good evidence to support the use of glucosamine for hip or knee OA and an absence of evidence to support specific consideration of glucosamine for any clinically relevant OA subgroup according to baseline pain severity, BMI, sex, structural abnormalities or presence of inflammation. © 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.

  7. Sexual and Gender Minority Youth Suicide: Understanding Subgroup Differences to Inform Interventions.

    Science.gov (United States)

    O'Brien, Kimberly H McManama; Putney, Jennifer M; Hebert, Nicholas W; Falk, Amy M; Aguinaldo, Laika D

    2016-08-01

    Sexual and gender minority (SGM) youth are disproportionately affected by suicide-related thoughts and behaviors relative to their heterosexual and/or non-transgender peers. Theory and empirical evidence suggest that there are unique factors that contribute to this elevated risk, with distinguishable differences among SGM subgroups. Although SGM youth suicide prevention research is in its nascence, initial findings indicate that interventions which focus on family support and acceptance may be beneficial. It is critical that we develop and test tailored interventions for SGM youth at risk for suicide, with specific attention to subgroup differences and reductions in suicide-related thoughts and behaviors as outcomes.

  8. 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.

  9. The Clinical Features of Myositis-Associated Autoantibodies: a Review.

    Science.gov (United States)

    Gunawardena, Harsha

    2017-02-01

    The idiopathic inflammatory myopathies (IIM) are a group of autoimmune diseases traditionally defined by clinical manifestations including skeletal muscle weakness, skin rashes, elevated skeletal muscle enzymes, and neurophysiological and/or histological evidence of muscle inflammation. Patients with myositis overlap can develop other features including parenchymal lung disease, inflammatory arthritis, gastrointestinal manifestations and marked constitutional symptoms. Although patients may be diagnosed as having polymyositis (PM) or dermatomyositis (DM) under the IIM spectrum, it is quite clear that disease course between subgroups of patients is different. For example, interstitial lung disease may predominate in some, whereas cutaneous complications, cancer risk, or severe refractory myopathy may be a significant feature in others. Therefore, tools that facilitate diagnosis and indicate which patients require more detailed investigation for disease complications are invaluable in clinical practice. The expanding field of autoantibodies (autoAbs) associated with connective tissue disease (CTD)-myositis overlap has generated considerable interest over the last few years. Using an immunological diagnostic approach, this group of heterogeneous conditions can be separated into a number of distinct clinical phenotypes. Rather than diagnose a patient as simply having PM, DM or overlap CTD, we can define syndromes to differentiate disease subsets that emphasise clinical outcomes and guide management. There are now over 15 CTD-myositis overlap autoAbs found in patients with a range of clinical manifestations including interstitial pneumonia, cutaneous disease, cancer-associated myositis and autoimmune-mediated necrotising myopathy. This review describes their diagnostic utility, potential role in disease monitoring and response to treatment. In the future, routine use of these autoAb will allow a stratified approach to managing this complex set of conditions.

  10. A Newborn Case of “c” Subgroup Mismatch Presenting with Severe Hemolysis and Anemia

    OpenAIRE

    Ezgi Yangın Ergon; Senem Alkan Özdemir; Rüya Çolak; Kıymet Çelik; Özgür Olukman; Şebnem Çalkavur

    2017-01-01

    Hemolysis and jaundice related to Rh incompatibility in the neonatal period has decreased substantially due to the widespread use of anti-D gammaglobulin in recent years. Nevertheless, the rate of subgroup mismatch in the etiology of hemolytic diseases of the newborn has increased significantly. In this article an 8-day-old newborn infant with “c” subgroup incompatibility and presenting with severe anemia, in whom hemolysis could be controlled with intravenous immunoglobulin infusion and subg...

  11. Auditing the use and assessing the clinical utility of microscopy as a point-of-care test for Neisseria gonorrhoeae in a Sexual Health clinic.

    Science.gov (United States)

    Mensforth, Sarah; Thorley, Nicola; Radcliffe, Keith

    2018-02-01

    We assessed whether urethral microscopy was performed as per clinic protocol for male clinic attendees reporting contact with Neisseria gonorrhoeae (GC), urethral symptoms or given a diagnosis of epididymo-orchitis (EO) over a 12-month period (9732 patients). Prevalence of gonorrhoea in the contacts, urethral symptoms and EO groups was 50, 12.7 and 1.6%, respectively. Microscopy was performed reliably for contacts (96%), those with discharge/dysuria with evidence of urethritis on examination (98%), but not those with EO (43%). We explored the clinical utility of microscopy as a point-of-care test for identifying urethral GC in each subgroup, using the APTIMA Combo 2 CT/GC nucleic acid amplification test as the comparator (1710 patients). Sensitivity of microscopy for each subgroup was good; there was no statistical difference between subgroup sensitivity using Fisher's exact test. Microscopy is valuable to ensure prompt diagnosis and contact tracing. All GC contacts were treated 'epidemiologically'; however, half of GC contacts did not have GC. Microscopy identified the majority of GC cases, including amongst contacts (71% of heterosexual contacts, 66% of contacts reporting sex with men). We propose that epidemiological treatment for GC contacts should be reconsidered on the grounds of antibiotic stewardship, favouring use of microscopy to guide treatment decisions.

  12. Differential response of Acidobacteria subgroups to forest-to-pasture conversion and their biogeographic patterns in the western Brazilian Amazon

    Directory of Open Access Journals (Sweden)

    Acacio Aparecido Navarrete

    2015-12-01

    Full Text Available Members of the phylum Acidobacteria are among the most abundant soil bacteria on Earth, but little is known about their response to environmental changes. We asked how the relative abundance and biogeographic patterning of this phylum and its subgroups responded to forest-to-pasture conversion in soils of the western Brazilian Amazon. Pyrosequencing of 16S rRNA genes was employed to assess the abundance and composition of the Acidobacteria community across 54 soil samples taken using a spatially nested sampling scheme at the landscape level. Numerically, Acidobacteria represented 20% of the total bacterial community in forest soils and 11% in pasture soils. Overall, 15 different Acidobacteria subgroups of the current 26 subgroups were detected, with Acidobacteria subgroups 1, 3, 5, and 6 accounting together for 87% of the total Acidobacteria community in forest soils and 75% in pasture soils. Concomitant with changes in soil chemistry after forest-to-pasture conversion - particularly an increase in properties linked to soil acidity and nutrient availability - we observed an increase in the relative abundances of Acidobacteria subgroups 4, 10, 17, and 18, and a decrease in the relative abundances of other Acidobacteria subgroups in pasture relative to forest soils. The composition of the total Acidobacteria community as well as the most abundant Acidobacteria subgroups (1, 3, 5, and 6 was significantly more similar in composition across space in pasture soils than in forest soils. These results suggest that preponderant responses of Acidobacteria subgroups, especially subgroups 1, 3, 4, 5, and 6, to forest-to-pasture conversion effects in soils could be used to define management-indicators of agricultural practices in the Amazon Basin. These acidobacterial responses are at least in part through alterations on acidity- and nutrient-related properties of the Amazon soils.

  13. Differential Response of Acidobacteria Subgroups to Forest-to-Pasture Conversion and Their Biogeographic Patterns in the Western Brazilian Amazon

    Science.gov (United States)

    Navarrete, Acacio A.; Venturini, Andressa M.; Meyer, Kyle M.; Klein, Ann M.; Tiedje, James M.; Bohannan, Brendan J. M.; Nüsslein, Klaus; Tsai, Siu M.; Rodrigues, Jorge L. M.

    2015-01-01

    Members of the phylum Acidobacteria are among the most abundant soil bacteria on Earth, but little is known about their response to environmental changes. We asked how the relative abundance and biogeographic patterning of this phylum and its subgroups responded to forest-to-pasture conversion in soils of the western Brazilian Amazon. Pyrosequencing of 16S rRNA genes was employed to assess the abundance and composition of the Acidobacteria community across 54 soil samples taken using a spatially nested sampling scheme at the landscape level. Numerically, Acidobacteria represented 20% of the total bacterial community in forest soils and 11% in pasture soils. Overall, 15 different Acidobacteria subgroups of the current 26 subgroups were detected, with Acidobacteria subgroups 1, 3, 5, and 6 accounting together for 87% of the total Acidobacteria community in forest soils and 75% in pasture soils. Concomitant with changes in soil chemistry after forest-to-pasture conversion—particularly an increase in properties linked to soil acidity and nutrient availability—we observed an increase in the relative abundances of Acidobacteria subgroups 4, 10, 17, and 18, and a decrease in the relative abundances of other Acidobacteria subgroups in pasture relative to forest soils. The composition of the total Acidobacteria community as well as the most abundant Acidobacteria subgroups (1, 3, 5, and 6) was significantly more similar in composition across space in pasture soils than in forest soils. These results suggest that preponderant responses of Acidobacteria subgroups, especially subgroups 1, 3, 4, 5, and 6, to forest-to-pasture conversion effects in soils could be used to define management-indicators of agricultural practices in the Amazon Basin. These acidobacterial responses are at least in part through alterations on acidity- and nutrient-related properties of the Amazon soils. PMID:26733981

  14. A multisite study of the clinical diagnosis of different autism spectrum disorders.

    Science.gov (United States)

    Lord, Catherine; Petkova, Eva; Hus, Vanessa; Gan, Weijin; Lu, Feihan; Martin, Donna M; Ousley, Opal; Guy, Lisa; Bernier, Raphael; Gerdts, Jennifer; Algermissen, Molly; Whitaker, Agnes; Sutcliffe, James S; Warren, Zachary; Klin, Ami; Saulnier, Celine; Hanson, Ellen; Hundley, Rachel; Piggot, Judith; Fombonne, Eric; Steiman, Mandy; Miles, Judith; Kanne, Stephen M; Goin-Kochel, Robin P; Peters, Sarika U; Cook, Edwin H; Guter, Stephen; Tjernagel, Jennifer; Green-Snyder, Lee Anne; Bishop, Somer; Esler, Amy; Gotham, Katherine; Luyster, Rhiannon; Miller, Fiona; Olson, Jennifer; Richler, Jennifer; Risi, Susan

    2012-03-01

    Best-estimate clinical diagnoses of specific autism spectrum disorders (autistic disorder, pervasive developmental disorder-not otherwise specified, and Asperger syndrome) have been used as the diagnostic gold standard, even when information from standardized instruments is available. To determine whether the relationships between behavioral phenotypes and clinical diagnoses of different autism spectrum disorders vary across 12 university-based sites. Multisite observational study collecting clinical phenotype data (diagnostic, developmental, and demographic) for genetic research. Classification trees were used to identify characteristics that predicted diagnosis across and within sites. Participants were recruited through 12 university-based autism service providers into a genetic study of autism. A total of 2102 probands (1814 male probands) between 4 and 18 years of age (mean [SD] age, 8.93 [3.5] years) who met autism spectrum criteria on the Autism Diagnostic Interview-Revised and the Autism Diagnostic Observation Schedule and who had a clinical diagnosis of an autism spectrum disorder. Best-estimate clinical diagnoses predicted by standardized scores from diagnostic, cognitive, and behavioral measures. Although distributions of scores on standardized measures were similar across sites, significant site differences emerged in best-estimate clinical diagnoses of specific autism spectrum disorders. Relationships between clinical diagnoses and standardized scores, particularly verbal IQ, language level, and core diagnostic features, varied across sites in weighting of information and cutoffs. Clinical distinctions among categorical diagnostic subtypes of autism spectrum disorders were not reliable even across sites with well-documented fidelity using standardized diagnostic instruments. Results support the move from existing subgroupings of autism spectrum disorders to dimensional descriptions of core features of social affect and fixated, repetitive behaviors

  15. PROGNOSTIC SIGNIFICANCE OF CLINICAL, HISTOPATHOLOGICAL, AND MOLECULAR CHARACTERISTICS OF MEDULLOBLASTOMAS IN THE PROSPECTIVE HIT2000 MULTICENTER CLINICAL TRIAL COHORT

    Science.gov (United States)

    Pietsch, Torsten; Schmidt, Rene; Remke, Marc; Korshunov, Andrey; Hovestadt, Volker; Jones, David TW; Felsberg, Jörg; Kaulich, Kerstin; Goschzik, Tobias; Kool, Marcel; Northcott, Paul A.; von Hoff, Katja; von Bueren, André O.; Friedrich, Carsten; Skladny, Heyko; Fleischhack, Gudrun; Taylor, Michael D.; Cremer, Friedrich; Lichter, Peter; Faldum, Andreas; Reifenberger, Guido; Rutkowski, Stefan; Pfister, Stefan M.

    2014-01-01

    BACKGROUND: This study aimed to prospectively evaluate clinical, histopathological and molecular variables for outcome prediction in medulloblastoma patients. METHODS: Patients from the HIT2000 cooperative clinical trial were prospectively enrolled based on the availability of sufficient tumor material and complete clinical information. This revealed a cohort of 184 patients (median age 7.6 years), which was randomly split at a 2:1 ratio into a training (n = 127), and a validation (n = 57) dataset. All samples were subjected to thorough histopathological investigation, CTNNB1 mutation analysis, quantitative PCR, MLPA and FISH analyses for cytogenetic variables, and methylome analysis. RESULTS: By univariable analysis, clinical factors (M-stage), histopathological variables (large cell component, endothelial proliferation, synaptophysin pattern), and molecular features (chromosome 6q status, MYC amplification, TOP2A copy-number, subgrouping) were found to be prognostic. Molecular consensus subgrouping (WNT, SHH, Group 3, Group 4) was validated as an independent feature to stratify patients into different risk groups. When comparing methods for the identification of WNT-driven medulloblastoma, this study identified CTNNB1 sequencing and methylation profiling to most reliably identify these patients. After removing patients with particularly favorable (CTNNB1 mutation, extensive nodularity) or unfavorable (MYC amplification) markers, a risk score for the remaining “intermediate molecular risk” population dependent on age, M-stage, pattern of synaptophysin expression, and MYCN copy-number status was identified and validated, with speckled synaptophysin expression indicating worse outcome. CONCLUSIONS: Methylation subgrouping and CTNNB1 mutation status represent robust tools for the risk-stratification of medulloblastoma. A simple clinico-pathological risk score for “intermediate molecular risk” patients was identified, which deserves further validation

  16. OMERACT-based fibromyalgia symptom subgroups: an exploratory cluster analysis.

    Science.gov (United States)

    Vincent, Ann; Hoskin, Tanya L; Whipple, Mary O; Clauw, Daniel J; Barton, Debra L; Benzo, Roberto P; Williams, David A

    2014-10-16

    The aim of this study was to identify subsets of patients with fibromyalgia with similar symptom profiles using the Outcome Measures in Rheumatology (OMERACT) core symptom domains. Female patients with a diagnosis of fibromyalgia and currently meeting fibromyalgia research survey criteria completed the Brief Pain Inventory, the 30-item Profile of Mood States, the Medical Outcomes Sleep Scale, the Multidimensional Fatigue Inventory, the Multiple Ability Self-Report Questionnaire, the Fibromyalgia Impact Questionnaire-Revised (FIQ-R) and the Short Form-36 between 1 June 2011 and 31 October 2011. Hierarchical agglomerative clustering was used to identify subgroups of patients with similar symptom profiles. To validate the results from this sample, hierarchical agglomerative clustering was repeated in an external sample of female patients with fibromyalgia with similar inclusion criteria. A total of 581 females with a mean age of 55.1 (range, 20.1 to 90.2) years were included. A four-cluster solution best fit the data, and each clustering variable differed significantly (P FIQ-R total scores (P = 0.0004)). In our study, we incorporated core OMERACT symptom domains, which allowed for clustering based on a comprehensive symptom profile. Although our exploratory cluster solution needs confirmation in a longitudinal study, this approach could provide a rationale to support the study of individualized clinical evaluation and intervention.

  17. Distinctive pattern of expression of spermatogenic molecular markers in testes of azoospermic men with non-mosaic Klinefelter syndrome.

    Science.gov (United States)

    Kleiman, Sandra E; Yogev, Leah; Lehavi, Ofer; Yavetz, Haim; Hauser, Ron

    2016-06-01

    Mature sperm cells can be found in testicular specimens extracted from azoospermic men with non-mosaic Klinefelter syndrome (KS). The present study evaluates the expression of various known molecular markers of spermatogenesis in a population of men with KS and assesses the ability of those markers to predict spermatogenesis. Two groups of men with non-obstructive azoospermia who underwent testicular sperm-retrieval procedures were included in the study: 31 had non-mosaic KS (KS group) and 91 had normal karyotype (NK group). Each group was subdivided into mixed atrophy (containing some mature sperm cells) or Sertoli cell only syndrome according to testicular histology and cytology observations. Semi-quantitative histological morphometric analysis (interstitial hyperplasia and hyalinization, tubules with cells and abnormal thickness of the basement membrane) and expression of spermatogenetic markers (DAZ, RBM, BOLL, and CDY1) were evaluated and compared among those subgroups. Clear differences in the histological morphometry and spermatogenetic marker expression were noted between the KS and NK groups. There was a significant difference in the expression of spermatogenetic markers between the subgroups of the NK group (as expected), while no difference could be discerned between the two subgroups in the KS group. We conclude that molecular spermatogenetic markers have a pattern of expression in men with KS that is distinctively different from that of men with NK, and that it precludes and limits their use for predicting spermatogenesis in the former. It is suggested that this difference might be due to the specific highly abnormal histological morphometric parameters in KS specimens.

  18. Different letter-processing strategies in diagnostic subgroups of developmental dyslexia.

    Science.gov (United States)

    Lachmann, Thomas; van Leeuwen, Cees

    2008-07-01

    Normally reading adults (N = 15) and primary school children (N = 24) and two diagnostic subgroups of children with developmental dyslexia (N = 21)-all native German speakers-performed a successive same-different task with pairs of letters and nonletters (pseudoletters or geometrical shapes). The first item of a pair was always presented on its own, and the second either on its own or surrounded by a congruent or incongruent nontarget shape. Adults showed congruence effects with nonletters but not with letters, and children with both types of stimuli. Frequent-word reading-impaired dyslexics (N = 11) in addition showed dramatically slower overall reaction times. Nonword reading-impaired dyslexics (N = 10) showed congruence effects with nonletters but negative congruence effects with letters. The results support the notion that normal readers have established a special visual processing strategy for letters. Processing speed rather than reading expertise seems crucial for this strategy to emerge. The contrasting effects between subgroups of dyslexics reveal specific underlying deficits.

  19. Clinical examination, spondylolysis and adolescent athletes.

    Science.gov (United States)

    Sundell, C-G; Jonsson, H; Ådin, L; Larsén, K H

    2013-03-01

    Symptomatic spondylolysis is a stress reaction caused by microtrauma during physical exercise, an imaging diagnostic subgroup of Adolescent Low Back Pain (ALBP), found in adolescent athletes. Early diagnosis increases the possibility of healing. Thus, it is important to divide ALBP into subgroups. The aim of this study was to evaluate clinical tests that can distinguish symptomatic spondylolysis from other forms of ALBP in order to facilitate early referral for diagnostic imaging. The investigation subjects were a prospective case series with a control group, 25 subjects with ALBP and 13 subjects that had no history of LBP. The 2 groups were examined using the same clinical protocol. MRI of the whole lumbar spine was performed in both the case and control groups and CT investigations of the L4 and L5 vertebrae were performed in the case group. Significant differences between the 2 groups were found in 8 of our clinical tests. No clinical test, alone or in combination, could distinguish between spondylolysis and other forms of ALBP. As 88% of the subjects in the case group had MRI findings and almost 50% had spondylolysis, MRI should be performed at an early age in young athletes with ALBP. © Georg Thieme Verlag KG Stuttgart · New York.

  20. Do clinically anxious children cluster according to their expression of factors that maintain child anxiety?

    Science.gov (United States)

    Pearcey, Samantha; Alkozei, Anna; Chakrabarti, Bhismadev; Dodd, Helen; Murayama, Kou; Stuijfzand, Suzannah; Creswell, Cathy

    2018-03-15

    Cognitive Behaviour Therapy (CBT) is an effective treatment for childhood anxiety disorders, yet a significant proportion of children do not benefit from it. CBT for child anxiety disorders typically includes a range of strategies that may not all be applicable for all affected children. This study explored whether there are distinct subgroups of children with anxiety disorders who are characterized by their responses to measures of the key mechanisms that are targeted in CBT (i.e. interpretation bias, perceived control, avoidance, physiological arousal, and social communication). 379 clinically anxious children (7-12 years) provided indices of threat interpretation, perceived control, expected negative emotions and avoidance and measures of heart rate recovery following a speech task. Parents also reported on their children's social communication difficulties using the Social Communication Questionnaire (SCQ). Latent profile analysis identified three groups, reflecting (i) 'Typically anxious' (the majority of the sample and more likely to have Generalized anxiety disorder); (ii) 'social difficulties' (characterized by high SCQ and more likely to have social anxiety disorder and be male); (iii) 'Avoidant' (characterized by low threat interpretation but high avoidance and low perceived control). Some measures may have been influenced by confounding variables (e.g. physical variability in heart rate recovery). Sample characteristics of the group may limit the generalizability of the results. Clinically anxious children appear to fall in to subgroups that might benefit from more targeted treatments that focus on specific maintenance factors. Treatment studies are now required to establish whether this approach would lead to more effective and efficient treatments. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  1. A generalized Frattini subgroup of a finite group

    Directory of Open Access Journals (Sweden)

    Prabir Bhattacharya

    1989-01-01

    Full Text Available For a finite group G and an arbitrary prime p, let SP(G denote the intersection of all maximal subgroups M of G such that [G:M] is both composite and not divisible by p; if no such M exists we set SP(G = G. Some properties of G are considered involving SP(G. In particular, we obtain a characterization of G when each M in the definition of SP(G is nilpotent.

  2. Common and distinct brain networks underlying panic and social anxiety disorders.

    Science.gov (United States)

    Kim, Yong-Ku; Yoon, Ho-Kyoung

    2018-01-03

    Although panic disorder (PD) and phobic disorders are independent anxiety disorders with distinct sets of diagnostic criteria, there is a high level of overlap between them in terms of pathogenesis and neural underpinnings. Functional connectivity research using resting-state functional magnetic resonance imaging (rsfMRI) shows great potential in identifying the similarities and differences between PD and phobias. Understanding common and distinct networks between PD and phobic disorders is critical for identifying both specific and general neural characteristics of these disorders. We review recent rsfMRI studies and explore the clinical relevance of resting-state functional connectivity (rsFC) in PD and phobias. Although findings differ between studies, there are some meaningful, consistent findings. Social anxiety disorder (SAD) and PD share common default mode network alterations. Alterations within the sensorimotor network are observed primarily in PD. Increased connectivity in the salience network is consistently reported in SAD. This review supports hypotheses that PD and phobic disorders share common rsFC abnormalities and that the different clinical phenotypes between the disorders come from distinct brain functional network alterations. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Long-term future risk of severe exacerbations: Distinct 5-year trajectories of problematic asthma.

    Science.gov (United States)

    Yii, A C A; Tan, J H Y; Lapperre, T S; Chan, A K W; Low, S Y; Ong, T H; Tan, K L; Chotirmall, S H; Sterk, P J; Koh, M S

    2017-09-01

    Assessing future risk of exacerbations is an important component of asthma management. Existing studies have investigated short- but not long-term risk. Problematic asthma patients with unfavorable long-term disease trajectory and persistently frequent severe exacerbations need to be identified early to guide treatment. To identify distinct trajectories of severe exacerbation rates among "problematic asthma" patients and develop a risk score to predict the most unfavorable trajectory. Severe exacerbation rates over five years for 177 "problematic asthma" patients presenting to a specialist asthma clinic were tracked. Distinct trajectories of severe exacerbation rates were identified using group-based trajectory modeling. Baseline predictors of trajectory were identified and used to develop a clinical risk score for predicting the most unfavorable trajectory. Three distinct trajectories were found: 58.5% had rare intermittent severe exacerbations ("infrequent"), 32.0% had frequent severe exacerbations at baseline but improved subsequently ("nonpersistently frequent"), and 9.5% exhibited persistently frequent severe exacerbations, with the highest incidence of near-fatal asthma ("persistently frequent"). A clinical risk score composed of ≥2 severe exacerbations in the past year (+2 points), history of near-fatal asthma (+1 point), body mass index ≥25kg/m 2 (+1 point), obstructive sleep apnea (+1 point), gastroesophageal reflux (+1 point), and depression (+1 point) was predictive of the "persistently frequent" trajectory (area under the receiver operating characteristic curve: 0.84, sensitivity 72.2%, specificity 81.1% using cutoff ≥3 points). The trajectories and clinical risk score had excellent performance in an independent validation cohort. Patients with problematic asthma follow distinct illness trajectories over a period of five years. We have derived and validated a clinical risk score that accurately identifies patients who will have persistently

  4. Glioma CpG island methylator phenotype (G-CIMP): biological and clinical implications.

    Science.gov (United States)

    Malta, Tathiane M; de Souza, Camila F; Sabedot, Thais S; Silva, Tiago C; Mosella, Maritza S; Kalkanis, Steven N; Snyder, James; Castro, Ana Valeria B; Noushmehr, Houtan

    2018-04-09

    Gliomas are a heterogeneous group of brain tumors with distinct biological and clinical properties. Despite advances in surgical techniques and clinical regimens, treatment of high-grade glioma remains challenging and carries dismal rates of therapeutic success and overall survival. Challenges include the molecular complexity of gliomas, as well as inconsistencies in histopathological grading, resulting in an inaccurate prediction of disease progression and failure in the use of standard therapy. The updated 2016 World Health Organization (WHO) classification of tumors of the central nervous system reflects a refinement of tumor diagnostics by integrating the genotypic and phenotypic features, thereby narrowing the defined subgroups. The new classification recommends molecular diagnosis of isocitrate dehydrogenase (IDH) mutational status in gliomas. IDH-mutant gliomas manifest the cytosine-phosphate-guanine (CpG) island methylator phenotype (G-CIMP). Notably, the recent identification of clinically relevant subsets of G-CIMP tumors (G-CIMP-high and G-CIMP-low) provides a further refinement in glioma classification that is independent of grade and histology. This scheme may be useful for predicting patient outcome and may be translated into effective therapeutic strategies tailored to each patient. In this review, we highlight the evolution of our understanding of the G-CIMP subsets and how recent advances in characterizing the genome and epigenome of gliomas may influence future basic and translational research.

  5. K-theory for discrete subgroups of the Lorentz groups

    International Nuclear Information System (INIS)

    Schwalbe, D.A.

    1986-01-01

    In the thesis, a conjecture on the structure of the topological K theory groups associated to an action of a discrete group on a manifold is verified in the special case when the group is a closed discrete subgroup of a Lorentz group. The K theory is the topological K theory of the reduced crossed product C algebra arising from the action of a countable discrete group acting by diffeomorphisms on a smooth, Hausdorf, and second and countable manifold. The proof uses the geometric K theory of Baum and Connes. In this situation, they have developed a geometrically realized K theory which they conjecture to be isomorphic to the analytic K theory. Work of Kasparov is used to show the geometric K groups and the analytic K groups are isomorphic for actions of the Lorentz groups on a manifold. Work of Marc Rieffel on Morita equivalence of C/sup */ algebras, shows the analytic K theory for a closed discrete subgroup of a Lie group acting on a manifold is isomorphic to the K theory of the Lie group itself, acting on an induced manifold

  6. Do craniopharyngioma molecular signatures correlate with clinical characteristics?

    Science.gov (United States)

    Omay, Sacit Bulent; Chen, Yu-Ning; Almeida, Joao Paulo; Ruiz-Treviño, Armando Saul; Boockvar, John A; Stieg, Philip E; Greenfield, Jeffrey P; Souweidane, Mark M; Kacker, Ashutosh; Pisapia, David J; Anand, Vijay K; Schwartz, Theodore H

    2018-05-01

    OBJECTIVE Exome sequencing studies have recently demonstrated that papillary craniopharyngiomas (PCPs) and adamantinomatous craniopharyngiomas (ACPs) have distinct genetic origins, each primarily driven by mutually exclusive alterations: either BRAF ( V600E), observed in 95% of PCPs, or CTNNB1, observed in 75%-96% of ACPs. How the presence of these molecular signatures, or their absence, correlates with clinical, radiographic, and outcome variables is unknown. METHODS The pathology records for patients who underwent surgery for craniopharyngiomas between May 2000 and March 2015 at Weill Cornell Medical College were reviewed. Craniopharyngiomas were identified and classified as PCP or ACP. Patients were placed into 1 of 3 groups based on their genomic mutations: BRAF mutation only, CTNNB1 mutation only, and tumors with neither of these mutations detected (not detected [ND]). Demographic, radiological, and clinical variables were collected, and their correlation with each genomic group was tested. RESULTS Histology correlated strongly with mutation group. All BRAF tumors with mutations were PCPs, and all CTNNB1 with mutations and ND tumors were ACPs. Preoperative and postoperative clinical symptoms and radiographic features did not correlate with any mutation group. There was a statistically significant relationship (p = 0.0323) between the age group (pediatric vs adult) and the mutation groups. The ND group tumors were more likely to involve the sella (p = 0.0065). CONCLUSIONS The mutation signature in craniopharyngioma is highly predictive of histology. The subgroup of tumors in which these 2 mutations are not detected is more likely to occur in children, be located in the sella, and be of ACP histology.

  7. Clinical heterogeneity in newly diagnosed Parkinson's disease

    NARCIS (Netherlands)

    Post, Bart; Speelman, Johannes D.; de Haan, Rob J.

    2008-01-01

    OBJECTIVE: To determine clinical heterogeneity in newly diagnosed Parkinson's disease using cluster analysis and to describe the subgroups in terms of impairment, disability, perceived quality of life, and use of dopaminergic therapy. METHODS: We conducted a k-means cluster analysis in a prospective

  8. Efficacy and safety of palbociclib in combination with letrozole as first-line treatment of ER-positive, HER2-negative, advanced breast cancer: expanded analyses of subgroups from the randomized pivotal trial PALOMA-1/TRIO-18.

    Science.gov (United States)

    Finn, Richard S; Crown, John P; Ettl, Johannes; Schmidt, Marcus; Bondarenko, Igor M; Lang, Istvan; Pinter, Tamas; Boer, Katalin; Patel, Ravindranath; Randolph, Sophia; Kim, Sindy T; Huang, Xin; Schnell, Patrick; Nadanaciva, Sashi; Bartlett, Cynthia Huang; Slamon, Dennis J

    2016-06-28

    Palbociclib is an oral small-molecule inhibitor of cyclin-dependent kinases 4 and 6. In the randomized, open-label, phase II PALOMA-1/TRIO-18 trial, palbociclib in combination with letrozole improved progression-free survival (PFS) compared with letrozole alone as first-line treatment of estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, advanced breast cancer (20.2 months versus 10.2 months; hazard ratio (HR) = 0.488, 95 % confidence interval (CI) 0.319-0.748; one-sided p = 0.0004). Grade 3-4 neutropenia was the most common adverse event (AE) in the palbociclib + letrozole arm. We now present efficacy and safety analyses based on several specific patient and tumor characteristics, and present in detail the clinical patterns of neutropenia observed in the palbociclib + letrozole arm of the overall safety population. Postmenopausal women (n = 165) with ER+, HER2-negative, advanced breast cancer who had not received any systemic treatment for their advanced disease were randomized 1:1 to receive either palbociclib in combination with letrozole or letrozole alone. Treatment continued until disease progression, unacceptable toxicity, consent withdrawal, or death. The primary endpoint was PFS. We now analyze the difference in PFS for the treatment populations by subgroups, including age, histological type, history of prior neoadjuvant/adjuvant systemic treatment, and sites of distant metastasis, using the Kaplan-Meier method. HR and 95 % CI are derived from a Cox proportional hazards regression model. A clinically meaningful improvement in median PFS and clinical benefit response (CBR) rate was seen with palbociclib + letrozole in every subgroup evaluated. Grade 3-4 neutropenia was the most common AE with palbociclib + letrozole in all subgroups. Analysis of the frequency of neutropenia by grade during the first six cycles of treatment showed that there was a downward trend in Grade 3-4 neutropenia

  9. Characterization of toxin complex gene clusters and insect toxicity of bacteria representing four subgroups of Pseudomonas fluorescens

    Science.gov (United States)

    Ten strains representing four lineages of Pseudomonas (P. chlororaphis, P. corrugata, P. koreensis, and P. fluorescens subgroups) were evaluated for toxicity to the tobacco hornworm Manduca sexta and the fruit fly Drosophila melanogaster. The three strains within the P. chlororaphis subgroup exhibi...

  10. Clinical proteomics

    DEFF Research Database (Denmark)

    Albrethsen, Jakob; Frederiksen, Hanne; Johannsen, Trine Holm

    2018-01-01

    Clinical proteomics aims to deliver cost-effective multiplexing of potentially hundreds of diagnostic proteins, including distinct protein isoforms. The analytical strategy known as targeted proteomics is particularly promising because it is compatible with robust mass spectrometry (MS)-platforms...... standards and calibrants. The present challenge is to examine if targeted proteomics of IGF-I can truly measure up to the routine performance that must be expected from a clinical testing platform.......Clinical proteomics aims to deliver cost-effective multiplexing of potentially hundreds of diagnostic proteins, including distinct protein isoforms. The analytical strategy known as targeted proteomics is particularly promising because it is compatible with robust mass spectrometry (MS......)-platforms already implemented in many clinical laboratories for routine quantitation of small molecules (i.e. uHPLC coupled to triple-quadrupole MS). Progress in targeted proteomics of circulating insulin-like growth factor 1 (IGF-I) have provided valuable insights about tryptic peptides, transitions, internal...

  11. Clinically identified postpartum depression in Asian American mothers.

    Science.gov (United States)

    Goyal, Deepika; Wang, Elsie J; Shen, Jeremy; Wong, Eric C; Palaniappan, Latha P

    2012-01-01

    To identify the clinical diagnosis rate of postpartum depression (PPD) in Asian American subgroups (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese) compared to non-Hispanic Whites. Cross-sectional study using electronic health records (EHR). A large, outpatient, multiservice clinic in Northern California. A diverse clinical population of non-Hispanic White (N = 4582), Asian Indian (N = 1264), Chinese (N = 1160), Filipino (N = 347), Japanese (N = 124), Korean (N = 183), and Vietnamese (N = 147) mothers. Cases of PPD were identified from EHRs using physician diagnosis codes, medication usage, and age standardized for comparison. The relationship between PPD and other demographic variables (race/ethnicity, maternal age, delivery type, marital status, and infant gender) were examined in a multivariate logistic regression model. The PPD diagnosis rate for all Asian American mothers in aggregate was significantly lower than the diagnosis rate in non-Hispanic White mothers. Moreover, of the six Asian American subgroups, PPD diagnosis rates for Asian Indian, Chinese, and Filipino mothers were significantly lower than non-Hispanic White mothers. In multivariate analyses, race/ethnicity, age, and cesarean were significant predictors of PPD. In this insured population, PPD diagnosis rates were lower among Asian Americans, with variability in rates across the individual Asian American subgroups. It is unclear whether these lower rates are due to underreporting, underdiagnosis, or underutilization of mental health care in this setting. © 2012 AWHONN, the Association of Women's Health, Obstetric and Neonatal Nurses.

  12. Competing events and costs of clinical trials: Analysis of a randomized trial in prostate cancer

    International Nuclear Information System (INIS)

    Zakeri, Kaveh; Rose, Brent S.; D’Amico, Anthony V.; Jeong, Jong-Hyeon; Mell, Loren K.

    2015-01-01

    Background: Clinical trial costs may be reduced by identifying enriched subpopulations of patients with favorable risk profiles for the events of interest. However, increased selectivity affects accrual rates, with uncertain impact on clinical trial cost. Methods: We conducted a secondary analysis of Southwest Oncology Group (SWOG) 8794 randomized trial of adjuvant radiotherapy for high-risk prostate cancer. The primary endpoint was metastasis-free survival (MFS), defined as time to metastasis or death from any cause (competing mortality). We used competing risks regression models to identify an enriched subgroup at high risk for metastasis and low risk for competing mortality. We applied a cost model to estimate the impact of enrichment on trial cost and duration. Results: The treatment effect on metastasis was similar in the enriched subgroup (HR, 0.42; 95% CI, 0.23–0.76) compared to the whole cohort (HR, 0.50; 95% CI, 0.30–0.81) while the effect on competing mortality was not significant in the subgroup or the whole cohort (HR 0.70; 95% CI 0.39–1.23, vs. HR 0.94; 95% CI, 0.68–1.31). Due to the higher incidence of metastasis relative to competing mortality in the enriched subgroup, the treatment effect on MFS was greater in the subgroup compared to the whole cohort (HR 0.55; 95% CI 0.36–0.82, vs. HR 0.77; 95% CI, 0.58–1.01). Trial cost was 75% less in the subgroup compared to the whole cohort ($1.7 million vs. $6.8 million), and the trial duration was 30% shorter (8.4 vs. 12.0 years). Conclusion: Competing event enrichment can reduce clinical trial cost and duration, without sacrificing generalizability

  13. Racial/ethnic differences in correlates of psychological distress among five Asian-American subgroups and non-Hispanic Whites.

    Science.gov (United States)

    Park, Hyunjeong; Choi, Eunsuk; Wenzel, Jennifer A

    2018-05-29

    Despite their vastly different historical backgrounds, unique languages and variable pre- and post-immigration experiences, Asian-Americans are considered to share stressors surrounding immigration, but there is a gap in describing manifestations of possible mental distress. Thus, the purpose of this study was to explore and compare differences in factors associated with psychological distress among Asian subgroups including Chinese, Filipino, Vietnamese, Korean, Japanese, and non-Hispanic Whites. Using a cross-sectional study design, California Health Interview Survey (CHIS) 2011/2012 data were analyzed. The sample consisted of 29,142 participants: 25,645 non-Hispanic Whites, 3497 non-Hispanic Asian-Americans, 1156 Chinese, 471 Filipinos, 864 Vietnamese, 704 Koreans, and 302 Japanese. Sociodemographic characteristics included gender, age group, marital status, education, poverty level, working status, health insurance, level of acculturation, social cohesion, neighborhood safety, and civic engagement. Physical health status included disability and chronic illness. Psychological distress was evaluated using the Kessler 6 (K6) scale. Results showed that psychological distress levels ranged between 1.96 and 4.52 (p < .05) out of 24 and associated factors were significantly different among the five Asian subgroups and non-Hispanic Whites. The current study highlights the differences in characteristics of psychological distress among Asian subgroups. It underscores the significance of understanding individualized cultural and historical background in each Asian subgroup and subsequently developing and applying appropriate interventions for those groups. In addition, different influencing factors should be applied to assess and prioritize the needs of Asian subgroups to improve psychological distress. The study also warrants further investigation and careful description of each Asian subgroups.

  14. Clinical Effects of Synthetic Cannabinoid Receptor Agonists Compared with Marijuana in Emergency Department Patients with Acute Drug Overdose.

    Science.gov (United States)

    Zaurova, Milana; Hoffman, Robert S; Vlahov, David; Manini, Alex F

    2016-12-01

    Synthetic cannabinoid receptor agonists (SCRAs) are heterogeneous compounds originally intended as probes of the endogenous cannabinoid system or as potential therapeutic agents. We assessed the clinical toxicity associated with recent SCRA use in a large cohort of drug overdose patients. This subgroup analysis of a large (n = 3739) drug overdose cohort study involved consecutive ED patients at two urban teaching hospitals collected between 2009 and 2013. Clinical characteristics of patients with the exposure to SCRAs (SRCA subgroup) were compared with those from patients who smoked traditional cannabinoids (marijuana subgroup). Data included demographics, exposure details, vital signs, mental status, and basic chemistries gathered as part of routine clinical care. Study outcomes included altered mental status and cardiotoxicity. Eighty-seven patients reported exposure to any cannabinoid, of whom 17 reported SCRAs (17 cases, 70 controls, mean age 38.9 years, 77 % males, 31 % Hispanic). There were no significant differences between SRCA and marijuana with respect to demographics (age, gender, and race/ethnicity), exposure history (suicidality, misuse, and intent), vital signs, or serum chemistries. Mental status varied between SRCA and marijuana, with agitation significantly more likely in SCRA subgroup (OR = 3.8, CI = 1.2-11.9). Cardiotoxicity was more pronounced in the SCRA subgroup with dysrhythmia significantly more likely (OR = 9.2, CI = 1.0-108). In the first clinical study comparing the adverse effects of SCRA overdose vs. marijuana controls in an ED population, we found that SCRA overdoses had significantly pronounced neurotoxicity and cardiotoxicity compared with marijuana.

  15. Incidence and follow-up of Braunwald subgroups in unstable angina pectoris

    NARCIS (Netherlands)

    van Miltenburg-van Zijl, A. J.; Simoons, M. L.; Veerhoek, R. J.; Bossuyt, P. M.

    1995-01-01

    OBJECTIVES. This study was performed to establish the prognosis of patients with unstable angina within the subgroups of the Braunwald classification. BACKGROUND. Among many classifications of unstable angina, the Braunwald classification is frequently used. However, the incidence and risk for each

  16. General considerations for SSC scintillator calorimeters (For the scintillator general subgroup)

    International Nuclear Information System (INIS)

    Nodulman, L.

    1989-01-01

    The Scintillator Calorimetry group divided into three subgroups: a conventional uranium and plate design ala ZEUS, fiber design, and a group on general considerations. The considerations of the third group are reported here on geometrical and technical issues. 1 fig

  17. Genomic profiling using array comparative genomic hybridization define distinct subtypes of diffuse large b-cell lymphoma: a review of the literature

    Directory of Open Access Journals (Sweden)

    Tirado Carlos A

    2012-09-01

    Full Text Available Abstract Diffuse large B-cell lymphoma (DLBCL is the most common type of non-Hodgkin Lymphoma comprising of greater than 30% of adult non-Hodgkin Lymphomas. DLBCL represents a diverse set of lymphomas, defined as diffuse proliferation of large B lymphoid cells. Numerous cytogenetic studies including karyotypes and fluorescent in situ hybridization (FISH, as well as morphological, biological, clinical, microarray and sequencing technologies have attempted to categorize DLBCL into morphological variants, molecular and immunophenotypic subgroups, as well as distinct disease entities. Despite such efforts, most lymphoma remains undistinguishable and falls into DLBCL, not otherwise specified (DLBCL-NOS. The advent of microarray-based studies (chromosome, RNA, gene expression, etc has provided a plethora of high-resolution data that could potentially facilitate the finer classification of DLBCL. This review covers the microarray data currently published for DLBCL. We will focus on these types of data; 1 array based CGH; 2 classical CGH; and 3 gene expression profiling studies. The aims of this review were three-fold: (1 to catalog chromosome loci that are present in at least 20% or more of distinct DLBCL subtypes; a detailed list of gains and losses for different subtypes was generated in a table form to illustrate specific chromosome loci affected in selected subtypes; (2 to determine common and distinct copy number alterations among the different subtypes and based on this information, characteristic and similar chromosome loci for the different subtypes were depicted in two separate chromosome ideograms; and, (3 to list re-classified subtypes and those that remained indistinguishable after review of the microarray data. To the best of our knowledge, this is the first effort to compile and review available literatures on microarray analysis data and their practical utility in classifying DLBCL subtypes. Although conventional cytogenetic methods such

  18. Human Papilloma Virus as a Biomarker for Personalized Head and Neck Cancer Radiotherapy

    DEFF Research Database (Denmark)

    Eriksen, Jesper Grau; Lassen, Pernille

    2016-01-01

    A dramatic increase in the incidence of HPV-related oropharyngeal cancer has been reported in some parts of the western world over the past 30 years. They constitute a clinically distinct subgroup of cancers in terms of molecular biology, patient characteristics, and treatment outcome. This chapt...

  19. The expanding spectrum of clinically-distinctive, immunotherapy-responsive autoimmune encephalopathies

    Directory of Open Access Journals (Sweden)

    Sarosh R Irani

    2012-04-01

    Full Text Available The autoimmune encephalopathies are a group of conditions that are associated with autoantibodies against surface neuronal proteins, which are likely to mediate the disease. They are established as a frequent cause of encephalitis. Characteristic clinical features in individual patients often allow the specificity of the underlying antibody to be confidently predicted. Antibodies against the VGKC-complex, mainly LGI1(leucine-rich glioma-inactivated 1, CASPR2 (contactin-associated protein 2, and contactin-2, and NMDA (N-methyl, D-aspartate -receptor are the most frequently established serological associations. In the minority of cases, an underlying tumour can be responsible. Early administration of immunotherapies, and tumour removal, where it is relevant, offer the greatest chance of improvement. Prolonged courses of immunotherapies may be required, and clinical improvements often correlate well with the antibody levels. In the present article, we have summarised recent developments in the clinical and laboratory findings within this rapidly expanding field.

  20. 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

    1. Introduction. The main purpose of this article is to study the relations between the structures of primary abelian groups and their ..... Case 2. γ − 2 exists. Let Gγ −1 be a direct summand of Gγ . We remark, in connection with Case 1, that any pγ −1. -high subgroup of Gγ is isomorphic to Gγ −1. As far as Case 2 is concerned, ...

  1. Quantum Distinction: Quantum Distinctiones!

    OpenAIRE

    Zeps, Dainis

    2009-01-01

    10 pages; How many distinctions, in Latin, quantum distinctiones. We suggest approach of anthropic principle based on anthropic reference system which should be applied equally both in theoretical physics and in mathematics. We come to principle that within reference system of life subject of mathematics (that of thinking) should be equated with subject of physics (that of nature). For this reason we enter notions of series of distinctions, quantum distinction, and argue that quantum distinct...

  2. The infiltration, and prognostic importance, of Th1 lymphocytes vary in molecular subgroups of colorectal cancer.

    Science.gov (United States)

    Ling, Agnes; Lundberg, Ida V; Eklöf, Vincy; Wikberg, Maria L; Öberg, Åke; Edin, Sofia; Palmqvist, Richard

    2016-01-01

    Giving strong prognostic information, T-cell infiltration is on the verge of becoming an additional component in the routine clinical setting for classification of colorectal cancer (CRC). With a view to further improving the tools for prognostic evaluation, we have studied how Th1 lymphocyte infiltration correlates with prognosis not only by quantity, but also by subsite, within CRCs with different molecular characteristics (microsatellite instability, CpG island methylator phenotype status, and BRAF and KRAS mutational status). We evaluated the Th1 marker T-bet by immunohistochemistry in 418 archival tumour tissue samples from patients who underwent surgical resection for CRC. We found that a high number of infiltrating Th1 lymphocytes is strongly associated with an improved prognosis in patients with CRC, irrespective of intratumoural subsite, and that both extent of infiltration and patient outcome differ according to molecular subgroup. In brief, microsatellite instability, CpG island methylator phenotype-high and BRAF mutated tumours showed increased infiltration of Th1 lymphocytes, and the most pronounced prognostic effect of Th1 infiltration was found in these tumours. Interestingly, BRAF mutated tumours were found to be more highly infiltrated by Th1 lymphocytes than BRAF wild-type tumours whereas the opposite was seen for KRAS mutated tumours. These differences could be explained at least partly by our finding that BRAF mutated, in contrast to KRAS mutated, CRC cell lines and tumour specimens expressed higher levels of the Th1-attracting chemokine CXCL10, and reduced levels of CCL22 and TGFB1, stimulating Th2/Treg recruitment and polarisation. In conclusion, the strong prognostic importance of Th1 lymphocyte infiltration in CRC was found at all subsites evaluated, and it remained significant in multivariable analyses, indicating that T-bet may be a valuable marker in the clinical setting. Our results also indicate that T-bet is of value when analysed in

  3. A prospective examination of circulating tumor cell profiles in non-small-cell lung cancer molecular subgroups.

    Science.gov (United States)

    Lindsay, C R; Faugeroux, V; Michiels, S; Pailler, E; Facchinetti, F; Ou, D; Bluthgen, M V; Pannet, C; Ngo-Camus, M; Bescher, G; Caramella, C; Billiot, F; Remon, J; Planchard, D; Soria, J-C; Besse, B; Farace, F

    2017-07-01

    We report the first study examining the clinical, numerical and biological properties of circulating tumor cells according to molecular subtypes of non-small-cell lung cancer. 125 patients with treatment-naïve stage IIIb-IV NSCLC were prospectively recruited for CellSearch analysis. Anti-vimentin antibody was included for examination of CTCs to assess their mesenchymal character. Associations of total CTCs and vimentin-positive (vim +) CTCs with clinical characteristics, tumor genotype, and survival were assessed. 51/125 patients (40.8%) were total CTC+ and 26/125 (20.8%) were vim CTC+ at baseline. Multivariate analysis showed patients with ≥5 total CTCs had significantly reduced OS (HR 0.55, 95% CI 0.33-0.92, P = 0.022) but not PFS (HR 0.68, 95% CI 0.42-1.1, P = 0.118) compared to patients with <5 total CTCs. No OS difference was evident between vim+ CTC and vim-negative CTC patients overall (HR 1.24, 95% CI 0.67-2.28, P = 0.494), but after subdivision according to NSCLC driver mutation, we found an increase of vim+ CTCs in the EGFR-mutated subgroup (N = 21/94 patients; mean 1.24 vs 1.22 vim+ CTCs, P = 0.013), a reduction of total CTCs in the ALK-rearranged subgroup (N = 13/90 patients; mean 1.69 vs 5.82 total CTCs, P = 0.029), and a total absence of vim+ CTCs in KRAS-mutated adenocarcinomas (N = 19/78 patients; mean 0 vs 1.4 vim+ CTCs, P = 0.006). We validate that the baseline presence of ≥5 total CTCs in advanced NSCLC confers a poor prognosis. CTCs from EGFR-mutant NSCLC express epithelial-mesenchymal transition characteristics, not seen in CTCs from patients with KRAS-mutant adenocarcinoma. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  4. Medical teachers conceptualize a distinctive form of clinical knowledge.

    Science.gov (United States)

    Barrett, J; Yates, L; McColl, G

    2015-05-01

    For over four decades, there have been efforts to specify the types of knowledge that medical students need, how that knowledge is acquired and how its constituent parts are related. It is one of the areas of continuing concern underlying medical education reform. Despite their importance to medical students' learning and development, the perspectives of medical teachers in hospitals are not always considered in such discourse. This study sought to generate an understanding of these teachers' values, perspectives and approaches by listening to them and seeing them in their everyday teaching work, finding and understanding the meanings they bring to the work of medical teaching in hospitals. In interviews, all of the teachers talked more about the optimal forms of knowledge that are important for students than they talked about the form of the teaching itself. Many revealed to students what knowledge they do and do not value. They had a particular way of thinking about clinical knowledge as existing in the people and the places in which the teaching and the clinical practice happen, and represented this as 'real' knowledge. By implication, there is other knowledge in medical education or in students' heads that is not real and needs to be transformed. Their values, practices and passions add texture and vitality to existing ways of thinking about the characteristics of clinical knowledge, how it is depicted in the discourse and the curriculum and how it is more dynamically related to other knowledge than is suggested in traditional conceptualizations of knowledge relationships.

  5. Summary of the activities of the subgroup on data acquisition and processing

    International Nuclear Information System (INIS)

    Connolly, P.L.; Doughty, D.C.; Elias, J.E.

    1981-01-01

    A data acquisition and handling subgroup consisting of approximately 20 members met during the 1981 ISABELLE summer study. Discussions were led by members of the BNL ISABELLE Data Acquisition Group (DAG) with lively participation from outside users. Particularly large contributions were made by representatives of BNL experiments 734, 735, and the MPS, as well as the Fermilab Colliding Detector Facility and the SLAC LASS Facility. In contrast to the 1978 study, the subgroup did not divide its activities into investigations of various individual detectors, but instead attempted to review the current state-of-the-art in the data acquisition, trigger processing, and data handling fields. A series of meetings first reviewed individual pieces of the problem, including status of the Fastbus Project, the Nevis trigger processor, the SLAC 168/E and 3081/E emulators, and efforts within DAG. Additional meetings dealt with the question involving specifying and building complete data acquisition systems. For any given problem, a series of possible solutions was proposed by the members of the subgroup. In general, any given solution had both advantages and disadvantages, and there was never any consensus on which approach was best. However, there was agreement that certain problems could only be handled by systems of a given power or greater. what will be given here is a review of various solutions with associated powers, costs, advantages, and disadvantages

  6. Going flat: examining heterogeneity in the soda-obesity relationship by subgroup and place of birth among Asian Americans.

    Science.gov (United States)

    Alcalá, Héctor E; Sharif, Mienah Z

    2017-06-01

    To determine if the association between soda consumption and obesity is uniform among Asian-American population subgroups. We conducted multivariate logistic regression analyses on odds of being obese among seven Asian subgroups and by place of birth using data from the 2009 California Health Interview Survey. An omnibus population-based health survey. Non-institutionalized adults, aged 18 years or over, residing in California (n 36 271). Despite low levels of soda consumption in several Asian-American ethnic groups, soda consumption increased the odds of being obese among Chinese, Koreans and Other Asians but not for Whites. Obesity risk varied across Asian subgroups and by place of birth within these subgroups. More public health efforts addressing soda consumption in Asian-American communities are needed as a strategy for not only preventing chronic diseases but also disparities, considering the varying levels of soda intake across subgroups. Results support the growing body of literature critiquing acculturation theory in immigrant health research by documenting inconsistent findings by place of birth. Future research should take into account the heterogeneity among Asian Americans to advance our understanding of health outcomes and disparities.

  7. Prevalence and Profile of Phonological and Surface Subgroups in College Students with a History of Reading Disability

    Science.gov (United States)

    Birch, Stacy L.

    2016-01-01

    The purpose of the present study was to identify and characterize surface and phonological subgroups of readers among college students with a prior diagnosis of developmental reading disability (RD). Using a speeded naming task derived from Castles and Coltheart's subtyping study, we identified subgroups of readers from among college students with…

  8. 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...... and is capable of determining links between terrorism plots occurred in the past, their affiliation with terrorist camps, travel record, funds transfer, etc. The findings are represented by a network in the form of an Attributed Relational Graph (ARG). Paths from a node to any other node in the network indicate...

  9. 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.

  10. Effect of duloxetine in patients with fibromyalgia: tiredness subgroups

    OpenAIRE

    Bradley, Laurence A; Bennett, Robert; Russell, Irwin J; Wohlreich, Madelaine M; Chappell, Amy S; Wang, Fujun; D'Souza, Deborah N; Moldofsky, Harvey

    2010-01-01

    Introduction This study tested the hypothesis that baseline ratings of fatigue/tiredness would be negatively associated with the efficacy of duloxetine on measures of pain and functional ability in patients with fibromyalgia. Methods A post hoc analysis of pooled data from 4 double-blind, placebo-controlled studies of duloxetine in fibromyalgia was performed. The fibromyalgia impact questionnaire (FIQ) tiredness item score (0 to 10 scale) was used to define tiredness subgroups. Patients were ...

  11. Parakeratosis pustulosa - a distinct but less familiar disease

    Directory of Open Access Journals (Sweden)

    Pandhi Deepika

    2003-01-01

    Full Text Available Parakeratosis pustulosa (PP is a distinct but less commonly known skin disease, which is frequently seen, in young girls. We describe the clinical and histological features of PP in a 7 month old female baby. Further, it is stressed that unless carefully looked for, this entity may be easily misdiagnosed as chronic paronychia, acrodermatitis of Hallopeau, pustular psoriasis, atopic dermatitis, tinea pedis or dry fissured eczematoid dermatitis and mistreated subsequently.

  12. Minimal unitary realizations of exceptional U-duality groups and their subgroups as quasiconformal groups

    International Nuclear Information System (INIS)

    Gunaydin, Murat; Pavlyk, Oleksandr

    2005-01-01

    We study the minimal unitary representations of noncompact exceptional groups that arise as U-duality groups in extended supergravity theories. First we give the unitary realizations of the exceptional group E 8(-24) in SU*(8) as well as SU(6,2) covariant bases. E 8(-24) has E 7 x SU(2) as its maximal compact subgroup and is the U-duality group of the exceptional supergravity theory in d=3. For the corresponding U-duality group E 8(8) of the maximal supergravity theory the minimal realization was given. The minimal unitary realizations of all the lower rank noncompact exceptional groups can be obtained by truncation of those of E 8(-24) and E 8(8) . By further truncation one can obtain the minimal unitary realizations of all the groups of the 'Magic Triangle'. We give explicitly the minimal unitary realizations of the exceptional subgroups of E 8(-24) as well as other physically interesting subgroups. These minimal unitary realizations correspond, in general, to the quantization of their geometric actions as quasi-conformal groups. (author)

  13. Development of degenerate and species-specific primers for the differential and simultaneous RT-PCR detection of grapevine-infecting nepoviruses of subgroups A, B and C.

    Science.gov (United States)

    Digiaro, Michele; Elbeaino, Toufic; Martelli, Giovanni Paolo

    2007-04-01

    Based on the nucleotide sequence homology of RNA-1 and RNA-2 of nepoviruses isolated from grapevines, three sets of degenerate primers, one for each of the three subgroups of the genus (A, B and C), were designed and proved effective for RT-PCR detection of subgroups in infected grapevines and herbaceous hosts. Primers designed specifically for detecting subgroup A species amplified a fragment of 255 bp from samples infected by Grapevine fanleaf virus (GFLV), Arabis mosaic virus (ArMV), Tobacco ringspot virus (TRSV) and Grapevine deformation virus (GDefV), but not from samples infected by other nepovirus species. Similarly, primers for detection of subgroup B nepoviruses amplified a 390 bp product from samples infected by Grapevine chrome mosaic virus (GCMV), Tomato black ring virus (TBRV), Grapevine Anatolian ringspot virus (GARSV) and Artichoke Italian latent virus (AILV). The third set of primers amplified a 640 bp fragment, only from samples infected by subgroup C nepoviruses, i.e Tomato ringspot virus (ToRSV) Grapevine Bulgarian latent virus (GBLV), and Grapevine Tunisian ringspot virus (GTRSV). These primers were able to detect simultaneously all viral species belonging to the same subgroup and to discriminate species of different subgroups. Multiplex-PCR detection of subgroup A and B nepoviruses was obtained using a specific primer (sense for subgroup A and antisense for subgroup B) for each of the species of the same subgroup in combination with the degenerate subgroup-specific primers. In this way it was possible to detect four different viral species in single samples containing mixtures of viruses of the same subgroup. In particular, for viruses of subgroup A (TRSV, GFLV, ArMV and GDefV) amplicons of 190, 259, 301 and 371 bp were obtained, whereas amplicons of 190, 278, 425 and 485 bp, respectively, were obtained from samples infected with viruses of subgroup B (GCMV, AILV, GARSV and TBRV).

  14. Impact of BCL2 and p53 on postmastectomy radiotherapy response in high-risk breast cancer. A subgroup analysis of DBCG82 b and c

    International Nuclear Information System (INIS)

    Kyndi, M.; Alsner, J.; Nielsen, H.M.; Overgaard, J.; Soerensen, F.B.; Knudsen, H.; Overgaard, M.

    2008-01-01

    Purpose. To examine p53 and BCL2 expression in high-risk breast cancer patients randomized to postmastectomy radiotherapy (PMRT). Patients and methods. The present analysis included 1 000 of 3 083 high-risk breast cancer patients randomly assigned to PMRT in the DBCG82 b and c studies. Tissue microarray sections were stained with immunohistochemistry for p53 and BCL2. Median potential follow-up was 17 years. Clinical endpoints were locoregional recurrence (LRR), distant metastases (DM), overall mortality, and overall survival (OS). Statistical analyses included Kappa statistics, χ2 or exact tests, Kaplan-Meier probability plots, Log-rank test, and Cox univariate and multivariate regression analyses. Results. p53 accumulation was not significantly associated with increased overall mortality, DM or LRR probability in univariate or multivariate Cox regression analyses. Kaplan-Meier probability plots showed reduced OS and improved DM and LRR probabilities after PMRT within subgroups of both p53 negative and p53 positive patients. Negative BCL2 expression was significantly associated with increased overall mortality, DM and LRR probability in multivariate Cox regression analyses. Kaplan-Meier probability plots showed a significantly improved overall survival after PMRT for the BCL2 positive subgroup, whereas practically no survival improvement was seen after PMRT for the BCL2 negative subgroup. In multivariate analysis of OS, however, no significant interaction was found between BCL2 and randomization status. Significant reductions in LRR probability after PMRT were recorded within both the BCL2 positive and BCL2 negative subgroups. Conclusion. p53 was not associated with survival after radiotherapy in high-risk breast cancer, but BCL2 might be

  15. A regional mineralogical study of the manganese-bearing Voelwater subgroup in the northern Cape Province

    International Nuclear Information System (INIS)

    Kleyenstueber, A.S.E.

    1985-11-01

    The Voelwater Subgroup, of the Proterozoic Transvaal Sequence, in the Hotazel area, is preserved in five structurally controlled basins, on the eastern side of the Dimoten syncline. The Subgroup represents a relatively undisturbed unit of mixed volcanogenic - chemical sedimentary rocks. The Hotazel Formation within the Voelwater Subgroup, consists of a finely banded carbonate - silicate - hematite - manganese lutite sequence of banded iron-formation and must be unique in that it contains the world's largest land-based repository of manganese. Twenty-one drill cores, sampled lithologically at intervals of approximately one metre through the total sedimentary sequence, were studied by microscopic, X-ray diffraction and electron microprobe methods. The mineralogy of the Voelwater Subgroup was studied on a regional scale, with the emphasis on the minerals within the manganese beds of the Hotazel Formation. The objective of the study was: a. To study the variation and distrubution of minerals in the various manganese ores on a regional scale. b. To compare the mineralogical differences of the different ores mined, in order to gain a better understanding of their metallurgical behaviour. c. To try to locate high-grade manganese ore target areas for future exploration, with the aid of mineralogical information. d. To try to establish the origin of the manganese in the Voelwater Formation. e. To study the relationship of the manganese units with the adjacent chemical sediments of the Hotazel Formation

  16. Classification of cognitive performance in bipolar disorder.

    Science.gov (United States)

    Sparding, Timea; Silander, Katja; Pålsson, Erik; Östlind, Josefin; Ekman, Carl Johan; Sellgren, Carl M; Joas, Erik; Hansen, Stefan; Landén, Mikael

    2017-09-01

    To understand the etiology of cognitive impairment associated with bipolar disorder, we need to clarify potential heterogeneity in cognitive functioning. To this end, we used multivariate techniques to study if the correlation structure of cognitive abilities differs between persons with bipolar disorder and controls. Clinically stable patients with bipolar disorder (type I: n = 64; type II: n = 44) and healthy controls (n = 86) were assessed with a wide range of cognitive tests measuring executive function, speed, memory, and verbal skills. Data were analysed with multivariate techniques. A distinct subgroup (∼30%) could be identified that performed significantly poorer on tests concerning memory function. This cognitive phenotype subgroup did not differ from the majority of bipolar disorder patients with respect to other demographic or clinical characteristics. Whereas the majority of patients performed similar to controls, a subgroup of patients with bipolar disorder differed substantially from healthy controls in the correlation pattern of low-level cognitive abilities. This suggests that cognitive impairment is not a general trait in bipolar disorder but characteristic of a cognitive subgroup. This has important clinical implications for cognitive rehabilitation and remediation.

  17. CKM and PMNS Mixing Matrices from Discrete Subgroups of SU(2

    Directory of Open Access Journals (Sweden)

    Potter F.

    2014-07-01

    Full Text Available One of the greatest challenges in particle physics is to determine the first principles origin of the quark and lepton mixing matrices CKM and PMNS that relate the flavor states to the mass states. This first principles derivation of both the PMNS and CKM matrices utilizes quaternion generators of the three discrete (i.e., finite binary rotational subgroups of SU(2 called [3,3,2], [4,3,2], and [5,3,2] for three lepton families in R 3 and four related discrete binary rotational subgroups [3,3,3], [4,3,3], [3,4,3], and [5,3,3] represented by four quark families in R 4 . The traditional 3 3 CKM matrix is extracted as a submatrix of the 4 4 CKM4 matrix. The predicted fourth family of quarks has not been discovered yet. If these two additional quarks exist, there is the possibility that the Standard Model lagrangian may apply all the way down to the Planck scale.

  18. Advances in the development of a subgroup method for the self-shielding of resonant isotopes in arbitrary geometries

    International Nuclear Information System (INIS)

    Hebert, A.

    1997-01-01

    The subgroup method is used to compute self-shielded cross sections defined over coarse energy groups in the resolved energy domain. The validity of the subgroup approach was extended beyond the unresolved energy domain by partially taking into account correlation effects between the slowing-down source with the collision probability terms of the transport equation. This approach enables one to obtain a pure subgroup solution of the self-shielding problem without relying on any form of equivalence in dilution. Specific improvements are presented on existing subgroup methods: an N-term rational approximation for the fuel-to-fuel collision probability, a new Pade deflation technique for computing probability tables, and the introduction of a superhomogenization correction. The absorption rates obtained after self-shielding are compared with exact values obtained using an elastic slowing-down calculation where each resonance is modeled individually in the resolved energy domain

  19. 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

  20. Aggressive Angiomyxoma of the Vulva: a Distinct Clinical Entity

    Directory of Open Access Journals (Sweden)

    Sevgi Bakaris

    2015-12-01

    Full Text Available Aggressive angiomyxoma is a rare mesenchmal tumour arising from connective tissue of the perineum or the lower pelvis, and affect predominantly young women. Our case was 20-year-old female who was operated for a vulvar mass clinically misdiagnosed as Polyp . Histopathological examination of the surgical specimen revealed, haphazardly scattered spindle or stellate shaped mesenchymal cells and vessels of medium size having dilated lumens within a loose hyposellular myxoid stroma No mitoses were evident.The spindle-or stellate-shaped tumor cells were diffusely positive for vimentin, but negative for cytokeratin, S-100 protein, and myoglobin and and #945;-smooth muscle actin by immunohistochemistry. These histologic and immunohistochemical findings were compatible with diagnosis of AA. Clinically AA is mixed with Bartholin's duct cyst, vulvar abscess, lipoma, vaginal cysts in diagnosis AA of the vulva must be distinguished from the more common benign and malignant myxoid tumors including myxoma, myxoid neurofibroma, pseudosarcoma, myxoid liposarcoma, myxoid leiomyosarcoma and other soft tissue tumors with secondary myxoid changes. [Cukurova Med J 2015; 40(4.000: 803-806

  1. Summary of the Very Large Hadron Collider Physics and Detector subgroup

    International Nuclear Information System (INIS)

    Denisov, D.; Keller, S.

    1996-01-01

    We summarize the activity of the Very Large Hadron Collider Physics and Detector subgroup during Snowmass 96. Members of the group: M. Albrow, R. Diebold, S. Feher, L. Jones, R. Harris, D. Hedin, W. Kilgore, J. Lykken, F. Olness, T. Rizzo, V. Sirotenko, and J. Womersley. 9 refs

  2. Patterns and Risk Factors of Soil-Transmitted Helminthiasis among Orang Asli Subgroups in Peninsular Malaysia

    Science.gov (United States)

    Ngui, Romano; Aziz, Shafie; Chua, Kek Heng; Aidil, Roslan Muhammad; Lee, Soo Ching; Tan, Tiong Kai; Sani, Mistam Mohd; Arine, Ahmad Fadzlun; Rohela, Mahmud; Lim, Yvonne A. L.

    2015-01-01

    A cross-sectional study was conducted to provide comprehensive data on the patterns and associated risk factors of soil-transmitted helminth (STH) infections among five Orang Asli subgroups in Peninsular Malaysia. The overall prevalence of STH infections was 59.9% (95% confidence interval [CI] = 56.1–63.7%). Trichuris trichiura (54.3%; 95% CI = 50.4–58.2%) was the predominant species followed by Ascaris lumbricoides (26.7%; 95% CI = 23.3–30.1%) and hookworm (9.1%; 95% CI = 6.9–11.3%). This study showed diversity for STH infections by subgroup with poverty and personal sanitary behavior as important risk factors for infection. Risk profile analyses indicating that Orang Kuala subgroup who has a generally well-developed infrastructure and better quality of life had a low rate of infection. There is a need for poverty reduction and promotion of deworming programs along with mass scale campaigns to create awareness about health and hygiene to reduce STH infections. PMID:26055746

  3. Upper bounds for reversible circuits based on Young subgroups

    DEFF Research Database (Denmark)

    Abdessaied, Nabila; Soeken, Mathias; Thomsen, Michael Kirkedal

    2014-01-01

    We present tighter upper bounds on the number of Toffoli gates needed in reversible circuits. Both multiple controlled Toffoli gates and mixed polarity Toffoli gates have been considered for this purpose. The calculation of the bounds is based on a synthesis approach based on Young subgroups...... that results in circuits using a more generalized gate library. Starting from an upper bound for this library we derive new bounds which improve the existing bound by around 77%....

  4. 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.

  5. One target, different effects: a comparison of distinct therapeutic antibodies against the same targets.

    Science.gov (United States)

    Shim, Hyunbo

    2011-10-31

    To date, more than 30 antibodies have been approved worldwide for therapeutic use. While the monoclonal antibody market is rapidly growing, the clinical use of therapeutic antibodies is mostly limited to treatment of cancers and immunological disorders. Moreover, antibodies against only five targets (TNF-α, HER2, CD20, EGFR, and VEGF) account for more than 80 percent of the worldwide market of therapeutic antibodies. The shortage of novel, clinically proven targets has resulted in the development of many distinct therapeutic antibodies against a small number of proven targets, based on the premise that different antibody molecules against the same target antigen have distinct biological and clinical effects from one another. For example, four antibodies against TNF-α have been approved by the FDA -- infliximab, adalimumab, golimumab, and certolizumab pegol -- with many more in clinical and preclinical development. The situation is similar for HER2, CD20, EGFR, and VEGF, each having one or more approved antibodies and many more under development. This review discusses the different binding characteristics, mechanisms of action, and biological and clinical activities of multiple monoclonal antibodies against TNF-α, HER-2, CD20, and EGFR and provides insights into the development of therapeutic antibodies.

  6. Improvement in Fatigue, Sleepiness, and Health-Related Quality of Life with Bright Light Treatment in Persons with Seasonal Affective Disorder and Subsyndromal SAD

    Directory of Open Access Journals (Sweden)

    Cecilia Rastad

    2011-01-01

    Full Text Available Objective. To investigate the effects of bright light treatment for secondary outcome measures and to explore and validate empirically derived subgroups and treatment effects in subgroups. Methods. A descriptive design. A sample of forty-nine persons (mean age of 45.8 with clinically assessed seasonal affective disorder (SAD or subsyndromal SAD (S-SAD participated in a two-group clinical trial evaluating the effects of treatment with bright light therapy. A person-oriented cluster analysis was applied to study treatment effects in subgroups. Results. For the merged group, sleepiness (Epworth Sleepiness Scale, fatigue (fatigue questionnaire, and health-related quality of life (SF-36 were improved at posttreatment, and results were maintained at the one-month followup. Three distinct subgroups had a high level of fatigue in common, while the level of excessive daytime sleepiness and depressed mood differed between the subgroups. Over time, all subgroups improved following ten days treatment in a light room. Conclusion. Fatigue, excessive daytime sleepiness, and health-related quality of life improve in a similar way as depressed mood following treatment with bright light. The treatment was effective irrespective of the severity of the disorder, that is, for persons with SAD and subsyndromal SAD.

  7. Neural correlates of the food/non-food visual distinction.

    Science.gov (United States)

    Tsourides, Kleovoulos; Shariat, Shahriar; Nejati, Hossein; Gandhi, Tapan K; Cardinaux, Annie; Simons, Christopher T; Cheung, Ngai-Man; Pavlovic, Vladimir; Sinha, Pawan

    2016-03-01

    An evolutionarily ancient skill we possess is the ability to distinguish between food and non-food. Our goal here is to identify the neural correlates of visually driven 'edible-inedible' perceptual distinction. We also investigate correlates of the finer-grained likability assessment. Our stimuli depicted food or non-food items with sub-classes of appealing or unappealing exemplars. Using data-classification techniques drawn from machine-learning, as well as evoked-response analyses, we sought to determine whether these four classes of stimuli could be distinguished based on the patterns of brain activity they elicited. Subjects viewed 200 images while in a MEG scanner. Our analyses yielded two successes and a surprising failure. The food/non-food distinction had a robust neural counterpart and emerged as early as 85 ms post-stimulus onset. The likable/non-likable distinction too was evident in the neural signals when food and non-food stimuli were grouped together, or when only the non-food stimuli were included in the analyses. However, we were unable to identify any neural correlates of this distinction when limiting the analyses only to food stimuli. Taken together, these positive and negative results further our understanding of the substrates of a set of ecologically important judgments and have clinical implications for conditions like eating-disorders and anhedonia. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Neuromyelitis optica spectrum disorders: comparison of clinical and magnetic resonance imaging characteristics of AQP4-IgG versus MOG-IgG seropositive cases in the Netherlands.

    Science.gov (United States)

    van Pelt, E D; Wong, Y Y M; Ketelslegers, I A; Hamann, D; Hintzen, R Q

    2016-03-01

    Neuromyelitis optica spectrum disorders (NMOSDs) are a group of rare inflammatory demyelinating disorders of the central nervous system. The identification of specific antibodies directed to aquaporin 4 (AQP4-IgG) led to the distinction from multiple sclerosis. However, up to 25% of the clinically diagnosed NMO patients are seronegative for AQP4-IgG. A subgroup of these patients might be identified by antibodies directed to myelin oligodendrocyte glycoprotein (MOG-IgG). Our objective was to investigate whether the clinical characteristics of these patients differ. Using a cell-based assay, samples of 61 AQP4-IgG seronegative patients and 41 AQP4-IgG seropositive patients with clinically NMOSD were analysed for the presence of MOG-IgG. Clinical characteristics of the AQP4-IgG, MOG-IgG seropositive and double seronegative NMOSD patients were compared. Twenty of the 61 AQP4-IgG seronegative patients tested MOG-IgG seropositive (33%). MOG-IgG seropositive patients were more frequently males in contrast to AQP4-IgG seropositive patients (55% vs. 15%, P < 0.01) and Caucasians (90% vs. 63%, P = 0.03). They more frequently presented with coincident optic neuritis and transverse myelitis (40% vs. 12%, P = 0.02) and had a monophasic disease course (70% vs. 29%, P < 0.01). AQP4-IgG seropositive patients were 2.4 times more likely to suffer from relapses compared with MOG-IgG seropositive patients (relative risk 2.4, 95% confidence interval 1.2-4.7). AQP4-IgG seropositive patients had higher Expanded Disability Status Scale levels at last follow-up (P < 0.01). Antibodies directed to MOG identify a subgroup of AQP4-IgG seronegative NMO patients with generally a favourable monophasic disease course. © 2015 EAN.

  9. Distinct types of primary cutaneous large B-cell lymphoma identified by gene expression profiling.

    Science.gov (United States)

    Hoefnagel, Juliette J; Dijkman, Remco; Basso, Katia; Jansen, Patty M; Hallermann, Christian; Willemze, Rein; Tensen, Cornelis P; Vermeer, Maarten H

    2005-05-01

    In the European Organization for Research and Treatment of Cancer (EORTC) classification 2 types of primary cutaneous large B-cell lymphoma (PCLBCL) are distinguished: primary cutaneous follicle center cell lymphomas (PCFCCL) and PCLBCL of the leg (PCLBCL-leg). Distinction between both groups is considered important because of differences in prognosis (5-year survival > 95% and 52%, respectively) and the first choice of treatment (radiotherapy or systemic chemotherapy, respectively), but is not generally accepted. To establish a molecular basis for this subdivision in the EORTC classification, we investigated the gene expression profiles of 21 PCLBCLs by oligonucleotide microarray analysis. Hierarchical clustering based on a B-cell signature (7450 genes) classified PCLBCL into 2 distinct subgroups consisting of, respectively, 8 PCFCCLs and 13 PCLBCLsleg. PCLBCLs-leg showed increased expression of genes associated with cell proliferation; the proto-oncogenes Pim-1, Pim-2, and c-Myc; and the transcription factors Mum1/IRF4 and Oct-2. In the group of PCFCCL high expression of SPINK2 was observed. Further analysis suggested that PCFCCLs and PCLBCLs-leg have expression profiles similar to that of germinal center B-cell-like and activated B-cell-like diffuse large B-cell lymphoma, respectively. The results of this study suggest that different pathogenetic mechanisms are involved in the development of PCFCCLs and PCLBCLs-leg and provide molecular support for the subdivision used in the EORTC classification.

  10. An unusual lump in the groin

    African Journals Online (AJOL)

    2008-05-14

    May 14, 2008 ... history of trauma, it was initially reported as a possible false aneurysm. This was at variance with the clinical ... There are two distinct histological subgroups, a more common hyaline vascular picture (as in our case) with ... is mediastinal, neck and abdominal. Castleman's disease, like Kaposi's sarcoma, is ...

  11. Stepwise classification of cancer samples using clinical and molecular data

    Directory of Open Access Journals (Sweden)

    Obulkasim Askar

    2011-10-01

    Full Text Available Abstract Background Combining clinical and molecular data types may potentially improve prediction accuracy of a classifier. However, currently there is a shortage of effective and efficient statistical and bioinformatic tools for true integrative data analysis. Existing integrative classifiers have two main disadvantages: First, coarse combination may lead to subtle contributions of one data type to be overshadowed by more obvious contributions of the other. Second, the need to measure both data types for all patients may be both unpractical and (cost inefficient. Results We introduce a novel classification method, a stepwise classifier, which takes advantage of the distinct classification power of clinical data and high-dimensional molecular data. We apply classification algorithms to two data types independently, starting with the traditional clinical risk factors. We only turn to relatively expensive molecular data when the uncertainty of prediction result from clinical data exceeds a predefined limit. Experimental results show that our approach is adaptive: the proportion of samples that needs to be re-classified using molecular data depends on how much we expect the predictive accuracy to increase when re-classifying those samples. Conclusions Our method renders a more cost-efficient classifier that is at least as good, and sometimes better, than one based on clinical or molecular data alone. Hence our approach is not just a classifier that minimizes a particular loss function. Instead, it aims to be cost-efficient by avoiding molecular tests for a potentially large subgroup of individuals; moreover, for these individuals a test result would be quickly available, which may lead to reduced waiting times (for diagnosis and hence lower the patients distress. Stepwise classification is implemented in R-package stepwiseCM and available at the Bioconductor website.

  12. 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.

  13. Contents of Stereotypes toward Woman Subgroups: An Investigation in the Framework of Stereotype Content Model

    Directory of Open Access Journals (Sweden)

    Timucin Aktan

    2016-12-01

    Full Text Available The aim of the study was to investigate the stereotype contents toward woman subgroups and relate these contents to social-structural predictors and sexism. In this respect, 119 university students were recruited for the first study and they were asked to rate 10 woman subgroups in terms of their competence and warmth, and their status and competitiveness. Participants' level of sexism was also measured using ambivalent sexism scale. The findings of the first study revealed that competence and warmth were the two fundamental dimensions of the stereotype contents, these stereotypes could be depicted in three clusters, the content of many women stereotypes were mixed, and status was linked to competence and competition was related to lack of warmth. Besides replicating the main hypotheses of stereotype content model, the findings supported its two basic assumptions, i.e. negative stereotypes are not necessary to reveal stereotype clusters and personal stereotypes are more open to motivational concerns. Finally, sexism was related only with competition, but not with stereotype contents. Since, high competent / high warm cluster was not observed in the first study, the number of woman subgroups was increased in the second study. Thus, 86 university students were asked to rate 18 women subgroups on the scales used in the first study. Results replicated the findings of the first study, supporting the main hypothesis of stereotype content model. The findings of the studies were discussed in the light of relevant literature.

  14. Does mortality vary between Asian subgroups in New Zealand: an application of hierarchical Bayesian modelling.

    Directory of Open Access Journals (Sweden)

    Santosh Jatrana

    Full Text Available The aim of this paper was to see whether all-cause and cause-specific mortality rates vary between Asian ethnic subgroups, and whether overseas born Asian subgroup mortality rate ratios varied by nativity and duration of residence. We used hierarchical Bayesian methods to allow for sparse data in the analysis of linked census-mortality data for 25-75 year old New Zealanders. We found directly standardised posterior all-cause and cardiovascular mortality rates were highest for the Indian ethnic group, significantly so when compared with those of Chinese ethnicity. In contrast, cancer mortality rates were lowest for ethnic Indians. Asian overseas born subgroups have about 70% of the mortality rate of their New Zealand born Asian counterparts, a result that showed little variation by Asian subgroup or cause of death. Within the overseas born population, all-cause mortality rates for migrants living 0-9 years in New Zealand were about 60% of the mortality rate of those living more than 25 years in New Zealand regardless of ethnicity. The corresponding figure for cardiovascular mortality rates was 50%. However, while Chinese cancer mortality rates increased with duration of residence, Indian and Other Asian cancer mortality rates did not. Future research on the mechanisms of worsening of health with increased time spent in the host country is required to improve the understanding of the process, and would assist the policy-makers and health planners.

  15. Mining geriatric assessment data for in-patient fall prediction models and high-risk subgroups.

    Science.gov (United States)

    Marschollek, Michael; Gövercin, Mehmet; Rust, Stefan; Gietzelt, Matthias; Schulze, Mareike; Wolf, Klaus-Hendrik; Steinhagen-Thiessen, Elisabeth

    2012-03-14

    Hospital in-patient falls constitute a prominent problem in terms of costs and consequences. Geriatric institutions are most often affected, and common screening tools cannot predict in-patient falls consistently. Our objectives are to derive comprehensible fall risk classification models from a large data set of geriatric in-patients' assessment data and to evaluate their predictive performance (aim#1), and to identify high-risk subgroups from the data (aim#2). A data set of n = 5,176 single in-patient episodes covering 1.5 years of admissions to a geriatric hospital were extracted from the hospital's data base and matched with fall incident reports (n = 493). A classification tree model was induced using the C4.5 algorithm as well as a logistic regression model, and their predictive performance was evaluated. Furthermore, high-risk subgroups were identified from extracted classification rules with a support of more than 100 instances. The classification tree model showed an overall classification accuracy of 66%, with a sensitivity of 55.4%, a specificity of 67.1%, positive and negative predictive values of 15% resp. 93.5%. Five high-risk groups were identified, defined by high age, low Barthel index, cognitive impairment, multi-medication and co-morbidity. Our results show that a little more than half of the fallers may be identified correctly by our model, but the positive predictive value is too low to be applicable. Non-fallers, on the other hand, may be sorted out with the model quite well. The high-risk subgroups and the risk factors identified (age, low ADL score, cognitive impairment, institutionalization, polypharmacy and co-morbidity) reflect domain knowledge and may be used to screen certain subgroups of patients with a high risk of falling. Classification models derived from a large data set using data mining methods can compete with current dedicated fall risk screening tools, yet lack diagnostic precision. High-risk subgroups may be identified

  16. Mining geriatric assessment data for in-patient fall prediction models and high-risk subgroups

    Directory of Open Access Journals (Sweden)

    Marschollek Michael

    2012-03-01

    Full Text Available Abstract Background Hospital in-patient falls constitute a prominent problem in terms of costs and consequences. Geriatric institutions are most often affected, and common screening tools cannot predict in-patient falls consistently. Our objectives are to derive comprehensible fall risk classification models from a large data set of geriatric in-patients' assessment data and to evaluate their predictive performance (aim#1, and to identify high-risk subgroups from the data (aim#2. Methods A data set of n = 5,176 single in-patient episodes covering 1.5 years of admissions to a geriatric hospital were extracted from the hospital's data base and matched with fall incident reports (n = 493. A classification tree model was induced using the C4.5 algorithm as well as a logistic regression model, and their predictive performance was evaluated. Furthermore, high-risk subgroups were identified from extracted classification rules with a support of more than 100 instances. Results The classification tree model showed an overall classification accuracy of 66%, with a sensitivity of 55.4%, a specificity of 67.1%, positive and negative predictive values of 15% resp. 93.5%. Five high-risk groups were identified, defined by high age, low Barthel index, cognitive impairment, multi-medication and co-morbidity. Conclusions Our results show that a little more than half of the fallers may be identified correctly by our model, but the positive predictive value is too low to be applicable. Non-fallers, on the other hand, may be sorted out with the model quite well. The high-risk subgroups and the risk factors identified (age, low ADL score, cognitive impairment, institutionalization, polypharmacy and co-morbidity reflect domain knowledge and may be used to screen certain subgroups of patients with a high risk of falling. Classification models derived from a large data set using data mining methods can compete with current dedicated fall risk screening tools, yet lack

  17. Clinical response to anti-TNFα therapy in patients with rheumatoid arthritis faulted or intolerance in non-biological DMARD in the Hospital San Juan de Dios in the period January 2006 to December 2011

    International Nuclear Information System (INIS)

    Salas Mena, Claudio

    2014-01-01

    Various clinical studies are performed globally using anti-TNFα therapy and has proven its clinical effectiveness in the management of rheumatoid arthritis patients, that have failed or have presented intolerance to the use of non-biological DMARDs. The clinical response to treatment of anti-TNFα was determined in patients with rheumatoid arthritis who have presented without respond, have showed intolerance or secondary effects to DMARDs no biological, in the Servicio de Reumatologia del Hospital San Juan de Dios, in the period January 2006 to December 2011. Study has been descriptive, retrospective, observational, by reviewing dossiers of patients with rheumatoid arthritis to initiate anti-TNFα therapy where has valued the DAS28 and initial VES, then at 6 months and 12 months after starting treatment. In the period analyzed, 47 patients evaluated with traditional DMARD failure who have received anti-TNFα therapy, according to DAS28, 32 patients were cataloged as severe activity and 15 of them with moderate activity. A total of 41 patients have used etanercept, with adalimumab 6 patients. The DAS28 initial average was 5,63 in all patients, 6,16 in the subgroup of patients with severe activity, and 4,49 in the subgroup of moderate activity. After 6 months of treatment, the DAS28 has descended to 3,25 in all patients, with 3,67 in the subgroup of severe clinical activity, and 2,35 in the subgroup of moderate clinical activity. One year after treatment values DAS28 have been 3,13 for all patients, 3,53 in severe activity and 2,28 in the subgroup of activity clinical moderate. In all groups and subgroups of patients, difference was demonstrated statistically significant at p less than 0,05. Between the subgroups of patients according to clinical activity is keeped without significant difference, or the type of anti-TNFα therapy employed. The anti-TNFα therapy has proven to be effective for improvement of clinical activity of rheumatoid arthritis, regardless of

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

    Directory of Open Access Journals (Sweden)

    Vogelmeier C

    2017-02-01

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

  20. The one-parameter subgroup of rotations generated by spin transformations in three-dimensional real space

    International Nuclear Information System (INIS)

    Gazoya, E.D.K.; Prempeh, E.; Banini, G.K.

    2015-01-01

    The relationship between the spin transformations of the special linear group of order 2, SL (2, C) and the aggregate SO(3) of the three-dimensional pure rotations when considered as a group in itself (and not as a subgroup of the Lorentz group), is investigated. It is shown, by the spinor map X - → AXA ct which is all action of SL(2. C) on the space of Hermitian matrices, that the one- parameter subgroup of rotations generated are precisely those of angles which are multiples 2π. (au)

  1. Clinical, physical and lifestyle indicators and relationship with cognition and mood in aging: a cross-sectional analysis of distinct educational groups

    Directory of Open Access Journals (Sweden)

    Nadine Correia Santos

    2014-02-01

    Full Text Available It is relevant to unravel the factors that may mediate the cognitive decline observed during aging. Previous reports indicate that education has a positive influence on cognitive performance, while age, female gender and, especially, depressed mood were associated with poorer performances across multiple cognitive dimensions (memory and general executive function. Herein, the present study aimed to characterize the cognitive performance of community-dwelling individuals within distinct educational groups categorized by the number of completed formal school years: less than 4, 4, completed primary education, and more than 4. Participants (n = 1051 were randomly selected from local health registries and representative of the Portuguese population for age and gender. Neurocognitive and clinical assessments were conducted in local health care centers. Structural equation modeling was used to derive a cognitive score, and hierarchical linear regressions were conducted for each educational group. Education, age and depressed mood were significant variables in directly explaining the obtained cognitive score, while gender was found to be an indirect variable. In all educational groups, mood was the most significant factor with effect on cognitive performance. Specifically, a depressed mood led to lower cognitive performance. The clinical disease indices cardiac and stroke associated with a more negative mood, while moderate increases in BMI, alcohol consumption and physical activity associated positively with improved mood and thus benefitted cognitive performance. Results warrant further research on the cause-effect (longitudinal relationship between clinical indices of disease and risk factors and mood and cognition throughout aging.

  2. 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.

  3. Evidence for a Priori Existence of Attentional Bias Subgroups in Emotional Processing of Aversive Stimuli

    Directory of Open Access Journals (Sweden)

    Casper H. van Heck

    2017-05-01

    Full Text Available Little is known regarding inter-individual differences in attentional biases for pain-related information; more knowledge is crucial, since these biases have been associated with differences in pain processing as well as in predicting the risk of postoperative pain. The present study investigated EEG correlates of attentional bias patterns for pain-related information, with specific focus on avoidance- and vigilance-like behavior. Forty-one participants performed a dot-probe task, where neutral and pain-related words were used to create neutral, congruent, incongruent, and double (two pain-related words trials. EEG was recorded, which was used to generate ERP's of the word-processing phase and the post-dot phase. Participants were placed in two subgroups based on the direction of their attentional bias (either positive; toward the pain-related words, or negative; away from pain-related words. Using t-profiles, four latency windows were identified on which the two subgroups differed significantly. These latency windows yield areas which correspond with the P1-N1 domain and the P3b for the word-processing phase, while the post-dot phase latency windows cover the areas of the P200 and the P3b. The two subgroups show differences on congruent, incongruent, and the double trials, but interestingly also on the neutral trials. Most notably, the area in the word-phase associated with the P3b is diminished in the subgroup showing a negative bias. The deflections associated with both early and late attentional components, including the P3B, as well as a positive deflection in the timeframe of proposed response evaluation processes differ significantly between subgroups. In this study we demonstrated that different attentional biases exist in the healthy population, by showing differences in ERP's. We also show differences in processing neutral trials, which suggests there are fundamental differences between these groups in processing words in general.

  4. Subgroup analyses of maraviroc in previously treated R5 HIV-1 infection

    NARCIS (Netherlands)

    Fätkenheuer, Gerd; Nelson, Mark; Lazzarin, Adriano; Konourina, Irina; Hoepelman, Andy I. M.; Lampiris, Harry; Hirschel, Bernard; Tebas, Pablo; Raffi, François; Trottier, Benoit; Bellos, Nicholaos; Saag, Michael; Cooper, David A.; Westby, Mike; Tawadrous, Margaret; Sullivan, John F.; Ridgway, Caroline; Dunne, Michael W.; Felstead, Steve; Mayer, Howard; van der Ryst, Elna; Angel, Jonathan; Conway, Brian; Gough, Kevin A.; Lalonde, Richard G.; Laplante, Francois; Leblanc, Roger P.; Montaner, Julio S. G.; Rachlis, Anita R.; Romanowski, Barbara; Rosser, Stuart J.; Rubinstein, Ethan; Shafran, Stephen David; Smaill, Fiona; Tremblay, Cecile; Trottier, Sylvie; Tsoukas, Christos; Walmsley, Sharon Lynn; Voskanian, Alen; Akil, Bisher; Arduino, Roberto Claudio; Asmuth, David; Beatty, George William; Becker, Stephen Lawrence; Bellos, Nicholaos C.; Blue, Sky Robert; Bolan, Robert Key; Brand, John D.; Burnazian, George Ghazaros; Prins, J. M.

    2008-01-01

    BACKGROUND: We conducted subanalyses of the combined results of the Maraviroc versus Optimized Therapy in Viremic Antiretroviral Treatment-Experienced Patients (MOTIVATE) 1 and MOTIVATE 2 studies to better characterize the efficacy and safety of maraviroc in key subgroups of patients. METHODS: We

  5. 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

    Respiratory syncytial virus (RSV) is a seasonal infectious disease, with epidemics occurring annually from October to March in the UK. It is a very common infection in infants and young children and can lead to hospitalisation, particularly in those who are premature or who have chronic lung disease (CLD) or congenital heart disease (CHD). Palivizumab (Synagis®, MedImmune) is a monoclonal antibody designed to provide passive immunity against RSV and thereby prevent or reduce the severity of RSV infection. It is licensed for the prevention of serious lower respiratory tract infection caused by RSV in children at high risk. While it is recognised that a policy of using palivizumab for all children who meet the licensed indication does not meet conventional UK standards of cost-effectiveness, most clinicians feel that its use is justified in some children. To use systematic review evidence to estimate the cost-effectiveness of immunoprophylaxis of RSV using palivizumab in different subgroups of children with or without CLD or CHD who are at high risk of serious morbidity from RSV infection. A systematic review of the literature and an economic evaluation was carried out. The bibliographic databases included the Cochrane Library [Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Database of Systematic Reviews (CDSR), Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment (HTA)] and five other databases, from inception to 2009. Research registries of ongoing trials including Current Controlled Trials metaRegister, Clinical Trials.gov and the National Institute for Health Research Clinical Research Network Portfolio were also searched. Searches were conducted for prognostic and hospitalisation studies covering 1950-2009 (the original report searches conducted in 2007 covering the period 1950-2007 were rerun in August 2009 to cover the period 2007-9) and the database of all references from the original report was sifted to

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

    Directory of Open Access Journals (Sweden)

    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

  7. Neuropsychological functioning in early-onset first-episode psychosis: comparison of diagnostic subgroups.

    Science.gov (United States)

    Zabala, Arantzazu; Rapado, Marta; Arango, Celso; Robles, Olalla; de la Serna, Elena; González, Cristina; Rodríguez-Sánchez, José Manuel; Andrés, Patricia; Mayoral, María; Bombín, Igor

    2010-04-01

    The aims of this study were to examine the nature and extent of cognitive impairment in first-episode early-onset psychosis (FE-EOP) soon after their stabilisation and to search for potential differences according to specific diagnostic sub-groups of patients. As part of a Spanish multicentre longitudinal study, 107 FE-EOP patients and 98 healthy controls were assessed on the following cognitive domains: attention, working memory, executive functioning, and verbal learning and memory. Three diagnostic categories were established in the patient sample: schizophrenia (n = 36), bipolar disorder (n = 19), and other psychosis (n = 52). Patients performed significantly worse than controls in all cognitive domains. The three diagnostic sub-groups did not differ in terms of impaired/preserved cognitive functions or degree of impairment. FE-EOP patients show significant cognitive impairment that, during this early phase, seems to be non-specific to differential diagnosis.

  8. Pooling of cross-cultural PRO data in multinational clinical trials: how much can poor measurement affect statistical power?

    Science.gov (United States)

    Regnault, Antoine; Hamel, Jean-François; Patrick, Donald L

    2015-02-01

    Cultural differences and/or poor linguistic validation of patient-reported outcome (PRO) instruments may result in differences in the assessment of the targeted concept across languages. In the context of multinational clinical trials, these measurement differences may add noise and potentially measurement bias to treatment effect estimation. Our objective was to explore the potential effect on treatment effect estimation of the "contamination" of a cultural subgroup by a flawed PRO measurement. We ran a simulation exercise in which the distribution of the score in the overall sample was considered a mixture of two normal distributions: a standard normal distribution was assumed in a "main" subgroup and a normal distribution which differed either in mean (bias) or in variance (noise) in a "contaminated" subgroup (the subgroup with potential flaws in the PRO measurement). The observed power was compared to the expected power (i.e., the power that would have been observed if the subgroup had not been contaminated). Even if differences between the expected and observed power were small, some substantial differences were obtained (up to a 0.375 point drop in power). No situation was systematically protected against loss of power. The impact of poor PRO measurement in a cultural subgroup may induce a notable drop in the study power and consequently reduce the chance of showing an actual treatment effect. These results illustrate the importance of the efforts to optimize conceptual and linguistic equivalence of PRO measures when pooling data in international clinical trials.

  9. Specific gene expression profiles and chromosomal abnormalities are associated with infant disseminated neuroblastoma

    Directory of Open Access Journals (Sweden)

    Kushner Brian

    2009-02-01

    Full Text Available Abstract Background Neuroblastoma (NB tumours have the highest incidence of spontaneous remission, especially among the stage 4s NB subgroup affecting infants. Clinical distinction of stage 4s from lethal stage 4 can be difficult, but critical for therapeutic decisions. The aim of this study was to investigate chromosomal alterations and differential gene expression amongst infant disseminated NB subgroups. Methods Thirty-five NB tumours from patients diagnosed at Results All stage 4s patients underwent spontaneous remission, only 48% stage 4 patients survived despite combined modality therapy. Stage 4 tumours were 90% near-diploid/tetraploid, 44% MYCN amplified, 77% had 1p LOH (50% 1p36, 23% 11q and/or 14q LOH (27% and 47% had 17q gain. Stage 4s were 90% near-triploid, none MYCN amplified and LOH was restricted to 11q. Initial comparison analyses between stage 4s and 4 P P = 0.0054, 91% with higher expression in stage 4. Less definite expression profiles were observed between stage 4s and 4 P P = 0.005 was maintained. Distinct gene expression profiles but no significant association with specific chromosomal region localization was observed between stage 4s and stage 4 Conclusion Specific chromosomal aberrations are associated with distinct gene expression profiles which characterize spontaneously regressing or aggressive infant NB, providing the biological basis for the distinct clinical behaviour.

  10. Plasma homovanillic acid differences in clinical subgroups of first episode schizophrenic patients.

    Science.gov (United States)

    Baeza, Immaculada; Castro-Fornieles, Josefina; Deulofeu, Ramon; de la Serna, Elena; Goti, Javier; Salvà, Joan; Bernardo, Miquel

    2009-07-30

    This study evaluates the relationship between plasma homovanillic acid (pHVA) levels, which have been used to study the role of central dopamine in schizophrenia, and the positive/negative syndrome in first episode schizophrenic patients before and after antipsychotic treatment. Forty neuroleptic-naive first episode schizophrenic patients were monitored at baseline and on days 7, 14 and 28. Clinical status was evaluated with the Scale for the Assessment of Positive Symptoms (SAPS), the Scale for the Assessment of Negative Symptoms (SANS), and the Brief Psychotic Rating Scale. Plasma HVA levels were also measured. Patients were divided into predominantly positive or negative syndrome groups by subtracting SAPS from SANS scores, at baseline. A healthy control group was also enrolled. Schizophrenic patients as a group had significantly higher pHVA levels than controls at baseline (20.50+/-11.85 vs. 13.04+/-7.22 ng/ml). Moreover, 12 predominantly negative syndrome patients had similar mean baseline pHVA levels (21.30+/-12.36 ng/ml) to those of 28 predominantly positive syndrome patients (19.40+/-11.33 ng/ml). During follow-up, there was a different evolution of pHVA levels in the predominantly positive syndrome group than in the predominantly negative syndrome group, with a significantly greater global reduction of pHVA levels in the former. Although both groups showed clinical improvement following 4 weeks of treatment with risperidone, pHVA levels at endpoint were lower (13.29+/-5.91 ng/ml) than at baseline in patients in the predominantly positive syndrome group, while among those in the predominantly negative syndrome group there was no difference in pHVA levels before and after treatment (21.02+/-13.06 ng/ml). The different pHVA level profiles observed in predominantly positive and negative syndrome first episode patients after 4 weeks of treatment with risperidone suggest that each syndrome may have a different underlying neurobiology.

  11. Efficacy of Cladribine Tablets in high disease activity subgroups of patients with relapsing multiple sclerosis: A post hoc analysis of the CLARITY study.

    Science.gov (United States)

    Giovannoni, Gavin; Soelberg Sorensen, Per; Cook, Stuart; Rammohan, Kottil W; Rieckmann, Peter; Comi, Giancarlo; Dangond, Fernando; Hicking, Christine; Vermersch, Patrick

    2018-04-01

    In the CLARITY (CLAdRIbine Tablets treating multiple sclerosis orallY) study, Cladribine Tablets significantly improved clinical and magnetic resonance imaging (MRI) outcomes (vs placebo) in patients with relapsing-remitting multiple sclerosis. Describe two clinically relevant definitions for patients with high disease activity (HDA) at baseline of the CLARITY study (utility verified in patients receiving placebo) and assess the treatment effects of Cladribine Tablets 3.5 mg/kg compared with the overall study population. Outcomes of patients randomised to Cladribine Tablets 3.5 mg/kg or placebo were analysed for subgroups using HDA definitions based on high relapse activity (HRA; patients with ⩾2 relapses during the year prior to study entry, whether on DMD treatment or not) or HRA plus disease activity on treatment (HRA + DAT; patients with ⩾2 relapses during the year prior to study entry, whether on DMD treatment or not, PLUS patients with ⩾1 relapse during the year prior to study entry while on therapy with other DMDs and ⩾1 T1 Gd+ or ⩾9 T2 lesions). In the overall population, Cladribine Tablets 3.5 mg/kg reduced the risk of 6-month-confirmed Expanded Disability Status Scale (EDSS) worsening by 47% vs placebo. A risk reduction of 82% vs placebo was seen in both the HRA and HRA + DAT subgroups (vs 19% for non-HRA and 18% for non-HRA + DAT), indicating greater responsiveness to Cladribine Tablets 3.5 mg/kg in patients with HDA. There were consistent results for other efficacy endpoints. The safety profile in HDA patients was consistent with the overall CLARITY population. Patients with HDA showed clinical and MRI responses to Cladribine Tablets 3.5 mg/kg that were generally better than, or at least comparable with, the outcomes seen in the overall CLARITY population.

  12. Prolonged survival in patients with breast cancer and a history of brain metastases: results of a preplanned subgroup analysis from the randomized phase III BEACON trial.

    Science.gov (United States)

    Cortés, Javier; Rugo, Hope S; Awada, Ahmad; Twelves, Chris; Perez, Edith A; Im, Seock-Ah; Gómez-Pardo, Patricia; Schwartzberg, Lee S; Diéras, Veronique; Yardley, Denise A; Potter, David A; Mailliez, Audrey; Moreno-Aspitia, Alvaro; Ahn, Jin-Seok; Zhao, Carol; Hoch, Ute; Tagliaferri, Mary; Hannah, Alison L; O'Shaughnessy, Joyce

    2017-09-01

    Conventional chemotherapy has limited activity in patients with breast cancer and brain metastases (BCBM). Etirinotecan pegol (EP), a novel long-acting topoisomerase-1 inhibitor, was designed using advanced polymer technology to preferentially accumulate in tumor tissue including brain metastases, providing sustained cytotoxic SN38 levels. The phase 3 BEACON trial enrolled 852 women with heavily pretreated locally recurrent or metastatic breast cancer between 2011 and 2013. BEACON compared EP with treatment of physician's choice (TPC; eribulin, vinorelbine, gemcitabine, nab-paclitaxel, paclitaxel, ixabepilone, or docetaxel) in patients previously treated with anthracycline, taxane, and capecitabine, including those with treated, stable brain metastases. The primary endpoint, overall survival (OS), was assessed in a pre-defined subgroup of BCBM patients; an exploratory post hoc analysis adjusting for the diagnosis-specific graded prognostic assessment (GPA) index was also conducted. In the trial, 67 BCBM patients were randomized (EP, n = 36; TPC, n = 31). Treatment subgroups were balanced for baseline characteristics and GPA indices. EP was associated with a significant reduction in the risk of death (HR 0.51; P BEACON population, fewer patients on EP experienced grade ≥3 toxicity (50 vs. 70%). The significant improvement in survival in BCBM patients provides encouraging data for EP in this difficult-to-treat subgroup of patients. A phase three trial of EP in BCBM patients is underway (ClinicalTrials.gov NCT02915744).

  13. Patterns and Risk Factors of Soil-Transmitted Helminthiasis Among Orang Asli Subgroups in Peninsular Malaysia.

    Science.gov (United States)

    Ngui, Romano; Aziz, Shafie; Chua, Kek Heng; Aidil, Roslan Muhammad; Lee, Soo Ching; Tan, Tiong Kai; Sani, Mistam Mohd; Arine, Ahmad Fadzlun; Rohela, Mahmud; Lim, Yvonne A L

    2015-08-01

    A cross-sectional study was conducted to provide comprehensive data on the patterns and associated risk factors of soil-transmitted helminth (STH) infections among five Orang Asli subgroups in Peninsular Malaysia. The overall prevalence of STH infections was 59.9% (95% confidence interval [CI] = 56.1-63.7%). Trichuris trichiura (54.3%; 95% CI = 50.4-58.2%) was the predominant species followed by Ascaris lumbricoides (26.7%; 95% CI = 23.3-30.1%) and hookworm (9.1%; 95% CI = 6.9-11.3%). This study showed diversity for STH infections by subgroup with poverty and personal sanitary behavior as important risk factors for infection. Risk profile analyses indicating that Orang Kuala subgroup who has a generally well-developed infrastructure and better quality of life had a low rate of infection. There is a need for poverty reduction and promotion of deworming programs along with mass scale campaigns to create awareness about health and hygiene to reduce STH infections. © The American Society of Tropical Medicine and Hygiene.

  14. Infinite families of superintegrable systems separable in subgroup coordinates

    International Nuclear Information System (INIS)

    Lévesque, Daniel; Post, Sarah; Winternitz, Pavel

    2012-01-01

    A method is presented that makes it possible to embed a subgroup separable superintegrable system into an infinite family of systems that are integrable and exactly-solvable. It is shown that in two dimensional Euclidean or pseudo-Euclidean spaces the method also preserves superintegrability. Two infinite families of classical and quantum superintegrable systems are obtained in two-dimensional pseudo-Euclidean space whose classical trajectories and quantum eigenfunctions are investigated. In particular, the wave-functions are expressed in terms of Laguerre and generalized Bessel polynomials. (paper)

  15. Anticancer Properties of Distinct Antimalarial Drug Classes

    Science.gov (United States)

    Hooft van Huijsduijnen, Rob; Guy, R. Kiplin; Chibale, Kelly; Haynes, Richard K.; Peitz, Ingmar; Kelter, Gerhard; Phillips, Margaret A.; Vennerstrom, Jonathan L.; Yuthavong, Yongyuth; Wells, Timothy N. C.

    2013-01-01

    We have tested five distinct classes of established and experimental antimalarial drugs for their anticancer potential, using a panel of 91 human cancer lines. Three classes of drugs: artemisinins, synthetic peroxides and DHFR (dihydrofolate reductase) inhibitors effected potent inhibition of proliferation with IC50s in the nM- low µM range, whereas a DHODH (dihydroorotate dehydrogenase) and a putative kinase inhibitor displayed no activity. Furthermore, significant synergies were identified with erlotinib, imatinib, cisplatin, dasatinib and vincristine. Cluster analysis of the antimalarials based on their differential inhibition of the various cancer lines clearly segregated the synthetic peroxides OZ277 and OZ439 from the artemisinin cluster that included artesunate, dihydroartemisinin and artemisone, and from the DHFR inhibitors pyrimethamine and P218 (a parasite DHFR inhibitor), emphasizing their shared mode of action. In order to further understand the basis of the selectivity of these compounds against different cancers, microarray-based gene expression data for 85 of the used cell lines were generated. For each compound, distinct sets of genes were identified whose expression significantly correlated with compound sensitivity. Several of the antimalarials tested in this study have well-established and excellent safety profiles with a plasma exposure, when conservatively used in malaria, that is well above the IC50s that we identified in this study. Given their unique mode of action and potential for unique synergies with established anticancer drugs, our results provide a strong basis to further explore the potential application of these compounds in cancer in pre-clinical or and clinical settings. PMID:24391728

  16. Anticancer properties of distinct antimalarial drug classes.

    Directory of Open Access Journals (Sweden)

    Rob Hooft van Huijsduijnen

    Full Text Available We have tested five distinct classes of established and experimental antimalarial drugs for their anticancer potential, using a panel of 91 human cancer lines. Three classes of drugs: artemisinins, synthetic peroxides and DHFR (dihydrofolate reductase inhibitors effected potent inhibition of proliferation with IC50s in the nM- low µM range, whereas a DHODH (dihydroorotate dehydrogenase and a putative kinase inhibitor displayed no activity. Furthermore, significant synergies were identified with erlotinib, imatinib, cisplatin, dasatinib and vincristine. Cluster analysis of the antimalarials based on their differential inhibition of the various cancer lines clearly segregated the synthetic peroxides OZ277 and OZ439 from the artemisinin cluster that included artesunate, dihydroartemisinin and artemisone, and from the DHFR inhibitors pyrimethamine and P218 (a parasite DHFR inhibitor, emphasizing their shared mode of action. In order to further understand the basis of the selectivity of these compounds against different cancers, microarray-based gene expression data for 85 of the used cell lines were generated. For each compound, distinct sets of genes were identified whose expression significantly correlated with compound sensitivity. Several of the antimalarials tested in this study have well-established and excellent safety profiles with a plasma exposure, when conservatively used in malaria, that is well above the IC50s that we identified in this study. Given their unique mode of action and potential for unique synergies with established anticancer drugs, our results provide a strong basis to further explore the potential application of these compounds in cancer in pre-clinical or and clinical settings.

  17. De Novo and Inherited Loss-of-Function Variants in TLK2: Clinical and Genotype-Phenotype Evaluation of a Distinct Neurodevelopmental Disorder.

    Science.gov (United States)

    Reijnders, Margot R F; Miller, Kerry A; Alvi, Mohsan; Goos, Jacqueline A C; Lees, Melissa M; de Burca, Anna; Henderson, Alex; Kraus, Alison; Mikat, Barbara; de Vries, Bert B A; Isidor, Bertrand; Kerr, Bronwyn; Marcelis, Carlo; Schluth-Bolard, Caroline; Deshpande, Charu; Ruivenkamp, Claudia A L; Wieczorek, Dagmar; Baralle, Diana; Blair, Edward M; Engels, Hartmut; Lüdecke, Hermann-Josef; Eason, Jacqueline; Santen, Gijs W E; Clayton-Smith, Jill; Chandler, Kate; Tatton-Brown, Katrina; Payne, Katelyn; Helbig, Katherine; Radtke, Kelly; Nugent, Kimberly M; Cremer, Kirsten; Strom, Tim M; Bird, Lynne M; Sinnema, Margje; Bitner-Glindzicz, Maria; van Dooren, Marieke F; Alders, Marielle; Koopmans, Marije; Brick, Lauren; Kozenko, Mariya; Harline, Megan L; Klaassens, Merel; Steinraths, Michelle; Cooper, Nicola S; Edery, Patrick; Yap, Patrick; Terhal, Paulien A; van der Spek, Peter J; Lakeman, Phillis; Taylor, Rachel L; Littlejohn, Rebecca O; Pfundt, Rolph; Mercimek-Andrews, Saadet; Stegmann, Alexander P A; Kant, Sarina G; McLean, Scott; Joss, Shelagh; Swagemakers, Sigrid M A; Douzgou, Sofia; Wall, Steven A; Küry, Sébastien; Calpena, Eduardo; Koelling, Nils; McGowan, Simon J; Twigg, Stephen R F; Mathijssen, Irene M J; Nellaker, Christoffer; Brunner, Han G; Wilkie, Andrew O M

    2018-06-07

    Next-generation sequencing is a powerful tool for the discovery of genes related to neurodevelopmental disorders (NDDs). Here, we report the identification of a distinct syndrome due to de novo or inherited heterozygous mutations in Tousled-like kinase 2 (TLK2) in 38 unrelated individuals and two affected mothers, using whole-exome and whole-genome sequencing technologies, matchmaker databases, and international collaborations. Affected individuals had a consistent phenotype, characterized by mild-borderline neurodevelopmental delay (86%), behavioral disorders (68%), severe gastro-intestinal problems (63%), and facial dysmorphism including blepharophimosis (82%), telecanthus (74%), prominent nasal bridge (68%), broad nasal tip (66%), thin vermilion of the upper lip (62%), and upslanting palpebral fissures (55%). Analysis of cell lines from three affected individuals showed that mutations act through a loss-of-function mechanism in at least two case subjects. Genotype-phenotype analysis and comparison of computationally modeled faces showed that phenotypes of these and other individuals with loss-of-function variants significantly overlapped with phenotypes of individuals with other variant types (missense and C-terminal truncating). This suggests that haploinsufficiency of TLK2 is the most likely underlying disease mechanism, leading to a consistent neurodevelopmental phenotype. This work illustrates the power of international data sharing, by the identification of 40 individuals from 26 different centers in 7 different countries, allowing the identification, clinical delineation, and genotype-phenotype evaluation of a distinct NDD caused by mutations in TLK2. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  18. Distinct clinical characteristics and therapeutic modalities for diabetic ketoacidosis in type 1 and type 2 diabetes mellitus.

    Science.gov (United States)

    Kamata, Yuji; Takano, Koji; Kishihara, Eriko; Watanabe, Michiko; Ichikawa, Raishi; Shichiri, Masayoshi

    2017-02-01

    Patients with type 1 diabetes often develop diabetic ketoacidosis (DKA). Reportedly, DKA in type 2 diabetes has higher mortality despite its limited occurrence. The exact clinical characteristics and therapeutic modalities yielding successful outcomes in DKA type 2 diabetes remain unknown. This retrospective study compared the clinical features and detailed treatment of consecutive type 1 and type 2 diabetes patients hospitalized with DKA between January 2001 and December 2014. We report on 127 patients with type 1 and 74 patients with type 2 diabetes whose DKA was successfully treated. The most frequent precipitating cause for DKA was infectious disease for patients with type 1 diabetes and consumption of sugar-containing beverages for those with type 2 diabetes. Type 2 diabetes patients showed higher mean plasma glucose levels than those with type 1 diabetes (48.4±21.6, vs. 37.1±16.4mmol/l, P1) and higher serum creatinine, blood urea nitrogen, and hemoglobin levels, which normalized after DKA resolution. Compared with type 1 diabetes patients, those with type 2 diabetes required distinctly higher daily total insulin dosage (35.9±37.0U, vs. 20.2±23.3U, P1), larger replacement fluid volumes (4.17±2.69L, vs. 2.29±1.57L, P1) and greater potassium supplementation (23.9±36.5mEq, vs. 11.2±17.9mEq, P1) to resolve DKA and reduce plasma glucose level to ≤16.7mmol/l. DKA patients with type 2 diabetes required management with a modified treatment protocol to resolve their profound hyperglycemia and dehydration compared with those with type 1 diabetes. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Distinct clinical characteristics and helminth co-infections in adult tuberculosis patients from urban compared to rural Tanzania.

    Science.gov (United States)

    Sikalengo, George; Hella, Jerry; Mhimbira, Francis; Rutaihwa, Liliana K; Bani, Farida; Ndege, Robert; Sasamalo, Mohamed; Kamwela, Lujeko; Said, Khadija; Mhalu, Grace; Mlacha, Yeromin; Hatz, Christoph; Knopp, Stefanie; Gagneux, Sébastien; Reither, Klaus; Utzinger, Jürg; Tanner, Marcel; Letang, Emilio; Weisser, Maja; Fenner, Lukas

    2018-03-24

    Differences in rural and urban settings could account for distinct characteristics in the epidemiology of tuberculosis (TB). We comparatively studied epidemiological features of TB and helminth co-infections in adult patients from rural and urban settings of Tanzania. Adult patients (≥ 18 years) with microbiologically confirmed pulmonary TB were consecutively enrolled into two cohorts in Dar es Salaam, with ~ 4.4 million inhabitants (urban), and Ifakara in the sparsely populated Kilombero District with ~ 400 000 inhabitants (rural). Clinical data were obtained at recruitment. Stool and urine samples were subjected to diagnose helminthiases using Kato-Katz, Baermann, urine filtration, and circulating cathodic antigen tests. Differences between groups were assessed by χ 2 , Fisher's exact, and Wilcoxon rank sum tests. Logistic regression models were used to determine associations. Between August 2015 and February 2017, 668 patients were enrolled, 460 (68.9%) at the urban and 208 (31.1%) at the rural site. Median patient age was 35 years (interquartile range [IQR]: 27-41.5 years), and 454 (68%) were males. Patients from the rural setting were older (median age 37 years vs. 34 years, P = 0.003), had a lower median body mass index (17.5 kg/m 2 vs. 18.5 kg/m 2 , P urban Tanzania. There was no significant difference in frequencies of HIV infection, diabetes mellitus, and haemoglobin concentration levels between the two settings. The overall prevalence of helminth co-infections was 22.9% (95% confidence interval [CI]: 20.4-27.0%). The significantly higher prevalence of helminth infections at the urban site (25.7% vs. 17.3%, P = 0.018) was predominantly driven by Strongyloides stercoralis (17.0% vs. 4.8%, P rural setting (adjusted odds ratio [aOR]: 3.97, 95% CI: 1.16-13.67) and increasing age (aOR: 1.06, 95% CI: 1.02-1.10). Clinical characteristics and helminth co-infections pattern differ in TB patients in urban and rural Tanzania. The

  20. Everolimus in advanced, progressive, well-differentiated, non-functional neuroendocrine tumors: RADIANT-4 lung subgroup analysis.

    Science.gov (United States)

    Fazio, Nicola; Buzzoni, Roberto; Delle Fave, Gianfranco; Tesselaar, Margot E; Wolin, Edward; Van Cutsem, Eric; Tomassetti, Paola; Strosberg, Jonathan; Voi, Maurizio; Bubuteishvili-Pacaud, Lida; Ridolfi, Antonia; Herbst, Fabian; Tomasek, Jiri; Singh, Simron; Pavel, Marianne; Kulke, Matthew H; Valle, Juan W; Yao, James C

    2018-01-01

    In the phase III RADIANT-4 study, everolimus improved median progression-free survival (PFS) by 7.1 months in patients with advanced, progressive, well-differentiated (grade 1 or grade 2), non-functional lung or gastrointestinal neuroendocrine tumors (NETs) vs placebo (hazard ratio, 0.48; 95% confidence interval [CI], 0.35-0.67; P < .00001). This exploratory analysis reports the outcomes of the subgroup of patients with lung NETs. In RADIANT-4, patients were randomized (2:1) to everolimus 10 mg/d or placebo, both with best supportive care. This is a post hoc analysis of the lung subgroup with PFS, by central radiology review, as the primary endpoint; secondary endpoints included objective response rate and safety measures. Ninety of the 302 patients enrolled in the study had primary lung NET (everolimus, n = 63; placebo, n = 27). Median PFS (95% CI) by central review was 9.2 (6.8-10.9) months in the everolimus arm vs 3.6 (1.9-5.1) months in the placebo arm (hazard ratio, 0.50; 95% CI, 0.28-0.88). More patients who received everolimus (58%) experienced tumor shrinkage compared with placebo (13%). Most frequently reported (≥5% incidence) grade 3-4 drug-related adverse events (everolimus vs. placebo) included stomatitis (11% vs. 0%), hyperglycemia (10% vs. 0%), and any infections (8% vs. 0%). In patients with advanced, progressive, well-differentiated, non-functional lung NET, treatment with everolimus was associated with a median PFS improvement of 5.6 months, with a safety profile similar to that of the overall RADIANT-4 cohort. These results support the use of everolimus in patients with advanced, non-functional lung NET. The trial is registered with ClinicalTrials.gov (no. NCT01524783). © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  1. Pediatric schwannomatosis, a rare but distinct form of neurofibromatosis

    Energy Technology Data Exchange (ETDEWEB)

    Thomas, Anna K. [University of Tennessee Health Science Center, Department of Radiology, Le Bonheur Children' s Hospital, Memphis, TN (United States); Egelhoff, John C.; Curran, John G. [Phoenix Children' s Hospital, Department of Radiology, Phoenix, AZ (United States); Thomas, Bobby

    2016-03-15

    Schwannomatosis is the third major form of neurofibromatosis, distinct from neurofibromatosis type 2 (NF2) and type 1 (NF1). This condition is rare with a variable phenotypic presentation and complex molecular and genetic findings. In this case, a previously healthy teenager was found to have multiple spinal lesions and an enhancing right parotid mass on MRI. On extensive further work-up, this patient met the existing clinical criteria for schwannomatosis. This case report aims to review the clinical features and current diagnostic criteria for schwannomatosis and compare it to NF1 and NF2. Special emphasis will be placed on imaging features that should prompt the radiologist to suggest this rare diagnosis. (orig.)

  2. Keele Aches and Pains Study protocol: validity, acceptability, and feasibility of the Keele STarT MSK tool for subgrouping musculoskeletal patients in primary care

    Directory of Open Access Journals (Sweden)

    Campbell P

    2016-10-01

    Full Text Available Paul Campbell,1 Jonathan C Hill,1 Joanne Protheroe,1 Ebenezer K Afolabi,1 Martyn Lewis,1 Ruth Beardmore,1 Elaine M Hay,1 Christian D Mallen,1 Bernadette Bartlam,1 Benjamin Saunders,1 Danielle A van der Windt,1 Sue Jowett,2 Nadine E Foster,1 Kate M Dunn1 1Arthritis Research UK Primary Care Centre, Research Institute of Primary Care and Health Sciences, Keele University, Keele, 2Health Economics Unit, University of Birmingham, Birmingham, UK Abstract: Musculoskeletal conditions represent a considerable burden worldwide, and are predominantly managed in primary care. Evidence suggests that many musculoskeletal conditions share similar prognostic factors. Systematically assessing patient’s prognosis and matching treatments based on prognostic subgroups (stratified care has been shown to be both clinically effective and cost-effective. This study (Keele Aches and Pains Study aims to refine and examine the validity of a brief questionnaire (Keele STarT MSK tool designed to enable risk stratification of primary care patients with the five most common musculoskeletal pain presentations. We also describe the subgroups of patients, and explore the acceptability and feasibility of using the tool and how the tool is best implemented in clinical practice. The study design is mixed methods: a prospective, quantitative observational cohort study with a linked qualitative focus group and interview study. Patients who have consulted their GP or health care practitioner about a relevant musculoskeletal condition will be recruited from general practice. Participating patients will complete a baseline questionnaire (shortly after consultation, plus questionnaires 2 and 6 months later. A subsample of patients, along with participating GPs and health care practitioners, will be invited to take part in qualitative focus groups and interviews. The Keele STarT MSK tool will be refined based on face, discriminant, construct, and predictive validity at baseline and 2

  3. Responsiveness of Clinical Outcome Measures

    DEFF Research Database (Denmark)

    Lauridsen, Henrik Hein

    Background The Oswestry Disability Index (ODI) is one of two standardised functional health measurement scales (HMS) recommended. Despite extensive psychometric testing, little is known about HMS behaviour and the minimal clinically important difference (MCID) in subgroups of LBP patients. Moreover...... obtainable by a certain treatment. Chronic LBP patients seem to have a reasonable idea of an acceptable change in pain but overestimate change in functional and psychological /affective domains....

  4. High-risk subgroup of inferior myocardial infarction. Importance of anterior wall motion and right ventricular function

    Energy Technology Data Exchange (ETDEWEB)

    Nishimura, Tsunehiko; Yasuda, Tsunehiro; Gold, H K; Leinbach, R C; Boucher, C A; McKusick, K A; Strauss, H W

    1986-12-01

    To identify high-risk subgroups of inferior myocardial infarction, 75 patients presenting with their first inferior infarction were investigated by sequential gated blood pool scans. The patients were divided into four groups based on the right ventricular function (RVF) and anterior wall motion (AWM) of the left ventricle by scan at the time of admission. A second blood pool scan was performed at ten days to evaluate RV and LV function. Thirty-eight patients had cardiac catheterization before discharge and all patients were followed up for one year to determine their clinical outcome. Depressed RVF and reduced AWM were observed in 26 (35%) (Group A); depressed RVF and normal AWM were found in 20 (27%) (Group B); reduced AWM and normal RVE in 10 (13%) (Group C); and normal RVF and AWM in 19 (25%) (Group D). The mean values of biventricular function (LVEF, RVEF) in groups A, B, C, and D were (44.9 +- 8.4%, 32.5 +- 9.9%), (59.9 +- 8.6%, 34.5 +- 8.0%), (44.9 +- 15.7%, 48.2 +- 3.3%), and (60.4 +- 9.1%, 51.6 +- 10.6%), respectively, at admission. In serial measurements, LVEF did not change significantly in any group, however, RVEF improved nearly 10 points in groups A and B at 10 days. Group A also had the highest incidence (82 %) of left anterior descending coronary artery involvement, and the highest mean creatine phosphokinase levels (762 +- 318 U/1): Furthermore, group A had a high incidence of major complications during their hospital course and high mortality during the one-year follow-up. These data clearly identified group A as a high-risk subgroup of patients with inferior infarction.

  5. SiglecF+Gr1hi eosinophils are a distinct subpopulation within the lungs of allergen-challenged mice.

    Science.gov (United States)

    Percopo, Caroline M; Brenner, Todd A; Ma, Michelle; Kraemer, Laura S; Hakeem, Reem M A; Lee, James J; Rosenberg, Helene F

    2017-01-01

    Although eosinophils as a group are readily identified by their unique morphology and staining properties, flow cytometry provides an important means for identification of subgroups based on differential expression of distinct surface Ags. Here, we characterize an eosinophil subpopulation defined by high levels of expression of the neutrophil Ag Gr1 (CD45 + CD11c - SiglecF + Gr1 hi ). SiglecF + Gr1 hi eosinophils, distinct from the canonical SiglecF + Gr1 - eosinophil population, were detected in allergen-challenged wild-type and granule protein-deficient (EPX -/- and MBP-1 -/- ) mice, but not in the eosinophil-deficient ΔdblGATA strain. In contrast to Gr1 + neutrophils, which express both cross-reacting Ags Ly6C and Ly6G, SiglecF + Gr1 hi eosinophils from allergen-challenged lung tissue are uniquely Ly6G + Although indistinguishable from the more-numerous SiglecF + Gr1 - eosinophils under light microscopy, FACS-isolated populations revealed prominent differences in cytokine contents. The lymphocyte-targeting cytokines CXCL13 and IL-27 were identified only in the SiglecF + Gr1 hi eosinophil population (at 3.9 and 4.8 pg/10 6 cells, respectively), as was the prominent proinflammatory mediator IL-13 (72 pg/10 6 cells). Interestingly, bone marrow-derived (SiglecF + ), cultured eosinophils include a more substantial Gr1 + subpopulation (∼50%); Gr1 + bmEos includes primarily a single Ly6C + and a smaller, double-positive (Ly6C + Ly6G + ) population. Taken together, our findings characterize a distinct SiglecF + Gr1 hi eosinophil subset in lungs of allergen-challenged, wild-type and granule protein-deficient mice. SiglecF + Gr1 hi eosinophils from wild-type mice maintain a distinct subset of cytokines, including those active on B and T lymphocytes. These cytokines may facilitate eosinophil-mediated immunomodulatory responses in the allergen-challenged lung as well as in other distinct microenvironments. © Society for Leukocyte Biology.

  6. PTSD's factor structure and measurement invariance across subgroups with differing count of trauma types.

    Science.gov (United States)

    Contractor, Ateka A; Caldas, Stephanie V; Dolan, Megan; Lagdon, Susan; Armour, Chérie

    2018-06-01

    To investigate the effect of the count of traumatizing event (TE) types on post-trauma mental health, several studies have compared posttraumatic stress disorder (PTSD) severity between individuals experiencing one versus multiple TE types. However, the validity of these studies depends on the establishment of measurement invariance of the construct(s) of interest. The current study examined the stability of the most optimal PTSD Model symptom cluster constructs (assessed by the PTSD Checklist for DSM-5 [PCL-5]) across subgroups experiencing one versus multiple TE types. The sample included university students (n = 556) endorsing at least one TE (Stressful Life Events Screening Questionnaire). Using data from the entire sample, results suggest that the PCL-5-assessed Hybrid Model provided a significantly better fit compared to other models. Results also indicated invariance of factor loadings (metric), and intercepts (scalar) for the PCL-5-assessed Hybrid Model factors across subgroups endorsing one (n = 191) versus multiple TE types (n = 365). Our findings thus support the stability, applicability, and meaningful comparison of the PCL-assessed Hybrid Model factor structure (including subscale severity scores) across subgroups experiencing one versus multiple TE types. Copyright © 2018 Elsevier B.V. All rights reserved.

  7. Thiocarbomide coordination compounds of yttrium subgroup rare earth chlorides

    International Nuclear Information System (INIS)

    Sakharova, Yu.G.; Perov, V.N.; Loginov, V.I.

    1978-01-01

    Thiocarbamide coordination compounds of chlorides of elements of the yttrium subgroup 4MeCl 3 x5Cs(NH 2 ) 2 x2OH 2 O (where Me stands for Tb, Dy, Ho, Er, Tm, Yb, Lu, Y) were produced for the first time. The compounds obtained are stable in air, have definite melting points, are highly soluble in methyl and ethyl alcohols, and are unstable in water. They recrystallize from ethyl alcohol without changing their chemical composition. The identity of these compounds was confirmed by X-ray analysis

  8. Pleomorphic Malignant Mesothelioma in a Broiler Breeder Infected with Avian Leucosis Virus Subgroup J.

    Science.gov (United States)

    Murakami, T; Sassa, Y

    2018-04-01

    Avian leucosis virus (ALV) is an oncogenic retrovirus that induces tumours including lymphoid leucosis and myeloid leucosis. Pleomorphic malignant mesothelioma and myelocytoma, which were thought to be induced by ALV subgroup J (ALV-J) infection, were identified in a 432-day-old broiler breeder. The bird showed no clinical signs; however, at necropsy examination there were multiple nodules in the alimentary tract. Microscopical analysis showed that these consisted of pleomorphic cells and myelocyte-like cells. Immunohistochemistry revealed that the pleomorphic cells were atypical and expressed cytokeratin, vimentin, c-kit, calretinin and ALV. The myelocyte-like cells were also positive for ALV. Retroviral type C particles were observed by electron microscopy. ALV-E and ALV-J nucleotide sequences were detected in DNA extracted from formalin-fixed and paraffin wax-embedded small intestinal tissue. Based on these results, the tumours were diagnosed as pleomorphic malignant mesothelioma and myelocytoma and were thought to have been induced by ALV-J infection. This is the first report of malignant mesothelioma associated with naturally acquired ALV-J infection. Copyright © 2018 Elsevier Ltd. All rights reserved.

  9. Quantum algorithms for the hidden subgroup problem on some semi-direct product groups by reduction to Abelian cases

    International Nuclear Information System (INIS)

    Chi, Dong Pyo; Kim, Jeong San; Lee, Soojoon

    2006-01-01

    We consider the hidden subgroup problem on the semi-direct product of cyclic groups Z N -bar Z p , where p is a prime that does not divide p j -1 for any of the prime factors p j of N, and show that the hidden subgroup problem can be reduced to other ones for which solutions are already known

  10. Contribution of Dietary Supplements to Nutritional Adequacy by Socioeconomic Subgroups in Adults of the United States

    Directory of Open Access Journals (Sweden)

    Jeffrey B. Blumberg

    2017-12-01

    Full Text Available Many Americans have inadequate intakes of several nutrients, and the Dietary Guidelines for Americans 2015–2020 identified vitamins A, C, D, and E, in addition to calcium, magnesium, iron, potassium, choline, and fiber as “underconsumed nutrients”. Based on nationally representative data on 10,698 adults from National Health and Nutrition Examination Surveys (NHANES, 2009–2012, assessments were made of socioeconomic differences, based on the Poverty Income Ratio (PIR, in terms of the association of dietary supplement use on nutrient intake and nutrient inadequacies. Compared to food alone, the use of any dietary supplement plus food was associated with significantly (p < 0.01 higher intakes of 15–16 of 19 nutrients examined in all socioeconomic groups; and significantly reduced rates of inadequacy for 10/17 nutrients in the subgroup PIR > 1.85 (not poor, but only 4–5/17 nutrients (calcium and vitamins A, C, D, E for the poor and nearly poor subgroups (PIR < 1.35 and PIR 1.35 to ≤1.85, respectively. An increased prevalence of intakes above the Tolerable Upper Intake Level (UL was seen for 3–9/13 nutrients, but all were less than 5% in the PIR subgroups. In conclusion, dietary supplement use was associated with an increased micronutrient intake, decreased inadequacies, and a slight increase in the prevalence of intakes above the UL, with greater benefits seen in the PIR > 1.85 subgroup.

  11. Low birthweight among US Hispanic/Latino subgroups: the effect of maternal foreign-born status and education.

    Science.gov (United States)

    Acevedo-Garcia, Dolores; Soobader, Mah-J; Berkman, Lisa F

    2007-12-01

    We investigated whether maternal foreign-born status confers a protective effect against low birthweight (LBW) across US Hispanic/Latino subgroups (i.e., Mexicans, Puerto Ricans, Cubans and Central/South Americans) in the USA, and whether the association between maternal education and LBW varies by Hispanic/Latino subgroup and by foreign-born status. We conducted logistic regression analyses of the 2002 US Natality Detail Data (n=634,797). Overall, foreign-born Latino women are less likely to have LBW infants than US-born Latino women. The protective effect of foreign-born status is stronger among Latino women with less than high school education. The maternal education gradient is significantly flatter among foreign-born Latino women than among their US-born counterparts (peducation (i.e., 0-11 and 12 years) than among women with more education (i.e., 13-15 and 16+ years). The educational gradient in LBW is less pronounced among foreign-born Mexicans and Central/South Americans than among their US-born counterparts. As such, maternal foreign-born status and education are associated with LBW, though the direction and strength of these associations vary across Latino subgroups. A "health paradox" is apparent for foreign-born Mexican and Central/South American women among whom there is a weak maternal educational gradient in LBW. Future research may test hypotheses regarding the mechanisms underlying these variations in LBW among Latino subgroups, i.e., different gradients in sending countries, health selection of immigrants, cultural factors, and social support.

  12. Gene expression profiling reveals distinct molecular signatures associated with the rupture of intracranial aneurysm.

    Science.gov (United States)

    Nakaoka, Hirofumi; Tajima, Atsushi; Yoneyama, Taku; Hosomichi, Kazuyoshi; Kasuya, Hidetoshi; Mizutani, Tohru; Inoue, Ituro

    2014-08-01

    The rupture of intracranial aneurysm (IA) causes subarachnoid hemorrhage associated with high morbidity and mortality. We compared gene expression profiles in aneurysmal domes between unruptured IAs and ruptured IAs (RIAs) to elucidate biological mechanisms predisposing to the rupture of IA. We determined gene expression levels of 8 RIAs, 5 unruptured IAs, and 10 superficial temporal arteries with the Agilent microarrays. To explore biological heterogeneity of IAs, we classified the samples into subgroups showing similar gene expression patterns, using clustering methods. The clustering analysis identified 4 groups: superficial temporal arteries and unruptured IAs were aggregated into their own clusters, whereas RIAs segregated into 2 distinct subgroups (early and late RIAs). Comparing gene expression levels between early RIAs and unruptured IAs, we identified 430 upregulated and 617 downregulated genes in early RIAs. The upregulated genes were associated with inflammatory and immune responses and phagocytosis including S100/calgranulin genes (S100A8, S100A9, and S100A12). The downregulated genes suggest mechanical weakness of aneurysm walls. The expressions of Krüppel-like family of transcription factors (KLF2, KLF12, and KLF15), which were anti-inflammatory regulators, and CDKN2A, which was located on chromosome 9p21 that was the most consistently replicated locus in genome-wide association studies of IA, were also downregulated. We demonstrate that gene expression patterns of RIAs were different according to the age of patients. The results suggest that macrophage-mediated inflammation is a key biological pathway for IA rupture. The identified genes can be good candidates for molecular markers of rupture-prone IAs and therapeutic targets. © 2014 American Heart Association, Inc.

  13. Scrub typhus: radiological and clinical findings in abdominopelvic involvement.

    Science.gov (United States)

    Kim, Kun Yung; Song, Ji Soo; Park, Eun Hae; Jin, Gong Yong

    2017-03-01

    To describe the clinical and radiological findings of abdominopelvic involvement in scrub typhus. Abdominopelvic computed tomography (CT) of 78 patients with scrub typhus were evaluated by two readers. The presence of gallbladder wall thickening, arterial inhomogeneous enhancement of the liver, periportal edema, splenic infarction, hepatomegaly, splenomegaly, ascites, pleural effusion, and sites of lymphadenopathy were evaluated. Patients were divided into four clinical subgroups according to laboratory findings. Association between imaging findings and subgroups was analyzed by Chi squared test or Fisher's exact test. The most common CT finding was hepatomegaly (74.4%), followed by splenomegaly (66.7%). The majority of patients had at least three areas of abdominopelvic lymphadenopathy (71.8%). Pelvic lymphadenopathy was most commonly seen when eschar was found in the ipsilateral lower extremity (left, n = 5/7; right, n = 8/13). Significant association between hepatic dysfunction and perigastric lymphadenopathy was documented (p = 0.03). Scrub typhus has a spectrum of variable clinical and radiological findings mimicking those of acute hepatitis. Diffuse abdominopelvic lymphadenopathy involving the retroperitoneum and pelvic area may aid in early diagnosis of scrub typhus. Perigastric lymphadenopathy could be a sign of severe scrub typhus combined with hepatic dysfunction.

  14. Frequency of ABO, subgroup ABO and Rh(D) blood groups in major sudanese ethnic groups

    International Nuclear Information System (INIS)

    Hassan, F.M.

    2010-01-01

    Background: There are differences in the distribution of ABO, sub group A BO and Rh(D) blood groups in different populations of the world. Relatively little information is available about blood group distributions in Sudanese population. To see the frequency of ABO, subgroup ABO and Rh(D) blood groups in major Sudanese ethnic groups(Danagla Shaygia and Gaaleen). Blood testing for ABO, subgroup ABO and Rh(D) typing was done over six months, in 300 unrelated individuals, from both genders. Blood samples were collected from students of the college of medical laboratory science - Sudan University of Science and Technology using finger prick method and following routine slide method. Blood group 'O' was the most predominant ( 52.7%) in both Rh positive and negative subjects followed by blood group A, B and AB. Majority (98.0%)o f the subjects were Rh(D) positive and only 2% were Rh negative. The predominant subgroup of ABO was A2 (14.1% ). The frequency of ABO blood groups in both Rh positive and negative subjects among the major Sudanese ethnic group was similar to that reported from neighbouring regions. (author)

  15. Topic Modeling Reveals Distinct Interests within an Online Conspiracy Forum

    Directory of Open Access Journals (Sweden)

    Colin Klein

    2018-02-01

    Full Text Available Conspiracy theories play a troubling role in political discourse. Online forums provide a valuable window into everyday conspiracy theorizing, and can give a clue to the motivations and interests of those who post in such forums. Yet this online activity can be difficult to quantify and study. We describe a unique approach to studying online conspiracy theorists which used non-negative matrix factorization to create a topic model of authors' contributions to the main conspiracy forum on Reddit.com. This subreddit provides a large corpus of comments which spans many years and numerous authors. We show that within the forum, there are multiple sub-populations distinguishable by their loadings on different topics in the model. Further, we argue, these differences are interpretable as differences in background beliefs and motivations. The diversity of the distinct subgroups places constraints on theories of what generates conspiracy theorizing. We argue that traditional “monological” believers are only the tip of an iceberg of commenters. Neither simple irrationality nor common preoccupations can account for the observed diversity. Instead, we suggest, those who endorse conspiracies seem to be primarily brought together by epistemological concerns, and that these central concerns link an otherwise heterogenous group of individuals.

  16. Using a psychosocial subgroup assignment to predict sickness absence in a working population with neck and back pain

    Directory of Open Access Journals (Sweden)

    Jensen Irene

    2011-04-01

    Full Text Available Abstract Background The overall objective was to evaluate the predictive validity of a subgroup classification based on the Swedish version of the MPI, the MPI-S, among gainfully employed workers with neck pain (NP and/or low back pain (LBP during a follow-up period of 18 and 36 months. Methods This is a prospective cohort study that is part of a larger longitudinal multi-centre study entitled Work and Health in the Process and Engineering Industries (AHA. The attempt was to classify individuals at risk for developing chronic disabling NP and LBP. This is the first study using the MPI-questionnaire in a working population with NP and LBP. Results Dysfunctional individuals (DYS demonstrated more statistically significant sickness absence compared to adaptive copers (AC after 36 months. DYS also had a threefold increase in the risk ratio of long-term sickness absence at 18 months. Interpersonally distressed (ID subgroup showed overall more sickness absence compared to the AC subgroup at the 36-month follow-up and had a twofold increase in the risk ratio of long-term sickness absence at 18 months. There was a significant difference in bodily pain, mental and physical health for ID and DYS subgroups compared to the AC group at both follow-ups. Conclusions The present study shows that this multidimensional approach to the classification of individuals based on psychological and psychosocial characteristics can distinguish different groups in gainfully employed working population with NP/LBP. The results in this study confirm the predictive validity of the MPI-S subgroup classification system.

  17. Basophil responsiveness and clinical picture of acetylsalicylic acid intolerance.

    Science.gov (United States)

    Korosec, Peter; Mavsar, Nusa; Bajrovic, Nissera; Silar, Mira; Mrhar, Ales; Kosnik, Mitja

    2011-01-01

    Exposure to acetylsalicylic acid (ASA) may exacerbate respiratory or skin diseases or induce anaphylactoid reactions in apparently healthy individuals. We wanted to evaluate specific responsiveness of basophils to ASA in correlation with the clinical picture. We performed a prospective single-blind study of 59 subjects involved in clinical evaluation and/or ASA provocation testing. Whole blood basophils were stained with anti-CD63/CD123/HLA-DR mAbs after stimulation with 0.25 or 1 mg/ml ASA. We found that 40 subjects were ASA tolerant and 19 were ASA intolerant. Both groups had comparable manifestations of asthma and/or rhinitis (13 in the tolerant and 9 in the intolerant group). Intolerant subjects showed significantly higher basophil responsiveness to ASA in comparison to tolerant subjects, which was concentration-dependent in both groups. The ratio between responses at 1 mg/ml of ASA and at baseline (activation index) was analyzed according to the clinical picture. We demonstrate that the activation index was higher only in the intolerant subjects with anaphylactoid reactions, but not in a subgroup of subjects with asthma/rhinitis. The ROC calculations show that the optimal threshold activation index was more than 2.18. The sensitivity was 80% and the specificity was 83% in the subgroup with anaphylactoid reactions. In the asthma/rhinitis subgroup, the sensitivity was 78% and the specificity was 50%. Our study demonstrates that there is a significantly higher in vitro basophil response to ASA in intolerant as compared to tolerant subjects. ROC analyses suggest that this measurement might only have a diagnostic value in subjects without asthma and/or rhinitis. Copyright © 2011 S. Karger AG, Basel.

  18. 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.

  19. Accounting for subgroup structure in line-transect abundance estimates of false killer whales (Pseudorca crassidens in Hawaiian waters.

    Directory of Open Access Journals (Sweden)

    Amanda L Bradford

    Full Text Available For biological populations that form aggregations (or clusters of individuals, cluster size is an important parameter in line-transect abundance estimation and should be accurately measured. Cluster size in cetaceans has traditionally been represented as the total number of individuals in a group, but group size may be underestimated if group members are spatially diffuse. Groups of false killer whales (Pseudorca crassidens can comprise numerous subgroups that are dispersed over tens of kilometers, leading to a spatial mismatch between a detected group and the theoretical framework of line-transect analysis. Three stocks of false killer whales are found within the U.S. Exclusive Economic Zone of the Hawaiian Islands (Hawaiian EEZ: an insular main Hawaiian Islands stock, a pelagic stock, and a Northwestern Hawaiian Islands (NWHI stock. A ship-based line-transect survey of the Hawaiian EEZ was conducted in the summer and fall of 2010, resulting in six systematic-effort visual sightings of pelagic (n = 5 and NWHI (n = 1 false killer whale groups. The maximum number and spatial extent of subgroups per sighting was 18 subgroups and 35 km, respectively. These sightings were combined with data from similar previous surveys and analyzed within the conventional line-transect estimation framework. The detection function, mean cluster size, and encounter rate were estimated separately to appropriately incorporate data collected using different methods. Unlike previous line-transect analyses of cetaceans, subgroups were treated as the analytical cluster instead of groups because subgroups better conform to the specifications of line-transect theory. Bootstrap values (n = 5,000 of the line-transect parameters were randomly combined to estimate the variance of stock-specific abundance estimates. Hawai'i pelagic and NWHI false killer whales were estimated to number 1,552 (CV = 0.66; 95% CI = 479-5,030 and 552 (CV = 1.09; 95% CI = 97

  20. The prevalence of clinically diagnosed ankylosing spondylitis and its clinical manifestations

    DEFF Research Database (Denmark)

    Exarchou, Sofia; Lindström, Ulf; Askling, Johan

    2015-01-01

    -economic factors, and according to subgroups with ankylosing spondylitis-related clinical manifestations and pharmacological treatment. METHODS: All individuals diagnosed with ankylosing spondylitis according to the World Health Organization International Classification of Disease codes, between 1967 and 2009......, were identified from the National Patient Register. Data regarding disease manifestations, patient demographics, level of education, pharmacological treatment, and geographical region were retrieved from the National Patient Register and other national registers. RESULTS: A total of 11,030 cases...... prevalence of ankylosing spondylitis (0.23% versus 0.14%, P uveitis (25.5% versus 20.0%, P