Comparative genome analysis of Pseudomonas genomes including Populus-associated isolates

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Jun, Se Ran; Wassenaar, Trudy; Nookaew, Intawat; ...

2016-01-01

The Pseudomonas genus contains a metabolically versatile group of organisms that are known to occupy numerous ecological niches including the rhizosphere and endosphere of many plants influencing phylogenetic diversity and heterogeneity. In this study, comparative genome analysis was performed on over one thousand Pseudomonas genomes, including 21 Pseudomonas strains isolated from the roots of native Populus deltoides. Based on average amino acid identity, genomic clusters were identified within the Pseudomonas genus, which showed agreements with clades by NCBI and cliques by IMG. The P. fluorescens group was organized into 20 distinct genomic clusters, representing enormous diversity and heterogeneity. The speciesmore » P. aeruginosa showed clear distinction in their genomic relatedness compared to other Pseudomonas species groups based on the pan and core genome analysis. The 19 isolates of our 21 Populus-associated isolates formed three distinct subgroups within the P. fluorescens major group, supported by pathway profiles analysis, while two isolates were more closely related to P. chlororaphis and P. putida. The specific genes to Populus-associated subgroups were identified where genes specific to subgroup 1 include several sensory systems such as proteins which act in two-component signal transduction, a TonB-dependent receptor, and a phosphorelay sensor; specific genes to subgroup 2 contain unique hypothetical genes; and genes specific to subgroup 3 organisms have a different hydrolase activity. IMPORTANCE The comparative genome analyses of the genus Pseudomonas that included Populus-associated isolates resulted in novel insights into high diversity of Pseudomonas. Consistent and robust genomic clusters with phylogenetic homogeneity were identified, which resolved species-clades that are not clearly defined by 16S rRNA gene sequence analysis alone. The genomic clusters may be reflective of distinct ecological niches to which the organisms have adapted, but this needs to be experimentally characterized with ecologically relevant phenotype properties. This study justifies the need to sequence multiple isolates, especially from P. fluorescens group in order to study functional capabilities from a pangenomic perspective. This information will prove useful when choosing Pseudomonas strains for use to promote growth and increase disease resistance in plants.« less

Spiroplasmas: serological grouping of strains associated with plants and insects.

PubMed

Davis, R E; Lee, I M; Basciano, L K

1979-08-01

Spiroplasma strains from plant and arthropod hosts, and from surfaces of flowers, were classified into three serological groups (designated I, II, and III) based on results from growth-inhibition tests. No significant cross reactions were observed among groups. The groupings were confirmed by ring-interface precipitin and microprecipitin tests, using membrane preparations as test antigens, and by organism-deformation tests. Serogroup I contained three subgroups: subgroup A (Spiroplasma citri strains Maroc R8A2 and C189), subgroup B (strain AS 576 and closely related strains from honeybee or flowers), and subgroup C (corn stunt spiroplasma strains). Serogroup II contained strains 23-6 and 27-31 isolated from flowers of the tulip tree (Liriodendron tulipifera L.) growing in Maryland. Serogroup III contained strains SR 3 and SR 9 isolated from flowers of the tulip growing in Connecticut. The subgroups of serogroup I were based on organism deformation, microprecipitin, and ring-interface precipitin tests. The data are consistent with the hypothesis that the three serogroups represent no less than three distinct spiroplasma species.

Genetic and molecular alterations across medulloblastoma subgroups.

PubMed

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

2015-10-01

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

An observational study identifying obese subgroups among older adults at increased risk of mobility disability: do perceptions of the neighborhood environment matter?

PubMed

King, Abby C; Salvo, Deborah; Banda, Jorge A; Ahn, David K; Gill, Thomas M; Miller, Michael; Newman, Anne B; Fielding, Roger A; Siordia, Carlos; Moore, Spencer; Folta, Sara; Spring, Bonnie; Manini, Todd; Pahor, Marco

2015-12-18

Obesity is an increasingly prevalent condition among older adults, yet relatively little is known about how built environment variables may be associated with obesity in older age groups. This is particularly the case for more vulnerable older adults already showing functional limitations associated with subsequent disability. The Lifestyle Interventions and Independence for Elders (LIFE) trial dataset (n = 1600) was used to explore the associations between perceived built environment variables and baseline obesity levels. Age-stratified recursive partitioning methods were applied to identify distinct subgroups with varying obesity prevalence. Among participants aged 70-78 years, four distinct subgroups, defined by combinations of perceived environment and race-ethnicity variables, were identified. The subgroups with the lowest obesity prevalence (45.5-59.4%) consisted of participants who reported living in neighborhoods with higher residential density. Among participants aged 79-89 years, the subgroup (of three distinct subgroups identified) with the lowest obesity prevalence (19.4%) consisted of non-African American/Black participants who reported living in neighborhoods with friends or acquaintances similar in demographic characteristics to themselves. Overall support for the partitioned subgroupings was obtained using mixed model regression analysis. The results suggest that, in combination with race/ethnicity, features of the perceived neighborhood built and social environments differentiated distinct groups of vulnerable older adults from different age strata that differed in obesity prevalence. Pending further verification, the results may help to inform subsequent targeting of such subgroups for further investigation. Clinicaltrials.gov Identifier =  NCT01072500.

Disentangling Heterogeneity of Childhood Disruptive Behavior Problems Into Dimensions and Subgroups.

PubMed

Bolhuis, Koen; Lubke, Gitta H; van der Ende, Jan; Bartels, Meike; van Beijsterveldt, Catharina E M; Lichtenstein, Paul; Larsson, Henrik; Jaddoe, Vincent W V; Kushner, Steven A; Verhulst, Frank C; Boomsma, Dorret I; Tiemeier, Henning

2017-08-01

Irritable and oppositional behaviors are increasingly considered as distinct dimensions of oppositional defiant disorder. However, few studies have explored this multidimensionality across the broader spectrum of disruptive behavior problems (DBPs). This study examined the presence of dimensions and distinct subgroups of childhood DBPs, and the cross-sectional and longitudinal associations between these dimensions. Using factor mixture models (FMMs), the presence of dimensions and subgroups of DBPs was assessed in the Generation R Study at ages 6 (n = 6,209) and 10 (n = 4,724) years. Replications were performed in two population-based cohorts (Netherlands Twin Registry, n = 4,402, and Swedish Twin Study of Child and Adolescent Development, n = 1,089) and a clinical sample (n = 1,933). We used cross-lagged modeling in the Generation R Study to assess cross-sectional and longitudinal associations between dimensions. DBPs were assessed using mother-reported responses to the Child Behavior Checklist. Empirically obtained dimensions of DBPs were oppositional behavior (age 6 years), disobedient behavior, rule-breaking behavior (age 10 years), physical aggression, and irritability (both ages). FMMs suggested that one-class solutions had the best model fit for all dimensions in all three population-based cohorts. Similar results were obtained in the clinical sample. All three dimensions, including irritability, predicted subsequent physical aggression (range, 0.08-0.16). This study showed that childhood DBPs should be regarded as a multidimensional phenotype rather than comprising distinct subgroups. Incorporating multidimensionality will improve diagnostic accuracy and refine treatment. Future studies need to address the biological validity of the DBP dimensions observed in this study; herein lies an important opportunity for neuroimaging and genetic measures. Copyright © 2017 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Distinctive ribonucleic acid patterns of human rotavirus subgroups 1 and 2.

PubMed Central

Kalica, A R; Greenberg, H B; Espejo, R T; Flores, J; Wyatt, R G; Kapikian, A Z; Chanock, R M

1981-01-01

The ribonucleic acid migration patterns of 7 subgroup 1 and 16 subgroup 2 human rotaviruses recovered from four geographic areas were compared. The subgroup 1 ribonucleic acid patterns had strikingly slower-moving segments 10 and 11, suggesting a correlation between the ribonucleic acid pattern and the subgroup specificity. Images PMID:6270002

Developmental typologies of serious mental illness and violence: Evidence from a forensic psychiatric setting.

PubMed

Simpson, Alexander I; Grimbos, Teresa; Chan, Christine; Penney, Stephanie R

2015-11-01

To identify subgroups of forensic psychiatric patients based on the age onset of serious mental illness and offending and assess the external validity of the subgroups with theoretically based sociodemographic, clinical, legal and risk-related variables. The age onset of serious mental illness and criminal contact was ascertained for a sample of 232 patients. A range of sociodemographic, clinical, legal and risk-related variables were coded to assess whether age onset subgroups differed in a manner consistent with the literature on typologies of mentally ill offenders. One-quarter of the sample was classified as early starters (patients whose first offense occurred before becoming mentally ill), while two-thirds were late starters (where first offense occurred following illness onset). A small percentage (8%) of patients were deemed late late starters, defined as late starters who had experienced 10+ years of illness and were >37 years upon first arrest. A larger proportion of early starters had a substance use disorder, antisocial personality disorder and a greater number of static/historical risk factors for violence. Early starters were younger upon first arrest and had more previous criminal contacts compared to late starters and late late starters. Mental illness was found to start later in life for late late starters; this group was also more likely to have been married and to have a spouse as victim in the index offense. We found support for distinct subgroups of mentally ill offenders based on the age onset of illness and criminal contact. Compared to late starters, offenses committed by early starters may be motivated more frequently by antisocial lifestyle and attitudes, as well as more instrumental behaviors related to substance abuse. In addition, late late starters may represent a distinct third subgroup within late starters, characterized by relatively higher levels of functioning and social stability; future work should replicate. Findings suggest different rehabilitation needs of the subgroups. © The Royal Australian and New Zealand College of Psychiatrists 2015.

Informant discrepancy defines discrete, clinically useful autism spectrum disorder subgroups.

PubMed

Lerner, Matthew D; De Los Reyes, Andres; Drabick, Deborah A G; Gerber, Alan H; Gadow, Kenneth D

2017-07-01

Discrepancy between informants (parents and teachers) in severity ratings of core symptoms commonly arise when assessing autism spectrum disorder (ASD). Whether such discrepancy yields unique information about the ASD phenotype and its clinical correlates has not been examined. We examined whether degree of discrepancy between parent and teacher ASD symptom ratings defines discrete, clinically meaningful subgroups of youth with ASD using an efficient, cost-effective procedure. Children with ASD (N = 283; 82% boys; M age  = 10.5 years) were drawn from a specialty ASD clinic. Parents and teachers provided ratings of the three core DSM-IV-TR domains of ASD symptoms (communication, social, and perseverative behavior) with the Child and Adolescent Symptom Inventory-4R (CASI-4R). External validators included child psychotropic medication status, frequency of ASD-relevant school-based services, and the Autism Diagnostic Observation Schedule (ADOS-2). Four distinct subgroups emerged that ranged from large between-informant discrepancy (informant-specific) to relative lack of discrepancy (i.e. informant agreement; cross-situational): Moderate Parent/Low Teacher or Low Parent/Moderate Teacher Severity (Discrepancy), and Moderate or High Symptom Severity (Agreement). Subgroups were highly distinct (mean probability of group assignment = 94%). Relative to Discrepancy subgroups, Agreement subgroups were more likely to receive psychotropic medication, school-based special education services, and an ADOS-2 diagnosis. These differential associations would not have been identified based solely on CASI-4R scores from one informant. The degree of parent-teacher discrepancy about ASD symptom severity appears to provide more clinically useful information than reliance on a specific symptom domain or informant, and thus yields an innovative, cost-effective approach to assessing functional impairment. This conclusion stands in contrast to existing symptom clustering approaches in ASD, which treat within-informant patterns of symptom severity as generalizable across settings. Within-child variability in symptom expression across settings may yield uniquely useful information for characterizing the ASD phenotype. © 2017 Association for Child and Adolescent Mental Health.

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

PubMed

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.

Polymorphisms in Tumor Necrosis Factor-α Are Associated With Higher Anxiety Levels in Women After Breast Cancer Surgery.

PubMed

Miaskowski, Christine; Elboim, Charles; Paul, Steven M; Mastick, Judy; Cooper, Bruce A; Levine, Jon D; Aouizerat, Bradley E

2016-02-01

Before and after breast cancer surgery, women have reported varying anxiety levels. Recent evidence has suggested that anxiety has a genetic basis and is associated with inflammation. The purposes of the present study were to identify the subgroups of women with distinct anxiety trajectories; to evaluate for differences in the phenotypic characteristics between these subgroups; and to evaluate for associations between polymorphisms in cytokine genes and subgroup membership. Patients with breast cancer (n = 398) were recruited before surgery and followed up for 6 months. The patients completed the Spielberger State Anxiety Inventory and provided a blood sample for genomic analyses. Growth mixture modeling was used to identify the subgroups of patients with distinct anxiety trajectories. Two distinct anxiety subgroups were identified. The women in the higher anxiety subgroup were younger and had a lower functional status score. Two single nucleotide polymorphisms in tumor necrosis factor-α (rs1799964, rs3093662) were associated with the higher anxiety subgroup. The results of the present exploratory study suggest that polymorphisms in cytokine genes could partially explain the interindividual variability in anxiety. The determination of phenotypic and molecular markers associated with greater levels of anxiety can assist clinicians to identify high-risk patients and initiate appropriate interventions. Copyright © 2016 Elsevier Inc. All rights reserved.

Individual, Cultural and Structural Predictors of Vaccine Safety Confidence and Influenza Vaccination Among Hispanic Female Subgroups.

PubMed

Moran, Meghan Bridgid; Chatterjee, Joyee S; Frank, Lauren B; Murphy, Sheila T; Zhao, Nan; Chen, Nancy; Ball-Rokeach, Sandra

2017-08-01

Rates of influenza vaccination among US Hispanics are lower than for non-Hispanic whites, yet little is known about factors affecting vaccination in this population. Additionally, although Hispanics are a diverse population with culturally distinct subgroups, they are often treated as a homogenous population. This study (1) examines how confidence in vaccine safety and influenza vaccine use vary by Hispanic subgroup and (2) identifies individual, cultural and structural correlates of these outcomes. This study analyzed survey data from 1565 Hispanic women who were recruited at clinic- and community-based sites in Los Angeles. Education, healthcare coverage, acculturation, fatalism, and religiosity were predictors of influenza vaccination behavior and predictors varied by subgroup. These findings provide guidance for how influenza vaccine promotion efforts can be developed for Hispanic subgroups. Confidence in the safety of a vaccine is a major predictor of flu vaccination and an important modifiable target for intervention.

Thoughts of Death and Suicide in Early Adolescence

ERIC Educational Resources Information Center

Vander Stoep, Ann; McCauley, Elizabeth; Flynn, Cynthia; Stone, Andrea

2009-01-01

The prevalence and persistence of thoughts of death and suicide during early adolescence were estimated in a community-based cohort. A latent class approach was used to identify distinct subgroups based on endorsements to depression items administered repeatedly over 24 months. Two classes emerged, with 75% in a low ideation class across four…

DNA homology among diverse spiroplasma strains representing several serological groups.

PubMed

Lee, I M; Davis, R E

1980-11-01

Deoxyribonucleic acid (DNA) homology among 10 strains of spiroplasma associated with plants and insects was assessed by analysis of DNA-DNA hybrids with single strand specific S1 nuclease. Based on DNA homology, the spiroplasmas could be divided into three genetically distinct groups (designated I, II, and III), corresponding to three separate serogroups described previously. DNA sequence homology between the three groups was less than or equal to 5%. Based on DNA homology, group I could be divided into three subgroups (A, B, and C) that corresponded to three serological subgroups of serogroup I. Subgroup A contained Spiroplasma citri strains Maroc R8A2 and C 189; subgroup B contained strains AS 576 from honey bee and G 1 from flowers; subgroup C contained corn stunt spiroplasma strains I-747 and PU 8-17. There was 27-54% DNA sequence homology among these three subgroups. Group II contained strains 23-6 and 27-31 isolated from flowers of tulip tree (Liriodendron tulipifera L.). Group III contained strains SR 3 and SR 9, other isolates from flowers of tulip tree. Based on thermal denaturation, guanine plus cytosine contents of DNA from five type strains representing all groups and subgroups were estimated to be close to 26 mol% for group I strains, close to 25 mol% for group II strains, and close to 29 mol% for group III strains. The genome molecular weights of these five type strains were all estimated to bae about 10(9).

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

PubMed

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 < .001) and were similarly functionally impaired (eg, global functioning [GAF] Ps < .001), but showed markedly different patterns on 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.

Intergroup Leadership Across Distinct Subgroups and Identities.

PubMed

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.

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

PubMed

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.

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

PubMed Central

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

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

PubMed

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 inhibition (conditioned pain modulation, the diffuse noxious inhibitory control-like effect), as well as measurement of the plasma levels of nerve growth factor and endocannabinoids. The identification of the underlying pathophysiologic mechanisms in different subgroups of chronic musculoskeletal pain patients will contribute to a mechanism-based subgroup classification. This will foster the development of mechanism-based treatments and holds promise to treat patients more sufficient.

Novel mutations target distinct subgroups of medulloblastoma

PubMed Central

Robinson, Giles; Parker, Matthew; Kranenburg, Tanya A.; Lu, Charles; Chen, Xiang; Ding, Li; Phoenix, Timothy N.; Hedlund, Erin; Wei, Lei; Zhu, Xiaoyan; Chalhoub, Nader; Baker, Suzanne J.; Huether, Robert; Kriwacki, Richard; Curley, Natasha; Thiruvenkatam, Radhika; Wang, Jianmin; Wu, Gang; Rusch, Michael; Hong, Xin; Beckford, Jared; Gupta, Pankaj; Ma, Jing; Easton, John; Vadodaria, Bhavin; Onar-Thomas, Arzu; Lin, Tong; Li, Shaoyi; Pounds, Stanley; Paugh, Steven; Zhao, David; Kawauchi, Daisuke; Roussel, Martine F.; Finkelstein, David; Ellison, David W.; Lau, Ching C.; Bouffet, Eric; Hassall, Tim; Gururangan, Sridharan; Cohn, Richard; Fulton, Robert S.; Fulton, Lucinda L.; Dooling, David J.; Ochoa, Kerri; Gajjar, Amar; Mardis, Elaine R.; Wilson, Richard K.; Downing, James R.; Zhang, Jinghui; Gilbertson, Richard J.

2012-01-01

Summary Medulloblastoma is a malignant childhood brain tumour comprising four discrete subgroups. To identify mutations that drive medulloblastoma we sequenced the entire genomes of 37 tumours and matched normal blood. One hundred and thirty-six genes harbouring somatic mutations in this discovery set were sequenced in an additional 56 medulloblastomas. Recurrent mutations were detected in 41 genes not yet implicated in medulloblastoma: several target distinct components of the epigenetic machinery in different disease subgroups, e.g., regulators of H3K27 and H3K4 trimethylation in subgroup-3 and 4 (e.g., KDM6A and ZMYM3), and CTNNB1-associated chromatin remodellers in WNT-subgroup tumours (e.g., SMARCA4 and CREBBP). Modelling of mutations in mouse lower rhombic lip progenitors that generate WNT-subgroup tumours, identified genes that maintain this cell lineage (DDX3X) as well as mutated genes that initiate (CDH1) or cooperate (PIK3CA) in tumourigenesis. These data provide important new insights into the pathogenesis of medulloblastoma subgroups and highlight targets for therapeutic development. PMID:22722829

Somatic POLE mutations cause an ultramutated giant cell high-grade glioma subtype with better prognosis

PubMed Central

Erson-Omay, E. Zeynep; Çağlayan, Ahmet Okay; Schultz, Nikolaus; Weinhold, Nils; Omay, S. Bülent; Özduman, Koray; Köksal, Yavuz; Li, Jie; Serin Harmancı, Akdes; Clark, Victoria; Carrión-Grant, Geneive; Baranoski, Jacob; Çağlar, Caner; Barak, Tanyeri; Coşkun, Süleyman; Baran, Burçin; Köse, Doğan; Sun, Jia; Bakırcıoğlu, Mehmet; Moliterno Günel, Jennifer; Pamir, M. Necmettin; Mishra-Gorur, Ketu; Bilguvar, Kaya; Yasuno, Katsuhito; Vortmeyer, Alexander; Huttner, Anita J.; Sander, Chris; Günel, Murat

2015-01-01

Background Malignant high-grade gliomas (HGGs), including the most aggressive form, glioblastoma multiforme, show significant clinical and genomic heterogeneity. Despite recent advances, the overall survival of HGGs and their response to treatment remain poor. In order to gain further insight into disease pathophysiology by correlating genomic landscape with clinical behavior, thereby identifying distinct HGG molecular subgroups associated with improved prognosis, we performed a comprehensive genomic analysis. Methods We analyzed and compared 720 exome-sequenced gliomas (136 from Yale, 584 from The Cancer Genome Atlas) based on their genomic, histological, and clinical features. Results We identified a subgroup of HGGs (6 total, 4 adults and 2 children) that harbored a statistically significantly increased number of somatic mutations (mean = 9257.3 vs 76.2, P = .002). All of these “ultramutated” tumors harbored somatic mutations in the exonuclease domain of the polymerase epsilon gene (POLE), displaying a distinctive genetic profile, characterized by genomic stability and increased C-to-A transversions. Histologically, they all harbored multinucleated giant or bizarre cells, some with predominant infiltrating immune cells. One adult and both pediatric patients carried homozygous germline mutations in the mutS homolog 6 (MSH6) gene. In adults, POLE mutations were observed in patients younger than 40 years and were associated with a longer progression-free survival. Conclusions We identified a genomically, histologically, and clinically distinct subgroup of HGGs that harbored somatic POLE mutations and carried an improved prognosis. Identification of distinctive molecular and pathological HGG phenotypes has implications not only for improved classification but also for potential targeted treatments. PMID:25740784

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

PubMed Central

Xin, Xiuhong; Ming, Qingsen; Zhang, Jibiao; Wang, Yuping; Liu, Mingli; Yao, Shuqiao

2016-01-01

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. PMID:27392132

Diagnosis and classification of Idiopathic Inflammatory Myopathies

PubMed Central

Lundberg, Ingrid E.; Miller, Frederick W.; Tjärnlund, Anna; Bottai, Matteo

2016-01-01

The idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of diseases, collectively named myositis, sharing symptoms of muscle weakness and muscle fatigue and inflammation in muscle tissue. Other organs are frequently involved supporting that these are systemic inflammatory diseases. The IIMs can be sub-grouped into dermatomyositis, polymyositis and inclusion body myositis. The myositis-specific autoantibodies (MSAs) identify other and often more distinct clinical phenotypes, such as the anti-synthetase syndrome with antisynthetase autoantibodies and frequent interstitial lung disease (ILD) and anti-SRP and anti-HMGCR autoantibodies that identify necrotizing myopathy. The MSAs are important both to support myositis diagnosis and to identify subgroups with different patterns of extramuscular organ involvement such as ILD. Another cornerstone in the diagnostic procedure is muscle biopsy to identify inflammation and to exclude non-inflammatory myopathies. Treatment effect and prognosis varies by subgroup. To develop new and better therapies, validated classification criteria that identify distinct subgroups of myositis are critical.. The lack of such criteria was the main rationale for the development of new classification criteria for inflammatory myopathies, which are summarized in this review, along with an historical background on previous diagnostic and classification criteria. As these are rare diseases with a prevalence of 10 in 100 000 individuals an international collaboration was essential, as was the interdisciplinary effort including adult and paediatric experts in rheumatology, neurology, dermatology and epidemiology. The new criteria have been developed based on data from more than 1 500 patients from 47 centers world-wide and are based on clinically easily available variables. PMID:27320359

Developmental continuity and change in physical, verbal, and relational aggression and peer victimization from childhood to adolescence.

PubMed

Ettekal, Idean; Ladd, Gary W

2017-09-01

To investigate the developmental course of aggression and peer victimization in childhood and adolescence, distinct subgroups of children were identified based on similarities and differences in their physical, verbal and relational aggression, and victimization. Developmental continuity and change were assessed by examining transitions within and between subgroups from Grades 1 to 11. This longitudinal study consisted of 482 children (50% females) and was based on peer report data on multiple forms of aggression and peer victimization. Using person-centered methods including latent profile and latent transition analyses, most of the identified subgroups were distinguishable by their frequencies (i.e., levels) of aggression and victimization, rather than forms (physical, verbal, and relational), with the exception of 1 group that appeared to be more form-specific. Across subgroups, multiple developmental patterns emerged characterized as early and late-onset, social interactional continuity, desistance, and heterotypic pathways. Collectively, these pathways support the perspective that the development of aggression and peer victimization in childhood and adolescence is characterized by heterogeneity. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Data-Driven Subclassification of Speech Sound Disorders in Preschool Children

PubMed Central

Vick, Jennell C.; Campbell, Thomas F.; Shriberg, Lawrence D.; Green, Jordan R.; Truemper, Klaus; Rusiewicz, Heather Leavy; Moore, Christopher A.

2015-01-01

Purpose The purpose of the study was to determine whether distinct subgroups of preschool children with speech sound disorders (SSD) could be identified using a subgroup discovery algorithm (SUBgroup discovery via Alternate Random Processes, or SUBARP). Of specific interest was finding evidence of a subgroup of SSD exhibiting performance consistent with atypical speech motor control. Method Ninety-seven preschool children with SSD completed speech and nonspeech tasks. Fifty-three kinematic, acoustic, and behavioral measures from these tasks were input to SUBARP. Results Two distinct subgroups were identified from the larger sample. The 1st subgroup (76%; population prevalence estimate = 67.8%–84.8%) did not have characteristics that would suggest atypical speech motor control. The 2nd subgroup (10.3%; population prevalence estimate = 4.3%– 16.5%) exhibited significantly higher variability in measures of articulatory kinematics and poor ability to imitate iambic lexical stress, suggesting atypical speech motor control. Both subgroups were consistent with classes of SSD in the Speech Disorders Classification System (SDCS; Shriberg et al., 2010a). Conclusion Characteristics of children in the larger subgroup were consistent with the proportionally large SDCS class termed speech delay; characteristics of children in the smaller subgroup were consistent with the SDCS subtype termed motor speech disorder—not otherwise specified. The authors identified candidate measures to identify children in each of these groups. PMID:25076005

Prevalence of BK virus subtype I in Germany.

PubMed

Krumbholz, Andi; Zell, Roland; Egerer, Renate; Sauerbrei, Andreas; Helming, Andrea; Gruhn, Bernd; Wutzler, Peter

2006-12-01

The primary infection with human polyomavirus BK (BKV) occurs in early childhood and leads to viral latency within the urogenital tract. Up to 90% of the adult population are seropositive. In immunosuppressed patients, the BKV may be reactivated resulting in typical disease patterns like hemorrhagic cystitis and tubulointerstitial nephritis. Based on serological and molecular methods, BKV isolates were classified into four subtypes previously. Sixty specimens obtained from German renal and bone marrow transplant recipients were analyzed to gain data on the prevalence of BKV subtypes in Germany. With 90.9%, BKV subtype I was found to be predominant in both patient groups. 6.1% of BKV strains were classified as subtype IV. This pattern of phylogenetic distribution is similar to that demonstrated previously in England, Tanzania, the United States and Japan. Remarkably, there was one German BKV virus with a sequence which clusters together with strain SB in subtype II. The BKV subtype I was found to consist of at least three subgroups designated as Ia, Ib, and Ic. While the majority of the German sequences represent subgroup Ic, most of the Japanese sequences are clearly distinct. These findings support the hypothesis of distinct geographical prevalence of BKV subgroups. For the genotyping region, a relationship of BKV subgroups to disease patterns like hemorrhagic cystitis or tubulointerstitial nephritis could not be demonstrated. (c) 2006 Wiley-Liss, Inc.

Cytogenetic prognostication within medulloblastoma subgroups.

PubMed

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.

Cytogenetic Prognostication Within Medulloblastoma Subgroups

PubMed Central

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

2014-01-01

Purpose Medulloblastoma comprises four distinct molecular subgroups: WNT, SHH, Group 3, and Group 4. Current medulloblastoma protocols stratify patients based on clinical features: patient age, metastatic stage, extent of resection, and histologic variant. Stark prognostic and genetic differences among the four subgroups suggest that subgroup-specific molecular biomarkers could improve patient prognostication. Patients and Methods Molecular biomarkers were identified from a discovery set of 673 medulloblastomas from 43 cities around the world. Combined risk stratification models were designed based on clinical and cytogenetic biomarkers identified by multivariable Cox proportional hazards analyses. Identified biomarkers were tested using fluorescent in situ hybridization (FISH) on a nonoverlapping medulloblastoma tissue microarray (n = 453), with subsequent validation of the risk stratification models. Results Subgroup information improves the predictive accuracy of a multivariable survival model compared with clinical biomarkers alone. Most previously published cytogenetic biomarkers are only prognostic within a single medulloblastoma subgroup. Profiling six FISH biomarkers (GLI2, MYC, chromosome 11 [chr11], chr14, 17p, and 17q) on formalin-fixed paraffin-embedded tissues, we can reliably and reproducibly identify very low-risk and very high-risk patients within SHH, Group 3, and Group 4 medulloblastomas. Conclusion Combining subgroup and cytogenetic biomarkers with established clinical biomarkers substantially improves patient prognostication, even in the context of heterogeneous clinical therapies. The prognostic significance of most molecular biomarkers is restricted to a specific subgroup. We have identified a small panel of cytogenetic biomarkers that reliably identifies very high-risk and very low-risk groups of patients, making it an excellent tool for selecting patients for therapy intensification and therapy de-escalation in future clinical trials. PMID:24493713

Reasons for Vaping Among U.S. 12th Graders.

PubMed

Evans-Polce, Rebecca J; Patrick, Megan E; Lanza, Stephanie T; Miech, Richard A; O'Malley, Patrick M; Johnston, Lloyd D

2018-04-01

Vaping has recently increased in popularity among adolescents. Little is known about heterogeneity of vapers, particularly in terms of why they vape. Identifying major subgroups of adolescent vapers by reasons for vaping is important to understand adolescent vaping behavior and to identify those most at risk for other substance use. Monitoring Future data from 2015 and 2016 were used in a latent class analysis to identify subgroups of 12th graders based on their endorsement of 10 potential reasons for vaping. Multinomial regression with a latent class outcome was used to predict class membership. Three distinct classes of vapers were identified: adolescents who were (1) Vaping to Experiment (29.4%), (2) Vaping to Replace Cigarettes (7.3%), and (3) Vaping for Taste + Entertainment (63.4%). Vaping only flavors was associated with lower odds of membership and cigarette use was associated with higher odds of membership in the Vaping to Replace Cigarettes subgroup, and marijuana was associated with lower odds of membership in the Vaping to Experiment subgroup, compared with the Vaping for Taste + Entertainment subgroup. This study identified multiple subgroups of vapers based on reasons for vaping. Whereas a small subgroup vaped for reasons related to cigarette use, most adolescent vapers reported vaping for reasons unrelated to cigarette use. There were considerable differences in primary reasons for vaping and risk for traditional cigarette and other substance use, suggesting different intervention strategies may be needed for different subgroups of vapers. Copyright © 2017 The Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Distinct subtypes of behavioral-variant frontotemporal dementia based on patterns of network degeneration

PubMed Central

Ranasinghe, Kamalini G; Rankin, Katherine P; Pressman, Peter S; Perry, David C; Lobach, Iryna V; Seeley, William W; Coppola, Giovanni; Karydas, Anna M; Grinberg, Lea T; Shany-Ur, Tal; Lee, Suzee E; Rabinovici, Gil D; Rosen, Howard J; Gorno-Tempini, Maria Luisa; Boxer, Adam L; Miller, Zachary A; Chiong, Winston; DeMay, Mary; Kramer, Joel H; Possin, Katherine L; Sturm, Virginia E; Bettcher, Brianne M; Neylan, Michael; Zackey, Diana D; Nguyen, Lauren A; Ketelle, Robin; Block, Nikolas; Wu, Teresa Q; Dallich, Alison; Russek, Natanya; Caplan, Alyssa; Geschwind, Daniel H; Vossel, Keith A; Miller, Bruce L

2016-01-01

Importance Clearer delineation of the phenotypic heterogeneity within behavioral variant frontotemporal dementia (bvFTD) will help uncover underlying biological mechanisms, and will improve clinicians’ ability to predict disease course and design targeted management strategies. Objective To identify subtypes of bvFTD syndrome based on distinctive patterns of atrophy defined by selective vulnerability of specific functional networks targeted in bvFTD, using statistical classification approaches. Design, Setting and Participants In this retrospective observational study, 104 patients meeting the Frontotemporal Dementia Consortium consensus criteria for bvFTD were evaluated at the Memory and Aging Center of Department of Neurology at University of California, San Francisco. Patients underwent a multidisciplinary clinical evaluation, including clinical demographics, genetic testing, symptom evaluation, neurological exam, neuropsychological bedside testing, and socioemotional assessments. Ninety patients underwent structural Magnetic Resonance Imaging at their earliest evaluation at the memory clinic. From each patients’ structural imaging, the mean volumes of 18 regions of interest (ROI) comprising the functional networks specifically vulnerable in bvFTD, including the ‘salience network’ (SN), with key nodes in the frontoinsula and pregenual anterior cingulate, and the ‘semantic appraisal network’ (SAN) anchored in the anterior temporal lobe and subgenual cingulate, were estimated. Principal component and cluster analyses of ROI volumes were used to identify patient clusters with anatomically distinct atrophy patterns. Main Outcome Measures We evaluated brain morphology and other clinical features including presenting symptoms, neurologic exam signs, neuropsychological performance, rate of dementia progression, and socioemotional function in each patient cluster. Results We identified four subgroups of bvFTD patients with distinct anatomic patterns of network degeneration, including two separate salience network–predominant subgroups: frontal/temporal (SN-FT), and frontal (SN-F), and a semantic appraisal network–predominant group (SAN), and a subcortical–predominant group. Subgroups demonstrated distinct patterns of cognitive, socioemotional, and motor symptoms, as well as genetic compositions and estimated rates of disease progression. Conclusions Divergent patterns of vulnerability in specific functional network components make an important contribution to clinical heterogeneity of bvFTD. The data-driven anatomical classification identifies biologically meaningful phenotypes and provides a replicable approach to disambiguate the bvFTD syndrome. PMID:27429218

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

PubMed

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 total ME/CFS cohort. In ME/CFS subgroups, symptom severity measures including pain, fatigue, and reduced motivation were correlated with the abundance of distinct bacterial taxa and metabolic pathways. Independent of IBS, ME/CFS is associated with dysbiosis and distinct bacterial metabolic disturbances that may influence disease severity. However, our findings indicate that dysbiotic features that are uniquely ME/CFS-associated may be masked by disturbances arising from the high prevalence of IBS co-morbidity in ME/CFS. These insights may enable more accurate diagnosis and lead to insights that inform the development of specific therapeutic strategies in ME/CFS subgroups.

Collaboration processes and perceived effectiveness of integrated care projects in primary care: a longitudinal mixed-methods study.

PubMed

Valentijn, Pim P; Ruwaard, Dirk; Vrijhoef, Hubertus J M; de Bont, Antoinette; Arends, Rosa Y; Bruijnzeels, Marc A

2015-10-09

Collaborative partnerships are considered an essential strategy for integrating local disjointed health and social services. Currently, little evidence is available on how integrated care arrangements between professionals and organisations are achieved through the evolution of collaboration processes over time. The first aim was to develop a typology of integrated care projects (ICPs) based on the final degree of integration as perceived by multiple stakeholders. The second aim was to study how types of integration differ in changes of collaboration processes over time and final perceived effectiveness. A longitudinal mixed-methods study design based on two data sources (surveys and interviews) was used to identify the perceived degree of integration and patterns in collaboration among 42 ICPs in primary care in The Netherlands. We used cluster analysis to identify distinct subgroups of ICPs based on the final perceived degree of integration from a professional, organisational and system perspective. With the use of ANOVAs, the subgroups were contrasted based on: 1) changes in collaboration processes over time (shared ambition, interests and mutual gains, relationship dynamics, organisational dynamics and process management) and 2) final perceived effectiveness (i.e. rated success) at the professional, organisational and system levels. The ICPs were classified into three subgroups with: 'United Integration Perspectives (UIP)', 'Disunited Integration Perspectives (DIP)' and 'Professional-oriented Integration Perspectives (PIP)'. ICPs within the UIP subgroup made the strongest increase in trust-based (mutual gains and relationship dynamics) as well as control-based (organisational dynamics and process management) collaboration processes and had the highest overall effectiveness rates. On the other hand, ICPs with the DIP subgroup decreased on collaboration processes and had the lowest overall effectiveness rates. ICPs within the PIP subgroup increased in control-based collaboration processes (organisational dynamics and process management) and had the highest effectiveness rates at the professional level. The differences across the three subgroups in terms of the development of collaboration processes and the final perceived effectiveness provide evidence that united stakeholders' perspectives are achieved through a constructive collaboration process over time. Disunited perspectives at the professional, organisation and system levels can be aligned by both trust-based and control-based collaboration processes.

Subgroups of Chemotherapy Patients With Distinct Morning and Evening Fatigue Trajectories

PubMed Central

Kober, Kord M.; Cooper, Bruce A.; Paul, Steven M.; Dunn, Laura B.; Levine, Jon D.; Wright, Fay; Hammer, Marilyn J.; Mastick, Judy; Venook, Alan; Aouizerat, Bradley E.; Miaskowski, Christine

2017-01-01

Purpose Purposes of this study were to: identify subgroups of patients with distinct trajectories for morning and evening fatigue; evaluate for differences in demographic and clinical characteristics among these subgroups; and compare and contrast the predictors of subgroup membership for morning and evening fatigue. Methods Outpatients with breast, gastrointestinal, gynecological, or lung cancer (n=582) completed questionnaires a total of six times over two cycles of CTX. Morning and evening fatigue severity were evaluated using the Lee Fatigue Scale. Latent profile analysis (LPA) was used to identify distinct subgroups. Results Three latent classes were identified for morning fatigue (i.e., Low (31.8%), High (51.4%), and Very High (16.8%)) and for evening evening fatigue (i.e., Moderate (20.0%), High (21.8%), and Very High (58.2%)). Most of the disease and treatment characteristics did not distinguish among the morning and evening fatigue classes. Compared to the Low class, patients in the High and Very High morning fatigue class were younger, had a lower functional status and higher level of comorbidity. Compared to the Moderate class, patients in the Very High evening fatigue class were younger, more likely to be female, had child care responsibilities, had a lower functional status, and a higher level of comorbidity. Conclusion LPA allows for the identification of risk factors for more severe fatigue. Since an overlap was not observed across the morning and evening fatigue classes and unique predictors for morning and evening fatigue were identified, these findings suggest that morning and evening fatigue may have distinct underlying mechanisms. PMID:26361758

Serological analysis of the subgroup protein of rotavirus, using monoclonal antibodies.

PubMed Central

Greenberg, H; McAuliffe, V; Valdesuso, J; Wyatt, R; Flores, J; Kalica, A; Hoshino, Y; Singh, N

1983-01-01

Ten monoclones directed to the 42,000-dalton inner structural protein of rotavirus were analyzed. Eight monoclones reacted broadly with antigenic domains common to virtually all mammalian rotaviruses. Two monoclones had specificities similar or identical to previously characterized subgroup specificities. These subgroup monoclones were more efficient in detecting subgroup antigen than either hyperimmune or postinfection antisera. Using the subgroup monoclones, we determined that some animal as well as human rotavirus strains carry subgroup 2 specificity and that epizootic diarrhea of infant mice virus and turkey rotavirus are antigenically distinct from other mammalian rotavirus strains. Images PMID:6185436

Identifying Predictors of Negative Psychological Reactions to Stalking Victimization

ERIC Educational Resources Information Center

Johnson, Matthew C.; Kercher, Glen A.

2009-01-01

Victims of stalking often experience a number of negative psychological problems including such things as fear, symptoms of depression, and anger. However, research on factors that lead to these outcomes is limited. The goal of this study was to first identify distinct subgroups of stalking victims based on measures of psychological problems…

Developmental Continuity and Change in Physical, Verbal, and Relational Aggression and Peer Victimization from Childhood to Adolescence

ERIC Educational Resources Information Center

Ettekal, Idean; Ladd, Gary W.

2017-01-01

To investigate the developmental course of aggression and peer victimization in childhood and adolescence, distinct subgroups of children were identified based on similarities and differences in their physical, verbal and relational aggression, and victimization. Developmental continuity and change were assessed by examining transitions within and…

Advancing Bullying Research from a Social-Ecological Lens: An Introduction to the Special Issue

ERIC Educational Resources Information Center

Rose, Chad A.; Nickerson, Amanda B.; Stormont, Melissa

2015-01-01

Bullying has emerged as a distinct, pervasive subset of peer aggression that affects youth worldwide. Although bullying is a complex phenomenon, some subgroups of youth are at escalated risk based on individual characteristics, skill deficits, and peer group or societal norms. Therefore, the field needs reliable measurement systems, precise…

Distinct neuropsychological subgroups in typically developing youth inform heterogeneity in children with ADHD

PubMed Central

Fair, Damien A.; Bathula, Deepti; Nikolas, Molly A.; Nigg, Joel T.

2012-01-01

Research and clinical investigations in psychiatry largely rely on the de facto assumption that the diagnostic categories identified in the Diagnostic and Statistical Manual (DSM) represent homogeneous syndromes. However, the mechanistic heterogeneity that potentially underlies the existing classification scheme might limit discovery of etiology for most developmental psychiatric disorders. Another, perhaps less palpable, reality may also be interfering with progress—heterogeneity in typically developing populations. In this report we attempt to clarify neuropsychological heterogeneity in a large dataset of typically developing youth and youth with attention deficit/hyperactivity disorder (ADHD), using graph theory and community detection. We sought to determine whether data-driven neuropsychological subtypes could be discerned in children with and without the disorder. Because individual classification is the sine qua non for eventual clinical translation, we also apply support vector machine-based multivariate pattern analysis to identify how well ADHD status in individual children can be identified as defined by the community detection delineated subtypes. The analysis yielded several unique, but similar subtypes across both populations. Just as importantly, comparing typically developing children with ADHD children within each of these distinct subgroups increased diagnostic accuracy. Two important principles were identified that have the potential to advance our understanding of typical development and developmental neuropsychiatric disorders. The first tenet suggests that typically developing children can be classified into distinct neuropsychological subgroups with high precision. The second tenet proposes that some of the heterogeneity in individuals with ADHD might be “nested” in this normal variation. PMID:22474392

Trajectories of distress, anxiety, and depression among women with breast cancer: Looking beyond the mean.

PubMed

Bidstrup, Pernille Envold; Christensen, Jane; Mertz, Birgitte Goldschmidt; Rottmann, Nina; Dalton, Susanne Oksbjerg; Johansen, Christoffer

2015-05-01

Little is known about the development of psychological wellbeing over time among women who have been treated for breast cancer. The aim of this study was to identify distinct patterns of distress, anxiety, and depression in such women. We invited 426 consecutive women with newly diagnosed primary breast cancer to participate in this study, and 323 (76%) provided information on distress ('distress thermometer') and on symptoms of anxiety and depression ('hospital anxiety and depression scale'). Semiparametric group-based mixture modeling was used to identify distinct trajectories of distress, anxiety, and depressive symptoms assessed the week before surgery and four and eight months later. Logistic regression analysis was used to evaluate the characteristics of women in the distinct groups. Although no sub-group of women with chronic severe anxiety or depressive symptoms was found, we did identify a sub-group of 8% of the women who experienced continuously severe distress. Young age, having a partner, shorter education, and receiving chemotherapy but not radiotherapy might characterize women whose psychological symptoms remain strong eight months after diagnosis. By looking beyond the mean, we found that 8% of the women experienced chronic severe distress; no sub-groups with chronic severe anxiety or depression were identified. Several socio-demographic and treatment factors characterized the women whose distress level remained severe eight months after diagnosis. The results suggest that support could be focused on relatively small groups of patients most in need.

Latent class-derived subgroups of depressive symptoms in a community sample of older adults: the Cache County Study.

PubMed

Lee, Chien-Ti; Leoutsakos, Jeannie-Marie; Lyketsos, Constantine G; Steffens, David C; Breitner, John C S; Norton, Maria C

2012-10-01

We sought to identify possible subgroups of elders that varied in depressive symptomatology and to examine symptom patterns and health status differences between subgroups. The Cache County memory study is a population-based epidemiological study of dementia with 5092 participants. Depressive symptoms were measured with a modified version of the diagnostic interview schedule-depression. There were 400 nondemented participants who endorsed currently (i.e., in the past 2 weeks) experiencing at least one of the three "gateway" depressive symptoms and then completed a full depression interview. Responses to all nine current depressive symptoms were modeled using the latent class analysis. Three depression subgroups were identified: a significantly depressed subgroup (62%), with the remainder split evenly between a subgroup with low probability of all symptoms (21%), and a subgroup with primarily psychomotor changes, sleep symptoms, and fatigue (17%). Latent class analysis derived subgroups of depressive symptoms and Diagnostic and statistical manual of mental disorders, fourth edition depression diagnostic group were nonredundant. Age, gender, education, marital status, early or late onset, number of episodes, current episode duration, and functional status were not significant predictors of depression subgroup. The first subgroup was more likely to be recently bereaved and had less physical health problems, whereas the third subgroup were less likely to be using antidepressants compared with the second subgroup. There are distinct subgroups of depressed elders, which are not redundant with the Diagnostic and statistical manual of mental disorders, fourth edition classification scheme, offering an alternative diagnostic approach to clinicians and researchers. Future work will examine whether these depressive symptom profiles are predictive of incident dementia and earlier mortality. Copyright © 2011 John Wiley & Sons, Ltd.

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

PubMed Central

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

2014-01-01

Kuwaiti native population comprises three distinct genetic subgroups of Persian, “city-dwelling” Saudi Arabian tribe, and nomadic “tent-dwelling” Bedouin ancestry. Bedouin subgroup is characterized by presence of 17% African ancestry; it owes it origin to nomadic tribes of the deserts of Arabian Peninsula and North Africa. By sequencing whole genome of a Kuwaiti male from this subgroup at 41X coverage, we report 3,752,878 SNPs, 411,839 indels, and 8451 structural variations. Neighbor-joining tree, based on shared variant positions carrying disease-risk alleles between the Bedouin and other continental genomes, places Bedouin genome at the nexus of African, Asian, and European genomes in concordance with geographical location of Kuwait and Peninsula. In congruence with participant's medical history for morbid obesity and bronchial asthma, risk alleles are seen at deleterious SNPs associated with obesity and asthma. Many of the observed deleterious ‘novel’ variants lie in genes associated with autosomal recessive disorders characteristic of the region. PMID:26484159

Acoustic Features Influence Musical Choices Across Multiple Genres.

PubMed

Barone, Michael D; Bansal, Jotthi; Woolhouse, Matthew H

2017-01-01

Based on a large behavioral dataset of music downloads, two analyses investigate whether the acoustic features of listeners' preferred musical genres influence their choice of tracks within non-preferred, secondary musical styles. Analysis 1 identifies feature distributions for pairs of genre-defined subgroups that are distinct. Using correlation analysis, these distributions are used to test the degree of similarity between subgroups' main genres and the other music within their download collections. Analysis 2 explores the issue of main-to-secondary genre influence through the production of 10 feature-influence matrices, one per acoustic feature, in which cell values indicate the percentage change in features for genres and subgroups compared to overall population averages. In total, 10 acoustic features and 10 genre-defined subgroups are explored within the two analyses. Results strongly indicate that the acoustic features of people's main genres influence the tracks they download within non-preferred, secondary musical styles. The nature of this influence and its possible actuating mechanisms are discussed with respect to research on musical preference, personality, and statistical learning.

New Insights on Developmental Dyslexia Subtypes: Heterogeneity of Mixed Reading Profiles

PubMed Central

Zoubrinetzky, Rachel; Bielle, Frédérique; Valdois, Sylviane

2014-01-01

We examined whether classifications based on reading performance are relevant to identify cognitively homogeneous subgroups of dyslexic children. Each of the 71 dyslexic participants was selected to have a mixed reading profile, i.e. poor irregular word and pseudo-word reading performance (accuracy and speed). Despite their homogeneous reading profile, the participants were found to split into four distinct cognitive subgroups, characterized by a single phonological disorder, a single visual attention span disorder, a double deficit or none of these disorders. The two subgroups characterized by single and contrasted cognitive disorders were found to exhibit a very similar reading pattern but more contrasted spelling performance (quantitative analysis). A qualitative analysis of the error types produced in reading and spelling provided some cues about the participants' underlying cognitive deficit. The overall findings disqualify subtyping based on reading profiles as a classification method to identify cognitively homogeneous subgroups of dyslexic children. They rather show an opaque relationship between the cognitive underpinnings of developmental dyslexia and their behavioral manifestations in reading and spelling. Future neuroimaging and genetic studies should take this issue into account since synthesizing over cognitively heterogeneous children would entail potential pitfalls. PMID:24918441

Comparative sequence analyses of sixteen reptilian paramyxoviruses

USGS Publications Warehouse

Ahne, W.; Batts, W.N.; Kurath, G.; Winton, J.R.

1999-01-01

Viral genomic RNA of Fer-de-Lance virus (FDLV), a paramyxovirus highly pathogenic for reptiles, was reverse transcribed and cloned. Plasmids with significant sequence similarities to the hemagglutinin-neuraminidase (HN) and polymerase (L) genes of mammalian paramyxoviruses were identified by BLAST search. Partial sequences of the FDLV genes were used to design primers for amplification by nested polymerase chain reaction (PCR) and sequencing of 518-bp L gene and 352-bp HN gene fragments from a collection of 15 previously uncharacterized reptilian paramyxoviruses. Phylogenetic analyses of the partial L and HN sequences produced similar trees in which there were two distinct subgroups of isolates that were supported with maximum bootstrap values, and several intermediate isolates. Within each subgroup the nucleotide divergence values were less than 2.5%, while the divergence between the two subgroups was 20-22%. This indicated that the two subgroups represent distinct virus species containing multiple virus strains. The five intermediate isolates had nucleotide divergence values of 11-20% and may represent additional distinct species. In addition to establishing diversity among reptilian paramyxoviruses, the phylogenetic groupings showed some correlation with geographic location, and clearly demonstrated a low level of host species-specificity within these viruses. Copyright (C) 1999 Elsevier Science B.V.

Cost of health care utilization among homeless frequent emergency department users.

PubMed

Mitchell, Matthew S; León, Casey L K; Byrne, Thomas H; Lin, Wen-Chieh; Bharel, Monica

2017-05-01

Research demonstrates that homelessness is associated with frequent use of emergency department (ED) services, yet prior studies have not adequately examined the relationship between frequent ED use and utilization of non-ED health care services among those experiencing homelessness. There has also been little effort to assess heterogeneity among homeless individuals who make frequent use of ED services. To address these gaps, the present study used Medicaid claims data from 2010 to estimate the association between the number of ED visits and non-ED health care costs for a cohort of 6,338 Boston Health Care for the Homeless Program patients, and to identify distinct subgroups of persons in this cohort who made frequent use of ED services based on their clinical and demographic characteristics. A series of gamma regression models found more frequent ED use to be associated with higher non-ED costs, even after adjusting for demographic and clinical characteristics. Latent class analysis was used to examine heterogeneity among frequent ED users, and the results identified 6 characteristically distinct subgroups among these persons. The subgroup of persons with trimorbid illness had non-ED costs that far exceeded members of all 5 other subgroups. Study findings reinforce the connection between frequent ED use and high health care costs among homeless individuals and suggest that different groups of homeless frequent ED users may benefit from interventions that vary in terms of their composition and intensity. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Identifying Subgroups among Hardcore Smokers: a Latent Profile Approach

PubMed Central

Bommelé, Jeroen; Kleinjan, Marloes; Schoenmakers, Tim M.; Burk, William J.; van den Eijnden, Regina; van de Mheen, Dike

2015-01-01

Introduction Hardcore smokers are smokers who have little to no intention to quit. Previous research suggests that there are distinct subgroups among hardcore smokers and that these subgroups vary in the perceived pros and cons of smoking and quitting. Identifying these subgroups could help to develop individualized messages for the group of hardcore smokers. In this study we therefore used the perceived pros and cons of smoking and quitting to identify profiles among hardcore smokers. Methods A sample of 510 hardcore smokers completed an online survey on the perceived pros and cons of smoking and quitting. We used these perceived pros and cons in a latent profile analysis to identify possible subgroups among hardcore smokers. To validate the profiles identified among hardcore smokers, we analysed data from a sample of 338 non-hardcore smokers in a similar way. Results We found three profiles among hardcore smokers. ‘Receptive’ hardcore smokers (36%) perceived many cons of smoking and many pros of quitting. ‘Ambivalent’ hardcore smokers (59%) were rather undecided towards quitting. ‘Resistant’ hardcore smokers (5%) saw few cons of smoking and few pros of quitting. Among non-hardcore smokers, we found similar groups of ‘receptive’ smokers (30%) and ‘ambivalent’ smokers (54%). However, a third group consisted of ‘disengaged’ smokers (16%), who saw few pros and cons of both smoking and quitting. Discussion Among hardcore smokers, we found three distinct profiles based on perceived pros and cons of smoking. This indicates that hardcore smokers are not a homogenous group. Each profile might require a different tobacco control approach. Our findings may help to develop individualized tobacco control messages for the particularly hard-to-reach group of hardcore smokers. PMID:26207829

Health Assessment Questionnaire disability progression in early rheumatoid arthritis: Systematic review and analysis of two inception cohorts

PubMed Central

Norton, Sam; Fu, Bo; Scott, David L.; Deighton, Chris; Symmons, Deborah P.M.; Wailoo, Allan J.; Tosh, Jonathan; Lunt, Mark; Davies, Rebecca; Young, Adam; Verstappen, Suzanne M.M

2014-01-01

Objective The Health Assessment Questionnaire is widely used for patients with inflammatory polyarthritis (IP) and its subset, rheumatoid arthritis (RA). In this study, we evaluated the progression of HAQ scores in RA (i) by systematically reviewing the published literature on the methods used to assess changes in functional disability over time and (ii) to study in detail HAQ progression in two large prospective observational studies from the UK. Methods Data from two large inception cohorts, ERAS and NOAR, were studied to determine trajectories of HAQ progression over time by applying latent class growth models (LCGMs) to each dataset separately. Age, sex, baseline DAS28, symptom duration, rheumatoid factor, fulfilment of the 1987 ACR criteria and socio-economic status (SES) were included as potential predictors of HAQ trajectory subgroup membership. Results The literature search identified 49 studies showing that HAQ progression has mainly been based on average changes in the total study population. In the HAQ progression study, a LCGM with four HAQ trajectory subgroups was selected as providing the best fit in both cohorts. In both the cohorts, older age, female sex, longer symptom duration, fulfilment of the 1987 ACR criteria, higher DAS28 and lower SES were associated with increased likelihood of membership of subgroups with worse HAQ progression. Conclusion Four distinct HAQ trajectory subgroups were derived from the ERAS and NOAR cohorts. The fact that the subgroups identified were nearly identical supports their validity. Identifying distinct groups of patients who are at risk of poor functional outcome may help to target therapy to those who are most likely to benefit. PMID:24925692

The Distinction between Exclusivity and Comorbidity within NSSI

ERIC Educational Resources Information Center

Goldberg, Shira; Israelashvili, Moshe

2017-01-01

Based on notions posited by problem behavior theory, the primary goal of the current study was to examine the possibility that adolescents who engage in NSSI are not a homogeneous group but are rather divided into 2 subgroups: (a) adolescents who exclusively engage in NSSI, and (b) adolescents who are involved in NSSI alongside other problem…

Relationship between Attitudes and Indicators of Obesity for Midlife Women

ERIC Educational Resources Information Center

Sudo, Noriko; Degeneffe, Dennis; Vue, Houa; Merkle, Emily; Kinsey, Jean; Ghosh, Koel; Reicks, Marla

2009-01-01

This study uses segmentation analyses to identify five distinct subgroups of U.S. midlife women (n = 200) based on their prevailing attitudes toward food and its preparation and consumption. Mean age of the women is 46 years and they are mostly White (86%), highly educated, and employed. Attitude segments (clusters of women sharing similar…

HTLV-1 subgroups associated with the risk of HAM/TSP are related to viral and host gene expression in peripheral blood mononuclear cells, independent of the transactivation functions of the viral factors.

PubMed

Yasuma, Keiko; Matsuzaki, Toshio; Yamano, Yoshihisa; Takashima, Hiroshi; Matsuoka, Masao; Saito, Mineki

2016-08-01

Among human T cell leukemia virus type 1 (HTLV-1)-infected individuals, the risk of developing HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) across lifetime differs between ethnic groups. There is an association between HTLV-1 tax gene subgroups (subgroup-A or subgroup-B) and the risk of HAM/TSP in the Japanese population. In this study, we investigated the full-length proviral genome sequences of various HTLV-1-infected cell lines and patient samples. The functional differences in the viral transcriptional regulators Tax and HTLV-1 bZIP factor (HBZ) between each subgroup and the relationships between subgroups and the clinical and laboratory characteristics of HAM/TSP patients were evaluated. The results of these analyses indicated the following: (1) distinct nucleotide substitutions corresponding to each subgroup were associated with nucleotide substitutions in viral structural, regulatory, and accessory genes; (2) the HBZ messenger RNA (mRNA) expression in HTLV-1-infected cells was significantly higher in HAM/TSP patients with subgroup-B than in those with subgroup-A; (3) a positive correlation was observed between the expression of HBZ mRNA and its target Foxp3 mRNA in HAM/TSP patients with subgroup-B, but not in patients with subgroup-A; (4) no clear differences were noted in clinical and laboratory characteristics between HAM/TSP patients with subgroup-A and subgroup-B; and (5) no functional differences were observed in Tax and HBZ between each subgroup based on reporter gene assays. Our results indicate that although different HTLV-1 subgroups are characterized by different patterns of viral and host gene expression in HAM/TSP patients via independent mechanisms of direct transcriptional regulation, these differences do not significantly affect the clinical and laboratory characteristics of HAM/TSP patients.

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

PubMed Central

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. p<0.05, fold-change>1.5). 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 rather than enrichment of the subgroup of interest revealed proteins that define subclasses of TRPV1-positive neurons and suggests a novel paracrine circuit. PMID:25551770

Interpersonal differentiation within depression diagnosis: relating interpersonal subgroups to symptom load and the quality of the early therapeutic alliance.

PubMed

Grosse Holtforth, Martin; Altenstein, David; Krieger, Tobias; Flückiger, Christoph; Wright, Aidan G C; Caspar, Franz

2014-01-01

We examined interpersonal problems in psychotherapy outpatients with a principal diagnosis of a depressive disorder in routine care (n=361). These patients were compared to a normative non-clinical sample and to outpatients with other principal diagnoses (n=959). Furthermore, these patients were statistically assigned to interpersonally defined subgroups that were compared regarding symptoms and the quality of the early alliance. The sample of depressive patients reported higher levels of interpersonal problems than the normative sample and the sample of outpatients without a principal diagnosis of depression. Latent Class Analysis identified eight distinct interpersonal subgroups, which differed regarding self-reported symptom load and the quality of the early alliance. However, therapists' alliance ratings did not differentiate between the groups. This interpersonal differentiation within the group of patients with a principal diagnosis of depression may add to a personalized psychotherapy based on interpersonal profiles.

Identification of clinically relevant phenotypes in patients with Ebstein anomaly.

PubMed

Cabrera, Rodrigo; Miranda-Fernández, Marta Catalina; Huertas-Quiñones, Victor Manuel; Carreño, Marisol; Pineda, Ivonne; Restrepo, Carlos M; Silva, Claudia Tamar; Quero, Rossi; Cano, Juan David; Manrique, Diana Carolina; Camacho, Camila; Tabares, Sebastián; García, Alberto; Sandoval, Néstor; Moreno Medina, Karen Julieth; Dennis Verano, Rodolfo José

2018-03-01

Ebstein anomaly (EA) is a heterogeneous congenital heart defect (CHD), frequently accompanied by diverse cardiac and extracardiac comorbidities, resulting in a wide range of clinical outcomes. Phenotypic characterization of EA patients has the potential to identify variables that influence prognosis and subgroups with distinct contributing factors. A comprehensive cross-sectional phenotypic characterization of 147 EA patients from one of the main referral institutions for CHD in Colombia was carried out. The most prevalent comorbidities and distinct subgroups within the patient cohort were identified through cluster analysis. The most prevalent cardiac comorbidities identified were atrial septal defect (61%), Wolff-Parkinson-White syndrome (WPW; 27%), and right ventricular outflow tract obstruction (25%). Cluster analysis showed that patients can be classified into 2 distinct subgroups with defined phenotypes that determine disease severity and survival. Patients in cluster 1 represented a particularly homogeneous subgroup with a milder spectrum of disease, including only patients with WPW and/or supraventricular tachycardia (SVT). Cluster 2 included patients with more diverse cardiovascular comorbidities. This study represents one of the largest phenotypic characterizations of EA patients reported. The data show that EA is a heterogeneous disease, very frequently associated with cardiovascular and noncardiovascular comorbidities. Patients with WPW and SVT represent a homogeneous subgroup that presents with a less severe spectrum of disease and better survival when adequately managed. This should be considered when searching for genetic causes of EA and in the clinical setting. © 2018 Wiley Periodicals, Inc.

Subgroups of haemodialysis patients in relation to fluid intake restrictions: a cluster analytical approach.

PubMed

Lindberg, Magnus; Wikström, Björn; Lindberg, Per

2010-11-01

To determine whether definable subgroups exist in a sample of haemodialysis patients with regard to self-efficacy, attentional style and depressive symptomatology and to compare whether interdialytic weight gain varies between patients in groups with different cognitive profiles. Theory-based research suggests that cognitive factors (e.g. self-efficacy and attentional style) and depressive symptomatology undermine adherence to health protective regimens. Preventing negative outcomes of fluid overload is essential for haemodialysis patients but many patients cannot achieve fluid control, and nursing interventions aimed to help the patients reduce fluid intake are ineffective. Understanding the interaction between cognitive factors and how this is related to adherence outcomes might therefore lead to the development of helpful nursing interventions. Explorative cross-sectional multicentre survey. The sample consisted of 133 haemodialysis patients. Data were collected using structured questionnaires. A brief self-report form and data on interdialytic weight gain was also used. Two-step cluster analysis was used to identify subgroups. One-way analysis of variance (anova) or Pearson's chi-square test was used for comparing subgroups. Three distinct subgroups were found and subsequently labelled: (1) low self-efficacy, (2) distraction and depressive symptoms and (3) high self-efficacy. The subgroups differed in fluid intake, but not in age, dialysis vintage, gender, residual urine output or in receiving any fluid intake advice. Clinically relevant subgroups of haemodialysis patients could be defined by their profiles regarding self-efficacy, attentional style and depressive symptoms. Based on this study, we would encourage clinical practitioners to take into account cognitive profiles while performing their work. This is especially important when a targeted nursing intervention, which aims to encourage and maintain the patient's fluid control, is introduced. © 2010 Blackwell Publishing Ltd.

Exploring Disparities and Variability in Perceptions and Self-Reported Colorectal Cancer Screening Among Three Ethnic Subgroups of U.S. Blacks

PubMed Central

Gwede, Clement K.; William, Claire M.; Thomas, Kamilah B.; Tarver, Will L.; Quinn, Gwendolyn P.; Vadaparampil, Susan T.; Kim, Jongphil; Lee, Ji-Hyun; Meade, Cathy D.

2010-01-01

Purpose/Objectives To explore perceptions of colorectal cancer (CRC) and self-reported CRC screening behaviors among ethnic subgroups of U.S. blacks. Design Descriptive, cross-sectional, exploratory, developmental pilot. Setting Medically underserved areas in Hillsborough County, FL. Sample 62 men and women aged 50 years or older. Ethnic subgroup distribution included 22 African American, 20 English-speaking Caribbean-born, and 20 Haitian-born respondents. Methods Community-based participatory research methods were used to conduct face-to-face individual interviews in the community. Main Research Variables Ethnic subgroup, health access, perceptions of CRC (e.g., awareness of screening tests, perceived risk, perceived barriers to screening), healthcare provider recommendation, and self-reported CRC screening. Findings Awareness of CRC screening tests, risk perception, healthcare provider recommendation, and self-reported use of screening were low across all subgroups. However, only 55% of Haitian-born participants had heard about the fecal occult blood test compared to 84% for English-speaking Caribbean-born participants and 91% for African Americans. Similarly, only 15% of Haitian-born respondents had had a colonoscopy compared to 50% for the English-speaking Caribbean and African American subgroups. Conclusions This exploratory, developmental pilot study identified lack of awareness, low risk perception, and distinct barriers to screening. The findings support the need for a larger community-based study to elucidate and address disparities among subgroups. Implications for Nursing Nurses play a major role in reducing cancer health disparities through research, education, and quality care. Recognition of the cultural diversity of the U.S. black population can help nurses address health disparities and contribute to the health of the community. PMID:20797950

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

PubMed

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 molecular mechanisms in the origins of this disease.

Patterns of Depressive Symptoms, Drinking Motives, and Sexual Behavior among Substance Abusing Adolescents: Implications for Health Risk

ERIC Educational Resources Information Center

Tubman, Jonathan G.; Wagner, Eric F.; Langer, Lilly M.

2003-01-01

Adolescents with substance use problems were classified into four distinct and meaningful subgroups based on patterns of depressive symptoms and motives for drinking before sex (i.e., avoidance, enhancement and social motives) using cluster analysis. Data were collected in face-to-face interviews from 120 adolescents and young adults (87 men, 33…

Acoustic Features Influence Musical Choices Across Multiple Genres

PubMed Central

Barone, Michael D.; Bansal, Jotthi; Woolhouse, Matthew H.

2017-01-01

Based on a large behavioral dataset of music downloads, two analyses investigate whether the acoustic features of listeners' preferred musical genres influence their choice of tracks within non-preferred, secondary musical styles. Analysis 1 identifies feature distributions for pairs of genre-defined subgroups that are distinct. Using correlation analysis, these distributions are used to test the degree of similarity between subgroups' main genres and the other music within their download collections. Analysis 2 explores the issue of main-to-secondary genre influence through the production of 10 feature-influence matrices, one per acoustic feature, in which cell values indicate the percentage change in features for genres and subgroups compared to overall population averages. In total, 10 acoustic features and 10 genre-defined subgroups are explored within the two analyses. Results strongly indicate that the acoustic features of people's main genres influence the tracks they download within non-preferred, secondary musical styles. The nature of this influence and its possible actuating mechanisms are discussed with respect to research on musical preference, personality, and statistical learning. PMID:28725200

Veterans Affairs Intensive Case Management for older veterans.

PubMed

Mohamed, Somaia; Neale, Michael S; Rosenheck, Robert

2009-08-01

There is a growing need for information on evidence-based practices that may potentially address needs of elderly people with severe mental illness (SMI), and more specifically on community-based services such as assertive community treatment (ACT). This study examines national evaluation data from fiscal year 2001-2005 from Veterans Affairs Mental Health Intensive Case Management (MHICM) program (N = 5,222), an ACT-based service model, to characterize the age distribution of participants and the distinctive needs, patterns of service delivery, and treatment outcomes for elderly veterans. Altogether, 24.8% of participants were 55-64 years; 7.4% 65-74 years; and 2.8% were older than 75. Veterans over 75 formed a distinct subgroup that had a later age of onset of primarily nonpsychotic illnesses without comorbid substance abuse and had experienced more limited lifetime hospital treatment than younger participants. Older veterans were less symptomatic and more satisfied with their social relationships than younger clients. They mostly live independently or in minimally restrictive housing, but they received less recovery-focused services and more crisis intervention and medical services. They thus do not appear to be young patients with SMI who have aged but rather constitute a distinct group with serious late-onset problems. It is possible that MHICM services keep them in the community and avoid costly nursing home placement while providing a respite service that reduces family burden. These data highlight the unique characteristics of older veterans receiving ACT-like services and the need to focus greater attention on recovery-oriented services as well as community support for this subgroup.

BASE COMPOSITION OF THE DEOXYRIBONUCLEIC ACID OF SULFATE-REDUCING BACTERIA.

PubMed

SIGAL, N; SENEZ, J C; LEGALL, J; SEBALD, M

1963-06-01

Sigal, Nicole (Laboratoire de Chimie Bactérienne du CNRS, Marseille, France), Jacques C. Senez, Jean Le Gall, and Madeleine Sebald. Base composition of the deoxyribonucleic acid of sulfate-reducing bacteria. J. Bacteriol. 85:1315-1318. 1963-The deoxyribonucleic acid constitution of several strains of sulfate-reducing bacteria has been analytically determined. The results of these studies show that this group of microorganisms includes at least four subgroups characterized by significantly different values of the adenine plus thymine to guanine plus cytosine ratio. The nonsporulated forms with polar flagellation, containing both cytochrome c(3) and desulfoviridin, are divided into two subgroups. One includes the fresh-water, nonhalophilic strains with base ratio from 0.54 to 0.59, and the other includes the halophilic or halotolerant strains with base ratio from 0.74 to 0.77. The sporulated, peritrichous strains without cytochrome and desulfoviridin ("nigrificans" and "orientis") are distinct from the above two types and differ from each other, having base ratios of 1.20 and 1.43, respectively.

Delineation of Two Clinically and Molecularly Distinct Subgroups of Posterior Fossa Ependymoma

PubMed Central

Witt, Hendrik; Mack, Stephen C.; Ryzhova, Marina; Bender, Sebastian; Sill, Martin; Isserlin, Ruth; Benner, Axel; Hielscher, Thomas; Milde, Till; Remke, Marc; Jones, David T.W.; Northcott, Paul A.; Garzia, Livia; Bertrand, Kelsey C.; Wittmann, Andrea; Yao, Yuan; Roberts, Stephen S.; Massimi, Luca; Van Meter, Tim; Weiss, William A.; Gupta, Nalin; Grajkowska, Wiesia; Lach, Boleslaw; Cho, Yoon-Jae; von Deimling, Andreas; Kulozik, Andreas E.; Witt, Olaf; Bader, Gary D.; Hawkins, Cynthia E.; Tabori, Uri; Guha, Abhijit; Rutka, James T.; Lichter, Peter; Korshunov, Andrey

2014-01-01

Summary Despite the histological similarity of ependymomas from throughout the neuroaxis, the disease likely comprises multiple independent entities, each with a distinct molecular pathogenesis. Transcriptional profiling of two large independent cohorts of ependymoma reveals the existence of two demographically, transcriptionally, genetically, and clinically distinct groups of posterior fossa (PF) ependymomas. Group A patients are younger, have laterally located tumors with a balanced genome, and are much more likely to exhibit recurrence, metastasis at recurrence, and death compared with Group B patients. Identification and optimization of immunohistochemical (IHC) markers for PF ependymoma subgroups allowed validation of our findings on a third independent cohort, using a human ependymoma tissue microarray, and provides a tool for prospective prognostication and stratification of PF ependymoma patients. PMID:21840481

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

PubMed

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.

Behavioral approach and avoidance in schizophrenia: an evaluation of motivational profiles.

PubMed

Felice Reddy, L; Green, Michael F; Rizzo, Shemra; Sugar, Catherine A; Blanchard, Jack J; Gur, Raquel E; Kring, Ann M; Horan, William P

2014-10-01

Schizophrenia is associated with motivational deficits that interfere with a wide range of goal directed activities. Despite their clinical importance, our current understanding of these motivational impairments is limited. Furthermore, different types of motivational problems are commonly seen among individuals within the broad diagnosis of schizophrenia. The goal of the current study was to examine whether clinically meaningful subgroups could be identified based on approach and avoidance motivational tendencies. We measured these tendencies in 151 individuals with schizophrenia. Although prior studies demonstrate elevated BIS sensitivity in schizophrenia at the overall group level, none have explored various combinations of BIS/BAS sensitivities within this disorder. Cluster analyses yielded five subgroups with different combinations of low, moderate, or high BIS and BAS. The subgroups had interpretable differences in clinically rated negative symptoms and self-reported anhedonia/socio-emotional attitudes, which were not detectable with the more commonly used linear BIS/BAS scores. Two of the subgroups had significantly elevated negative symptoms but different approach/avoidance profiles: one was characterized by markedly low BIS, low BAS and an overall lack of social approach motivation; the other had markedly high BIS but moderate BAS and elevated social avoidance motivation. The two subgroups with relatively good clinical functioning showed patterns of BAS greater than BIS. Our findings indicate that there are distinct motivational pathways that can lead to asociality in schizophrenia and highlight the value of considering profiles based on combined patterns of BIS and BAS in schizophrenia. Published by Elsevier B.V.

Histopathological subgroups in knee osteoarthritis.

PubMed

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.

Smoking Initiation Associated With Specific Periods in the Life Course From Birth to Young Adulthood: Data From the National Longitudinal Survey of Youth 1997

PubMed Central

Chen, Xinguang

2014-01-01

Objectives. Guided by the life-course perspective, we examined whether there were subgroups with different likelihood curves of smoking onset associated with specific developmental periods. Methods. Using 12 waves of panel data from 4088 participants in the National Longitudinal Survey of Youth 1997, we detected subgroups with distinctive risk patterns by employing developmental trajectory modeling analysis. Results. From birth to age 29 years, 72% of female and 74% of US males initiated smoking. We detected 4 exclusive groups with distinctive risk patterns for both genders: the Pre-Teen Risk Group initiated smoking by age 12 years, the Teenage Risk Group initiated smoking by age 18 years, the Young Adult Risk Group initiated smoking by age 25 years, and the Low Risk Group experienced little or no risk over time. Groups differed on several etiological and outcome variables. Conclusions. The process of smoking initiation from birth to young adulthood is nonhomogeneous, with distinct subgroups whose risk of smoking onset is linked to specific stages in the life course. PMID:24328611

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

PubMed

Tanniou, Julien; van der Tweel, Ingeborg; Teerenstra, Steven; Roes, Kit C B

2016-02-18

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. 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. 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). It is important that researchers developing methodology for subgroup analysis explicitly clarify the objectives of their methods in terms that can be understood from a patient's, health care provider's and/or regulator's perspective. A clear operational definition for consistency of treatment effects across subgroups is lacking, but is needed to improve the usability of subgroup analyses in this setting. Finally, methods to particularly explore benefit-risk systematically across subgroups need more research.

International collaboration including patients is essential to develop new therapies for patients with myositis.

PubMed

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.

Precision Medicine: The New Frontier in Idiopathic Pulmonary Fibrosis.

PubMed

Brownell, Robert; Kaminski, Naftali; Woodruff, Prescott G; Bradford, Williamson Z; Richeldi, Luca; Martinez, Fernando J; Collard, Harold R

2016-06-01

Precision medicine is defined by the National Institute of Health's Precision Medicine Initiative Working Group as an approach to disease treatment that takes into account individual variability in genes, environment, and lifestyle. There has been increased interest in applying the concept of precision medicine to idiopathic pulmonary fibrosis, in particular to search for genetic and molecular biomarker-based profiles (so called endotypes) that identify mechanistically distinct disease subgroups. The relevance of precision medicine to idiopathic pulmonary fibrosis is yet to be established, but we believe that it holds great promise to provide targeted and highly effective therapies to patients. In this manuscript, we describe the field's nascent efforts in genetic/molecular endotype identification and how environmental and behavioral subgroups may also be relevant to disease management.

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

PubMed Central

Bialosky, Joel E.; Robinson, Michael E.

2014-01-01

Background Cluster analysis can be used to identify individuals similar in profile based on response to multiple pain sensitivity measures. There are limited investigations into how empirically derived pain sensitivity subgroups influence clinical outcomes for individuals with spine pain. Objective The purposes of this study were: (1) to investigate empirically derived subgroups based on pressure and thermal pain sensitivity in individuals with spine pain and (2) to examine subgroup influence on 2-week clinical pain intensity and disability outcomes. Design A secondary analysis of data from 2 randomized trials was conducted. Methods Baseline and 2-week outcome data from 157 participants with low back pain (n=110) and neck pain (n=47) were examined. Participants completed demographic, psychological, and clinical information and were assessed using pain sensitivity protocols, including pressure (suprathreshold pressure pain) and thermal pain sensitivity (thermal heat threshold and tolerance, suprathreshold heat pain, temporal summation). A hierarchical agglomerative cluster analysis was used to create subgroups based on pain sensitivity responses. Differences in data for baseline variables, clinical pain intensity, and disability were examined. Results Three pain sensitivity cluster groups were derived: low pain sensitivity, high thermal static sensitivity, and high pressure and thermal dynamic sensitivity. There were differences in the proportion of individuals meeting a 30% change in pain intensity, where fewer individuals within the high pressure and thermal dynamic sensitivity group (adjusted odds ratio=0.3; 95% confidence interval=0.1, 0.8) achieved successful outcomes. Limitations Only 2-week outcomes are reported. Conclusions Distinct pain sensitivity cluster groups for individuals with spine pain were identified, with the high pressure and thermal dynamic sensitivity group showing worse clinical outcome for pain intensity. Future studies should aim to confirm these findings. PMID:24764070

Differences in Language Skills: Heritage Language Learner Subgroups and Foreign Language Learners

ERIC Educational Resources Information Center

Kondo-Brown, Kimi

2005-01-01

Using both proficiency tests and self-assessment measures, this study investigated (a) whether 3 subgroups of Japanese heritage language (JHL) learners would demonstrate language behaviors distinctively different from those of traditional Japanese as a foreign language (JFL) learners, and (b) which domains of language use and skills would…

Mining Health App Data to Find More and Less Successful Weight Loss Subgroups

PubMed Central

2016-01-01

Background More than half of all smartphone app downloads involve weight, diet, and exercise. If successful, these lifestyle apps may have far-reaching effects for disease prevention and health cost-savings, but few researchers have analyzed data from these apps. Objective The purposes of this study were to analyze data from a commercial health app (Lose It!) in order to identify successful weight loss subgroups via exploratory analyses and to verify the stability of the results. Methods Cross-sectional, de-identified data from Lose It! were analyzed. This dataset (n=12,427,196) was randomly split into 24 subsamples, and this study used 3 subsamples (combined n=972,687). Classification and regression tree methods were used to explore groupings of weight loss with one subsample, with descriptive analyses to examine other group characteristics. Data mining validation methods were conducted with 2 additional subsamples. Results In subsample 1, 14.96% of users lost 5% or more of their starting body weight. Classification and regression tree analysis identified 3 distinct subgroups: “the occasional users” had the lowest proportion (4.87%) of individuals who successfully lost weight; “the basic users” had 37.61% weight loss success; and “the power users” achieved the highest percentage of weight loss success at 72.70%. Behavioral factors delineated the subgroups, though app-related behavioral characteristics further distinguished them. Results were replicated in further analyses with separate subsamples. Conclusions This study demonstrates that distinct subgroups can be identified in “messy” commercial app data and the identified subgroups can be replicated in independent samples. Behavioral factors and use of custom app features characterized the subgroups. Targeting and tailoring information to particular subgroups could enhance weight loss success. Future studies should replicate data mining analyses to increase methodology rigor. PMID:27301853

Compensatory processing during rule-based category learning in older adults.

PubMed

Bharani, Krishna L; Paller, Ken A; Reber, Paul J; Weintraub, Sandra; Yanar, Jorge; Morrison, Robert G

2016-01-01

Healthy older adults typically perform worse than younger adults at rule-based category learning, but better than patients with Alzheimer's or Parkinson's disease. To further investigate aging's effect on rule-based category learning, we monitored event-related potentials (ERPs) while younger and neuropsychologically typical older adults performed a visual category-learning task with a rule-based category structure and trial-by-trial feedback. Using these procedures, we previously identified ERPs sensitive to categorization strategy and accuracy in young participants. In addition, previous studies have demonstrated the importance of neural processing in the prefrontal cortex and the medial temporal lobe for this task. In this study, older adults showed lower accuracy and longer response times than younger adults, but there were two distinct subgroups of older adults. One subgroup showed near-chance performance throughout the procedure, never categorizing accurately. The other subgroup reached asymptotic accuracy that was equivalent to that in younger adults, although they categorized more slowly. These two subgroups were further distinguished via ERPs. Consistent with the compensation theory of cognitive aging, older adults who successfully learned showed larger frontal ERPs when compared with younger adults. Recruitment of prefrontal resources may have improved performance while slowing response times. Additionally, correlations of feedback-locked P300 amplitudes with category-learning accuracy differentiated successful younger and older adults. Overall, the results suggest that the ability to adapt one's behavior in response to feedback during learning varies across older individuals, and that the failure of some to adapt their behavior may reflect inadequate engagement of prefrontal cortex.

Compensatory Processing During Rule-Based Category Learning in Older Adults

PubMed Central

Bharani, Krishna L.; Paller, Ken A.; Reber, Paul J.; Weintraub, Sandra; Yanar, Jorge; Morrison, Robert G.

2016-01-01

Healthy older adults typically perform worse than younger adults at rule-based category learning, but better than patients with Alzheimer's or Parkinson's disease. To further investigate aging's effect on rule-based category learning, we monitored event-related potentials (ERPs) while younger and neuropsychologically typical older adults performed a visual category-learning task with a rule-based category structure and trial-by-trial feedback. Using these procedures, we previously identified ERPs sensitive to categorization strategy and accuracy in young participants. In addition, previous studies have demonstrated the importance of neural processing in the prefrontal cortex and the medial temporal lobe for this task. In this study, older adults showed lower accuracy and longer response times than younger adults, but there were two distinct subgroups of older adults. One subgroup showed near-chance performance throughout the procedure, never categorizing accurately. The other subgroup reached asymptotic accuracy that was equivalent to that in younger adults, although they categorized more slowly. These two subgroups were further distinguished via ERPs. Consistent with the compensation theory of cognitive aging, older adults who successfully learned showed larger frontal ERPs when compared with younger adults. Recruitment of prefrontal resources may have improved performance while slowing response times. Additionally, correlations of feedback-locked P300 amplitudes with category-learning accuracy differentiated successful younger and older adults. Overall, the results suggest that the ability to adapt one's behavior in response to feedback during learning varies across older individuals, and that the failure of some to adapt their behavior may reflect inadequate engagement of prefrontal cortex. PMID:26422522

Differences in performance and learning proficiency on the Wisconsin Card Sorting Test in schizophrenia: do they reflect distinct neurocognitive subtypes with distinct functional profiles?

PubMed

Kurtz, Matthew M; Wexler, Bruce E

2006-01-31

The aim of this study was two-fold: 1) to determine whether a priori subtyping of patients with schizophrenia based on both overall performance on a measure of executive-function, the Wisconsin Card Sorting Test (WCST), and ability to learn the task with expanded instruction, could be confirmed with other, independent measures of executive-function and learning, and, if so, 2) to determine whether these groups have different neurocognitive profiles and show differences in functional capacity. Fifty-four outpatients with schizophrenia were divided by WCST performance into three groups: intact executive-function (n=28), "good learner" (n=13), and "poor learner" (n=13) groups. These groups were then assessed with a comprehensive neurocognitive test battery and a performance-based measure of functional status, the UCSD Performance-based Skills Assessment (UPSA). The WCST-intact subgroup performed significantly better than other groups on a second measure of executive-function and in working memory, and speeded motor sequencing. Impaired WCST patients who benefited from expanded WCST instruction ("good learners") also showed better performance than patients who did not benefit from instruction ("poor-learners") on a second measure of learning, as well as on a measure of auditory divided attention. The intact WCST subgroup had greater functional capacity than either "strong" or "poor" learners. These subtypes may have implications for response to behavioral treatment interventions.

G-cimp status prediction of glioblastoma samples using mRNA expression data.

PubMed

Baysan, Mehmet; Bozdag, Serdar; Cam, Margaret C; Kotliarova, Svetlana; Ahn, Susie; Walling, Jennifer; Killian, Jonathan K; Stevenson, Holly; Meltzer, Paul; Fine, Howard A

2012-01-01

Glioblastoma Multiforme (GBM) is a tumor with high mortality and no known cure. The dramatic molecular and clinical heterogeneity seen in this tumor has led to attempts to define genetically similar subgroups of GBM with the hope of developing tumor specific therapies targeted to the unique biology within each of these subgroups. Recently, a subset of relatively favorable prognosis GBMs has been identified. These glioma CpG island methylator phenotype, or G-CIMP tumors, have distinct genomic copy number aberrations, DNA methylation patterns, and (mRNA) expression profiles compared to other GBMs. While the standard method for identifying G-CIMP tumors is based on genome-wide DNA methylation data, such data is often not available compared to the more widely available gene expression data. In this study, we have developed and evaluated a method to predict the G-CIMP status of GBM samples based solely on gene expression data.

G-Cimp Status Prediction Of Glioblastoma Samples Using mRNA Expression Data

PubMed Central

Baysan, Mehmet; Bozdag, Serdar; Cam, Margaret C.; Kotliarova, Svetlana; Ahn, Susie; Walling, Jennifer; Killian, Jonathan K.; Stevenson, Holly; Meltzer, Paul; Fine, Howard A.

2012-01-01

Glioblastoma Multiforme (GBM) is a tumor with high mortality and no known cure. The dramatic molecular and clinical heterogeneity seen in this tumor has led to attempts to define genetically similar subgroups of GBM with the hope of developing tumor specific therapies targeted to the unique biology within each of these subgroups. Recently, a subset of relatively favorable prognosis GBMs has been identified. These glioma CpG island methylator phenotype, or G-CIMP tumors, have distinct genomic copy number aberrations, DNA methylation patterns, and (mRNA) expression profiles compared to other GBMs. While the standard method for identifying G-CIMP tumors is based on genome-wide DNA methylation data, such data is often not available compared to the more widely available gene expression data. In this study, we have developed and evaluated a method to predict the G-CIMP status of GBM samples based solely on gene expression data. PMID:23139755

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

PubMed

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.

At-risk depressive symptoms and alcohol use trajectories in adolescence: a person-centred analysis of co-occurrence.

PubMed

Willoughby, Teena; Fortner, Adrian

2015-04-01

Long-term longitudinal studies that examine whether there are distinct trajectories of at-risk depressive symptoms and alcohol use across the high school years (e.g., high co-occurrence) are rare in normative samples of adolescent boys and girls; yet, this assessment is of critical importance for developing effective prevention and intervention strategies. Moreover, the role of self-regulation and novelty-seeking behavior in differentiating among distinct subgroups of adolescents is not clear. To address these gaps, the present study sought to identify subgroups of adolescent boys and girls that indicated at-risk trajectories across the high school years for both depressive symptoms and alcohol use, and examined the role of delay of gratification and novelty seeking at baseline in differentiating among the subgroups. Canadian adolescents (N = 4,412; 49 % female) were surveyed at four time points (grades 9, 10, 11, and 12). Parallel process latent class growth analyses revealed four distinct subgroups for both boys and girls, encompassing high co-occurrence, depressive symptoms only, alcohol use only, and low co-occurrence. Across gender, delay of gratification at baseline differentiated among the four subgroups, with the High Co-Occurrence Group group scoring the lowest and the Low Co-Occurrence Group the highest. Lower novelty-seeking scores at baseline were associated more with being in the Depressive Symptoms Only Group relative to the other groups, particularly the Alcohol Use Only Group for boys. Thus, delay of gratification and novelty seeking may be useful in identifying youth at risk for co-occurring depressive symptoms and alcohol use trajectories, as well as at-risk trajectories for only one of these behaviors.

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

PubMed

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 < 0.001) compared with 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.

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

PubMed

Vaegter, Henrik B; Graven-Nielsen, Thomas

2016-07-01

Pain biomarkers are warranted for individualized pain management. Based on different pain modulatory phenotypes, the objectives of this study were to explore the existence of subgroups within patients with nonmalignant chronic pain and to investigate differences in clinical pain and pain hypersensitivity between subgroups. Cuff algometry was performed on lower legs in 400 patients with chronic pain to assess pressure pain threshold, pressure pain tolerance, temporal summation of pain (TSP: increase in pain scores to 10 repeated stimulations), and conditioned pain modulation (CPM: increase in cuff pressure pain threshold during cuff pain conditioning on the contralateral leg). Heat detection and heat pain thresholds at clinical painful and nonpainful body areas were assessed. Based on TSP and CPM, 4 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; and group 4 (n = 122) had normal CPM and normal TSP. Group 1 showed more pain regions than the other 3 groups (P < 0.001), indicating that impaired CPM and facilitated TSP play an important role in widespread pain. Groups 1 and 2 compared with group 4 had lower heat pain threshold at nonpainful areas and lower cuff pressure pain tolerance (P < 0.02), indicating that CPM plays a role for widespread hyperalgesia. Moreover, group 1 demonstrated higher clinical pain scores than group 4 (P < 0.05). Although not different between subgroups, patients were profiled on demographics, disability, pain catastrophizing, and fear of movement. Future research should investigate interventions tailored towards these subgroups.

Young People with Harmful Sexual Behaviour: Do Those with Learning Disabilities Form a Distinct Subgroup?

ERIC Educational Resources Information Center

Almond, Louise; Giles, Susan

2008-01-01

The study examines 102 young people with Learning Disabilities (n = 51) and without a learning disability (NLD; n = 51) to explore ways in which LD young people with harmful sexual behaviours (HSB) should be recognized as a subgroup requiring specialized treatment and intervention. Throughout this comparison of perpetrator, victim and abuse…

Commognitive Analysis of Undergraduate Mathematics Students' Responses in Proving Subgroup's Non-Emptiness

ERIC Educational Resources Information Center

Ioannou, Marios

2016-01-01

Proving that a given set is indeed a subgroup, one needs to show that it is non-empty, and closed under operation and inverses. This study focuses on the first condition, analysing students' responses to this task. Results suggest that there are three distinct problematic responses: the total absence of proving this condition, the problematic…

Co-occurring genomic alterations define major subsets of KRAS-mutant lung adenocarcinoma with distinct biology, immune profiles, and therapeutic vulnerabilities.

PubMed

Skoulidis, Ferdinandos; Byers, Lauren A; Diao, Lixia; Papadimitrakopoulou, Vassiliki A; Tong, Pan; Izzo, Julie; Behrens, Carmen; Kadara, Humam; Parra, Edwin R; Canales, Jaime Rodriguez; Zhang, Jianjun; Giri, Uma; Gudikote, Jayanthi; Cortez, Maria A; Yang, Chao; Fan, Youhong; Peyton, Michael; Girard, Luc; Coombes, Kevin R; Toniatti, Carlo; Heffernan, Timothy P; Choi, Murim; Frampton, Garrett M; Miller, Vincent; Weinstein, John N; Herbst, Roy S; Wong, Kwok-Kin; Zhang, Jianhua; Sharma, Padmanee; Mills, Gordon B; Hong, Waun K; Minna, John D; Allison, James P; Futreal, Andrew; Wang, Jing; Wistuba, Ignacio I; Heymach, John V

2015-08-01

The molecular underpinnings that drive the heterogeneity of KRAS-mutant lung adenocarcinoma are poorly characterized. We performed an integrative analysis of genomic, transcriptomic, and proteomic data from early-stage and chemorefractory lung adenocarcinoma and identified three robust subsets of KRAS-mutant lung adenocarcinoma dominated, respectively, by co-occurring genetic events in STK11/LKB1 (the KL subgroup), TP53 (KP), and CDKN2A/B inactivation coupled with low expression of the NKX2-1 (TTF1) transcription factor (KC). We further revealed biologically and therapeutically relevant differences between the subgroups. KC tumors frequently exhibited mucinous histology and suppressed mTORC1 signaling. KL tumors had high rates of KEAP1 mutational inactivation and expressed lower levels of immune markers, including PD-L1. KP tumors demonstrated higher levels of somatic mutations, inflammatory markers, immune checkpoint effector molecules, and improved relapse-free survival. Differences in drug sensitivity patterns were also observed; notably, KL cells showed increased vulnerability to HSP90-inhibitor therapy. This work provides evidence that co-occurring genomic alterations identify subgroups of KRAS-mutant lung adenocarcinoma with distinct biology and therapeutic vulnerabilities. Co-occurring genetic alterations in STK11/LKB1, TP53, and CDKN2A/B-the latter coupled with low TTF1 expression-define three major subgroups of KRAS-mutant lung adenocarcinoma with distinct biology, patterns of immune-system engagement, and therapeutic vulnerabilities. ©2015 American Association for Cancer Research.

BASE COMPOSITION OF THE DEOXYRIBONUCLEIC ACID OF SULFATE-REDUCING BACTERIA

PubMed Central

Sigal, Nicole; Senez, Jacques C.; Le Gall, Jean; Sebald, Madeleine

1963-01-01

Sigal, Nicole (Laboratoire de Chimie Bactérienne du CNRS, Marseille, France), Jacques C. Senez, Jean Le Gall, and Madeleine Sebald. Base composition of the deoxyribonucleic acid of sulfate-reducing bacteria. J. Bacteriol. 85:1315–1318. 1963—The deoxyribonucleic acid constitution of several strains of sulfate-reducing bacteria has been analytically determined. The results of these studies show that this group of microorganisms includes at least four subgroups characterized by significantly different values of the adenine plus thymine to guanine plus cytosine ratio. The nonsporulated forms with polar flagellation, containing both cytochrome c3 and desulfoviridin, are divided into two subgroups. One includes the fresh-water, nonhalophilic strains with base ratio from 0.54 to 0.59, and the other includes the halophilic or halotolerant strains with base ratio from 0.74 to 0.77. The sporulated, peritrichous strains without cytochrome and desulfoviridin (“nigrificans” and “orientis”) are distinct from the above two types and differ from each other, having base ratios of 1.20 and 1.43, respectively. PMID:14047223

SPIB and BATF provide alternate determinants of IRF4 occupancy in diffuse large B-cell lymphoma linked to disease heterogeneity

PubMed Central

Care, Matthew A.; Cocco, Mario; Laye, Jon P.; Barnes, Nicholas; Huang, Yuanxue; Wang, Ming; Barrans, Sharon; Du, Ming; Jack, Andrew; Westhead, David R.; Doody, Gina M.; Tooze, Reuben M.

2014-01-01

Interferon regulatory factor 4 (IRF4) is central to the transcriptional network of activated B-cell-like diffuse large B-cell lymphoma (ABC-DLBCL), an aggressive lymphoma subgroup defined by gene expression profiling. Since cofactor association modifies transcriptional regulatory input by IRF4, we assessed genome occupancy by IRF4 and endogenous cofactors in ABC-DLBCL cell lines. IRF4 partners with SPIB, PU.1 and BATF genome-wide, but SPIB provides the dominant IRF4 partner in this context. Upon SPIB knockdown IRF4 occupancy is depleted and neither PU.1 nor BATF acutely compensates. Integration with ENCODE data from lymphoblastoid cell line GM12878, demonstrates that IRF4 adopts either SPIB- or BATF-centric genome-wide distributions in related states of post-germinal centre B-cell transformation. In primary DLBCL high-SPIB and low-BATF or the reciprocal low-SPIB and high-BATF mRNA expression links to differential gene expression profiles across nine data sets, identifying distinct associations with SPIB occupancy, signatures of B-cell differentiation stage and potential pathogenetic mechanisms. In a population-based patient cohort, SPIBhigh/BATFlow-ABC-DLBCL is enriched for mutation of MYD88, and SPIBhigh/BATFlow-ABC-DLBCL with MYD88-L265P mutation identifies a small subgroup of patients among this otherwise aggressive disease subgroup with distinct favourable outcome. We conclude that differential expression of IRF4 cofactors SPIB and BATF identifies biologically and clinically significant heterogeneity among ABC-DLBCL. PMID:24875472

Diffusion-weighted MRI derived apparent diffusion coefficient identifies prognostically distinct subgroups of pediatric diffuse intrinsic pontine glioma.

PubMed

Lober, Robert M; Cho, Yoon-Jae; Tang, Yujie; Barnes, Patrick D; Edwards, Michael S; Vogel, Hannes; Fisher, Paul G; Monje, Michelle; Yeom, Kristen W

2014-03-01

While pediatric diffuse intrinsic pontine gliomas (DIPG) remain fatal, recent data have shown subgroups with distinct molecular biology and clinical behavior. We hypothesized that diffusion-weighted MRI can be used as a prognostic marker to stratify DIPG subsets with distinct clinical behavior. Apparent diffusion coefficient (ADC) values derived from diffusion-weighted MRI were computed in 20 consecutive children with treatment-naïve DIPG tumors. The median ADC for the cohort was used to stratify the tumors into low and high ADC groups. Survival, gender, therapy, and potential steroid effects were compared between the ADC groups. Median age at diagnosis was 6.6 (range 2.3-13.2) years, with median follow-up seven (range 1-36) months. There were 14 boys and six girls. Seventeen patients received radiotherapy, five received chemotherapy, and six underwent cerebrospinal fluid diversion. The median ADC of 1,295 × 10(-6) mm(2)/s for the cohort partitioned tumors into low or high diffusion groups, which had distinct median survivals of 3 and 13 months, respectively (log-rank p < 0.001). Low ADC tumors were found only in boys, whereas high ADC tumors were found in both boys and girls. Available tissue specimens in three low ADC tumors demonstrated high-grade histology, whereas one high ADC tumor demonstrated low-grade histology with a histone H3.1 K27M mutation and high-grade metastatic lesion at autopsy. ADC derived from diffusion-weighted MRI may identify prognostically distinct subgroups of pediatric DIPG.

Re-evaluation of hypoplastic left heart syndrome from a developmental and morphological perspective.

PubMed

Crucean, A; Alqahtani, A; Barron, D J; Brawn, W J; Richardson, R V; O'Sullivan, J; Anderson, R H; Henderson, D J; Chaudhry, B

2017-08-10

Hypoplastic left heart syndrome (HLHS) covers a spectrum of rare congenital anomalies characterised by a non-apex forming left ventricle and stenosis/atresia of the mitral and aortic valves. Despite many studies, the causes of HLHS remain unclear and there are conflicting views regarding the role of flow, valvar or myocardial abnormalities in its pathogenesis, all of which were proposed prior to the description of the second heart field. Our aim was to re-evaluate the patterns of malformation in HLHS in relation to recognised cardiac progenitor populations, with a view to providing aetiologically useful sub-groupings for genomic studies. We examined 78 hearts previously classified as HLHS, with subtypes based on valve patency, and re-categorised them based on their objective ventricular phenotype. Three distinct subgroups could be identified: slit-like left ventricle (24%); miniaturised left ventricle (6%); and thickened left ventricle with endocardial fibroelastosis (EFE; 70%). Slit-like ventricles were always found in combination with aortic atresia and mitral atresia. Miniaturised left ventricles all had normally formed, though smaller aortic and mitral valves. The remaining group were found to have a range of aortic valve malformations associated with thickened left ventricular walls despite being described as either atresia or stenosis. The degree of myocardial thickening was not correlated to the degree of valvar stenosis. Lineage tracing in mice to investigate the progenitor populations that form the parts of the heart disrupted by HLHS showed that whereas Nkx2-5-Cre labelled myocardial and endothelial cells within the left and right ventricles, Mef2c-AHF-Cre, which labels second heart field-derived cells only, was largely restricted to the endocardium and myocardium of the right ventricle. However, like Nkx2-5-Cre, Mef2c-AHF-Cre lineage cells made a significant contribution to the aortic and mitral valves. In contrast, Wnt1-Cre made a major contribution only to the aortic valve. This suggests that discrete cardiac progenitors might be responsible for the patterns of defects observed in the distinct ventricular sub-groups. Only the slit-like ventricle grouping was found to map to the current nomenclature: the combination of mitral atresia with aortic atresia. It appears that slit-like and miniature ventricles also form discrete sub-groups. Thus, reclassification of HLHS into subgroups based on ventricular phenotype, might be useful in genetic and developmental studies in investigating the aetiology of this severe malformation syndrome.

Precision Medicine: The New Frontier in Idiopathic Pulmonary Fibrosis

PubMed Central

Brownell, Robert; Kaminski, Naftali; Woodruff, Prescott G.; Bradford, Williamson Z.; Richeldi, Luca; Martinez, Fernando J.

2016-01-01

Precision medicine is defined by the National Institute of Health’s Precision Medicine Initiative Working Group as an approach to disease treatment that takes into account individual variability in genes, environment, and lifestyle. There has been increased interest in applying the concept of precision medicine to idiopathic pulmonary fibrosis, in particular to search for genetic and molecular biomarker-based profiles (so called endotypes) that identify mechanistically distinct disease subgroups. The relevance of precision medicine to idiopathic pulmonary fibrosis is yet to be established, but we believe that it holds great promise to provide targeted and highly effective therapies to patients. In this manuscript, we describe the field’s nascent efforts in genetic/molecular endotype identification and how environmental and behavioral subgroups may also be relevant to disease management. PMID:26991475

Patterns of Functioning and Predictive Factors in Children Born Moderately Preterm or at Term

ERIC Educational Resources Information Center

Cserjesi, Renata; van Braeckel, Koenraad N. J. A.; Timmerman, Marieke; Butcher, Phillipa R.; Kerstjens, Jorien M.; Reijneveld, Sijmen A.; Bouma, Anke; Bos, Arend F.; Geuze, Reint H.

2012-01-01

Aim: The aim of this study was to identify subgroups of children born moderately preterm (MPT) and term with distinctive levels and patterns of functioning, and the perinatal and demographic factors that predict subgroup membership. Method: A total of 378 children aged 7 years, 248 MPT (138 males, 110 females; gestational age 32-36 wks) and a…

Adolescent Male Conduct-Disordered Patients in Substance Use Disorder Treatment: Examining the "Limited Prosocial Emotions" Specifier.

PubMed

Sakai, Joseph T; Mikulich-Gilbertson, Susan K; Young, Susan E; Rhee, Soo Hyun; McWilliams, Shannon K; Dunn, Robin; Salomonsen-Sautel, Stacy; Thurstone, Christian; Hopfer, Christian J

2016-01-01

To our knowledge, this is the first study to examine the DSM-5-defined conduct disorder (CD) with limited prosocial emotions (LPE) among adolescents in substance use disorder (SUD) treatment, despite the high rates of CD in this population. We tested previously published methods of LPE categorization in a sample of male conduct-disordered patients in SUD treatment (n=196). CD with LPE patients did not demonstrate a distinct pattern in terms of demographics or co-morbidity regardless of the categorization method utilized. In conclusion, LPE, as operationalized here, does not identify a distinct subgroup of patients based on psychiatric comorbidity, SUD diagnoses, or demographics.

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

PubMed

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.

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

PubMed Central

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

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

PubMed Central

Gao, Beile; Gupta, Radhey S

2007-01-01

Background The Archaea are highly diverse in terms of their physiology, metabolism and ecology. Presently, very few molecular characteristics are known that are uniquely shared by either all archaea or the different main groups within archaea. The evolutionary relationships among different groups within the Euryarchaeota branch are also not clearly understood. Results We have carried out comprehensive analyses on each open reading frame (ORFs) in the genomes of 11 archaea (3 Crenarchaeota – Aeropyrum pernix, Pyrobaculum aerophilum and Sulfolobus acidocaldarius; 8 Euryarchaeota – Pyrococcus abyssi, Methanococcus maripaludis, Methanopyrus kandleri, Methanococcoides burtonii, Halobacterium sp. NCR-1, Haloquadratum walsbyi, Thermoplasma acidophilum and Picrophilus torridus) to search for proteins that are unique to either all Archaea or for its main subgroups. These studies have identified 1448 proteins or ORFs that are distinctive characteristics of Archaea and its various subgroups and whose homologues are not found in other organisms. Six of these proteins are unique to all Archaea, 10 others are only missing in Nanoarchaeum equitans and a large number of other proteins are specific for various main groups within the Archaea (e.g. Crenarchaeota, Euryarchaeota, Sulfolobales and Desulfurococcales, Halobacteriales, Thermococci, Thermoplasmata, all methanogenic archaea or particular groups of methanogens). Of particular importance is the observation that 31 proteins are uniquely present in virtually all methanogens (including M. kandleri) and 10 additional proteins are only found in different methanogens as well as A. fulgidus. In contrast, no protein was exclusively shared by various methanogen and any of the Halobacteriales or Thermoplasmatales. These results strongly indicate that all methanogenic archaea form a monophyletic group exclusive of other archaea and that this lineage likely evolved from Archaeoglobus. In addition, 15 proteins that are uniquely shared by M. kandleri and Methanobacteriales suggest a close evolutionary relationship between them. In contrast to the phylogenomics studies, a monophyletic grouping of archaea is not supported by phylogenetic analyses based on protein sequences. Conclusion The identified archaea-specific proteins provide novel molecular markers or signature proteins that are distinctive characteristics of Archaea and all of its major subgroups. The species distributions of these proteins provide novel insights into the evolutionary relationships among different groups within Archaea, particularly regarding the origin of methanogenesis. Most of these proteins are of unknown function and further studies should lead to discovery of novel biochemical and physiological characteristics that are unique to either all archaea or its different subgroups. PMID:17394648

Lipids as a principle for the identification of Archaebacteria

NASA Technical Reports Server (NTRS)

Tornabene, T. G.; Lloyd, R. E.; Holzer, G.; Oro, J.

1980-01-01

The 'Archaebacteria' consist of several distinct subgroups including methanogens, extreme halophiles and specific thermoacidophiles. These bacteria are distinct from other bacteria with respect to their characteristic RNA compositions, the absence of muramic acid in the cell walls and the predominance of nonsaponifable lipids. The lipid composition of the Archaebacteria consists of isoprenoid and hydroisoprenoid hydrocarbons and isopranyl glycerol ether lipids. The pathways for the biosynthesis of the lipid components are those shared by most microorganisms and demonstrate a close relationship; however, an independent line of descent is indicated by the formation of the isopranyl glycerol ether lipids. This discontinuity formulates a point for delineating the early stages of biological evolution and for dividing bacteria into two subgroups.

Biology and management of ependymomas

PubMed Central

Wu, Jing; Armstrong, Terri S.; Gilbert, Mark R.

2016-01-01

Ependymomas are rare primary tumors of the central nervous system in children and adults that comprise histologically similar but genetically distinct subgroups. The tumor biology is typically more associated with the site of origin rather than being age-specific. Genetically distinct subgroups have been identified by genomic studies based on locations in classic grade II and III ependymomas. They are supratentorial ependymomas with C11orf95-RELA fusion or YAP1 fusion, infratentorial ependymomas with or without a hypermethylated phenotype (CIMP), and spinal cord ependymomas. Myxopapillary ependymomas and subependymomas have different biology than ependymomas with typical WHO grade II or III histology. Surgery and radiotherapy are the mainstays of treatment, while the role of chemotherapy has not yet been established. An in-depth understanding of tumor biology, developing reliable animal models that accurately reflect tumor molecule features, and high throughput drug screening are essential for developing new therapies. Collaborative efforts between scientists, physicians, and advocacy groups will enhance the translation of laboratory findings into clinical trials. Improvements in disease control underscore the need to incorporate assessment and management of patients' symptoms to ensure that treatment advances translate into improvement in quality of life. PMID:27022130

Equivalent brain SPECT perfusion changes underlying therapeutic efficiency in pharmacoresistant depression using either high-frequency left or low-frequency right prefrontal rTMS.

PubMed

Richieri, Raphaëlle; Boyer, Laurent; Padovani, Romain; Adida, Marc; Colavolpe, Cécile; Mundler, Olivier; Lançon, Christophe; Guedj, Eric

2012-12-03

Functional neuroimaging studies have suggested similar mechanisms underlying antidepressant effects of distinct therapeutics. This study aimed to determine and compare functional brain patterns underlying the antidepressant response of 2 distinct protocols of repetitive transcranial magnetic stimulation (rTMS). 99mTc-ECD SPECT was performed before and after rTMS of dorsolateral prefrontal cortex in 61 drug-resistant right-handed patients with major depression, using high frequency (10Hz) left-side stimulation in 33 patients, and low frequency (1Hz) right-side stimulation in 28 patients. Efficiency of rTMS response was defined as at least 50% reduction of the baseline Beck Depression Inventory score. We compared the whole-brain voxel-based brain SPECT changes in perfusion after rTMS, between responders and non-responders in the whole sample (p<0.005, uncorrected), and separately in the subgroup of patients with left- and right-stimulation. Before rTMS, the left- and right-prefrontal stimulation groups did not differ from clinical data and brain SPECT perfusion. rTMS efficiency (evaluated on % of responders) was statistically equivalent in the two groups of patients. In the whole-group of responder patients, a perfusion decrease was found after rTMS, in comparison to non-responders, within the left perirhinal cortex (BA35, BA36). This result was secondarily confirmed separately in the two subgroups, i.e. after either left stimulation (p=0.017) or right stimulation (p<0.001), without significant perfusion differences between these two subgroups. These data show that distinct successful rTMS protocols induce equivalent brain functional changes associated to antidepressive efficiency, consisting to a remote brain limbic activity decrease within the left perirhinal cortex. However, these results will have to be confirmed in a double-blind randomized trial using a sham control group. Copyright © 2012 Elsevier Inc. All rights reserved.

Victimization and health risk factors among weapon-carrying youth.

PubMed

Stayton, Catherine; McVeigh, Katharine H; Olson, E Carolyn; Perkins, Krystal; Kerker, Bonnie D

2011-11-01

To compare health risks of 2 subgroups of weapon carriers: victimized and nonvictimized youth. 2003-2007 NYC Youth Risk Behavior Surveys were analyzed using bivariate analyses and multinomial logistic regression. Among NYC teens, 7.5% reported weapon carrying without victimization; 6.9% reported it with victimization. Both subgroups were more likely than non-weapon carriers to binge drink, use marijuana, smoke, fight, and have multiple sex partners; weapon carriers with victimization also experienced persistent sadness and attempted suicide. Subgroups of weapon carriers have distinct profiles. Optimal response should pair disciplinary action with screening for behavioral and mental health concerns and victimization.

Dissecting psychiatric spectrum disorders by generative embedding☆☆☆

PubMed Central

Brodersen, Kay H.; Deserno, Lorenz; Schlagenhauf, Florian; Lin, Zhihao; Penny, Will D.; Buhmann, Joachim M.; Stephan, Klaas E.

2013-01-01

This proof-of-concept study examines the feasibility of defining subgroups in psychiatric spectrum disorders by generative embedding, using dynamical system models which infer neuronal circuit mechanisms from neuroimaging data. To this end, we re-analysed an fMRI dataset of 41 patients diagnosed with schizophrenia and 42 healthy controls performing a numerical n-back working-memory task. In our generative-embedding approach, we used parameter estimates from a dynamic causal model (DCM) of a visual–parietal–prefrontal network to define a model-based feature space for the subsequent application of supervised and unsupervised learning techniques. First, using a linear support vector machine for classification, we were able to predict individual diagnostic labels significantly more accurately (78%) from DCM-based effective connectivity estimates than from functional connectivity between (62%) or local activity within the same regions (55%). Second, an unsupervised approach based on variational Bayesian Gaussian mixture modelling provided evidence for two clusters which mapped onto patients and controls with nearly the same accuracy (71%) as the supervised approach. Finally, when restricting the analysis only to the patients, Gaussian mixture modelling suggested the existence of three patient subgroups, each of which was characterised by a different architecture of the visual–parietal–prefrontal working-memory network. Critically, even though this analysis did not have access to information about the patients' clinical symptoms, the three neurophysiologically defined subgroups mapped onto three clinically distinct subgroups, distinguished by significant differences in negative symptom severity, as assessed on the Positive and Negative Syndrome Scale (PANSS). In summary, this study provides a concrete example of how psychiatric spectrum diseases may be split into subgroups that are defined in terms of neurophysiological mechanisms specified by a generative model of network dynamics such as DCM. The results corroborate our previous findings in stroke patients that generative embedding, compared to analyses of more conventional measures such as functional connectivity or regional activity, can significantly enhance both the interpretability and performance of computational approaches to clinical classification. PMID:24363992

Homogeneous Combinations of ASD-ADHD Traits and Their Cognitive and Behavioral Correlates in a Population-Based Sample.

PubMed

van der Meer, Jolanda M J; Lappenschaar, Martijn G A; Hartman, Catharina A; Greven, Corina U; Buitelaar, Jan K; Rommelse, Nanda N J

2017-07-01

Autism Spectrum Disorders (ASD) and ADHD are assumed to be the extreme manifestations of continuous heterogeneous traits that frequently co-occur. This study aims to identify subgroups of children with distinct ASD-ADHD trait profiles in the general population, using measures sensitive across both trait continua, and show how these subgroups differ in cognitive functioning. We examined 378 children (6-13 years) from a population-based sample. Latent class analyses (LCA) detected three concordant classes with low (10.1%), medium (54.2%), or high (13.2%) scores on both traits, and two discordant classes with more ADHD than ASD characteristics (ADHD > ASD, 18.3%) and vice versa (ASD > ADHD, 4.2%). Findings suggest that ASD and ADHD traits usually are strongly related in the unaffected population, and that a minority of children displays atypical discordant trait profiles characterized by differential visual-spatial functioning. This dissociation suggests that heterogeneity in ASD and ADHD is rooted in heterogeneity in the lower unaffected end of the distribution.

Identification of novel Theileria genotypes from Grant's gazelle

PubMed Central

Hooge, Janis; Howe, Laryssa; Ezenwa, Vanessa O.

2015-01-01

Blood samples collected from Grant's gazelles (Nanger granti) in Kenya were screened for hemoparasites using a combination of microscopic and molecular techniques. All 69 blood smears examined by microscopy were positive for hemoparasites. In addition, Theileria/Babesia DNA was detected in all 65 samples screened by PCR for a ~450-base pair fragment of the V4 hypervariable region of the 18S rRNA gene. Sequencing and BLAST analysis of a subset of PCR amplicons revealed widespread co-infection (25/39) and the existence of two distinct Grant's gazelle Theileria subgroups. One group of 11 isolates clustered as a subgroup with previously identified Theileria ovis isolates from small ruminants from Europe, Asia and Africa; another group of 3 isolates clustered with previously identified Theileria spp. isolates from other African antelope. Based on extensive levels of sequence divergence (1.2–2%) from previously reported Theileria species within Kenya and worldwide, the Theileria isolates detected in Grant's gazelles appear to represent at least two novel Theileria genotypes. PMID:25973394

Identification of novel Theileria genotypes from Grant's gazelle.

PubMed

Hooge, Janis; Howe, Laryssa; Ezenwa, Vanessa O

2015-08-01

Blood samples collected from Grant's gazelles (Nanger granti) in Kenya were screened for hemoparasites using a combination of microscopic and molecular techniques. All 69 blood smears examined by microscopy were positive for hemoparasites. In addition, Theileria/Babesia DNA was detected in all 65 samples screened by PCR for a ~450-base pair fragment of the V4 hypervariable region of the 18S rRNA gene. Sequencing and BLAST analysis of a subset of PCR amplicons revealed widespread co-infection (25/39) and the existence of two distinct Grant's gazelle Theileria subgroups. One group of 11 isolates clustered as a subgroup with previously identified Theileria ovis isolates from small ruminants from Europe, Asia and Africa; another group of 3 isolates clustered with previously identified Theileria spp. isolates from other African antelope. Based on extensive levels of sequence divergence (1.2-2%) from previously reported Theileria species within Kenya and worldwide, the Theileria isolates detected in Grant's gazelles appear to represent at least two novel Theileria genotypes.

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

ERIC Educational Resources Information Center

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…

Low back related leg pain: an investigation of construct validity of a new classification system.

PubMed

Schäfer, Axel G M; Hall, Toby M; Rolke, Roman; Treede, Rolf-Detlef; Lüdtke, Kerstin; Mallwitz, Joachim; Briffa, Kathryn N

2014-01-01

Leg pain is associated with back pain in 25-65% of all cases and classified as somatic referred pain or radicular pain. However, distinction between the two may be difficult as different pathomechanisms may cause similar patterns of pain. Therefore a pathomechanism based classification system was proposed, with four distinct hierarchical and mutually exclusive categories: Neuropathic Sensitization (NS) comprising major features of neuropathic pain with sensory sensitization; Denervation (D) arising from significant axonal compromise; Peripheral Nerve Sensitization (PNS) with marked nerve trunk mechanosensitivity; and Musculoskeletal (M) with pain referred from musculoskeletal structures. To investigate construct validity of the classification system. Construct validity was investigated by determining the relationship of nerve functioning with subgroups of patients and asymptomatic controls. Thus somatosensory profiles of subgroups of patients with low back related leg pain (LBRLP) and healthy controls were determined by a comprehensive quantitative sensory test (QST) protocol. It was hypothesized that subgroups of patients and healthy controls would show differences in QST profiles relating to underlying pathomechanisms. 77 subjects with LBRLP were recruited and classified in one of the four groups. Additionally, 18 age and gender matched asymptomatic controls were measured. QST revealed signs of pain hypersensitivity in group NS and sensory deficits in group D whereas Groups PNS and M showed no significant differences when compared to the asymptomatic group. These findings support construct validity for two of the categories of the new classification system, however further research is warranted to achieve construct validation of the classification system as a whole.

Distribution and molecular diversity of three cucurbit-infecting poleroviruses in China.

PubMed

Shang, Qiao-xia; Xiang, Hai-ying; Han, Cheng-gui; Li, Da-wei; Yu, Jia-lin

2009-11-01

Cucurbit aphid-borne yellows virus (CABYV) and Melon aphid-borne yellows virus (MABYV) have been found to be associated with cucurbit yellowing disease in China. Our report identifies for the first time a third distinct polerovirus, tentatively named Suakwa aphid-borne yellows virus (SABYV), infecting Suakwa vegetable sponge. To better understand the distribution and molecular diversity of these three poleroviruses infecting cucurbits, a total of 214 cucurbitaceous crop samples were collected from 25 provinces in China, and were investigated by RT-PCR and sequencing. Of these, 108 samples tested positive for CABYV, while 40 samples from five provinces were positive for MABYV, and SABYV was detected in only 4 samples which were collected in the southern part of China. Forty-one PCR-amplified fragments containing a portion of the RdRp gene, intergenic NCR and CP gene were cloned and sequenced. Sequence comparisons showed that CABYV isolates shared 78.0-79.2% nucleotide sequence identity with MABYV isolates, and 69.7-70.8% with SABYV. Sequence identity between MABYV and SABYV was 73.3-76.5%. In contrast, the nucleotide identities within each species were 93.2-98.7% (CABYV), 98.1-99.9% (MABYV), and 96.1-98.6% (SABYV). Phylogenetic analyses revealed that the polerovirus isolates fit into three distinct groups, corresponding to the three species. The CABYV group could be further divided into two subgroups: the Asia subgroup and the Mediterranean subgroup, based on CP gene and partial RdRp gene sequences. Recombination analysis suggested that MABYV may be a recombinant virus.

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

PubMed

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, poor coping and altered affective status. Gait analysis may provide additional information in the identification of subgroups among fibromyalgia patients. Gait analysis provided relevant information about physical and cognitive status, and pain behavior. Further studies are needed to better understand gait analysis implications in FM.

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

PubMed Central

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 distinguished by high FIQ, poor coping and altered affective status. Conclusion Gait analysis may provide additional information in the identification of subgroups among fibromyalgia patients. Gait analysis provided relevant information about physical and cognitive status, and pain behavior. Further studies are needed to better understand gait analysis implications in FM. PMID:22078002

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

PubMed Central

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

Identification of Distinct Psychosis Biotypes Using Brain-Based Biomarkers.

PubMed

Clementz, Brett A; Sweeney, John A; Hamm, Jordan P; Ivleva, Elena I; Ethridge, Lauren E; Pearlson, Godfrey D; Keshavan, Matcheri S; Tamminga, Carol A

2016-04-01

Clinical phenomenology remains the primary means for classifying psychoses despite considerable evidence that this method incompletely captures biologically meaningful differentiations. Rather than relying on clinical diagnoses as the gold standard, this project drew on neurobiological heterogeneity among psychosis cases to delineate subgroups independent of their phenomenological manifestations. A large biomarker panel (neuropsychological, stop signal, saccadic control, and auditory stimulation paradigms) characterizing diverse aspects of brain function was collected on individuals with schizophrenia, schizoaffective disorder, and bipolar disorder with psychosis (N=711), their first-degree relatives (N=883), and demographically comparable healthy subjects (N=278). Biomarker variance across paradigms was exploited to create nine integrated variables that were used to capture neurobiological variance among the psychosis cases. Data on external validating measures (social functioning, structural magnetic resonance imaging, family biomarkers, and clinical information) were collected. Multivariate taxometric analyses identified three neurobiologically distinct psychosis biotypes that did not respect clinical diagnosis boundaries. The same analysis procedure using clinical DSM diagnoses as the criteria was best described by a single severity continuum (schizophrenia worse than schizoaffective disorder worse than bipolar psychosis); this was not the case for biotypes. The external validating measures supported the distinctiveness of these subgroups compared with clinical diagnosis, highlighting a possible advantage of neurobiological versus clinical categorization schemes for differentiating psychotic disorders. These data illustrate how multiple pathways may lead to clinically similar psychosis manifestations, and they provide explanations for the marked heterogeneity observed across laboratories on the same biomarker variables when DSM diagnoses are used as the gold standard.

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

PubMed

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

2013-01-01

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

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

PubMed

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 <90% amino acid identities to most members of Betacoronavirus 1 in ADP-ribose 1″-phosphatase (ADRP) and nidoviral uridylate-specific endoribonuclease (NendoU), indicating that RbCoV HKU14 should represent a separate species. RbCoV HKU14 also possessed genomic features distinct from those of other Betacoronavirus subgroup A coronaviruses, including a unique NS2a region with a variable number of small open reading frames (ORFs). Recombination analysis revealed possible recombination events during the evolution of RbCoV HKU14 and members of Betacoronavirus 1, which may have occurred during cross-species transmission. Molecular clock analysis using RNA-dependent RNA polymerase (RdRp) genes dated the most recent common ancestor of RbCoV HKU14 to around 2002, suggesting that this virus has emerged relatively recently. Antibody against RbCoV was detected in 20 (67%) of 30 rabbit sera tested by an N-protein-based Western blot assay, whereas neutralizing antibody was detected in 1 of these 20 rabbits.

Prognostic value of DNA repair based stratification of hepatocellular carcinoma

PubMed Central

Lin, Zhuo; Xu, Shi-Hao; Wang, Hai-Qing; Cai, Yi-Jing; Ying, Li; Song, Mei; Wang, Yu-Qun; Du, Shan-Jie; Shi, Ke-Qing; Zhou, Meng-Tao

2016-01-01

Aberrant activation of DNA repair is frequently associated with tumor progression and response to therapy in hepatocellular carcinoma (HCC). Bioinformatics analyses of HCC data in the Cancer Genome Atlas (TCGA) were performed to define DNA repair based molecular classification that could predict the prognosis of patients with HCC. Furthermore, we tested its predictive performance in 120 independent cases. Four molecular subgroups were identified on the basis of coordinate DNA repair cluster (CDRC) comprising 15 genes in TCGA dataset. Increasing expression of CDRC genes were significantly associated with TP53 mutation. High CDRC was significantly correlated with advanced tumor grades, advanced pathological stage and increased vascular invasion rate. Multivariate Cox regression analysis indicated that the molecular subgrouping was an independent prognostic parameter for both overall survival (p = 0.004, hazard ratio (HR): 2.989) and tumor-free survival (p = 0.049, HR: 3.366) in TCGA dataset. Similar results were also obtained by analyzing the independent cohort. These data suggest that distinct dysregulation of DNA repair constituents based molecular classes in HCC would be useful for predicting prognosis and designing clinical trials for targeted therapy. PMID:27174663

The impact of subgroup type and subgroup configurational properties on work team performance.

PubMed

Carton, Andrew M; Cummings, Jonathon N

2013-09-01

Scholars have invoked subgroups in a number of theories related to teams, yet certain tensions in the literature remain unresolved. In this article, we address 2 of these tensions, both relating to how subgroups are configured in work teams: (a) whether teams perform better with a greater number of subgroups and (b) whether teams perform better when they have imbalanced subgroups (majorities and minorities are present) or balanced subgroups (subgroups are of equal size). We predict that the impact of the number and balance of subgroups depends on the type of subgroup-whether subgroups are formed according to social identity (i.e., identity-based subgroups) or information processing (i.e., knowledge-based subgroups). We first propose that teams are more adversely affected by 2 identity-based subgroups than by any other number, yet the uniquely negative impact of a 2-subgroup configuration is not apparent for knowledge-based subgroups. Instead, a larger number of knowledge-based subgroups is beneficial for performance, such that 2 subgroups is worse for performance when compared with 3 or more subgroups but better for performance when compared with no subgroups or 1 subgroup. Second, we argue that teams perform better when identity-based subgroups are imbalanced yet knowledge-based subgroups are balanced. We also suggest that there are interactive effects between the number and balance of subgroups-however, the nature of this interaction depends on the type of subgroup. To test these predictions, we developed and validated an algorithm that measures the configurational properties of subgroups in organizational work teams. Results of a field study of 326 work teams from a multinational organization support our predictions. PsycINFO Database Record (c) 2013 APA, all rights reserved

Who are the obese? A cluster analysis exploring subgroups of the obese.

PubMed

Green, M A; Strong, M; Razak, F; Subramanian, S V; Relton, C; Bissell, P

2016-06-01

Body mass index (BMI) can be used to group individuals in terms of their height and weight as obese. However, such a distinction fails to account for the variation within this group across other factors such as health, demographic and behavioural characteristics. The study aims to examine the existence of subgroups of obese individuals. Data were taken from the Yorkshire Health Study (2010-12) including information on demographic, health and behavioural characteristics. Individuals with a BMI of ≥30 were included. A two-step cluster analysis was used to define groups of individuals who shared common characteristics. The cluster analysis found six distinct groups of individuals whose BMI was ≥30. These subgroups were heavy drinking males, young healthy females; the affluent and healthy elderly; the physically sick but happy elderly; the unhappy and anxious middle aged and a cluster with the poorest health. It is important to account for the important heterogeneity within individuals who are obese. Interventions introduced by clinicians and policymakers should not target obese individuals as a whole but tailor strategies depending upon the subgroups that individuals belong to. © The Author 2015. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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

PubMed

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

2017-03-01

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

Policy options for alcohol price regulation: the importance of modelling population heterogeneity.

PubMed

Meier, Petra Sylvia; Purshouse, Robin; Brennan, Alan

2010-03-01

Context and aims Internationally, the repertoire of alcohol pricing policies has expanded to include targeted taxation, inflation-linked taxation, taxation based on alcohol-by-volume (ABV), minimum pricing policies (general or targeted), bans of below-cost selling and restricting price-based promotions. Policy makers clearly need to consider how options compare in reducing harms at the population level, but are also required to demonstrate proportionality of their actions, which necessitates a detailed understanding of policy effects on different population subgroups. This paper presents selected findings from a policy appraisal for the UK government and discusses the importance of accounting for population heterogeneity in such analyses. Method We have built a causal, deterministic, epidemiological model which takes account of differential preferences by population subgroups defined by age, gender and level of drinking (moderate, hazardous, harmful). We consider purchasing preferences in terms of the types and volumes of alcoholic beverages, prices paid and the balance between bars, clubs and restaurants as opposed to supermarkets and off-licenses. Results Age, sex and level of drinking fundamentally affect beverage preferences, drinking location, prices paid, price sensitivity and tendency to substitute for other beverage types. Pricing policies vary in their impact on different product types, price points and venues, thus having distinctly different effects on subgroups. Because population subgroups also have substantially different risk profiles for harms, policies are differentially effective in reducing health, crime, work-place absence and unemployment harms. Conclusion Policy appraisals must account for population heterogeneity and complexity if resulting interventions are to be well considered, proportionate, effective and cost-effective.

Molecular phylogeny of edge hill virus supports its position in the yellow Fever virus group and identifies a new genetic variant.

PubMed

Macdonald, Joanne; Poidinger, Michael; Mackenzie, John S; Russell, Richard C; Doggett, Stephen; Broom, Annette K; Phillips, Debra; Potamski, Joseph; Gard, Geoff; Whelan, Peter; Weir, Richard; Young, Paul R; Gendle, Debra; Maher, Sheryl; Barnard, Ross T; Hall, Roy A

2010-06-15

Edge Hill virus (EHV) is a mosquito-borne flavivirus isolated throughout Australia during mosquito surveillance programs. While not posing an immediate threat to the human population, EHV is a taxonomically interesting flavivirus since it remains the only member of the yellow fever virus (YFV) sub-group to be detected within Australia. Here we present both an antigenic and genetic investigation of collected isolates, and confirm taxonomic classification of the virus within the YFV-group. Isolates were not clustered based on geographical origin or time of isolation, suggesting that minimal genetic evolution of EHV has occurred over geographic distance or time within the EHV cluster. However, two isolates showed significant differences in antigenic reactivity patterns, and had a much larger divergence from the EHV prototype (19% nucleotide and 6% amino acid divergence), indicating a distinct subtype or variant within the EHV subgroup.

Using existing questionnaires in latent class analysis: should we use summary scores or single items as input? A methodological study using a cohort of patients with low back pain.

PubMed

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

2016-01-01

Latent class analysis (LCA) is increasingly being used in health research, but optimal approaches to handling complex clinical data are unclear. One issue is that commonly used questionnaires are multidimensional, but expressed as summary scores. Using the example of low back pain (LBP), the aim of this study was to explore and descriptively compare the application of LCA when using questionnaire summary scores and when using single items to subgrouping of patients based on multidimensional data. Baseline data from 928 LBP patients in an observational study were classified into four health domains (psychology, pain, activity, and participation) using the World Health Organization's International Classification of Functioning, Disability, and Health framework. LCA was performed within each health domain using the strategies of summary-score and single-item analyses. The resulting subgroups were descriptively compared using statistical measures and clinical interpretability. For each health domain, the preferred model solution ranged from five to seven subgroups for the summary-score strategy and seven to eight subgroups for the single-item strategy. There was considerable overlap between the results of the two strategies, indicating that they were reflecting the same underlying data structure. However, in three of the four health domains, the single-item strategy resulted in a more nuanced description, in terms of more subgroups and more distinct clinical characteristics. In these data, application of both the summary-score strategy and the single-item strategy in the LCA subgrouping resulted in clinically interpretable subgroups, but the single-item strategy generally revealed more distinguishing characteristics. These results 1) warrant further analyses in other data sets to determine the consistency of this finding, and 2) warrant investigation in longitudinal data to test whether the finer detail provided by the single-item strategy results in improved prediction of outcomes and treatment response.

Kinematic foot types in youth with equinovarus secondary to hemiplegia.

PubMed

Krzak, Joseph J; Corcos, Daniel M; Damiano, Diane L; Graf, Adam; Hedeker, Donald; Smith, Peter A; Harris, Gerald F

2015-02-01

Elevated kinematic variability of the foot and ankle segments exists during gait among individuals with equinovarus secondary to hemiplegic cerebral palsy (CP). Clinicians have previously addressed such variability by developing classification schemes to identify subgroups of individuals based on their kinematics. To identify kinematic subgroups among youth with equinovarus secondary to CP using 3-dimensional multi-segment foot and ankle kinematics during locomotion as inputs for principal component analysis (PCA), and K-means cluster analysis. In a single assessment session, multi-segment foot and ankle kinematics using the Milwaukee Foot Model (MFM) were collected in 24 children/adolescents with equinovarus and 20 typically developing children/adolescents. PCA was used as a data reduction technique on 40 variables. K-means cluster analysis was performed on the first six principal components (PCs) which accounted for 92% of the variance of the dataset. The PCs described the location and plane of involvement in the foot and ankle. Five distinct kinematic subgroups were identified using K-means clustering. Participants with equinovarus presented with variable involvement ranging from primary hindfoot or forefoot deviations to deformtiy that included both segments in multiple planes. This study provides further evidence of the variability in foot characteristics associated with equinovarus secondary to hemiplegic CP. These findings would not have been detected using a single segment foot model. The identification of multiple kinematic subgroups with unique foot and ankle characteristics has the potential to improve treatment since similar patients within a subgroup are likely to benefit from the same intervention(s). Copyright © 2014 Elsevier B.V. All rights reserved.

Kinematic foot types in youth with equinovarus secondary to hemiplegia

PubMed Central

Krzak, Joseph J.; Corcos, Daniel M.; Damiano, Diane L.; Graf, Adam; Hedeker, Donald; Smith, Peter A.; Harris, Gerald F.

2015-01-01

Background Elevated kinematic variability of the foot and ankle segments exists during gait among individuals with equinovarus secondary to hemiplegic cerebral palsy (CP). Clinicians have previously addressed such variability by developing classification schemes to identify subgroups of individuals based on their kinematics. Objective To identify kinematic subgroups among youth with equinovarus secondary to CP using 3-dimensional multi-segment foot and ankle kinematics during locomotion as inputs for principal component analysis (PCA), and K-means cluster analysis. Methods In a single assessment session, multi-segment foot and ankle kinematics using the Milwaukee Foot Model (MFM) were collected in 24 children/adolescents with equinovarus and 20 typically developing children/adolescents. Results PCA was used as a data reduction technique on 40 variables. K-means cluster analysis was performed on the first six principal components (PCs) which accounted for 92% of the variance of the dataset. The PCs described the location and plane of involvement in the foot and ankle. Five distinct kinematic subgroups were identified using K-means clustering. Participants with equinovarus presented with variable involvement ranging from primary hindfoot or forefoot deviations to deformtiy that included both segments in multiple planes. Conclusion This study provides further evidence of the variability in foot characteristics associated with equinovarus secondary to hemiplegic CP. These findings would not have been detected using a single segment foot model. The identification of multiple kinematic subgroups with unique foot and ankle characteristics has the potential to improve treatment since similar patients within a subgroup are likely to benefit from the same intervention(s). PMID:25467429

Peripheral neuropathic pain: a mechanism-related organizing principle based on sensory profiles

PubMed Central

Baron, Ralf; Maier, Christoph; Attal, Nadine; Binder, Andreas; Bouhassira, Didier; Cruccu, Giorgio; Finnerup, Nanna B.; Haanpää, Maija; Hansson, Per; Hüllemann, Philipp; Jensen, Troels S.; Freynhagen, Rainer; Kennedy, Jeffrey D.; Magerl, Walter; Mainka, Tina; Reimer, Maren; Rice, Andrew S.C.; Segerdahl, Märta; Serra, Jordi; Sindrup, Sören; Sommer, Claudia; Tölle, Thomas; Vollert, Jan; Treede, Rolf-Detlef

2016-01-01

Abstract Patients with neuropathic pain are heterogeneous in etiology, pathophysiology, and clinical appearance. They exhibit a variety of pain-related sensory symptoms and signs (sensory profile). Different sensory profiles might indicate different classes of neurobiological mechanisms, and hence subgroups with different sensory profiles might respond differently to treatment. The aim of the investigation was to identify subgroups in a large sample of patients with neuropathic pain using hypothesis-free statistical methods on the database of 3 large multinational research networks (German Research Network on Neuropathic Pain (DFNS), IMI-Europain, and Neuropain). Standardized quantitative sensory testing was used in 902 (test cohort) and 233 (validation cohort) patients with peripheral neuropathic pain of different etiologies. For subgrouping, we performed a cluster analysis using 13 quantitative sensory testing parameters. Three distinct subgroups with characteristic sensory profiles were identified and replicated. Cluster 1 (sensory loss, 42%) showed a loss of small and large fiber function in combination with paradoxical heat sensations. Cluster 2 (thermal hyperalgesia, 33%) was characterized by preserved sensory functions in combination with heat and cold hyperalgesia and mild dynamic mechanical allodynia. Cluster 3 (mechanical hyperalgesia, 24%) was characterized by a loss of small fiber function in combination with pinprick hyperalgesia and dynamic mechanical allodynia. All clusters occurred across etiologies but frequencies differed. We present a new approach of subgrouping patients with peripheral neuropathic pain of different etiologies according to intrinsic sensory profiles. These 3 profiles may be related to pathophysiological mechanisms and may be useful in clinical trial design to enrich the study population for treatment responders. PMID:27893485

Visualizing variations in organizational safety culture across an inter-hospital multifaceted workforce.

PubMed

Kobuse, Hiroe; Morishima, Toshitaka; Tanaka, Masayuki; Murakami, Genki; Hirose, Masahiro; Imanaka, Yuichi

2014-06-01

To develop a reliable and valid questionnaire that can distinguish features of organizational culture for patient safety across subgroups such as hospitals, professions, management/non-management positions and units/wards. We developed a Hospital Organizational Culture Questionnaire based on a conceptual framework incorporating items from a review of existing literature. The questionnaire was administered to hospital staff including doctors, nurses, allied health personnel, and administrative staff at six public hospitals in Japan. Reliability and validity were assessed through exploratory factor analysis, multitrait scaling analysis, Cronbach's alpha coefficient and multiple regression analysis using staff-perceived achievement of safety as the response variable. Discriminative power across subgroups was assessed with radar chart profiling. Of the 3304 hospital staff surveyed, 2924 (88.5%) responded. After exploratory factor analysis and multitrait analysis, the finalized questionnaire was composed of 24 items in the following eight dimensions: improvement orientation, passion for mission, professional growth, resource allocation prioritization, inter-sectional collaboration, responsibility and authority, teamwork, and information sharing. Construct validity and internal consistency of dimensions were confirmed with multitrait analysis and Cronbach's alpha coefficients, respectively. Multiple regression analysis showed that improvement orientation, passion for mission, resource allocation prioritization and information sharing were significantly associated with higher achievement in safety practices. Our questionnaire tool was able to distinguish features of safety culture among different subgroups. Our questionnaire demonstrated excellent validity and reliability, and revealed distinct cultural patterns among different subgroups. Quantitative assessment of organizational safety culture with this tool may further the understanding of associated characteristics of each subgroup and provide insight into organizational readiness for patient safety improvement. © 2014 John Wiley & Sons, Ltd.

Memory profiles in parents of patients with schizophrenia.

PubMed

Sitskoorn, Margriet M; Ebisch, Sjoerd J H; Appels, Melanie; Nuyen, Jasper; Kahn, René S

2004-08-30

Recent research shows that categorizing patients with schizophrenia based on frontal-striatal and frontal-temporal memory profiles may yield neurobiologically meaningful disease subtypes. We hypothesize that parents of patients exhibit similar memory profiles. Both parents of 36 patients with schizophrenia (N = 72) and 26 healthy married control couples (N = 52) participated in this study. All subjects were physically healthy and had no history of neurological illness or alcohol/drug abuse. The presence of a psychiatric and/or personality disorder was assessed with the Comprehensive Assessment of Symptoms and History (CASH) interview, the Schedule for Affective Disorders and Schizophrenia-lifetime (SADS-L) interview and the Structured Interview for DSM-IV Personality Disorders (SIDP-IV), respectively. Cluster analysis of selected measures from the Dutch version of the California Verbal Learning Test (CVLT) delineated parents into two subgroups with distinct memory deficits and a third subgroup without impairments. Specific frontal-striatal and frontal-temporal subgroups, however, were not found. In addition, our results indicated that mothers seem to be more protected against the negative effects of genetic liability to schizophrenia than fathers. Furthermore, relatives with a higher level of intelligence may have more cognitive reserve to compensate for the negative impact of implied brain dysfunction on verbal memory than relatives with a low level of intelligence. Although the parents of patients with schizophrenia could be delineated into subgroups with primary memory deficits, frontal-striatal and frontal-temporal subgroups could not be unambiguously identified. The association that emerged between level of intelligence, gender and severity of memory impairment deserves further exploration.

Peripheral neuropathic pain: a mechanism-related organizing principle based on sensory profiles.

PubMed

Baron, Ralf; Maier, Christoph; Attal, Nadine; Binder, Andreas; Bouhassira, Didier; Cruccu, Giorgio; Finnerup, Nanna B; Haanpää, Maija; Hansson, Per; Hüllemann, Philipp; Jensen, Troels S; Freynhagen, Rainer; Kennedy, Jeffrey D; Magerl, Walter; Mainka, Tina; Reimer, Maren; Rice, Andrew S C; Segerdahl, Märta; Serra, Jordi; Sindrup, Sören; Sommer, Claudia; Tölle, Thomas; Vollert, Jan; Treede, Rolf-Detlef

2017-02-01

Patients with neuropathic pain are heterogeneous in etiology, pathophysiology, and clinical appearance. They exhibit a variety of pain-related sensory symptoms and signs (sensory profile). Different sensory profiles might indicate different classes of neurobiological mechanisms, and hence subgroups with different sensory profiles might respond differently to treatment. The aim of the investigation was to identify subgroups in a large sample of patients with neuropathic pain using hypothesis-free statistical methods on the database of 3 large multinational research networks (German Research Network on Neuropathic Pain (DFNS), IMI-Europain, and Neuropain). Standardized quantitative sensory testing was used in 902 (test cohort) and 233 (validation cohort) patients with peripheral neuropathic pain of different etiologies. For subgrouping, we performed a cluster analysis using 13 quantitative sensory testing parameters. Three distinct subgroups with characteristic sensory profiles were identified and replicated. Cluster 1 (sensory loss, 42%) showed a loss of small and large fiber function in combination with paradoxical heat sensations. Cluster 2 (thermal hyperalgesia, 33%) was characterized by preserved sensory functions in combination with heat and cold hyperalgesia and mild dynamic mechanical allodynia. Cluster 3 (mechanical hyperalgesia, 24%) was characterized by a loss of small fiber function in combination with pinprick hyperalgesia and dynamic mechanical allodynia. All clusters occurred across etiologies but frequencies differed. We present a new approach of subgrouping patients with peripheral neuropathic pain of different etiologies according to intrinsic sensory profiles. These 3 profiles may be related to pathophysiological mechanisms and may be useful in clinical trial design to enrich the study population for treatment responders.

Therapeutic Impact of Cytoreductive Surgery and Irradiation of Posterior Fossa Ependymoma in the Molecular Era: A Retrospective Multicohort Analysis.

PubMed

Ramaswamy, Vijay; Hielscher, Thomas; Mack, Stephen C; Lassaletta, Alvaro; Lin, Tong; Pajtler, Kristian W; Jones, David T W; Luu, Betty; Cavalli, Florence M G; Aldape, Kenneth; Remke, Marc; Mynarek, Martin; Rutkowski, Stefan; Gururangan, Sridharan; McLendon, Roger E; Lipp, Eric S; Dunham, Christopher; Hukin, Juliette; Eisenstat, David D; Fulton, Dorcas; van Landeghem, Frank K H; Santi, Mariarita; van Veelen, Marie-Lise C; Van Meir, Erwin G; Osuka, Satoru; Fan, Xing; Muraszko, Karin M; Tirapelli, Daniela P C; Oba-Shinjo, Sueli M; Marie, Suely K N; Carlotti, Carlos G; Lee, Ji Yeoun; Rao, Amulya A Nageswara; Giannini, Caterina; Faria, Claudia C; Nunes, Sofia; Mora, Jaume; Hamilton, Ronald L; Hauser, Peter; Jabado, Nada; Petrecca, Kevin; Jung, Shin; Massimi, Luca; Zollo, Massimo; Cinalli, Giuseppe; Bognár, László; Klekner, Almos; Hortobágyi, Tibor; Leary, Sarah; Ermoian, Ralph P; Olson, James M; Leonard, Jeffrey R; Gardner, Corrine; Grajkowska, Wieslawa A; Chambless, Lola B; Cain, Jason; Eberhart, Charles G; Ahsan, Sama; Massimino, Maura; Giangaspero, Felice; Buttarelli, Francesca R; Packer, Roger J; Emery, Lyndsey; Yong, William H; Soto, Horacio; Liau, Linda M; Everson, Richard; Grossbach, Andrew; Shalaby, Tarek; Grotzer, Michael; Karajannis, Matthias A; Zagzag, David; Wheeler, Helen; von Hoff, Katja; Alonso, Marta M; Tuñon, Teresa; Schüller, Ulrich; Zitterbart, Karel; Sterba, Jaroslav; Chan, Jennifer A; Guzman, Miguel; Elbabaa, Samer K; Colman, Howard; Dhall, Girish; Fisher, Paul G; Fouladi, Maryam; Gajjar, Amar; Goldman, Stewart; Hwang, Eugene; Kool, Marcel; Ladha, Harshad; Vera-Bolanos, Elizabeth; Wani, Khalida; Lieberman, Frank; Mikkelsen, Tom; Omuro, Antonio M; Pollack, Ian F; Prados, Michael; Robins, H Ian; Soffietti, Riccardo; Wu, Jing; Metellus, Phillipe; Tabori, Uri; Bartels, Ute; Bouffet, Eric; Hawkins, Cynthia E; Rutka, James T; Dirks, Peter; Pfister, Stefan M; Merchant, Thomas E; Gilbert, Mark R; Armstrong, Terri S; Korshunov, Andrey; Ellison, David W; Taylor, Michael D

2016-07-20

Posterior fossa ependymoma comprises two distinct molecular variants termed EPN_PFA and EPN_PFB that have a distinct biology and natural history. The therapeutic value of cytoreductive surgery and radiation therapy for posterior fossa ependymoma after accounting for molecular subgroup is not known. Four independent nonoverlapping retrospective cohorts of posterior fossa ependymomas (n = 820) were profiled using genome-wide methylation arrays. Risk stratification models were designed based on known clinical and newly described molecular biomarkers identified by multivariable Cox proportional hazards analyses. Molecular subgroup is a powerful independent predictor of outcome even when accounting for age or treatment regimen. Incompletely resected EPN_PFA ependymomas have a dismal prognosis, with a 5-year progression-free survival ranging from 26.1% to 56.8% across all four cohorts. Although first-line (adjuvant) radiation is clearly beneficial for completely resected EPN_PFA, a substantial proportion of patients with EPN_PFB can be cured with surgery alone, and patients with relapsed EPN_PFB can often be treated successfully with delayed external-beam irradiation. The most impactful biomarker for posterior fossa ependymoma is molecular subgroup affiliation, independent of other demographic or treatment variables. However, both EPN_PFA and EPN_PFB still benefit from increased extent of resection, with the survival rates being particularly poor for subtotally resected EPN_PFA, even with adjuvant radiation therapy. Patients with EPN_PFB who undergo gross total resection are at lower risk for relapse and should be considered for inclusion in a randomized clinical trial of observation alone with radiation reserved for those who experience recurrence. © 2016 by American Society of Clinical Oncology.

Cluster analysis reveals seasonal variation of sperm subpopulations in extended boar semen

PubMed Central

IBĂNESCU, Iulian; LEIDING, Claus; BOLLWEIN, Heinrich

2017-01-01

This study aimed to identify motile sperm subpopulations in extended boar semen and to observe the presumptive seasonal variation in their distribution. Data from 4837 boar ejaculates collected over a two-year period were analyzed in terms of kinematic parameters by Computer Assisted Sperm Analysis (CASA). Individual sperm data were used to determine subgroups of motile sperm within the ejaculates using cluster analysis. Four motile sperm subpopulations (SP) were identified, with distinct movement patterns: SP1 sperm with high velocity and high linearity; SP2 sperm with high velocity but low linearity; SP3 sperm with low velocity but high linearity; and SP4 sperm with low velocity and low linearity. SP1 constituted the least overall proportion within the ejaculates (P < 0.05). Season of semen collection significantly influenced the different proportions of sperm subpopulations. Spring was characterized by similar proportions of SP1 and SP4 (NS) and higher proportions of SP3. Summer brought a decrease in both subgroups containing fast sperm (SP1 and SP2) (P < 0.05). During autumn, increases in SP2 and SP4 were recorded. Winter substantially affected the proportions of all sperm subpopulations (P < 0.05) and SP2 became the most represented subgroup, while SP1 (fast and linear) reached its highest proportion compared to other seasons. In conclusion, extended boar semen is structured in distinct motile sperm subpopulations whose proportions vary according to the season of collection. Summer and autumn seem to have a negative impact on the fast and linear subpopulation. Cluster analysis can be useful in revealing differences in semen quality that are not normally detected by classical evaluation based on mean values. PMID:29081440

Therapeutic Impact of Cytoreductive Surgery and Irradiation of Posterior Fossa Ependymoma in the Molecular Era: A Retrospective Multicohort Analysis

PubMed Central

Ramaswamy, Vijay; Hielscher, Thomas; Mack, Stephen C.; Lassaletta, Alvaro; Lin, Tong; Pajtler, Kristian W.; Jones, David T.W.; Luu, Betty; Cavalli, Florence M.G.; Aldape, Kenneth; Remke, Marc; Mynarek, Martin; Rutkowski, Stefan; Gururangan, Sridharan; McLendon, Roger E.; Lipp, Eric S.; Dunham, Christopher; Hukin, Juliette; Eisenstat, David D.; Fulton, Dorcas; van Landeghem, Frank K.H.; Santi, Mariarita; van Veelen, Marie-Lise C.; Van Meir, Erwin G.; Osuka, Satoru; Fan, Xing; Muraszko, Karin M.; Tirapelli, Daniela P.C.; Oba-Shinjo, Sueli M.; Marie, Suely K.N.; Carlotti, Carlos G.; Lee, Ji Yeoun; Rao, Amulya A. Nageswara; Giannini, Caterina; Faria, Claudia C.; Nunes, Sofia; Mora, Jaume; Hamilton, Ronald L.; Hauser, Peter; Jabado, Nada; Petrecca, Kevin; Jung, Shin; Massimi, Luca; Zollo, Massimo; Cinalli, Giuseppe; Bognár, László; Klekner, Almos; Hortobágyi, Tibor; Leary, Sarah; Ermoian, Ralph P.; Olson, James M.; Leonard, Jeffrey R.; Gardner, Corrine; Grajkowska, Wieslawa A.; Chambless, Lola B.; Cain, Jason; Eberhart, Charles G.; Ahsan, Sama; Massimino, Maura; Giangaspero, Felice; Buttarelli, Francesca R.; Packer, Roger J.; Emery, Lyndsey; Yong, William H.; Soto, Horacio; Liau, Linda M.; Everson, Richard; Grossbach, Andrew; Shalaby, Tarek; Grotzer, Michael; Karajannis, Matthias A.; Zagzag, David; Wheeler, Helen; von Hoff, Katja; Alonso, Marta M.; Tuñon, Teresa; Schüller, Ulrich; Zitterbart, Karel; Sterba, Jaroslav; Chan, Jennifer A.; Guzman, Miguel; Elbabaa, Samer K.; Colman, Howard; Dhall, Girish; Fisher, Paul G.; Fouladi, Maryam; Gajjar, Amar; Goldman, Stewart; Hwang, Eugene; Kool, Marcel; Ladha, Harshad; Vera-Bolanos, Elizabeth; Wani, Khalida; Lieberman, Frank; Mikkelsen, Tom; Omuro, Antonio M.; Pollack, Ian F.; Prados, Michael; Robins, H. Ian; Soffietti, Riccardo; Wu, Jing; Metellus, Phillipe; Tabori, Uri; Bartels, Ute; Bouffet, Eric; Hawkins, Cynthia E.; Rutka, James T.; Dirks, Peter; Pfister, Stefan M.; Merchant, Thomas E.; Gilbert, Mark R.; Armstrong, Terri S.; Korshunov, Andrey; Ellison, David W.

2016-01-01

Purpose Posterior fossa ependymoma comprises two distinct molecular variants termed EPN_PFA and EPN_PFB that have a distinct biology and natural history. The therapeutic value of cytoreductive surgery and radiation therapy for posterior fossa ependymoma after accounting for molecular subgroup is not known. Methods Four independent nonoverlapping retrospective cohorts of posterior fossa ependymomas (n = 820) were profiled using genome-wide methylation arrays. Risk stratification models were designed based on known clinical and newly described molecular biomarkers identified by multivariable Cox proportional hazards analyses. Results Molecular subgroup is a powerful independent predictor of outcome even when accounting for age or treatment regimen. Incompletely resected EPN_PFA ependymomas have a dismal prognosis, with a 5-year progression-free survival ranging from 26.1% to 56.8% across all four cohorts. Although first-line (adjuvant) radiation is clearly beneficial for completely resected EPN_PFA, a substantial proportion of patients with EPN_PFB can be cured with surgery alone, and patients with relapsed EPN_PFB can often be treated successfully with delayed external-beam irradiation. Conclusion The most impactful biomarker for posterior fossa ependymoma is molecular subgroup affiliation, independent of other demographic or treatment variables. However, both EPN_PFA and EPN_PFB still benefit from increased extent of resection, with the survival rates being particularly poor for subtotally resected EPN_PFA, even with adjuvant radiation therapy. Patients with EPN_PFB who undergo gross total resection are at lower risk for relapse and should be considered for inclusion in a randomized clinical trial of observation alone with radiation reserved for those who experience recurrence. PMID:27269943

A Guide to the Use of Market Segmentation for the Dissemination of Educational Innovations. Final Report of a Project to Study the Effectiveness of Marketing Programming for Educational Change.

ERIC Educational Resources Information Center

Wrausmann, Gale L.; And Others

Markets can be defined as groups of people or organizations that have resources that could be exchanged for distinct benefits. Market segmentation is one strategy for market management and involves describing the market in terms of the subgroups that compose it so that exchanges with those subgroups can be more effectively promoted or facilitated.…

Identification of Distinct Psychosis Biotypes Using Brain-Based Biomarkers

PubMed Central

Clementz, Brett A.; Sweeney, John A.; Hamm, Jordan P.; Ivleva, Elena I.; Ethridge, Lauren E.; Pearlson, Godfrey D.; Keshavan, Matcheri S.; Tamminga, Carol A.

2017-01-01

Objective Clinical phenomenology remains the primary means for classifying psychoses despite considerable evidence that this method incompletely captures biologically meaningful differentiations. Rather than relying on clinical diagnoses as the gold standard, this project drew on neurobiological heterogeneity among psychosis cases to delineate subgroups independent of their phenomenological manifestations. Method A large biomarker panel (neuropsychological, stop signal, saccadic control, and auditory stimulation paradigms) characterizing diverse aspects of brain function was collected on individuals with schizophrenia, schizoaffective disorder, and bipolar disorder with psychosis (N=711), their first-degree relatives (N=883), and demographically comparable healthy subjects (N=278). Biomarker variance across paradigms was exploited to create nine integrated variables that were used to capture neurobiological variance among the psychosis cases. Data on external validating measures (social functioning, structural magnetic resonance imaging, family biomarkers, and clinical information) were collected. Results Multivariate taxometric analyses identified three neurobiologically distinct psychosis biotypes that did not respect clinical diagnosis boundaries. The same analysis procedure using clinical DSM diagnoses as the criteria was best described by a single severity continuum (schizophrenia worse than schizoaffective disorder worse than bipolar psychosis); this was not the case for biotypes. The external validating measures supported the distinctiveness of these subgroups compared with clinical diagnosis, highlighting a possible advantage of neurobiological versus clinical categorization schemes for differentiating psychotic disorders. Conclusions These data illustrate how multiple pathways may lead to clinically similar psychosis manifestations, and they provide explanations for the marked heterogeneity observed across laboratories on the same biomarker variables when DSM diagnoses are used as the gold standard. PMID:26651391

Active medulloblastoma enhancers reveal subgroup-specific cellular origins

PubMed Central

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

2016-01-01

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

Vestibular blueprint in early vertebrates.

PubMed

Straka, Hans; Baker, Robert

2013-11-19

Central vestibular neurons form identifiable subgroups within the boundaries of classically outlined octavolateral nuclei in primitive vertebrates that are distinct from those processing lateral line, electrosensory, and auditory signals. Each vestibular subgroup exhibits a particular morpho-physiological property that receives origin-specific sensory inputs from semicircular canal and otolith organs. Behaviorally characterized phenotypes send discrete axonal projections to extraocular, spinal, and cerebellar targets including other ipsi- and contralateral vestibular nuclei. The anatomical locations of vestibuloocular and vestibulospinal neurons correlate with genetically defined hindbrain compartments that are well conserved throughout vertebrate evolution though some variability exists in fossil and extant vertebrate species. The different vestibular subgroups exhibit a robust sensorimotor signal processing complemented with a high degree of vestibular and visual adaptive plasticity.

Characterizing cosmochemical materials with genetic affinities to the Earth: Genetic and chronological diversity within the IAB iron meteorite complex

NASA Astrophysics Data System (ADS)

Worsham, Emily A.; Bermingham, Katherine R.; Walker, Richard J.

2017-06-01

The IAB iron meteorite complex consists of a main group (MG) and five chemical subgroups (sLL, sLM, sLH, sHL, and sHH). Here, mass-independent Mo and radiogenic 182W isotope compositions are reported for IAB complex meteorites to evaluate the genetics and chronology, respectively, of the MG and subgroups. Osmium isotopes are used to correct for cosmic ray exposure effects on isotopes of Mo and W. The MG and three subgroups (i.e., sLL, sLM, and sLH), characterized by low Au abundances, have the same Mo isotopic compositions within analytical uncertainty, consistent with a common genetic origin. These meteorites, together with winonaites, are the only cosmochemical materials yet identified with Mo isotopic compositions that are identical to Earth. The Mo isotopic compositions of two subgroups characterized by higher Au abundances (sHL and sHH) are identical to one another within uncertainty, but differ from the low Au subgroups, indicating derivation from genetically distinct materials. The MG has a 182W, post calcium-aluminum inclusion (CAI) formation model age of 3.4 ± 0.7 Ma. One of the low Au subgroups (sLM) is ∼1.7 Ma younger, whereas the high Au subgroups are ∼1.5-3 Ma older. The new Mo-W data, coupled with chemical data, indicate that the MG and the low Au subgroups formed in different impact-generated melts, some of which evidently formed on a chemically disparate, but genetically identical parent body. The high Au subgroups likely formed via core-formation processes on separate, internally-heated parent bodies from other IAB subgroups. The IAB complex meteorites fall on a linear trend defined by 94Mo/96Mo vs. 95Mo/96Mo, along with most other iron meteorite groups. Variation along this line was caused by mixing between at least two nebular components. One component was likely a pure s-process enriched nucleosynthetic carrier, and the other a homogenized nebular component. Sombrerete, currently classified as an sHL iron, has a Mo isotopic composition that is distinct from all IAB complex meteorites analyzed here. Along with group IVB iron meteorites and some ungrouped iron meteorites, it falls on a separate line from other meteorites which may reflect addition of an r-process-enriched component, and it should no longer be classified as a IAB iron.

Structure and content of Native American stereotypic subgroups: Not just (ig)noble.

PubMed

Burkley, Edward; Durante, Federica; Fiske, Susan T; Burkley, Melissa; Andrade, Angela

2017-04-01

Prejudice against Native Americans as an overall group generally polarizes into positive and negative stereotypic extremes, but distinct subgroups may explain this variability. Using college student samples (Study 1), a preliminary study identified common Native American subgroups and then a main study (N = 153, 74% women, 73% White, mean age = 19 years) had participants rate these subgroups on basic dimensions of stereotype content (i.e., warmth and competence), elicited emotions (e.g., admiration, contempt), and elicited behaviors (e.g., facilitation, harm). In Study 2, these preliminary study and main study procedures were replicated using nationwide samples (main study: N = 139, 51% women, 78% White, mean age = 35 years). For the most part, similar Native American subgroups emerged in both samples. Using the stereotype content model (SCM; Fiske, Cuddy, Glick, & Xu, 2002), the subgroups were found to vary along a competence-by-warmth space. The majority of subgroups (e.g., alcoholics, lazy) were judged low in both competence and warmth. Additional subgroups (e.g., casino operators, warriors) were ambivalently judged as high on competence but low on warmth. Subgroups perceived as high in both competence and warmth elicited more admiration, those low in both competence and warmth elicited more contempt, those high in competence elicited more passive facilitation and less passive harm, and those high in warmth elicited more active facilitation and less active harm. Native American stereotypes are apparently characterized by both noble and ignoble subgroups, highlighting the importance of studying stereotypes at the subgroup level. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Dysgraphia as a Mild Expression of Dystonia in Children with Absence Epilepsy

PubMed Central

Guerrini, Renzo; Melani, Federico; Brancati, Claudia; Ferrari, Anna Rita; Brovedani, Paola; Biggeri, Annibale; Grisotto, Laura; Pellacani, Simona

2015-01-01

Background Absence epilepsy (AE) is etiologically heterogeneous and has at times been associated with idiopathic dystonia. Objectives Based on the clinical observation that children with AE often exhibit, interictally, a disorder resembling writer’s cramp but fully definable as dysgraphia, we tested the hypothesis that in this particular population dysgraphia would represent a subtle expression of dystonia. Methods We ascertained the prevalence of dysgraphia in 82 children with AE (mean age 9.7) and average intelligence and compared them with 89 age-, gender- and class-matched healthy children (mean age 10.57) using tests for handwriting fluency and quality, based on which we divided patients and controls into four subgroups: AE/dysgraphia, AE without dysgraphia, controls with dysgraphia and healthy controls. We compared the blink reflex recovery cycle in children belonging to all four subgroups. Results We identified dysgraphia in 17/82 children with AE and in 7/89 controls (20.7 vs 7.8%; P = 0.016) with the former having a 3.4-times higher risk of dysgraphia regardless of age and gender (odd ratio: 3.49; 95% CI 1.2, 8.8%). The AE/dysgraphia subgroup performed worse than controls with dysgraphia in one test of handwriting fluency (P = 0.037) and in most trials testing handwriting quality (P< 0.02). In children with AE/dysgraphia the blink reflex showed no suppression at short interstimulus intervals, with a difference for each value emerging when comparing the study group with the three remaining subgroups (P<0.001). Conclusions In children with AE, dysgraphia is highly prevalent and has a homogeneous, distinctive pathophysiological substrate consistent with idiopathic dystonia. PMID:26132164

A population survey on legislative measures to restrict smoking in Ontario: 4. Variables related to knowledge of active and passive smoking health effects and to predicted behavior of smokers and nonsmokers.

PubMed

Pederson, L L; Bull, S B; Ashley, M J; Lefcoe, N M

1989-01-01

Results from the further analysis of a population survey on legislative measures to restrict smoking revealed that identification of subgroups of smokers is more reliable than identification of subgroups of nonsmokers when a variety of attitudes were the measures of interest. A similar pattern emerged when analyses were carried out on knowledge of active and passive smoking health effects and on predicted personal and general compliance. Because distinct sets of variables were found to be related to distinct outcomes, program planning for changes in knowledge and behavior might, of necessity, have to be different. Media messages might be useful for changes in knowledge, while actual experience might be more important for attitude and behavior change.

Unsheltered Homelessness Among Veterans: Correlates and Profiles.

PubMed

Byrne, Thomas; Montgomery, Ann Elizabeth; Fargo, Jamison D

2016-02-01

We identified correlates of unsheltered status among Veterans experiencing homelessness and described distinct subgroups within the unsheltered homeless Veteran population using data from a screening instrument for homelessness that is administered to all Veterans accessing outpatient care at a Veterans Health Administration (VHA) facility. Correlates of unsheltered homelessness included male gender, white race, older age, lower levels of VHA eligibility, substance use disorders, frequent use of VHA inpatient and infrequent use of VHA outpatient services, and residing in the West. We identified six distinct subgroups of unsheltered Veterans; the tri-morbid frequent users represented the highest need group, but the largest group was comprised of Veterans who made highly infrequent use of VHA healthcare services. Differences between sheltered and unsheltered Veterans and heterogeneity within the unsheltered Veteran population should be considered in targeting housing and other interventions.

Subtyping attention-deficit/hyperactivity disorder using temperament dimensions: toward biologically based nosologic criteria.

PubMed

Karalunas, Sarah L; Fair, Damien; Musser, Erica D; Aykes, Kamari; Iyer, Swathi P; Nigg, Joel T

2014-09-01

Psychiatric nosology is limited by behavioral and biological heterogeneity within existing disorder categories. The imprecise nature of current nosologic distinctions limits both mechanistic understanding and clinical prediction. We demonstrate an approach consistent with the National Institute of Mental Health Research Domain Criteria initiative to identify superior, neurobiologically valid subgroups with better predictive capacity than existing psychiatric categories for childhood attention-deficit/hyperactivity disorder (ADHD). To refine subtyping of childhood ADHD by using biologically based behavioral dimensions (i.e., temperament), novel classification algorithms, and multiple external validators. A total of 437 clinically well-characterized, community-recruited children, with and without ADHD, participated in an ongoing longitudinal study. Baseline data were used to classify children into subgroups based on temperament dimensions and examine external validators including physiological and magnetic resonance imaging measures. One-year longitudinal follow-up data are reported for a subgroup of the ADHD sample to address stability and clinical prediction. Parent/guardian ratings of children on a measure of temperament were used as input features in novel community detection analyses to identify subgroups within the sample. Groups were validated using 3 widely accepted external validators: peripheral physiological characteristics (cardiac measures of respiratory sinus arrhythmia and pre-ejection period), central nervous system functioning (via resting-state functional connectivity magnetic resonance imaging), and clinical outcomes (at 1-year longitudinal follow-up). The community detection algorithm suggested 3 novel types of ADHD, labeled as mild (normative emotion regulation), surgent (extreme levels of positive approach-motivation), and irritable (extreme levels of negative emotionality, anger, and poor soothability). Types were independent of existing clinical demarcations including DSM-5 presentations or symptom severity. These types showed stability over time and were distinguished by unique patterns of cardiac physiological response, resting-state functional brain connectivity, and clinical outcomes 1 year later. Results suggest that a biologically informed temperament-based typology, developed with a discovery-based community detection algorithm, provides a superior description of heterogeneity in the ADHD population than does any current clinical nosologic criteria. This demonstration sets the stage for more aggressive attempts at a tractable, biologically based nosology.

Latent class analysis on internet and smartphone addiction in college students.

PubMed

Mok, Jung-Yeon; Choi, Sam-Wook; Kim, Dai-Jin; Choi, Jung-Seok; Lee, Jaewon; Ahn, Heejune; Choi, Eun-Jeung; Song, Won-Young

2014-01-01

This study aimed to classify distinct subgroups of people who use both smartphone and the internet based on addiction severity levels. Additionally, how the classified groups differed in terms of sex and psychosocial traits was examined. A total of 448 university students (178 males and 270 females) in Korea participated. The participants were given a set of questionnaires examining the severity of their internet and smartphone addictions, their mood, their anxiety, and their personality. Latent class analysis and ANOVA (analysis of variance) were the statistical methods used. Significant differences between males and females were found for most of the variables (all <0.05). Specifically, in terms of internet usage, males were more addicted than females (P<0.05); however, regarding smartphone, this pattern was reversed (P<0.001). Due to these observed differences, classifications of the subjects into subgroups based on internet and smartphone addiction were performed separately for each sex. Each sex showed clear patterns with the three-class model based on likelihood level of internet and smartphone addiction (P<0.001). A common trend for psychosocial trait factors was found for both sexes: anxiety levels and neurotic personality traits increased with addiction severity levels (all P<0.001). However, Lie dimension was inversely related to the addiction severity levels (all P<0.01). Through the latent classification process, this study identified three distinct internet and smartphone user groups in each sex. Moreover, psychosocial traits that differed in terms of addiction severity levels were also examined. It is expected that these results should aid the understanding of traits of internet and smartphone addiction and facilitate further study in this field.

Latent class analysis on internet and smartphone addiction in college students

PubMed Central

Mok, Jung-Yeon; Choi, Sam-Wook; Kim, Dai-Jin; Choi, Jung-Seok; Lee, Jaewon; Ahn, Heejune; Choi, Eun-Jeung; Song, Won-Young

2014-01-01

Purpose This study aimed to classify distinct subgroups of people who use both smartphone and the internet based on addiction severity levels. Additionally, how the classified groups differed in terms of sex and psychosocial traits was examined. Methods A total of 448 university students (178 males and 270 females) in Korea participated. The participants were given a set of questionnaires examining the severity of their internet and smartphone addictions, their mood, their anxiety, and their personality. Latent class analysis and ANOVA (analysis of variance) were the statistical methods used. Results Significant differences between males and females were found for most of the variables (all <0.05). Specifically, in terms of internet usage, males were more addicted than females (P<0.05); however, regarding smartphone, this pattern was reversed (P<0.001). Due to these observed differences, classifications of the subjects into subgroups based on internet and smartphone addiction were performed separately for each sex. Each sex showed clear patterns with the three-class model based on likelihood level of internet and smartphone addiction (P<0.001). A common trend for psychosocial trait factors was found for both sexes: anxiety levels and neurotic personality traits increased with addiction severity levels (all P<0.001). However, Lie dimension was inversely related to the addiction severity levels (all P<0.01). Conclusion Through the latent classification process, this study identified three distinct internet and smartphone user groups in each sex. Moreover, psychosocial traits that differed in terms of addiction severity levels were also examined. It is expected that these results should aid the understanding of traits of internet and smartphone addiction and facilitate further study in this field. PMID:24899806

Triple-negative breast cancer: current state of the art.

PubMed

Rastelli, Francesca; Biancanelli, Sandra; Falzetta, Amalia; Martignetti, Angelo; Casi, Camilla; Bascioni, Romeo; Giustini, Lucio; Crispino, Sergio

2010-01-01

Triple-negative breast cancer, defined by a lack of expression of estrogen, progesterone and HER-2 receptors, accounts for 15% of all types of breast cancer. The subtype mainly includes a molecularly distinct subgroup, the basal-like subtype (accounting for 75% of all cases). We attempt to define triple-negative breast cancer and compare it with basal-like disease, review the molecular, pathologic and clinical features of triple-negative disease, provide an overview of a retrospective subset analysis of clinical trials, and outline ongoing therapeutic trials and possible paths for future research. We collected data regarding classification, molecular and clinical features and treatment, drawn from the existing literature, including abstracts and verbal accounts. By the term "basal-like", we defined all cases where gene expression array or more sophisticated immunophenotypes are used for identification. When the analysis is restricted to clinical assay (immunohistochemistry), we refer to "triple-negative". Basal-like breast cancer expresses genes characteristic of basal epithelial cells, which include high-molecular weight basal cytokeratins (CK5/6, CK14, CK17), vimentin, p-cadherin, alpha B crystalline, caveolins 1 and 2 and EGFR. The expression of basal markers (basal cytokeratins and EGFR) is related to a worse prognosis and identifies a clinically distinct subgroup within the triple-negative breast cancer. BRCA1 mutations are present in 11% of triple-negative tumors and even more rare is BRCA2 deficiency. BR-CA1-associated breast cancers types are typically characterized by a high rate of DNA aberrations and defective DNA repair pathways (the so-called "BRCAness"). The use of regimens based on DNA-damaging agents, such as anthracyclines, platinum derivatives and cyclophosphamide seems a sensible option for this breast cancer subtypes. Clinical data support a strong sensitivity to primary chemotherapy with pathologic response rates ranging from 27-45% (with anthracyclines and taxanes) to more than 60% with platinum-based triplets. However, based on retrospective data, major response to chemotherapy does not carry better survival ("triple-negative paradox"). There is no specific targeted therapy in the armamentarium: ongoing trials include anti-angiogenic agents, anti-EGFR and EGFR-TK inhibitors, epothilones and PARP inhibitors. A specific systemic regimen cannot yet be recommended. Moreover, only a few data are available on which treatment selection can be based. Use of the existing cytotoxic agents can be optimized for this patient subgroup by investigating the proliferative signals and the suitability of these signals as therapeutic targets, besides assessing the BRCA1-pathway in this subgroup as regards treatment. A greater understanding of the pathologic and molecular characteristics of this phenotype may lead to customized treatment for these patients.

Co-occurring genomic alterations define major subsets of KRAS - mutant lung adenocarcinoma with distinct biology, immune profiles, and therapeutic vulnerabilities

PubMed Central

Skoulidis, Ferdinandos; Byers, Lauren A.; Diao, Lixia; Papadimitrakopoulou, Vassiliki A.; Tong, Pan; Izzo, Julie; Behrens, Carmen; Kadara, Humam; Parra, Edwin R.; Canales, Jaime Rodriguez; Zhang, Jianjun; Giri, Uma; Gudikote, Jayanthi; Cortez, Maria A.; Yang, Chao; Fan, You Hong; Peyton, Michael; Girard, Luc; Coombes, Kevin R.; Toniatti, Carlo; Heffernan, Timothy P.; Choi, Murim; Frampton, Garrett M.; Miller, Vincent; Weinstein, John N.; Herbst, Roy S.; Wong, Kwok-Kin; Zhang, Jianhua; Sharma, Padmanee; Mills, Gordon B.; Hong, Waun K.; Minna, John D.; Allison, James P.; Futreal, Andrew; Wang, Jing; Wistuba, Ignacio I.; Heymach, John V.

2015-01-01

The molecular underpinnings that drive the heterogeneity of KRAS-mutant lung adenocarcinoma (LUAC) are poorly characterized. We performed an integrative analysis of genomic, transcriptomic and proteomic data from early-stage and chemo-refractory LUAC and identified three robust subsets of KRAS-mutant LUAC dominated, respectively, by co-occurring genetic events in STK11/LKB1 (the KL subgroup), TP53 (KP) and CDKN2A/B inactivation coupled with low expression of the NKX2-1 (TTF1) transcription factor (KC). We further reveal biologically and therapeutically relevant differences between the subgroups. KC tumors frequently exhibited mucinous histology and suppressed mTORC1 signaling. KL tumors had high rates of KEAP1 mutational inactivation and expressed lower levels of immune markers, including PD-L1. KP tumors demonstrated higher levels of somatic mutations, inflammatory markers, immune checkpoint effector molecules and improved relapse-free survival. Differences in drug sensitivity patterns were also observed; notably, KL cells showed increased vulnerability to HSP90-inhibitor therapy. This work provides evidence that co-occurring genomic alterations identify subgroups of KRAS-mutant LUAC with distinct biology and therapeutic vulnerabilities. PMID:26069186

Integrative genomic profiling of large-cell neuroendocrine carcinomas reveals distinct subtypes of high-grade neuroendocrine lung tumors.

PubMed

George, Julie; Walter, Vonn; Peifer, Martin; Alexandrov, Ludmil B; Seidel, Danila; Leenders, Frauke; Maas, Lukas; Müller, Christian; Dahmen, Ilona; Delhomme, Tiffany M; Ardin, Maude; Leblay, Noemie; Byrnes, Graham; Sun, Ruping; De Reynies, Aurélien; McLeer-Florin, Anne; Bosco, Graziella; Malchers, Florian; Menon, Roopika; Altmüller, Janine; Becker, Christian; Nürnberg, Peter; Achter, Viktor; Lang, Ulrich; Schneider, Peter M; Bogus, Magdalena; Soloway, Matthew G; Wilkerson, Matthew D; Cun, Yupeng; McKay, James D; Moro-Sibilot, Denis; Brambilla, Christian G; Lantuejoul, Sylvie; Lemaitre, Nicolas; Soltermann, Alex; Weder, Walter; Tischler, Verena; Brustugun, Odd Terje; Lund-Iversen, Marius; Helland, Åslaug; Solberg, Steinar; Ansén, Sascha; Wright, Gavin; Solomon, Benjamin; Roz, Luca; Pastorino, Ugo; Petersen, Iver; Clement, Joachim H; Sänger, Jörg; Wolf, Jürgen; Vingron, Martin; Zander, Thomas; Perner, Sven; Travis, William D; Haas, Stefan A; Olivier, Magali; Foll, Matthieu; Büttner, Reinhard; Hayes, David Neil; Brambilla, Elisabeth; Fernandez-Cuesta, Lynnette; Thomas, Roman K

2018-03-13

Pulmonary large-cell neuroendocrine carcinomas (LCNECs) have similarities with other lung cancers, but their precise relationship has remained unclear. Here we perform a comprehensive genomic (n = 60) and transcriptomic (n = 69) analysis of 75 LCNECs and identify two molecular subgroups: "type I LCNECs" with bi-allelic TP53 and STK11/KEAP1 alterations (37%), and "type II LCNECs" enriched for bi-allelic inactivation of TP53 and RB1 (42%). Despite sharing genomic alterations with adenocarcinomas and squamous cell carcinomas, no transcriptional relationship was found; instead LCNECs form distinct transcriptional subgroups with closest similarity to SCLC. While type I LCNECs and SCLCs exhibit a neuroendocrine profile with ASCL1 high /DLL3 high /NOTCH low , type II LCNECs bear TP53 and RB1 alterations and differ from most SCLC tumors with reduced neuroendocrine markers, a pattern of ASCL1 low /DLL3 low /NOTCH high , and an upregulation of immune-related pathways. In conclusion, LCNECs comprise two molecularly defined subgroups, and distinguishing them from SCLC may allow stratified targeted treatment of high-grade neuroendocrine lung tumors.

The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups.

PubMed

Curtis, Christina; Shah, Sohrab P; Chin, Suet-Feung; Turashvili, Gulisa; Rueda, Oscar M; Dunning, Mark J; Speed, Doug; Lynch, Andy G; Samarajiwa, Shamith; Yuan, Yinyin; Gräf, Stefan; Ha, Gavin; Haffari, Gholamreza; Bashashati, Ali; Russell, Roslin; McKinney, Steven; Langerød, Anita; Green, Andrew; Provenzano, Elena; Wishart, Gordon; Pinder, Sarah; Watson, Peter; Markowetz, Florian; Murphy, Leigh; Ellis, Ian; Purushotham, Arnie; Børresen-Dale, Anne-Lise; Brenton, James D; Tavaré, Simon; Caldas, Carlos; Aparicio, Samuel

2012-04-18

The elucidation of breast cancer subgroups and their molecular drivers requires integrated views of the genome and transcriptome from representative numbers of patients. We present an integrated analysis of copy number and gene expression in a discovery and validation set of 997 and 995 primary breast tumours, respectively, with long-term clinical follow-up. Inherited variants (copy number variants and single nucleotide polymorphisms) and acquired somatic copy number aberrations (CNAs) were associated with expression in ~40% of genes, with the landscape dominated by cis- and trans-acting CNAs. By delineating expression outlier genes driven in cis by CNAs, we identified putative cancer genes, including deletions in PPP2R2A, MTAP and MAP2K4. Unsupervised analysis of paired DNA–RNA profiles revealed novel subgroups with distinct clinical outcomes, which reproduced in the validation cohort. These include a high-risk, oestrogen-receptor-positive 11q13/14 cis-acting subgroup and a favourable prognosis subgroup devoid of CNAs. Trans-acting aberration hotspots were found to modulate subgroup-specific gene networks, including a TCR deletion-mediated adaptive immune response in the ‘CNA-devoid’ subgroup and a basal-specific chromosome 5 deletion-associated mitotic network. Our results provide a novel molecular stratification of the breast cancer population, derived from the impact of somatic CNAs on the transcriptome.

Complete genome sequence analysis identifies a new genotype of brassica yellows virus that infects cabbage and radish in China.

PubMed

Zhang, Xiao-Yan; Xiang, Hai-Ying; Zhou, Cui-Ji; Li, Da-Wei; Yu, Jia-Lin; Han, Cheng-Gui

2014-08-01

For brassica yellows virus (BrYV), proposed to be a member of a new polerovirus species, two clearly distinct genotypes (BrYV-A and BrYV-B) have been described. In this study, the complete nucleotide sequences of two BrYV isolates from radish and Chinese cabbage were determined. Sequence analysis suggested that these isolates represent a new genotype, referred to here as BrYV-C. The full-length sequences of the two BrYV-C isolates shared 93.4-94.8 % identity with BrYV-A and BrYV-B. Further phylogenetic analysis showed that the BrYV-C isolates formed a subgroup that was distinct from the BrYV-A and BrYV-B isolates based on all of the proteins except P5.

Egg cases of the genus Apristurus (Chondrichthyes: Scyliorhinidae): phylogenetic and ecological implications.

PubMed

Flammang, Brooke E; Ebert, David A; Cailliet, Gregor M

2007-01-01

The genus Apristurus has been divided formerly into three species subgroups based on morphological and molecular phylogenies. Previous studies have agreed on the separation into distinct species groups, the largest two of which have been described as the brunneus and spongiceps groups. An examination of the egg cases produced by these oviparous catsharks corroborates the distinction in species groups: egg cases of the brunneus group have long fibrous and curly tendrils at either end, whereas egg cases of the spongiceps group lack tendrils. The egg cases of A. kampae, A. manis, A. spongiceps and Apristurus sp. D are described for the first time, and the egg cases of A. brunneus and A. riveri are re-described to include comparable morphological characteristics. The ecological implications of egg case morphology on oviposition and ventilation are also discussed.

Widespread Volumetric Reductions in Schizophrenia and Schizoaffective Patients Displaying Compromised Cognitive Abilities.

PubMed

Van Rheenen, Tamsyn E; Cropley, Vanessa; Zalesky, Andrew; Bousman, Chad; Wells, Ruth; Bruggemann, Jason; Sundram, Suresh; Weinberg, Danielle; Lenroot, Roshel K; Pereira, Avril; Shannon Weickert, Cynthia; Weickert, Thomas W; Pantelis, Christos

2018-04-06

Progress toward understanding brain mechanisms in psychosis is hampered by failures to account for within-group heterogeneity that exists across neuropsychological domains. We recently identified distinct cognitive subgroups that might assist in identifying more biologically meaningful subtypes of psychosis. In the present study, we examined whether underlying structural brain abnormalities differentiate these cognitively derived subgroups. 1.5T T1 weighted structural scans were acquired for 168 healthy controls and 220 patients with schizophrenia/schizoaffective disorder. Based on previous work, 47 patients were categorized as being cognitively compromised (impaired premorbid and current IQ), 100 as cognitively deteriorated (normal premorbid IQ, impaired current IQ), and 73 as putatively cognitively preserved (premorbid and current IQ within 1 SD of controls). Global, subcortical and cortical volume, thickness, and surface area measures were compared among groups. Whole cortex, subcortical, and regional volume and thickness reductions were evident in all subgroups compared to controls, with the largest effect sizes in the compromised group. This subgroup also showed abnormalities in regions not seen in the other patient groups, including smaller left superior and middle frontal areas, left anterior and inferior temporal areas and right lateral medial and inferior frontal, occipital lobe and superior temporal areas. This pattern of more prominent brain structural abnormalities in the group with the most marked cognitive impairments-both currently and putatively prior to illness onset, is consistent with the concept of schizophrenia as a progressive neurodevelopmental disorder. In this group, neurodevelopmental and neurodegenerative factors may be important for cognitive function.

Discriminant factors for adolescent sexual offending: On the usefulness of considering both victim age and sibling incest.

PubMed

Joyal, Christian C; Carpentier, Julie; Martin, Caroline

2016-04-01

Understanding the pathways and circumstances of juvenile sexual offending is of utmost importance. However, juvenile sexual offenders (JSO) represent an especially diverse group of individuals, and several categorizations have been proposed to obtain more homogeneous subgroups. Victim age-based and family relation-based categorizations are particularly promising because they seem theoretically and clinically relevant. Empirical results however are still inconsistent, and most studies have not considered these two dimensions jointly. The first goal of this study was to further examine the value of subgrouping JSO according to the age of their victim. A second goal was to determine the supplementary value, if any, of considering sibling incest. Based on a sample of 351 male JSO, it was first confirmed that sexual abuse of children was more strongly related to asociality (social skill deficits) than sexual abuse of peers, the latter being more closely associated with antisociality (general delinquency). The relevance of considering mixed-type JSO (with both child and peer victims) separately was also confirmed. More importantly, multivariate statistical analyses demonstrated that adding sibling incest to the equation was useful. JSO of intra-familial child were significantly more likely to have been victimized during their own childhood compared to JSO with extra-familial victims. Nevertheless, adolescents who had committed sibling incest obtained middle ground results on most variables (except for crime severity), suggesting that they constitute a distinct but not extreme, subgroup. This study confirmed the utility of using both the age and the family relation with the victim in characterizing juvenile sexual offending. Copyright © 2016 Elsevier Ltd. All rights reserved.

Identifying cut points for biomarker defined subset effects in clinical trials with survival endpoints.

PubMed

He, Pei

2014-07-01

The advancements in biotechnology and genetics lead to an increasing research interest in personalized medicine, where a patient's genetic profile or biological traits contribute to choosing the most effective treatment for the patient. The process starts with finding a specific biomarker among all possible candidates that can best predict the treatment effect. After a biomarker is chosen, identifying a cut point of the biomarker value that splits the patients into treatment effective and non-effective subgroups becomes an important scientific problem. Numerous methods have been proposed to validate the predictive marker and select the appropriate cut points either prospectively or retrospectively using clinical trial data. In trials with survival outcomes, the current practice applies an interaction testing procedure and chooses the cut point that minimizes the p-values for the tests. Such method assumes independence between the baseline hazard and biomarker value. In reality, however, this assumption is often violated, as the chosen biomarker might also be prognostic in addition to its predictive nature for treatment effect. In this paper we propose a block-wise estimation and a sequential testing approach to identify the cut point in biomarkers that can group the patients into subsets based on their distinct treatment outcomes without assuming independence between the biomarker and baseline hazard. Numerical results based on simulated survival data show that the proposed method could pinpoint accurately the cut points in biomarker values that separate the patient subpopulations into subgroups with distinctive treatment outcomes. Copyright © 2014 Elsevier Inc. All rights reserved.

Distinct Evening Fatigue Profiles in Oncology Outpatients Receiving Chemotherapy

PubMed Central

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

An international study of intrachromosomal amplification of chromosome 21 (iAMP21): cytogenetic characterization and outcome

PubMed Central

Harrison, CJ; Moorman, AV; Schwab, C; Carroll, AJ; Raetz, EA; Devidas, M; Strehl, S; Nebral, K; Harbott, J; Teigler-Schlegel, A; Zimmerman, M; Dastuge, N; Baruchel, A; Soulier, J; Auclerc, M-F; Attarbaschi, A; Mann, G; Stark, B; Cazzaniga, G; Chilton, L; Vandenberghe, P; Forestier, E; Haltrich, I; Raimondi, SC; Parihar, M; Bourquin, J-P; Tchinda, J; Haferlach, C; Vora, A; Hunger, SP; Heerema, NA; Haas, OA

2014-01-01

Intrachromosomal amplification of chromosome 21 (iAMP21) defines a distinct cytogenetic subgroup of childhood B-cell precursor acute lymphoblastic leukaemia (BCP-ALL). To date, fluorescence in situ hybridisation (FISH), with probes specific for the RUNX1 gene, provides the only reliable detection method (five or more RUNX1 signals per cell). Patients with iAMP21 are older (median age 9 years) with a low white cell count. Previously, we demonstrated a high relapse risk when these patients were treated as standard risk. Recent studies have shown improved outcome on intensive therapy. In view of these treatment implications, accurate identification is essential. Here we have studied the cytogenetics and outcome of 530 iAMP21 patients that highlighted the association of specific secondary chromosomal and genetic changes with iAMP21 to assist in diagnosis, including the gain of chromosome X, loss or deletion of chromosome 7, ETV6 and RB1 deletions. These iAMP21 patients when treated as high risk showed the same improved outcome as those in trial-based studies regardless of the backbone chemotherapy regimen given. This study reinforces the importance of intensified treatment to reduce the risk of relapse in iAMP21 patients. This now well-defined patient subgroup should be recognised by World Health Organisation (WHO) as a distinct entity of BCP-ALL. PMID:24166298

An international study of intrachromosomal amplification of chromosome 21 (iAMP21): cytogenetic characterization and outcome.

PubMed

Harrison, C J; Moorman, A V; Schwab, C; Carroll, A J; Raetz, E A; Devidas, M; Strehl, S; Nebral, K; Harbott, J; Teigler-Schlegel, A; Zimmerman, M; Dastuge, N; Baruchel, A; Soulier, J; Auclerc, M-F; Attarbaschi, A; Mann, G; Stark, B; Cazzaniga, G; Chilton, L; Vandenberghe, P; Forestier, E; Haltrich, I; Raimondi, S C; Parihar, M; Bourquin, J-P; Tchinda, J; Haferlach, C; Vora, A; Hunger, S P; Heerema, N A; Haas, O A

2014-05-01

Intrachromosomal amplification of chromosome 21 (iAMP21) defines a distinct cytogenetic subgroup of childhood B-cell precursor acute lymphoblastic leukaemia (BCP-ALL). To date, fluorescence in situ hybridisation (FISH), with probes specific for the RUNX1 gene, provides the only reliable detection method (five or more RUNX1 signals per cell). Patients with iAMP21 are older (median age 9 years) with a low white cell count. Previously, we demonstrated a high relapse risk when these patients were treated as standard risk. Recent studies have shown improved outcome on intensive therapy. In view of these treatment implications, accurate identification is essential. Here we have studied the cytogenetics and outcome of 530 iAMP21 patients that highlighted the association of specific secondary chromosomal and genetic changes with iAMP21 to assist in diagnosis, including the gain of chromosome X, loss or deletion of chromosome 7, ETV6 and RB1 deletions. These iAMP21 patients when treated as high risk showed the same improved outcome as those in trial-based studies regardless of the backbone chemotherapy regimen given. This study reinforces the importance of intensified treatment to reduce the risk of relapse in iAMP21 patients. This now well-defined patient subgroup should be recognised by World Health Organisation (WHO) as a distinct entity of BCP-ALL.

Comparison of facial morphologies between adult Chinese and Houstonian Caucasian populations using three-dimensional imaging.

PubMed

Wirthlin, J; Kau, C H; English, J D; Pan, F; Zhou, H

2013-09-01

The objective of this study was to compare the facial morphologies of an adult Chinese population to a Houstonian white population. Three-dimensional (3D) images were acquired via a commercially available stereophotogrammetric camera system, 3dMDface™. Using the system, 100 subjects from a Houstonian population and 71 subjects from a Chinese population were photographed. A complex mathematical algorithm was performed to generate a composite facial average (one for males and one for females) for each subgroup. The computer-generated facial averages were then superimposed based on a previously validated superimposition method. The facial averages were evaluated for differences. Distinct facial differences were evident between the subgroups evaluated. These areas included the nasal tip, the peri-orbital area, the malar process, the labial region, the forehead, and the chin. Overall, the mean facial difference between the Chinese and Houstonian female averages was 2.73±2.20mm, while the difference between the Chinese and Houstonian males was 2.83±2.20mm. The percent similarity for the female population pairings and male population pairings were 10.45% and 12.13%, respectively. The average adult Chinese and Houstonian faces possess distinct differences. Different populations and ethnicities have different facial features and averages that should be considered in the planning of treatment. Copyright © 2013 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Molecular subgroups of medulloblastoma identification using noninvasive magnetic resonance spectroscopy.

PubMed

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.

Sequence determination and analysis of S-adenosyl-L-homocysteine hydrolase from yellow lupine (Lupinus luteus).

PubMed

Brzeziński, K; Janowski, R; Podkowiński, J; Jaskólski, M

2001-01-01

The coding sequences of two S-adenosyl-L-homocysteine hydrolases (SAHases) were identified in yellow lupine by screenig of a cDNA library. One of them, corresponding to the complete protein, was sequenced and compared with 52 other SAHase sequences. Phylogenetic analysis of these proteins identified three groups of the enzymes. Group A comprises only bacterial sequences. Group B is subdivided into two subgroups, one of which (B1) is formed by animal sequences. Subgroup B2 consist of two distinct clusters, B2a and B2b. Cluster B2b comprises all known plant sequences, including the yellow lupine enzyme, which are distinguished by a 50-residue insert. Group C is heterogeneous and contains SAHases from Archaea as well as a new class of animal enzymes, distinctly different from those in group B1.

Rate- and accuracy-disabled subtype profiles among adults with dyslexia in the Hebrew orthography.

PubMed

Shany, Michal; Breznitz, Zvia

2011-01-01

This study examined a subtyping scheme rooted in the dissociation between reading rate and accuracy in an exceptionally large sample of adult readers with dyslexia using a wide variety of behavioral and event-related potential (ERP) measures. Stage 1 was a behavioral study, in which basic reading skill, reading comprehension, linguistic and cognitive tasks were administered to 661 learning-disabled university students (n = 382) and their non-learning-disabled peers (n = 279). Based on a word reading measure, accuracy-disabled and rate-disabled subgroups were identified, as was a subgroup with deficits in both rate and accuracy. The results support the persistence of a rate versus accuracy dissociation into adulthood. Accuracy disability was related to a broad range of deficits affecting phonological, orthographic, and morphological processing, verbal memory, attention, and reading comprehension. Rate disability appeared to be associated with slower processing of printed material, alongside largely intact functioning resembling those of skilled readers. In stage 2, electroencephalogram (EEG)-ERP measurements were obtained from 140 participants recruited from the larger sample. Activation in visual association cortex, indicated by the N170 amplitude, was found to be lower for accuracy-disabled than skilled readers, and comparable between rate-disabled and skilled readers. The lowest amplitude was found in the double-deficit subgroup. The findings support the existence of distinctive reading disability profiles, based on selective deficits in reading rate versus accuracy and associated with different basic reading, linguistic, and cognitive skills as well as electrophysiological responses.

Area variations in multiple morbidity using a life table methodology.

PubMed

Congdon, Peter

Analysis of healthy life expectancy is typically based on a binary distinction between health and ill-health. By contrast, this paper considers spatial modelling of disease free life expectancy taking account of the number of chronic conditions. Thus the analysis is based on population sub-groups with no disease, those with one disease only, and those with two or more diseases (multiple morbidity). Data on health status is accordingly modelled using a multinomial likelihood. The analysis uses data for 258 small areas in north London, and shows wide differences in the disease burden related to multiple morbidity. Strong associations between area socioeconomic deprivation and multiple morbidity are demonstrated, as well as strong spatial clustering.

Genome-wide characterization of GRAS family genes in Medicago truncatula reveals their evolutionary dynamics and functional diversification

PubMed Central

Zhang, Hailing; Cao, Yingping; Shang, Chen; Li, Jikai; Wang, Jianli; Wu, Zhenying; Ma, Lichao; Qi, Tianxiong; Fu, Chunxiang; Hu, Baozhong

2017-01-01

The GRAS gene family is a large plant-specific family of transcription factors that are involved in diverse processes during plant development. Medicago truncatula is an ideal model plant for genetic research in legumes, and specifically for studying nodulation, which is crucial for nitrogen fixation. In this study, 59 MtGRAS genes were identified and classified into eight distinct subgroups based on phylogenetic relationships. Motifs located in the C-termini were conserved across the subgroups, while motifs in the N-termini were subfamily specific. Gene duplication was the main evolutionary force for MtGRAS expansion, especially proliferation of the LISCL subgroup. Seventeen duplicated genes showed strong effects of purifying selection and diverse expression patterns, highlighting their functional importance and diversification after duplication. Thirty MtGRAS genes, including NSP1 and NSP2, were preferentially expressed in nodules, indicating possible roles in the process of nodulation. A transcriptome study, combined with gene expression analysis under different stress conditions, suggested potential functions of MtGRAS genes in various biological pathways and stress responses. Taken together, these comprehensive analyses provide basic information for understanding the potential functions of GRAS genes, and will facilitate further discovery of MtGRAS gene functions. PMID:28945786

Symptom dimensions and subgroups in childhood-onset schizophrenia.

PubMed

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 p<3.57E-03). Our analysis found distinct symptom-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.

An algebraic aspect of Pareto mixture parameter estimation using censored sample: A Bayesian approach.

PubMed

Saleem, Muhammad; Sharif, Kashif; Fahmi, Aliya

2018-04-27

Applications of Pareto distribution are common in reliability, survival and financial studies. In this paper, A Pareto mixture distribution is considered to model a heterogeneous population comprising of two subgroups. Each of two subgroups is characterized by the same functional form with unknown distinct shape and scale parameters. Bayes estimators have been derived using flat and conjugate priors using squared error loss function. Standard errors have also been derived for the Bayes estimators. An interesting feature of this study is the preparation of components of Fisher Information matrix.

Computation of partially invariant solutions for the Einstein Walker manifolds' identifying equations

NASA Astrophysics Data System (ADS)

Nadjafikhah, Mehdi; Jafari, Mehdi

2013-12-01

In this paper, partially invariant solutions (PISs) method is applied in order to obtain new four-dimensional Einstein Walker manifolds. This method is based on subgroup classification for the symmetry group of partial differential equations (PDEs) and can be regarded as the generalization of the similarity reduction method. For this purpose, those cases of PISs which have the defect structure δ=1 and are resulted from two-dimensional subalgebras are considered in the present paper. Also it is shown that the obtained PISs are distinct from the invariant solutions that obtained by similarity reduction method.

Psychological, behavioral, and family characteristics of pediatric patients with chronic pain: a 1-year retrospective study and cluster analysis.

PubMed

Scharff, Lisa; Langan, Nicole; Rotter, Nancy; Scott-Sutherland, Jennifer; Schenck, Clorinda; Tayor, Neil; McDonald-Nolan, Lori; Masek, Bruce

2005-01-01

There has been a longstanding recognition that adult patients with chronic pain are not a homogenous population and that there are subgroups of patients who report high levels of distress and interpersonal difficulties as well as subgroups of patients who report little distress and high functioning. The purpose of the present study was to attempt to identify similar subgroups in a pediatric chronic pain population. The sample consisted of 117 children with chronic pain and their parents who were assessed in a multidisciplinary pain clinic during 2001. Participants completed a set of psychologic self-report questionnaires, as well as demographic and pain characteristic information. A cluster analysis was conducted to identify 3 distinct subgroups of patients to replicate similar studies of adult chronic pain sufferers. Overall, mean scores were within population norms on measures of distress and family functioning, with somatic symptoms at a level of clinical significance. The cluster analysis identified the 3 subgroups that were strikingly similar to those identified in adult chronic pain populations: one with high levels of distress and disability, another with relatively low scores on distress and disability, and a third group that scored in between the other 2 on these measures but with marked low family cohesion. The similarity of these subgroups to the adult chronic pain population subgroups as well as implications for future studies are discussed.

The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups

PubMed Central

Curtis, Christina; Shah, Sohrab P.; Chin, Suet-Feung; Turashvili, Gulisa; Rueda, Oscar M.; Dunning, Mark J.; Speed, Doug; Lynch, Andy G.; Samarajiwa, Shamith; Yuan, Yinyin; Gräf, Stefan; Ha, Gavin; Haffari, Gholamreza; Bashashati, Ali; Russell, Roslin; McKinney, Steven; Langerød, Anita; Green, Andrew; Provenzano, Elena; Wishart, Gordon; Pinder, Sarah; Watson, Peter; Markowetz, Florian; Murphy, Leigh; Ellis, Ian; Purushotham, Arnie; Børresen-Dale, Anne-Lise; Brenton, James D.; Tavaré, Simon; Caldas, Carlos; Aparicio, Samuel

2012-01-01

The elucidation of breast cancer subgroups and their molecular drivers requires integrated views of the genome and transcriptome from representative numbers of patients. We present an integrated analysis of copy number and gene expression in a discovery and validation set of 997 and 995 primary breast tumours, respectively, with long-term clinical follow-up. Inherited variants (copy number variants and single nucleotide polymorphisms) and acquired somatic copy number aberrations (CNAs) were associated with expression in ~40% of genes, with the landscape dominated by cis- and trans-acting CNAs. By delineating expression outlier genes driven in cis by CNAs, we identified putative cancer genes, including deletions in PPP2R2A, MTAP and MAP2K4. Unsupervised analysis of paired DNA–RNA profiles revealed novel subgroups with distinct clinical outcomes, which reproduced in the validation cohort. These include a high-risk, oestrogen-receptor-positive 11q13/14 cis-acting subgroup and a favourable prognosis subgroup devoid of CNAs. Trans-acting aberration hotspots were found to modulate subgroup-specific gene networks, including a TCR deletion-mediated adaptive immune response in the ‘CNA-devoid’ subgroup and a basal-specific chromosome 5 deletion-associated mitotic network. Our results provide a novel molecular stratification of the breast cancer population, derived from the impact of somatic CNAs on the transcriptome. PMID:22522925

Patterns of daily energy management at work: relations to employee well-being and job characteristics.

PubMed

Kinnunen, Ulla; Feldt, Taru; de Bloom, Jessica; Korpela, Kalevi

2015-11-01

The present study aimed at identifying subgroups of employees with similar daily energy management strategies at work and finding out whether well-being indicators and job characteristics differ between these subgroups. The study was conducted by electronic questionnaire among 1122 Finnish employees. First, subgroups of employees with unique and distinctive patterns of energy management strategies were identified using latent profile analysis. Second, differences in well-being indicators and job characteristics between the subgroups were investigated by means of ANCOVA. Four subgroups (i.e., patterns) were identified and named: Passives (n = 371), Averages (n = 390), Casuals (n = 272) and Actives (n = 89). Passives used all three (i.e., work-related, private micro-break and physical micro-break) strategies less frequently than other subgroups, whereas Actives used work-related and physical energy management strategies more frequently than other subgroups. Averages used all strategies on an average level. Casuals' use of all strategies came close to that of Actives, notably in a shared low use of private micro-break strategies. Active and Casual patterns maintained vigor and vitality. Autonomy and social support at work played a significant role in providing opportunities for the use of beneficial energy management strategies. Autonomy and support at work seem to support active and casual use of daily energy management, which is important in staying energized throughout the working day.

Subtyping attention-deficit/hyperactivity disorder using temperament dimensions: toward biologically based nosologic criteria

PubMed Central

Karalunas, Sarah L.; Fair, Damien; Musser, Erica D.; Aykes, Kamari; Iyer, Swathi P.; Nigg, Joel T.

2014-01-01

Importance Psychiatric nosology is limited by behavioral and biological heterogeneity within existing disorder categories. The imprecise nature of current nosological distinctions limits both mechanistic understanding and clinical prediction. Here, we demonstrate an approach consistent with the NIMH Research Domain Criteria (RDoC) initiative to identifying superior, neurobiologically-valid subgroups with better predictive capacity than existing psychiatric categories for childhood Attention-Deficit Hyperactivity Disorder (ADHD). Objective Refine subtyping of childhood ADHD by using biologically-based behavioral dimensions (i.e. temperament), novel classification algorithms, and multiple external validators. In doing so, we demonstrate how refined nosology is capable of improving on current predictive capacity of long-term outcomes relative to current DSM-based nosology. Design, Setting, Participants 437 clinically well-characterized, community-recruited children with and without ADHD participated in an on-going longitudinal study. Baseline data were used to classify children into subgroups based on temperament dimensions and to examine external validators including physiological and MRI measures. One-year longitudinal follow-up data are reported for a subgroup of the ADHD sample to address stability and clinical prediction. Main Outcome Measures Parent/guardian ratings of children on a measure of temperament were used as input features in novel community detection analyses to identify subgroups within the sample. Groups were validated using three widely-accepted external validators: peripheral physiology (cardiac measures of respiratory sinus arrhythmia and pre-ejection period), central nervous system functioning (via resting-state functional connectivity MRI), and clinical outcomes (at one-year longitudinal follow-up). Results The community detection algorithm suggested three novel types of ADHD, labeled as “Mild” (normative emotion regulation); “Surgent” (extreme levels of positive approach-motivation); and “Irritable” (extreme levels of negative emotionality, anger, and poor soothability). Types were independent of existing clinical demarcations, including DSM-5 presentations or symptom severity. These types showed stability over time and were distinguished by unique patterns of cardiac physiological response, resting-state functional brain connectivity, and clinical outcome one year later. Conclusions and Relevance Results suggest that a biologically-informed temperament-based typology, developed with a discovery-based community detection algorithm, provided a superior description of heterogeneity in the ADHD population than any current clinical nosology. This demonstration sets the stage for more aggressive attempts at a tractable, biologically-based nosology. PMID:25006969

Sequence Diversity, Intersubgroup Relationships, and Origins of the Mouse Leukemia Gammaretroviruses of Laboratory and Wild Mice.

PubMed

Bamunusinghe, Devinka; Naghashfar, Zohreh; Buckler-White, Alicia; Plishka, Ronald; Baliji, Surendranath; Liu, Qingping; Kassner, Joshua; Oler, Andrew J; Hartley, Janet; Kozak, Christine A

2016-04-01

Mouse leukemia viruses (MLVs) are found in the common inbred strains of laboratory mice and in the house mouse subspecies ofMus musculus Receptor usage and envelope (env) sequence variation define three MLV host range subgroups in laboratory mice: ecotropic, polytropic, and xenotropic MLVs (E-, P-, and X-MLVs, respectively). These exogenous MLVs derive from endogenous retroviruses (ERVs) that were acquired by the wild mouse progenitors of laboratory mice about 1 million years ago. We analyzed the genomes of seven MLVs isolated from Eurasian and American wild mice and three previously sequenced MLVs to describe their relationships and identify their possible ERV progenitors. The phylogenetic tree based on the receptor-determining regions ofenvproduced expected host range clusters, but these clusters are not maintained in trees generated from other virus regions. Colinear alignments of the viral genomes identified segmental homologies to ERVs of different host range subgroups. Six MLVs show close relationships to a small xenotropic ERV subgroup largely confined to the inbred mouse Y chromosome.envvariations define three E-MLV subtypes, one of which carries duplications of various sizes, sequences, and locations in the proline-rich region ofenv Outside theenvregion, all E-MLVs are related to different nonecotropic MLVs. These results document the diversity in gammaretroviruses isolated from globally distributedMussubspecies, provide insight into their origins and relationships, and indicate that recombination has had an important role in the evolution of these mutagenic and pathogenic agents. Laboratory mice carry mouse leukemia viruses (MLVs) of three host range groups which were acquired from their wild mouse progenitors. We sequenced the complete genomes of seven infectious MLVs isolated from geographically separated Eurasian and American wild mice and compared them with endogenous germ line retroviruses (ERVs) acquired early in house mouse evolution. We did this because the laboratory mouse viruses derive directly from specific ERVs or arise by recombination between different ERVs. The six distinctively different wild mouse viruses appear to be recombinants, often involving different host range subgroups, and most are related to a distinctive, largely Y-chromosome-linked MLV ERV subtype. MLVs with ecotropic host ranges show the greatest variability with extensive inter- and intrasubtype envelope differences and with homologies to other host range subgroups outside the envelope. The sequence diversity among these wild mouse isolates helps define their relationships and origins and emphasizes the importance of recombination in their evolution. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Latent profiles of problem behavior within learning, peer, and teacher contexts: identifying subgroups of children at academic risk across the preschool year.

PubMed

Bulotsky-Shearer, Rebecca J; Bell, Elizabeth R; Domínguez, Ximena

2012-12-01

Employing a developmental and ecological model, the study identified initial levels and rates of change in academic skills for subgroups of preschool children exhibiting problem behavior within routine classroom situations. Six distinct latent profile types of emotional and behavioral adjustment were identified for a cohort of low-income children early in the preschool year (N=4417). Profile types provided a descriptive picture of patterns of classroom externalizing, internalizing, and situational adjustment problems common to subgroups of children early in the preschool year. The largest profile type included children who exhibited low problem behavior and were characterized as well-adjusted to the preschool classroom early in the year. The other profile types were characterized by distinct combinations of elevated internalizing, externalizing, and situational problem behavior. Multinomial logistic regression identified younger children and boys at increased risk for classification in problem types, relative to the well-adjusted type. Latent growth models indicated that children classified within the extremely socially and academically disengaged profile type, started and ended the year with the lowest academic skills, relative to all other types. Implications for future research, policy, and practice are discussed. Copyright © 2012 Society for the Study of School Psychology. Published by Elsevier Ltd. All rights reserved.

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

PubMed

Smura, Teemu; Blomqvist, Soile; Vuorinen, Tytti; Ivanova, Olga; Samoilovich, Elena; Al-Hello, Haider; Savolainen-Kopra, Carita; Hovi, Tapani; Roivainen, Merja

2014-01-01

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.

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

PubMed

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.

Light Evokes Rapid Circadian Network Oscillator Desynchrony Followed by Gradual Phase Retuning of Synchrony

PubMed Central

Roberts, Logan; Leise, Tanya L.; Noguchi, Takako; Galschiodt, Alexis M.; Houl, Jerry H.; Welsh, David K.; Holmes, Todd C.

2015-01-01

Summary Background Circadian neural circuits generate near 24 hr physiological rhythms that can be entrained by light to coordinate animal physiology with daily solar cycles. To examine how a circadian circuit reorganizes its activity in response to light, we imaged period (per) clock gene cycling for up to 6 days at single neuron resolution in whole brain explant cultures prepared from per-luciferase transgenic flies. We compared cultures subjected to a phase-advancing light pulse (LP) to cultures maintained in darkness (DD). Results In DD, individual neuronal oscillators in all circadian subgroups are initially well synchronized, then show monotonic decrease in oscillator rhythm amplitude and synchrony with time. The s-LNvs and LNds exhibit this decrease at a slower relative rate. In contrast, the LP evokes a rapid loss of oscillator synchrony between and within most circadian neuronal subgroups followed by gradual phase retuning of whole circuit oscillator synchrony. The LNds maintain high rhythmic amplitude and synchrony following the LP along with the most rapid coherent phase advance. Immunocytochemical analysis of PER show these dynamics in DD and LP are recapitulated in vivo. Anatomically distinct circadian neuronal subgroups vary in their response to the LP, showing differences in the degree and kinetics of their loss, recovery and/or strengthening of synchrony and rhythmicity. Conclusions Transient desynchrony appears to be an integral feature of light response of the Drosophila multicellular circadian clock. Individual oscillators in different neuronal subgroups of the circadian circuit show distinct kinetic signatures of light response and phase retuning. PMID:25754644

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

PubMed Central

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

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

PubMed

Albert, Arianne Y K; Chaban, Bonnie; 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.

Reward and relief craving tendencies in patients with alcohol use disorders: results from the PREDICT study.

PubMed

Glöckner-Rist, Angelika; Lémenager, Tagrid; Mann, Karl

2013-02-01

Previous research suggests that patients' tendencies toward either reward or relief craving are distinct continuous factorial dimensions of craving for alcohol. According to these tendencies patients with alcohol use disorders (AUD) might also be allocated into distinct subgroups. In personalized treatment, patients of such different subgroups might respond differently to various psychotherapeutic and pharmacological interventions aimed at relapse prevention. To establish that the items of the subscale Temptation to Drink of the Alcohol Abstinence Self-Efficacy Scale (AASE) capture two continuous dimensions of reward and relief craving, and that they allow the identification of respective discrete class factors and subgroups of patients with AUD. Nonlinear confirmatory factor analysis (CFA) and latent class factor analysis (LCFA) were performed with data from 426 detoxified patients with AUD. The validity of continuous relief and reward dimensions, discrete class factors, and subtypes with different craving tendencies was established by including past drinking in positive and negative settings, gender, trait anxiety and perceived stress as covariates in the finally accepted CFA and LCFA measurement models. The AASE temptation items formed two continuous relief and reward craving factors. They also associated themselves to two binary class factors, which defined four craving subgroups. Two of them (21% and 29% of patients) were characterized by high levels of either reward or relief craving tendencies. A third subgroup (31%) rated both tendencies in an equal high measure, while a fourth (18%) reported almost no craving tendencies at all. Past drinking in negative and positive settings was significantly associated with relief or reward craving tendencies. Male patients reported reward drinking more frequently than female patients. Trait anxiety was positively related only to the relief craving tendency. Unexpectedly, patients' level of perceived stress was associated with both craving tendencies. The AASE temptation items are suited to identify relief and reward craving dimensions and to assign patients to according subtypes. Thus, they can be used to screen for corresponding patient subgroups, possibly allowing allocation to interventions that are specifically tailored to patient's particular craving tendencies. Hence: A relatively simple psychometric measure could help in improving treatment outcomes through a personalized approach to intervention. Copyright © 2012 Elsevier Ltd. All rights reserved.

Antiretroviral therapy suppressed participants with low CD4+ T-cell counts segregate according to opposite immunological phenotypes

PubMed Central

Pérez-Santiago, Josué; Ouchi, Dan; Urrea, Victor; Carrillo, Jorge; Cabrera, Cecilia; Villà-Freixa, Jordi; Puig, Jordi; Paredes, Roger; Negredo, Eugènia; Clotet, Bonaventura; Massanella, Marta; Blanco, Julià

2016-01-01

Background: The failure to increase CD4+ T-cell counts in some antiretroviral therapy suppressed participants (immunodiscordance) has been related to perturbed CD4+ T-cell homeostasis and impacts clinical evolution. Methods: We evaluated different definitions of immunodiscordance based on CD4+ T-cell counts (cutoff) or CD4+ T-cell increases from nadir value (ΔCD4) using supervised random forest classification of 74 immunological and clinical variables from 196 antiretroviral therapy suppressed individuals. Unsupervised clustering was performed using relevant variables identified in the supervised approach from 191 individuals. Results: Cutoff definition of CD4+ cell count 400 cells/μl performed better than any other definition in segregating immunoconcordant and immunodiscordant individuals (85% accuracy), using markers of activation, nadir and death of CD4+ T cells. Unsupervised clustering of relevant variables using this definition revealed large heterogeneity between immunodiscordant individuals and segregated participants into three distinct subgroups with distinct production, programmed cell-death protein-1 (PD-1) expression, activation and death of T cells. Surprisingly, a nonnegligible number of immunodiscordant participants (22%) showed high frequency of recent thymic emigrants and low CD4+ T-cell activation and death, very similar to immunoconcordant participants. Notably, human leukocyte antigen - antigen D related (HLA-DR) PD-1 and CD45RA expression in CD4+ T cells allowed reproducing subgroup segregation (81.4% accuracy). Despite sharp immunological differences, similar and persistently low CD4+ values were maintained in these participants over time. Conclusion: A cutoff value of CD4+ T-cell count 400 cells/μl classified better immunodiscordant and immunoconcordant individuals than any ΔCD4 classification. Immunodiscordance may present several, even opposite, immunological patterns that are identified by a simple immunological follow-up. Subgroup classification may help clinicians to delineate diverse approaches that may be needed to boost CD4+ T-cell recovery. PMID:27427875

Transitional Life Events and Trajectories of Cigarette and Alcohol Use During Emerging Adulthood: Latent Class Analysis and Growth Mixture Modeling

PubMed Central

Huh, Jimi; Huang, Zhaoqing; Liao, Yue; Pentz, Maryann; Chou, Chih-Ping

2013-01-01

Objective: Emerging adulthood (ages 18–25 years) has been associated with elevated substance use. Transitional life events (TLEs) during emerging adulthood in relation to substance use are usually examined separately, rather than as a constellation. The purposes of this study were (a) to explore distinct subgroups experiencing various TLEs during emerging adulthood, (b) to identify heterogeneous trajectories of cigarette and alcohol use during emerging adulthood, and (c) to examine the association of TLEs with cigarette and alcohol use trajectories. Method: Five waves of longitudinal data (mean age range: 19.5–26.0 years) were used from a community-based drug prevention program (n = 946, 49.9% female). Distinct subgroups of emerging adults who experienced various TLEs were identified using latent class analysis. Cigarette and alcohol use were examined using a latent growth mixture model. Results: A three-class model fit the data best in identifying TLE subgroups (new family, college attenders [NFCA]; uncommitted relationships, college attenders [URCA]; hibernators [HBN]). Three-trajectory models fit the data best for cigarette and alcohol use during emerging adulthood. The TLE categories were significantly associated with the cigarette (p < .05) and alcohol use groups (p < .001); specifically, the URCA and HBN groups were significantly more likely to be classified as accelerating cigarette users, relative to NFCA (ps < .05). The NFCA and HBN groups were significantly more likely to be classified as accelerating alcohol users, relative to URCA (ps < .01). Conclusions: To characterize an “at-risk” emerging adult group for cigarette and alcohol use over time, a range of life events during emerging adulthood should be considered. Interventions tailored to young adulthood may benefit from targeting the absence of these life events typifying “independence” as a potential marker for underlying substance use problems and provide supplemental screening methods to identify young adults with similar issues. PMID:23948532

Medulloblastoma in the Molecular Era

PubMed Central

Miranda Kuzan-Fischer, Claudia; Juraschka, Kyle; Taylor, Michael D.

2018-01-01

Medulloblastoma is the most common malignant brain tumor of childhood and remains a major cause of cancer related mortality in children. Significant scientific advancements have transformed the understanding of medulloblastoma, leading to the recognition of four distinct clinical and molecular subgroups, namely wingless (WNT), sonic hedgehog, group 3, and group 4. Subgroup classification combined with the recognition of subgroup specific molecular alterations has also led to major changes in risk stratification of medulloblastoma patients and these changes have begun to alter clinical trial design, in which the newly recognized subgroups are being incorporated as individualized treatment arms. Despite these recent advancements, identification of effective targeted therapies remains a challenge for several reasons. First, significant molecular heterogeneity exists within the four subgroups, meaning this classification system alone may not be sufficient to predict response to a particular therapy. Second, the majority of novel agents are currently tested at the time of recurrence, after which significant selective pressures have been exerted by radiation and chemotherapy. Recent studies demonstrate selection of tumor sub-clones that exhibit genetic divergence from the primary tumor, exist within metastatic and recurrent tumor populations. Therefore, tumor resampling at the time of recurrence may become necessary to accurately select patients for personalized therapy. PMID:29742881

Medulloblastoma in the Molecular Era.

PubMed

Miranda Kuzan-Fischer, Claudia; Juraschka, Kyle; Taylor, Michael D

2018-05-01

Medulloblastoma is the most common malignant brain tumor of childhood and remains a major cause of cancer related mortality in children. Significant scientific advancements have transformed the understanding of medulloblastoma, leading to the recognition of four distinct clinical and molecular subgroups, namely wingless (WNT), sonic hedgehog, group 3, and group 4. Subgroup classification combined with the recognition of subgroup specific molecular alterations has also led to major changes in risk stratification of medulloblastoma patients and these changes have begun to alter clinical trial design, in which the newly recognized subgroups are being incorporated as individualized treatment arms. Despite these recent advancements, identification of effective targeted therapies remains a challenge for several reasons. First, significant molecular heterogeneity exists within the four subgroups, meaning this classification system alone may not be sufficient to predict response to a particular therapy. Second, the majority of novel agents are currently tested at the time of recurrence, after which significant selective pressures have been exerted by radiation and chemotherapy. Recent studies demonstrate selection of tumor sub-clones that exhibit genetic divergence from the primary tumor, exist within metastatic and recurrent tumor populations. Therefore, tumor resampling at the time of recurrence may become necessary to accurately select patients for personalized therapy.

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

ERIC Educational Resources Information Center

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…

Intercontinental spread of asian-origin H5N8 to North America through Beringia by migratory birds

USGS Publications Warehouse

Lee, Dong-Hun; Kim Torchetti, Mia; Winker, Kevin; Ip, Hon S.; Swayne, David E.; Song, Chang-Seon

2015-01-01

Phylogenetic network analysis and understanding of waterfowl migration patterns suggest the Eurasian H5N8 clade 2.3.4.4 avian influenza virus emerged in late 2013 in China, spread in early 2014 to South Korea and Japan, and reached Siberia and Beringia by summer 2014 via migratory birds. Three genetically distinct subgroups emerged and subsequently spread along different flyways during fall 2014 into Europe, North America, and East Asia, respectively. All three subgroups reappeared in Japan, a wintering site for waterfowl from Eurasia and parts of North America.

Blood pressure-lowering effects of nifedipine/candesartan combinations in high-risk individuals: subgroup analysis of the DISTINCT randomised trial.

PubMed

Mancia, G; Cha, G; Gil-Extremera, B; Harvey, P; Lewin, A J; Villa, G; Kjeldsen, S E

2017-03-01

The DISTINCT study (reDefining Intervention with Studies Testing Innovative Nifedipine GITS-Candesartan Therapy) investigated the efficacy and safety of nifedipine GITS/candesartan cilexetil combinations vs respective monotherapies and placebo in patients with hypertension. This descriptive sub-analysis examined blood pressure (BP)-lowering effects in high-risk participants, including those with renal impairment (estimated glomerular filtration rate<90 ml min -1 , n=422), type 2 diabetes mellitus (n=202), hypercholesterolaemia (n=206) and cardiovascular (CV) risk factors (n=971), as well as the impact of gender, age and body mass index (BMI). Participants with grade I/II hypertension were randomised to treatment with nifedipine GITS (N) 20, 30, 60 mg and/or candesartan cilexetil (C) 4, 8, 16, 32 mg or placebo for 8 weeks. Mean systolic BP and diastolic BP reductions after treatment in high-risk participants were greater, overall, with N/C combinations vs respective monotherapies or placebo, with indicators of a dose-response effect. Highest rates of BP control (ESH/ESC 2013 guideline criteria) were also achieved with highest doses of N/C combinations in each high-risk subgroup. The benefits of combination therapy vs monotherapy were additionally observed in patient subgroups categorised by gender, age or BMI. All high-risk participants reported fewer vasodilatory adverse events in the pooled N/C combination therapy than the N monotherapy group. In conclusion, consistent with the DISTINCT main study outcomes, high-risk participants showed greater reductions in BP and higher control rates with N/C combinations compared with respective monotherapies and lesser vasodilatory side-effects compared with N monotherapy.

Location of the motoneurons of the mylohyoid muscle in the rat. A fluorescence and Nissl study.

PubMed

Badran, Darwish H; Al-Hadidi, Maher T; Ramadan, Hassan N; Abu-Ghaida, Jamal H

2005-01-01

To locate the neuronal motor cells of the mylohyoid muscle and discuss their topographical organization. The present study was conducted at the Department of Anatomy and Histology, Faculty of Medicine, University of Jordan, Amman, Jordan between 2002 and 2003. The mylohyoid muscle in 15 albino rats was injected with 15 mliter of a retrogradely transported fluorescent material DAPI-Pr. After a survival period of 48 hours, animals were sacrificed, fixed in situ and brains harvested. The caudorostral transverse sections of the hindbrains were examined under the fluorescence microscope to detect the fluorescing cells, which were immediately photographed. Sections containing the labeled cells were charted, stained with 1% thionine and photographs obtained through light and fluorescence microscopes at different magnifications. The place and shape of all labeled cells were singled out by asset of their charted referring photographs of hindbrain sections, which display the entire motor trigeminal nucleus. The results showed that the fluorescent cell increase was found to occupy the rostromedial part of the ipsilateral motor trigeminal nucleus. The nucleus was large at its caudal third; the labeled cells are mainly those of the medial "subgroup". These cells are rationally distinct and lie alongside the internal loop of the facial nerve. At the middle third, most of the medial "subgroup" was found labeled. At its middle, the nucleus found was well developed, attained an appreciable size and its medial "subgroup" was somewhat distinct. Whereas, at the rostral third, the nucleus was larger, the medial group was more distinct and all cells were labeled. The medial cellular mass of the nucleus showed reduced labeled cells at the rostral end. This study demonstrates that the rostromedial part of the motor trigeminal nucleus represents the absolute territorial domain of the mylohyoid muscle motoneurons.

Functional gastroduodenal disorders

PubMed Central

Talley, N; Stanghellini, V; Heading, R; Koch, K; Malagelada, J; Tytgat, G

1999-01-01

While widely used in research, the 1991 Rome criteria for the gastroduodenal disorders, especially symptom subgroups in dyspepsia, remain contentious. After a comprehensive literature search, a consensus-based approach was applied, supplemented by input from international experts who reviewed the report. Three functional gastroduodenal disorders are defined. Functional dyspepsia is persistent or recurrent pain or discomfort centered in the upper abdomen; evidence of organic disease likely to explain the symptoms is absent, including at upper endoscopy. Discomfort refers to a subjective, negative feeling that may be characterized by or associated with a number of non-painful symptoms including upper abdominal fullness, early satiety, bloating, or nausea. A dyspepsia subgroup classification is proposed for research purposes, based on the predominant (most bothersome) symptom: (a) ulcer-like dyspepsia when pain (from mild to severe) is the predominant symptom, and (b) dysmotility-like dyspepsia when discomfort (not pain) is the predominant symptom. This classification is supported by recent evidence suggesting that predominant symptoms, but not symptom clusters, identify subgroups with distinct underlying pathophysiological disturbances and responses to treatment. Aerophagia is an unusual complaint characterized by air swallowing that is objectively observed and troublesome repetitive belching. Functional vomiting refers to frequent episodes of recurrent vomiting that is not self-induced nor medication induced, and occurs in the absence of eating disorders, major psychiatric diseases, abnormalities in the gut or central nervous system, or metabolic diseases that can explain the symptom. The current classification requires careful validation but the criteria should be of value in future research.


Keywords: dyspepsia; functional dyspepsia; aerophagia; psychogenic vomiting; Rome II PMID:10457043

Close relationships between Asian American and European American college students.

PubMed

Chen, C; Edwards, K; Young, B; Greenberger, E

2001-02-01

The authors examined attitudes and behaviors regarding close relationships between European and Asian Americans, with a particular emphasis on 5 major subgroups of Asian Americans (Chinese, Japanese, Korean, Vietnamese, and Filipino Americans). Participants were 218 Asian American college students and 171 European American college students attending a culturally diverse university. The European Americans did not differentiate among the various subgroups of Asian Americans. Their attitudes regarding close relationships were less positive toward Asian Americans than toward Mexican and African Americans, a finding contrary to the prediction of social exchange theory (H. Tajfel, 1975). In contrast to the European Americans' view of homogeneity among Asian Americans, the 5 major subgroups of Asian Americans expressed a distinctive hierarchy of social preference among themselves. Results are discussed in terms of their implications for future research on interethnic relations involving Asian Americans.

Differentiation and classification of phytoplasmas in the pigeon pea witches'-broom group (16SrIX): an update based on multiple gene sequence analysis.

PubMed

Lee, I-M; Bottner-Parker, K D; Zhao, Y; Bertaccini, A; Davis, R E

2012-09-01

The pigeon pea witches'-broom phytoplasma group (16SrIX) comprises diverse strains that cause numerous diseases in leguminous trees and herbaceous crops, vegetables, a fruit, a nut tree and a forest tree. At least 14 strains have been reported worldwide. Comparative phylogenetic analyses of the highly conserved 16S rRNA gene and the moderately conserved rplV (rpl22)-rpsC (rps3) and secY genes indicated that the 16SrIX group consists of at least six distinct genetic lineages. Some of these lineages cannot be readily differentiated based on analysis of 16S rRNA gene sequences alone. The relative genetic distances among these closely related lineages were better assessed by including more variable genes [e.g. ribosomal protein (rp) and secY genes]. The present study demonstrated that virtual RFLP analyses using rp and secY gene sequences allowed unambiguous identification of such lineages. A coding system is proposed to designate each distinct rp and secY subgroup in the 16SrIX group.

Conceptualizing the Adventure-Sports Coach

ERIC Educational Resources Information Center

Collins, Loel; Collins, Dave

2012-01-01

As a comparatively recent development, the adventure-sports coach struggles for a clear and distinct identity. The generic term "instructor" no longer characterizes the role and function of this subgroup of outdoor professionals. Indeed, although the fields of adventure/outdoor education and leadership are comparatively well researched,…

Trajectories of Social Withdrawal from Middle Childhood to Early Adolescence

PubMed Central

Oh, Wonjung; Bowker, Julie C.; Booth-LaForce, Cathryn; Rose-Krasnor, Linda; Laursen, Brett

2013-01-01

Heterogeneity and individual differences in the developmental course of social withdrawal were examined longitudinally in a community sample (N=392). General Growth Mixture Modeling (GGMM) was used to identify distinct pathways of social withdrawal, differentiate valid subgroup trajectories, and examine factors that predicted change in trajectories within subgroups. Assessments of individual (social withdrawal), interactive (prosocial behavior), relationship (friendship involvement, stability and quality, best friend’s withdrawal and exclusion/victimization) and group- (exclusion/victimization) level characteristics were used to define growth trajectories from the final year of elementary school, across the transition to middle school, and then to the final year of middle school (fifth-to-eighth grades). Three distinct trajectory classes were identified: low stable, increasing, and decreasing. Peer exclusion, prosocial behavior, and mutual friendship involvement differentiated class membership. Friendlessness, friendship instability, and exclusion were significant predictors of social withdrawal for the increasing class, whereas lower levels of peer exclusion predicted a decrease in social withdrawal for the decreasing class. PMID:18193479

Trajectories of social withdrawal from middle childhood to early adolescence.

PubMed

Oh, Wonjung; Rubin, Kenneth H; Bowker, Julie C; Booth-LaForce, Cathryn; Rose-Krasnor, Linda; Laursen, Brett

2008-05-01

Heterogeneity and individual differences in the developmental course of social withdrawal were examined longitudinally in a community sample (N = 392). General Growth Mixture Modeling (GGMM) was used to identify distinct pathways of social withdrawal, differentiate valid subgroup trajectories, and examine factors that predicted change in trajectories within subgroups. Assessments of individual (social withdrawal), interactive (prosocial behavior), relationship (friendship involvement, stability and quality, best friend's withdrawal and exclusion/victimization) and group- (exclusion/victimization) level characteristics were used to define growth trajectories from the final year of elementary school, across the transition to middle school, and then to the final year of middle school (fifth-to-eighth grades). Three distinct trajectory classes were identified: low stable, increasing, and decreasing. Peer exclusion, prosocial behavior, and mutual friendship involvement differentiated class membership. Friendlessness, friendship instability, and exclusion were significant predictors of social withdrawal for the increasing class, whereas lower levels of peer exclusion predicted a decrease in social withdrawal for the decreasing class.

Recombination in the Evolution of Enterovirus C Species Sub-Group that Contains Types CVA-21, CVA-24, EV-C95, EV-C96 and EV-C99

PubMed Central

Smura, Teemu; Blomqvist, Soile; Vuorinen, Tytti; Ivanova, Olga; Samoilovich, Elena; Al-Hello, Haider; Savolainen-Kopra, Carita; Hovi, Tapani; Roivainen, Merja

2014-01-01

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. PMID:24722726

A distinct subgroup of cardiomyopathy patients characterized by transcriptionally active cardiotropic erythrovirus and altered cardiac gene expression.

PubMed

Kuhl, U; Lassner, D; Dorner, A; Rohde, M; Escher, F; Seeberg, B; Hertel, E; Tschope, C; Skurk, C; Gross, U M; Schultheiss, H-P; Poller, W

2013-09-01

Recent studies have detected erythrovirus genomes in the hearts of cardiomyopathy and cardiac transplant patients. Assessment of the functional status of viruses may provide clinically important information beyond detection of the viral genomes. Here, we report transcriptional activation of cardiotropic erythrovirus to be associated with strongly altered myocardial gene expression in a distinct subgroup of cardiomyopathy patients. Endomyocardial biopsies (EMBs) from 415 consecutive cardiac erythrovirus (B19V)-positive patients with clinically suspected cardiomyopathy were screened for virus-encoded VP1/VP2 mRNA indicating transcriptional activation of the virus, and correlated with cardiac host gene expression patterns in transcriptionally active versus latent infections, and in virus-free control hearts. Transcriptional activity was detected in baseline biopsies of only 66/415 patients (15.9 %) harbouring erythrovirus. At the molecular level, significant differences between cardiac B19V-positive patients with transcriptionally active versus latent virus were revealed by expression profiling of EMBs. Importantly, latent B19V infection was indistinguishable from controls. Genes involved encode proteins of antiviral immune response, B19V receptor complex, and mitochondrial energy metabolism. Thus, functional mapping of erythrovirus allows definition of a subgroup of B19V-infected cardiomyopathy patients characterized by virus-encoded VP1/VP2 transcripts and anomalous host myocardial transcriptomes. Cardiac B19V reactivation from latency, as reported here for the first time, is a key factor required for erythrovirus to induce altered cardiac gene expression in a subgroup of cardiomyopathy patients. Virus genome detection is insufficient to assess pathogenic potential, but additional transcriptional mapping should be incorporated into future pathogenetic and therapeutic studies both in cardiology and transplantation medicine.

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

PubMed

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.

Personalized medicine in interstitial lung diseases.

PubMed

Spagnolo, Paolo; Oldham, Justin M; Jones, Mark G; Lee, Joyce S

2017-05-01

A number of recent studies have explored the possibility to apply personalized medicine to interstitial lung diseases (ILDs), particularly idiopathic pulmonary fibrosis (IPF), the most common and deadly of the idiopathic interstitial pneumonias. In our review, we summarize and discuss the most recent literature on personalized medicine in IPF as well as hypersensitivity pneumonitis and sarcoidosis, with emphasis on patient subgroups for which a personalized approach to disease prognostication and management may become a reality in the near future. Most of the studies that have explored the applicability of personalized medicine to ILDs have been conducted in patients with IPF. Such studies have suggested the existence of several distinct disease subgroups defined by similar genetic profiles, molecular pathways, exposures and individual lifestyles. Personalized medicine in hypersensitivity pneumonitis is in its infancy. The development and applicability of personalized medicine to sarcoidosis, on the other hand, remains problematic for several reasons, including the lack of a diagnostic gold standard, the highly variable and unpredictable disease course, particularly across patients of different ethnicities, the poor correlation between disease activity and disease severity and the lack of a validated management algorithm. A number of distinct patient subgroups have been identified in ILDs. Although available data need to be validated longitudinally, the possibility to study homogeneous groups of patients may allow prediction of disease behavior and response to treatment with dramatic clinical implications.

Depression and Suicide in Schizophrenic Patients.

ERIC Educational Resources Information Center

Salama, Aziz A.

1988-01-01

Identified schizophrenic patients as distinctive subgroup of patients who can suffer from major depressive illness and can commit suicide. Found 22.4 percent of 620 schizophrenics in psychiatric facility showed symptoms of major depressive episode. Seven patients committed suicide during acute phase of illness, 9 attempted suicide while…

Trajectories of Social Withdrawal from Middle Childhood to Early Adolescence

ERIC Educational Resources Information Center

Oh, Wonjung; Rubin, Kenneth H.; Bowker, Julie C.; Booth-LaForce, Cathryn; Rose-Krasnor, Linda; Laursen, Brett

2008-01-01

Heterogeneity and individual differences in the developmental course of social withdrawal were examined longitudinally in a community sample (N = 392). General Growth Mixture Modeling (GGMM) was used to identify distinct pathways of social withdrawal, differentiate valid subgroup trajectories, and examine factors that predicted change in…

The gene for glycogen-storage disease type 1b maps to chromosome 11q23.

PubMed

Annabi, B; Hiraiwa, H; Mansfield, B C; Lei, K J; Ubagai, T; Polymeropoulos, M H; Moses, S W; Parvari, R; Hershkovitz, E; Mandel, H; Fryman, M; Chou, J Y

1998-02-01

Glycogen-storage disease type 1 (GSD-1), also known as "von Gierke disease," is caused by a deficiency in microsomal glucose-6-phosphatase (G6Pase) activity. There are four distinct subgroups of this autosomal recessive disorder: 1a, 1b, 1c, and 1d. All share the same clinical manifestations, which are caused by abnormalities in the metabolism of glucose-6-phosphate (G6P). However, only GSD-1b patients suffer infectious complications, which are due to both the heritable neutropenia and the functional deficiencies of neutrophils and monocytes. Whereas G6Pase deficiency in GSD-1a patients arises from mutations in the G6Pase gene, this gene is normal in GSD-1b patients, indicating a separate locus for the disorder in the 1b subgroup. We now report the linkage of the GSD-1b locus to genetic markers spanning a 3-cM region on chromosome 11q23. Eventual molecular characterization of this disease will provide new insights into the genetic bases of G6P metabolism and neutrophil-monocyte dysfunction.

Longitudinal Stability and Predictors of Poor Oral Comprehenders and Poor Decoders

PubMed Central

Elwér, Åsa; Keenan, Janice M.; Olson, Richard K.; Byrne, Brian; Samuelsson, Stefan

2012-01-01

Two groups of 4th grade children were selected from a population sample (N= 926) to either be Poor Oral Comprehenders (poor oral comprehension but normal word decoding), or Poor Decoders (poor decoding but normal oral comprehension). By examining both groups in the same study with varied cognitive and literacy predictors, and examining them both retrospectively and prospectively, we could assess how distinctive and stable the predictors of each deficit are. Predictors were assessed retrospectively at preschool, at the end of kindergarten, 1st, and 2nd grades. Group effects were significant at all test occasions, including those for preschool vocabulary (worse in poor oral comprehenders) and rapid naming (RAN) (worse in poor decoders). Preschool RAN and Vocabulary prospectively predicted grade 4 group membership (77–79% correct classification) within the selected samples. Reselection in preschool of at-risk poor decoder and poor oral comprehender subgroups based on these variables led to significant but relatively weak prediction of subtype membership at grade 4. Implications of the predictive stability of our results for identification and intervention of these important subgroups are discussed. PMID:23528975

RNA polymerase beta-subunit gene (rpoB) sequence analysis for the identification of Bacteroides spp.

PubMed

Ko, K S; Kuwahara, T; Haehwa, L; Yoon, Y-J; Kim, B-J; Lee, K-H; Ohnishi, Y; Kook, Y-H

2007-01-01

Partial rpoB sequences (317 bp) of 11 species of Bacteroides, two Porphyromonas spp. and two Prevotella spp. were compared to delineate the genetic relationships among Bacteroides and closely related anaerobic species. The high level of inter-species sequence dissimilarities (7.6-20.8%) allowed the various Bacteroides spp. to be distinguished. The position of the Bacteroides distasonis and Bacteriodes merdae cluster in the rpoB tree was different from the position in the 16S rRNA gene tree. Based on rpoB sequence similarity and clustering in the rpoB tree, it was possible to correctly re-identify 80 clinical isolates of Bacteroides. In addition to two subgroups, cfiA-negative (division I) and cfiA-positive (division II), of Bacteroides fragilis isolates, two distinct subgroups were also found among Bacteroides ovatus and Bacteroides thetaiotaomicron isolates. Bacteroides genus-specific rpoB PCR and B. fragilis species-specific rpoB PCR allowed Bacteroides spp. to be differentiated from Porphyromonas and Prevotella spp., and also allowed B. fragilis to be differentiated from other non-fragilisBacteroides spp. included in the present study.

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

PubMed

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 stages of the cancer experience. Earlier studies suggest that many patients recover from fatigue after treatment completion. Patients with cancer experience disturbance in their personal goals, which is related to poor psychological well-being. What does this study add? Developments of fatigue and goal disturbance differ between subgroups of patients with cancer but co-occur within these subgroups. About 30% of the patients experience severe fatigue after diagnosis, of which only few patients recover within 18 months post-diagnosis. Targeting goal disturbance might benefit patients with severe and ongoing symptoms. © 2017 The British Psychological Society.

Classification of Neuropsychiatric Symptoms Requiring Antipsychotic Treatment in Patients with Alzheimer's Disease: Analysis of the CATIE-AD Study.

PubMed

Nagata, Tomoyuki; Shinagawa, Shunichiro; Nakajima, Shinichiro; Plitman, Eric; Mihashi, Yukiko; Hayashi, Shogo; Mimura, Masaru; Nakayama, Kazuhiko

2016-01-01

The Neuropsychiatric Inventory (NPI) comprises 12 items, which were conventionally determined by psychopathological symptoms of patients with dementia. The clinical rating scales with structured questionnaires have been useful to evaluate neuropsychiatric symptoms (NPSs) of patients with dementia over the past twenty year. The aim of this study was to classify the conventional NPSs in patients with Alzheimer's disease (AD) requiring antipsychotic treatment for their NPSs into distinct clusters to simplify assessment of these numerous symptoms. Twelve items scores (product of severity and frequency of each symptom) in the NPI taken from the baseline visit were classified into subgroups by principle component analysis using data from 421 outpatients with AD enrolled in the Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer's Disease (CATIE-AD) Phase 1. Chi square tests were conducted to examine the co-occurrence of the subgroups. We found four distinct clusters: aggressiveness (agitation and irritabilities), apathy and eating problems (apathy and appetite/eating disturbance), psychosis (delusions and hallucinations), and emotion and disinhibition (depression, euphoria, and disinhibition). Anxiety, aberrant motor behavior, and sleep disturbance were not included by these clusters. Apathy and eating problems, and emotion and disinhibition co-occurred (p = 0.002), whereas aggressiveness and psychosis occurred independent of the other clusters. Four distinct category clusters were identified from NPSs in patients with AD requiring antipsychotic treatment. Future studies should investigate psychosocial backgrounds or risk factors of each distinct cluster, in addition to their longitudinal course over treatment intervention.

Spatial clustering of metal and metalloid mixtures in unregulated water sources on the Navajo Nation - Arizona, New Mexico, and Utah, USA.

PubMed

Hoover, Joseph H; Coker, Eric; Barney, Yolanda; Shuey, Chris; Lewis, Johnnye

2018-08-15

Contaminant mixtures are identified regularly in public and private drinking water supplies throughout the United States; however, the complex and often correlated nature of mixtures makes identification of relevant combinations challenging. This study employed a Bayesian clustering method to identify subgroups of water sources with similar metal and metalloid profiles. Additionally, a spatial scan statistic assessed spatial clustering of these subgroups and a human health metric was applied to investigate potential for human toxicity. These methods were applied to a dataset comprised of metal and metalloid measurements from unregulated water sources located on the Navajo Nation, in the southwest United States. Results indicated distinct subgroups of water sources with similar contaminant profiles and that some of these subgroups were spatially clustered. Several profiles had metal and metalloid concentrations that may have potential for human toxicity including arsenic, uranium, lead, manganese, and selenium. This approach may be useful for identifying mixtures in water sources, spatially evaluating the clusters, and help inform toxicological research investigating mixtures. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Age-Related Differences in Profiles of Mood-Change Trajectories

PubMed Central

Stanley, Jennifer Tehan; Isaacowitz, Derek M.

2010-01-01

As a group, older adults report positive affective lives. The extent to which there are subgroups of older adults whose moods are less positive, however, is unclear. The aim of the present study was to identify and characterize different subgroups of adults who exhibit distinct trajectories of mood-change across a relatively short time period. Seventy-nine young and 103 older adults continuously reported their moods while viewing emotional and neutral faces. Cluster analysis revealed four subgroups of mood-change trajectories. Both the most positive and the most negative subgroups included more older than younger adults (ps < .05), suggesting that not all older adults exhibit higher positive affect than young adults. Analyses of variance revealed that the most negative group exhibited slower processing speed, more state anxiety and neuroticism, and looked less at happy faces, than the other groups (ps < .05). The results are discussed from an adult developmental perspective, focusing on the increased variability of mood trajectories in the older adults and whether this is a reflection of adaptive functioning, or a potential harbinger of dysfunction. PMID:21171749

Distinct developmental profiles in typical speech acquisition

PubMed Central

Campbell, Thomas F.; Shriberg, Lawrence D.; Green, Jordan R.; Abdi, Hervé; Rusiewicz, Heather Leavy; Venkatesh, Lakshmi; Moore, Christopher A.

2012-01-01

Three- to five-year-old children produce speech that is characterized by a high level of variability within and across individuals. This variability, which is manifest in speech movements, acoustics, and overt behaviors, can be input to subgroup discovery methods to identify cohesive subgroups of speakers or to reveal distinct developmental pathways or profiles. This investigation characterized three distinct groups of typically developing children and provided normative benchmarks for speech development. These speech development profiles, identified among 63 typically developing preschool-aged speakers (ages 36–59 mo), were derived from the children's performance on multiple measures. These profiles were obtained by submitting to a k-means cluster analysis of 72 measures that composed three levels of speech analysis: behavioral (e.g., task accuracy, percentage of consonants correct), acoustic (e.g., syllable duration, syllable stress), and kinematic (e.g., variability of movements of the upper lip, lower lip, and jaw). Two of the discovered group profiles were distinguished by measures of variability but not by phonemic accuracy; the third group of children was characterized by their relatively low phonemic accuracy but not by an increase in measures of variability. Analyses revealed that of the original 72 measures, 8 key measures were sufficient to best distinguish the 3 profile groups. PMID:22357794

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

PubMed Central

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

Do animals and furniture items elicit different brain responses in human infants?

PubMed

Jeschonek, Susanna; Marinovic, Vesna; Hoehl, Stefanie; Elsner, Birgit; Pauen, Sabina

2010-11-01

One of the earliest categorical distinctions to be made by preverbal infants is the animate-inanimate distinction. To explore the neural basis for this distinction in 7-8-month-olds, an equal number of animal and furniture pictures was presented in an ERP-paradigm. The total of 118 pictures, all looking different from each other, were presented in a semi-randomized order for 1000ms each. Infants' brain responses to exemplars from both categories differed systematically regarding the negative central component (Nc: 400-600ms) at anterior channels. More specifically, the Nc was enhanced for animals in one subgroup of infants, and for furniture items in another subgroup of infants. Explorative analyses related to categorical priming further revealed category-specific differences in brain responses in the late time window (650-1550ms) at right frontal channels: Unprimed stimuli (preceded by a different-category item) elicited a more positive response as compared to primed stimuli (preceded by a same-category item). In sum, these findings suggest that the infant's brain discriminates exemplars from both global domains. Given the design of our task, we conclude that processes of category identification are more likely to account for our findings than processes of on-line category formation during the experimental session. Copyright © 2009 Elsevier B.V. All rights reserved.

Cross-species genomics matches driver mutations and cell compartments to model ependymoma

PubMed Central

Johnson, Robert A.; Wright, Karen D.; Poppleton, Helen; Mohankumar, Kumarasamypet M.; Finkelstein, David; Pounds, Stanley B.; Rand, Vikki; Leary, Sarah E.S.; White, Elsie; Eden, Christopher; Hogg, Twala; Northcott, Paul; Mack, Stephen; Neale, Geoffrey; Wang, Yong-Dong; Coyle, Beth; Atkinson, Jennifer; DeWire, Mariko; Kranenburg, Tanya A.; Gillespie, Yancey; Allen, Jeffrey C.; Merchant, Thomas; Boop, Fredrick A.; Sanford, Robert. A.; Gajjar, Amar; Ellison, David W.; Taylor, Michael D.; Grundy, Richard G.; Gilbertson, Richard J.

2010-01-01

Understanding the biology that underlies histologically similar but molecularly distinct subgroups of cancer has proven difficult since their defining genetic alterations are often numerous, and the cellular origins of most cancers remain unknown1–3. We sought to decipher this heterogeneity by integrating matched genetic alterations and candidate cells of origin to generate accurate disease models. First, we identified subgroups of human ependymoma, a form of neural tumor that arises throughout the central nervous system (CNS). Subgroup specific alterations included amplifications and homozygous deletions of genes not yet implicated in ependymoma. To select cellular compartments most likely to give rise to subgroups of ependymoma, we matched the transcriptomes of human tumors to those of mouse neural stem cells (NSCs), isolated from different regions of the CNS at different developmental stages, with an intact or deleted Ink4a/Arf locus. The transcriptome of human cerebral ependymomas with amplified EPHB2 and deleted INK4A/ARF matched only that of embryonic cerebral Ink4a/Arf−/− NSCs. Remarkably, activation of Ephb2 signaling in these, but not other NSCs, generated the first mouse model of ependymoma, which is highly penetrant and accurately models the histology and transcriptome of one subgroup of human cerebral tumor. Further comparative analysis of matched mouse and human tumors revealed selective deregulation in the expression and copy number of genes that control synaptogenesis, pinpointing disruption of this pathway as a critical event in the production of this ependymoma subgroup. Our data demonstrate the power of cross-species genomics to meticulously match subgroup specific driver mutations with cellular compartments to model and interrogate cancer subgroups. PMID:20639864

Carboplatin in BRCA1/2-mutated and triple-negative breast cancer BRCAness subgroups: the TNT Trial.

PubMed

Tutt, Andrew; Tovey, Holly; Cheang, Maggie Chon U; Kernaghan, Sarah; Kilburn, Lucy; Gazinska, Patrycja; Owen, Julie; Abraham, Jacinta; Barrett, Sophie; Barrett-Lee, Peter; Brown, Robert; Chan, Stephen; Dowsett, Mitchell; Flanagan, James M; Fox, Lisa; Grigoriadis, Anita; Gutin, Alexander; Harper-Wynne, Catherine; Hatton, Matthew Q; Hoadley, Katherine A; Parikh, Jyoti; Parker, Peter; Perou, Charles M; Roylance, Rebecca; Shah, Vandna; Shaw, Adam; Smith, Ian E; Timms, Kirsten M; Wardley, Andrew M; Wilson, Gregory; Gillett, Cheryl; Lanchbury, Jerry S; Ashworth, Alan; Rahman, Nazneen; Harries, Mark; Ellis, Paul; Pinder, Sarah E; Bliss, Judith M

2018-05-01

Germline mutations in BRCA1/2 predispose individuals to breast cancer (termed germline-mutated BRCA1/2 breast cancer, gBRCA-BC) by impairing homologous recombination (HR) and causing genomic instability. HR also repairs DNA lesions caused by platinum agents and PARP inhibitors. Triple-negative breast cancers (TNBCs) harbor subpopulations with BRCA1/2 mutations, hypothesized to be especially platinum-sensitive. Cancers in putative 'BRCAness' subgroups-tumors with BRCA1 methylation; low levels of BRCA1 mRNA (BRCA1 mRNA-low); or mutational signatures for HR deficiency and those with basal phenotypes-may also be sensitive to platinum. We assessed the efficacy of carboplatin and another mechanistically distinct therapy, docetaxel, in a phase 3 trial in subjects with unselected advanced TNBC. A prespecified protocol enabled biomarker-treatment interaction analyses in gBRCA-BC and BRCAness subgroups. The primary endpoint was objective response rate (ORR). In the unselected population (376 subjects; 188 carboplatin, 188 docetaxel), carboplatin was not more active than docetaxel (ORR, 31.4% versus 34.0%, respectively; P = 0.66). In contrast, in subjects with gBRCA-BC, carboplatin had double the ORR of docetaxel (68% versus 33%, respectively; biomarker, treatment interaction P = 0.01). Such benefit was not observed for subjects with BRCA1 methylation, BRCA1 mRNA-low tumors or a high score in a Myriad HRD assay. Significant interaction between treatment and the basal-like subtype was driven by high docetaxel response in the nonbasal subgroup. We conclude that patients with advanced TNBC benefit from characterization of BRCA1/2 mutations, but not BRCA1 methylation or Myriad HRD analyses, to inform choices on platinum-based chemotherapy. Additionally, gene expression analysis of basal-like cancers may also influence treatment selection.

Finding Groups in Gene Expression Data

PubMed Central

2005-01-01

The vast potential of the genomic insight offered by microarray technologies has led to their widespread use since they were introduced a decade ago. Application areas include gene function discovery, disease diagnosis, and inferring regulatory networks. Microarray experiments enable large-scale, high-throughput investigations of gene activity and have thus provided the data analyst with a distinctive, high-dimensional field of study. Many questions in this field relate to finding subgroups of data profiles which are very similar. A popular type of exploratory tool for finding subgroups is cluster analysis, and many different flavors of algorithms have been used and indeed tailored for microarray data. Cluster analysis, however, implies a partitioning of the entire data set, and this does not always match the objective. Sometimes pattern discovery or bump hunting tools are more appropriate. This paper reviews these various tools for finding interesting subgroups. PMID:16046827

A Simulation Study of Methods for Selecting Subgroup-Specific Doses in Phase I Trials

PubMed Central

Morita, Satoshi; Thall, Peter F.; Takeda, Kentaro

2016-01-01

Summary Patient heterogeneity may complicate dose-finding in phase I clinical trials if the dose-toxicity curves differ between subgroups. Conducting separate trials within subgroups may lead to infeasibly small sample sizes in subgroups having low prevalence. Alternatively, it is not obvious how to conduct a single trial while accounting for heterogeneity. To address this problem, we consider a generalization of the continual reassessment method (O’Quigley, et al., 1990) based on a hierarchical Bayesian dose-toxicity model that borrows strength between subgroups under the assumption that the subgroups are exchangeable. We evaluate a design using this model that includes subgroup-specific dose selection and safety rules. A simulation study is presented that includes comparison of this method to three alternative approaches, based on non-hierarchical models, that make different types of assumptions about within-subgroup dose-toxicity curves. The simulations show that the hierarchical model-based method is recommended in settings where the dose-toxicity curves are exchangeable between subgroups. We present practical guidelines for application, and provide computer programs for trial simulation and conduct. PMID:28111916

Intercontinental Spread of Asian-Origin H5N8 to North America through Beringia by Migratory Birds.

PubMed

Lee, Dong-Hun; Torchetti, Mia Kim; Winker, Kevin; Ip, Hon S; Song, Chang-Seon; Swayne, David E

2015-06-01

Phylogenetic network analysis and understanding of waterfowl migration patterns suggest that the Eurasian H5N8 clade 2.3.4.4 avian influenza virus emerged in late 2013 in China, spread in early 2014 to South Korea and Japan, and reached Siberia and Beringia by summer 2014 via migratory birds. Three genetically distinct subgroups emerged and subsequently spread along different flyways during fall 2014 into Europe, North America, and East Asia, respectively. All three subgroups reappeared in Japan, a wintering site for waterfowl from Eurasia and parts of North America. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Orientation Courses: Meeting the Needs of Different Student Populations.

ERIC Educational Resources Information Center

Higbee, Jeanne L.

A model that includes three distinct syllabi for orientation courses for different subgroups of the college or university freshman population is presented. Among the groups with special needs are underprepared students who may be motivated but need skill development, and underachieving students characterized by untapped potential. One means of…

Identification of Antigens of Pathogenic Free-Living Amoebae by Protein Immunoblotting with Rabbit Immune and Human Sera

DTIC Science & Technology

1994-09-01

development of immunoreactive bands was restricted to molecular masses of greater than 18.5 kDa for Naegleria , Hartmannella, and Vahlkampfia antigens. Two...detected between representative species of the three subgroups of Acanthamoeba. Naegleria antigen was likewise serologically distinct, as were

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

PubMed

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.

Machine-learned analysis of quantitative sensory testing responses to noxious cold stimulation in healthy subjects.

PubMed

Weyer-Menkhoff, I; Thrun, M C; Lötsch, J

2018-05-01

Pain in response to noxious cold has a complex molecular background probably involving several types of sensors. A recent observation has been the multimodal distribution of human cold pain thresholds. This study aimed at analysing reproducibility and stability of this observation and further exploration of data patterns supporting a complex background. Pain thresholds to noxious cold stimuli (range 32-0 °C, tonic: temperature decrease -1 °C/s, phasic: temperature decrease -8 °C/s) were acquired in 148 healthy volunteers. The probability density distribution was analysed using machine-learning derived methods implemented as Gaussian mixture modeling (GMM), emergent self-organizing maps and self-organizing swarms of data agents. The probability density function of pain responses was trimodal (mean thresholds at 25.9, 18.4 and 8.0 °C for tonic and 24.5, 18.1 and 7.5 °C for phasic stimuli). Subjects' association with Gaussian modes was consistent between both types of stimuli (weighted Cohen's κ = 0.91). Patterns emerging in self-organizing neuronal maps and swarms could be associated with different trends towards decreasing cold pain sensitivity in different Gaussian modes. On self-organizing maps, the third Gaussian mode emerged as particularly distinct. Thresholds at, roughly, 25 and 18 °C agree with known working temperatures of TRPM8 and TRPA1 ion channels, respectively, and hint at relative local dominance of either channel in respective subjects. Data patterns suggest involvement of further distinct mechanisms in cold pain perception at lower temperatures. Findings support data science approaches to identify biologically plausible hints at complex molecular mechanisms underlying human pain phenotypes. Sensitivity to pain is heterogeneous. Data-driven computational research approaches allow the identification of subgroups of subjects with a distinct pattern of sensitivity to cold stimuli. The subgroups are reproducible with different types of noxious cold stimuli. Subgroups show pattern that hints at distinct and inter-individually different types of the underlying molecular background. © 2018 European Pain Federation - EFIC®.

California parents' preferences and beliefs regarding school-based sex education policy.

PubMed

Constantine, Norman A; Jerman, Petra; Huang, Alice X

2007-09-01

Policy debates over the merits of abstinence-only versus comprehensive approaches to sex education are ongoing, despite well-documented public support for comprehensive sex education. Although parents are key stakeholders in the outcomes of these debates, their views have been less thoroughly considered. A random digit dial survey of 1,284 California parents was conducted in 2006. Parents were asked about their sex education policy preferences, the importance of teaching selected topics at different grade levels and reasons for their preferences. Cross-tabulations and odds ratios were used to assess regional and other subgroup differences. Overall, 89% of parents reported a preference for comprehensive sex education, and 11% for abstinence-only education. Support for comprehensive sex education was high in all regions (87-93%) and across all subgroup characteristics: race or ethnicity (79-92%), age (86-94%), education (84-93%), household income (87-92%), religious affiliation (86-91%), religious service attendance (69-96%) and ideological leaning (71-96%). Four types of reasons for preferences emerged: those focused on the consequences of actions, on the importance of providing complete information, on the inevitability of adolescents' engaging in sex and on religious or purity-based morality concerns. While 64% of abstinence-only supporters cited the last type (absolutist reasons), 94% of comprehensive sex education supporters cited one of the first three (pragmatic reasons). The high levels of support for comprehensive sex education across California's diverse regions and demographic subgroups suggest that such support may be generalizable to communities and school districts both in California and around the country. Furthermore, ideological differences might be less important to the sex education debates than the distinction between pragmatic and absolutist perspectives.

Gastric Activity and Gut Peptides in Patients With Functional Dyspepsia: Postprandial Distress Syndrome Versus Epigastric Pain Syndrome.

PubMed

Russo, Francesco; Chimienti, Guglielmina; Clemente, Caterina; Riezzo, Giuseppe; D'Attoma, Benedetta; Martulli, Manuela

2017-02-01

The goals of the study were to investigate in both postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS) the gastric electrical activity and the gastric emptying (GE) time together with the circulating concentrations of motilin, somatostatin, corticotrophin-releasing factor, and neurotensin, and to establish whether the genetic variability in the neurotensin system genes differs between these 2 categories of functional dyspepsia (FD). The current FD classification is based on symptoms and it has been proven not to be completely satisfying because of a high degree of symptom overlap between subgroups. Gastric electrical activity was evaluated by cutaneous electrogastrography: the GE time by C-octanoic acid breast test. Circulating concentrations of gut peptides were measured by a radioimmunoassay. NTS 479 A/G and NTSR1 rs6090453 SNPs were evaluated by PCR and endonuclease digestion. Fifty-four FD patients (50 female/4 male) were studied. Using a symptom questionnaire, 42 patients were classified as PDS and 12 as EPS, although an overlap between the symptom profiles of the 2 subgroups was recorded. The electrogastrographic parameters (the postprandial instability coefficient of dominant frequency, the dominant power, and the power ratio) were significantly different between the subgroups, whereas the GE time did not differ significantly. In addition, EPS was characterized by a different gut peptide profile compared with PDS. Finally, neurotensin polymorphism was shown to be associated with neurotensin levels. This evidence deserves further studies in consideration of an analgesic role of neurotensin. Analysis of gut peptide profiles could represent an interesting tool to enhance FD diagnosis and overcome limitations due to a distinction based solely on symptoms.

Biologically distinct subsets of nevi

PubMed Central

ROGERS, Tova; MARINO, Maria L.; RACITI, Patricia; JAIN, Manu; BUSAM, Klaus J.; MARCHETTI, Michael A.; MARGHOOB, Ashfaq A.

2017-01-01

Melanocytic nevi (MN) encompass a range of benign tumors with varying microscopic and macroscopic features. Their development is a multifactorial process under genetic and environmental influences. The clinical importance of MN lies in distinguishing them from melanoma and in recognizing their associations with melanoma risk and cancer syndromes. Historically, the distinction between the different types of MN, as well as between MN and melanoma, was based on clinical history, gross morphology, and histopathological features. While histopathology with clinical correlation remains the gold standard for differentiating and diagnosing melanocytic lesions, in some cases, this may not be possible. The use of dermoscopy has allowed for the assessment of subsurface skin structures and has contributed to the clinical evaluation and classification of MN. Genetic profiling, while still in its early stages, has the greatest potential to refine the classification of MN by clarifying their developmental processes, biological behaviors, and relationships to melanoma. Here we review the most salient clinical, dermoscopic, histopathological, and genetic features of different MN subgroups. PMID:27119653

Heterogeneous activation of the TGFβ pathway in glioblastomas identified by gene expression-based classification using TGFβ-responsive genes

PubMed Central

Xu, Xie L; Kapoun, Ann M

2009-01-01

Background TGFβ has emerged as an attractive target for the therapeutic intervention of glioblastomas. Aberrant TGFβ overproduction in glioblastoma and other high-grade gliomas has been reported, however, to date, none of these reports has systematically examined the components of TGFβ signaling to gain a comprehensive view of TGFβ activation in large cohorts of human glioma patients. Methods TGFβ activation in mammalian cells leads to a transcriptional program that typically affects 5–10% of the genes in the genome. To systematically examine the status of TGFβ activation in high-grade glial tumors, we compiled a gene set of transcriptional response to TGFβ stimulation from tissue culture and in vivo animal studies. These genes were used to examine the status of TGFβ activation in high-grade gliomas including a large cohort of glioblastomas. Unsupervised and supervised classification analysis was performed in two independent, publicly available glioma microarray datasets. Results Unsupervised and supervised classification using the TGFβ-responsive gene list in two independent glial tumor gene expression data sets revealed various levels of TGFβ activation in these tumors. Among glioblastomas, one of the most devastating human cancers, two subgroups were identified that showed distinct TGFβ activation patterns as measured from transcriptional responses. Approximately 62% of glioblastoma samples analyzed showed strong TGFβ activation, while the rest showed a weak TGFβ transcriptional response. Conclusion Our findings suggest heterogeneous TGFβ activation in glioblastomas, which may cause potential differences in responses to anti-TGFβ therapies in these two distinct subgroups of glioblastomas patients. PMID:19192267

Facial morphologies of an adult Egyptian population and an adult Houstonian white population compared using 3D imaging.

PubMed

Seager, Dennis Craig; Kau, Chung How; English, Jeryl D; Tawfik, Wael; Bussa, Harry I; Ahmed, Abou El Yazeed M

2009-09-01

To compare the facial morphologies of an adult Egyptian population with those of a Houstonian white population. The three-dimensional (3D) images were acquired via a commercially available stereophotogrammetric camera capture system. The 3dMDface System photographed 186 subjects from two population groups (Egypt and Houston). All of the participants from both population groups were between 18 and 30 years of age and had no apparent facial anomalies. All facial images were overlaid and superimposed, and a complex mathematical algorithm was performed to generate a composite facial average (one male and one female) for each subgroup (EGY-M: Egyptian male subjects; EGY-F: Egyptian female subjects; HOU-M: Houstonian male subjects; and HOU-F: Houstonian female subjects). The computer-generated facial averages were superimposed based on a previously validated superimposition method, and the facial differences were evaluated and quantified. Distinct facial differences were evident between the subgroups evaluated, involving various regions of the face including the slant of the forehead, and the nasal, malar, and labial regions. Overall, the mean facial differences between the Egyptian and Houstonian female subjects were 1.33 +/- 0.93 mm, while the differences in Egyptian and Houstonian male subjects were 2.32 +/- 2.23 mm. The range of differences for the female population pairings and the male population pairings were 14.34 mm and 13.71 mm, respectively. The average adult Egyptian and white Houstonian face possess distinct differences. Different populations and ethnicities have different facial features and averages.

Influence of alluvial cover and lithology on the adjustment characteristics of semi-alluvial bedrock channels

NASA Astrophysics Data System (ADS)

Ferguson, Sean P.; Rennie, Colin D.

2017-05-01

A growing body of research has focused on evaluating the adjustment characteristics of semi-alluvial channels containing proximate bedrock, mixed, and alluvial sections. Active orogens have been the focus of most empirical field-based studies with comparatively less focus on semi-alluvial bedrock channels located in other regions. In this study, we present an inventory of channel geometry data collected from semi-alluvial bedrock channels in Ontario and Québec, Canada, which are not subject to tectonic uplift. Data were sourced from a variety of physiographic settings, permitting evaluation of the influence of alluvial cover, lithology, and gradient on cross-sectional channel form. Our results show no substantial difference in channel width or scaling behaviour amongst bedrock, mixed, and alluvial channels included in our study, except for sedimentary bedrock channels virtually bare of alluvial cover that represent a uniquely wide, distinct subgroup. Channel gradient does not appear to exhibit any observable control on channel width amongst our study rivers, suggesting that sedimentary bedrock channels form a distinct subgroup because of lithology. Comparatively, the widths of our bedrock channels formed in igneous/metamorphic bedrock are comparable to the widths of mixed channels and alluvial channels for a given discharge and drainage area. Our findings also suggest that cross-sectional adjustment of sedimentary bedrock channels is achieved through lateral erosion of the channel banks and downward erosion of the channel bed, whereas cross-sectional adjustment of igneous/metamorphic bedrock is primarily achieved through downward erosion of the bed with limited lateral erosion of the banks.

Understanding Motivations to Participate in an Observational Research Study: Why do Patients Enroll?

PubMed Central

Soule, Michael C.; Beale, Eleanor E.; Suarez, Laura; Beach, Scott R.; Mastromauro, Carol A.; Celano, Christopher M; Moore, Shannon V; Huffman, Jeff C.

2016-01-01

By understanding common motivations for participating in observational research studies, clinicians may better understand the perceived benefits of research participation from their clients’ perspective. We enrolled 164 cardiac patients in a study about the effects of gratitude and optimism. Two weeks post-enrollment, participants completed a four-item questionnaire regarding motivations for study enrollment. Altruistic motivation ranked highest, while intellectual, health-related, and financial motivations rated lower. Four subgroups of participants emerged, each with distinct characteristics and different priorities for participating. These findings may help front-line clinicians to understand which motivations for participation apply to their clients who enroll in non-treatment-based research projects. PMID:26933943

Evolving molecular era of childhood medulloblastoma: time to revisit therapy.

PubMed

Khatua, Soumen

2016-01-01

Currently medulloblastoma is treated with a uniform therapeutic approach based on histopathology and clinico-radiological risk stratification, resulting in unpredictable treatment failure and relapses. Improved understanding of the biological, molecular and genetic make-up of these tumors now clearly identifies it as a compendium of four distinct subtypes (WNT, SHH, group 3 and 4). Advances in utilization of the genomic and epigenomic machinery have now delineated genetic aberrations and epigenetic perturbations in each subgroup as potential druggable targets. This has resulted in endeavors to profile targeted therapy. The challenge and future of medulloblastoma therapeutics will be to keep pace with the evolving novel biological insights and translating them into optimal targeted treatment regimens.

Emergence of a new human adenovirus type 4 (Ad4) genotype: identification of a novel inverted terminal repeated (ITR) sequence from majority of Ad4 isolates from US military recruits.

PubMed

Houng, Huo-Shu H; Clavio, Sarah; Graham, Katherine; Kuschner, Robert; Sun, Wellington; Russell, Kevin L; Binn, Leonard N

2006-04-01

Ad4 is the principal etiological agent of acute respiratory disease (ARD) in the US military. Discovery of the novel 208bp inverted terminal repeated (ITR) sequence from a recent Ad4 Jax78 field isolate was totally distinct from the analogous 116bp ITR of Ad4 prototype. To investigate the origin and distribution of the novel Ad4 ITR sequence from ARD infections. Direct sequencing of ligated Ad ITR termini. The new Ad4 ITR was highly homologous with the ITRs of human Ad subgroup B. The left post-ITR region of Ad4 Jax78 was found to be highly homologous to the corresponding region of subgroup B Ads: 81% for Ad11 and 98% for Ad3 and Ad7. The right post-ITR region of Ad4 Jax78 contained a truncated classic ITR of the Ad4 prototype. The Ad4 Jax78 ITR most likely evolved from Ad4 prototype by substituting the Ad4 prototype ITR with the subgroup B Ads ITR. The ITR-based PCR assays developed from this study can be used to distinguish the new Ad4 genotype from the classical Ad4 prototype. The new Ad4 genotype was first detected in 1976 from Georgia, USA, and is the main causative agent of ARD infections in US military population.

Maternal Prenatal Stress and Other Developmental Risk Factors for Adolescent Depression: Spotlight on Sex Differences.

PubMed

Maxwell, Seth D; Fineberg, Anna M; Drabick, Deborah A; Murphy, Shannon K; Ellman, Lauren M

2018-02-01

Maternal stress during pregnancy has been linked to premorbid abnormalities associated with depression (e.g., difficult temperament, cognitive deficits) in offspring. However, few studies have looked across developmental periods to examine maternal stress during pregnancy and offspring depression during adolescence and whether these associations differ by sex. The current study used data from 1711 mother-offspring dyads (offspring sex: 49.8% male) in a longitudinal birth cohort study. Maternal narratives collected during pregnancy were qualitatively coded for stress-related themes by independent raters. Latent class analysis (LCA) identified distinct subgroups of offspring based on exposure to maternal prenatal stress and other developmental factors from the prenatal, childhood, and adolescent periods that have been associated with depression and/or maternal prenatal stress. LCA identified subgroups that were compared to determine whether and to what extent they differed on adolescent depressive symptoms. LCA revealed a subgroup of "high-risk" individuals, characterized by maternal factors during pregnancy (higher ambivalence/negativity and lower positivity towards the pregnancy, higher levels of hassles, lower maternal education and higher maternal age at birth, higher pre-pregnancy BMI) and offspring developmental factors (decreased cognitive functioning during childhood and adolescence, lower perceived parental support during adolescence, and higher levels of maternal depression during adolescence). High-risk females exhibited elevated conduct symptoms and higher birth order, while high-risk males exhibited decreased internalizing symptoms and lower birth order. Both high-risk males and females reported elevated depressive symptoms during adolescence relative to their "low-risk" counterparts.

Expressed Emotion-Criticism and Risk of Depression Onset in Children

ERIC Educational Resources Information Center

Burkhouse, Katie L.; Uhrlass, Dorothy J.; Stone, Lindsey B.; Knopik, Valerie S.; Gibb, Brandon E.

2012-01-01

The primary goal of the current study was to examine the impact of maternal criticism (expressed emotion-criticism; EE-Crit) on the prospective development of depressive episodes in children. In addition to examining baseline levels of EE-Crit, we also sought to determine whether distinct subgroups (latent classes) of mothers could be identified…

Autism and Pitch Processing Splinter Skills: A Group and Subgroup Analysis

ERIC Educational Resources Information Center

Heaton, Pamela; Williams, Kerry; Cummins, Omar; Happe, Francesca

2008-01-01

Autism is characterized by an uneven profile of cognitive abilities and population studies show that approximately 10 percent of diagnosed individuals possess a skill that is significantly better than would be predicted by global IQ. Recent evidence suggests that individuals with autism who possess special skills may represent a distinct genetic…

The Possible Role of the Kynurenine Pathway in Adolescent Depression with Melancholic Features

ERIC Educational Resources Information Center

Gabbay, Vilma; Klein, Rachel G.; Katz, Yisrael; Mendoza, Sandra; Guttman, Leah E.; Alonso, Carmen M.; Babb, James S.; Hirsch, Glenn S.; Liebes, Leonard

2010-01-01

Background: Although adolescent major depressive disorder (MDD) is acknowledged to be a heterogeneous disorder, no studies have reported on biological correlates of its clinical subgroups. This study addresses this issue by examining whether adolescent MDD with and without melancholic features (M-MDD and NonM-MDD) have distinct biological features…

The Transcription Factor Orthodenticle Homeobox 2 Influences Axonal Projections and Vulnerability of Midbrain Dopaminergic Neurons

ERIC Educational Resources Information Center

Chung, Chee Yeun; Licznerski, Pawel; Alavian, Kambiz N.; Simeone, Antonio; Lin, Zhicheng; Martin, Eden; Vance, Jeffery; Isacson, Ole

2010-01-01

Two adjacent groups of midbrain dopaminergic neurons, A9 (substantia nigra pars compacta) and A10 (ventral tegmental area), have distinct projections and exhibit differential vulnerability in Parkinson's disease. Little is known about transcription factors that influence midbrain dopaminergic subgroup phenotypes or their potential role in disease.…

The Latent Classes of Subclinical ADHD Symptoms: Convergences of Multiple Informant Reports

ERIC Educational Resources Information Center

Kobor, Andrea; Takacs, Adam; Urban, Robert; Csepe, Valeria

2012-01-01

The purpose of the present study was to conduct latent class analysis on the Hyperactivity scale of the Strengths and Difficulties Questionnaire in order to identify distinct subgroups of subclinical ADHD in a multi-informant framework. We hypothesized a similar structure between teachers and parents, and differences in symptom severity across…

Reading and Spelling in Adults: Are There Lexical and Sub-Lexical Subtypes?

ERIC Educational Resources Information Center

Burt, Jennifer S.; Heffernan, Maree E.

2012-01-01

The dual-route model of reading proposes distinct lexical and sub-lexical procedures for word reading and spelling. Lexically reliant and sub-lexically reliant reader subgroups were selected from 78 university students on the basis of their performance on lexical (orthographic) and sub-lexical (phonological) choice tests, and on irregular and…

Subgroup Achievement and Gap Trends: New Hampshire

ERIC Educational Resources Information Center

Center on Education Policy, 2009

2009-01-01

This year the Center on Education Policy analyzed data on the achievement of different groups of students in two distinct ways. First, it looked at grade 4 test results to determine whether the performance of various groups improved at three achievement levels--basic and above, proficient and above, and advanced. Second, it looked at gaps between…

Ethical Challenges of Military Social Workers Serving in a Combat Zone

ERIC Educational Resources Information Center

Simmons, Catherine A.; Rycraft, Joan R.

2010-01-01

Often faced with ethical challenges that may appear extraordinary, military social workers comprise a distinctive subgroup of the social work profession. From the unique paradigms in which they practice their craft, obvious questions about how military social workers address the ethical challenges inherent to their wartime mission arise. Using a…

Common and distinct neural targets of treatment: changing brain function in substance addiction.

PubMed

Konova, Anna B; Moeller, Scott J; Goldstein, Rita Z

2013-12-01

Neuroimaging offers an opportunity to examine the neurobiological effects of therapeutic interventions for human drug addiction. Using activation likelihood estimation, the aim of the current meta-analysis was to quantitatively summarize functional neuroimaging studies of pharmacological and cognitive-based interventions for drug addiction, with an emphasis on their common and distinct neural targets. More exploratory analyses also contrasted subgroups of studies based on specific study and sample characteristics. The ventral striatum, a region implicated in reward, motivation, and craving, and the inferior frontal gyrus and orbitofrontal cortex, regions involved in inhibitory control and goal-directed behavior, were identified as common targets of pharmacological and cognitive-based interventions; these regions were observed when the analysis was limited to only studies that used established or efficacious interventions, and across imaging paradigms and types of addictions. Consistent with theoretical models, cognitive-based interventions were additionally more likely to activate the anterior cingulate cortex, middle frontal gyrus, and precuneus, implicated in self-referential processing, cognitive control, and attention. These results suggest that therapeutic interventions for addiction may target the brain structures that are altered across addictions and identify potential neurobiological mechanisms by which the tandem use of pharmacological and cognitive-based interventions may yield synergistic or complementary effects. These findings could inform the selection of novel functional targets in future treatment development for this difficult-to-treat disorder. Copyright © 2013 Elsevier Ltd. All rights reserved.

Common and distinct neural targets of treatment: changing brain function in substance addiction

PubMed Central

Konova, Anna B.; Moeller, Scott J.; Goldstein, Rita Z.

2013-01-01

Neuroimaging offers an opportunity to examine the neurobiological effects of therapeutic interventions for human drug addiction. Using activation likelihood estimation, the aim of the current meta-analysis was to quantitatively summarize functional neuroimaging studies of pharmacological and cognitive-based interventions for drug addiction, with an emphasis on their common and distinct neural targets. More exploratory analyses also contrasted subgroups of studies based on specific study and sample characteristics. The ventral striatum, a region implicated in reward, motivation, and craving, and the inferior frontal gyrus and orbitofrontal cortex, regions involved in inhibitory control goal-directed behavior, were identified as common targets of pharmacological and cognitive-based interventions; these regions were observed when the analysis was limited to only studies that used established or efficacious interventions, and across imaging paradigms and types of addictions. Consistent with theoretical models, cognitive-based interventions were additionally more likely to activate the anterior cingulate cortex, middle frontal gyrus, and precuneus, implicated in self-referential processing, cognitive control, and attention. These results suggest that therapeutic interventions for addiction may target the brain structures that are altered across addictions and identify potential neurobiological mechanisms by which the tandem use of pharmacological and cognitive-based interventions may yield synergistic or complementary effects. These findings could inform the selection of novel functional targets in future treatment development for this difficult-to-treat disorder. PMID:24140399

Differential Distributions of Synechococcus Subgroups Across the California Current System

PubMed Central

Paerl, Ryan W.; Johnson, Kenneth S.; Welsh, Rory M.; Worden, Alexandra Z.; Chavez, Francisco P.; Zehr, Jonathan P.

2011-01-01

Synechococcus is an abundant marine cyanobacterial genus composed of different populations that vary physiologically. Synechococcus narB gene sequences (encoding for nitrate reductase in cyanobacteria) obtained previously from isolates and the environment (e.g., North Pacific Gyre Station ALOHA, Hawaii or Monterey Bay, CA, USA) were used to develop quantitative PCR (qPCR) assays. These qPCR assays were used to quantify populations from specific narB phylogenetic clades across the California Current System (CCS), a region composed of dynamic zones between a coastal-upwelling zone and the oligotrophic Pacific Ocean. Targeted populations (narB subgroups) had different biogeographic patterns across the CCS, which appear to be driven by environmental conditions. Subgroups C_C1, D_C1, and D_C2 were abundant in coastal-upwelling to coastal-transition zone waters with relatively high to intermediate ammonium, nitrate, and chl. a concentrations. Subgroups A_C1 and F_C1 were most abundant in coastal-transition zone waters with intermediate nutrient concentrations. E_O1 and G_O1 were most abundant at different depths of oligotrophic open-ocean waters (either in the upper mixed layer or just below). E_O1, A_C1, and F_C1 distributions differed from other narB subgroups and likely possess unique ecologies enabling them to be most abundant in waters between coastal and open-ocean waters. Different CCS zones possessed distinct Synechococcus communities. Core California current water possessed low numbers of narB subgroups relative to counted Synechococcus cells, and coastal-transition waters contained high abundances of Synechococcus cells and total number of narB subgroups. The presented biogeographic data provides insight on the distributions and ecologies of Synechococcus present in an eastern boundary current system. PMID:21833315

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

PubMed

Lee, Joseph J; Rubin, Donald B

2015-10-30

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

Agreement Between Deoxyribonucleic Acid Base Composition and Taxometric Classification of Gram-Positive Cocci1

PubMed Central

Silvestri, L. G.; Hill, L. R.

1965-01-01

Silvestri, L. G. (Università Statale, Milan, Italy), and L. R. Hill. Agreement between deoxyribonucleic acid base composition and taxometric classification of gram-positive cocci. J. Bacteriol. 90:136–140. 1965.—It had been previously proposed, from taxometric analyses, that gram-positive, catalase-positive cocci be divided into two subgroups. Thirteen strains, representative of both subgroups, were examined for deoxyribonucleic acid (DNA) base composition, determined from melting temperatures. Per cent GC (guanine + cytosine/total bases) values fell into two groups: 30.8 to 36.5% GC and 69 to 75% GC. Strains with low per cent GC values belonged to the Staphylococcus aureus–S. saprophyticus–S. lactis taxometric subgroups, and those with high per cent GC values belonged to the S. roseus–S. afermentans subgroup. The hypothetical nature of any classification is emphasized, and, in the present work, the hypothesis derived from taxometric analyses of division into two subgroups is confirmed by the study of DNA base ratios. The two subgroups correspond, respectively, to the genera Staphylococcus and Micrococcus. PMID:16562008

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

PubMed

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.

The impact of ethnicity, family income, and parental education on children's health and use of health services.

PubMed Central

Flores, G; Bauchner, H; Feinstein, A R; Nguyen, U S

1999-01-01

OBJECTIVES: This study characterized ethnic disparities for children in demographics, health status, and use of services; explored whether ethnic subgroups (Puerto Rican, Cuban, and Mexican) have additional distinctive differences; and determined whether disparities are explained by differences in family income and parental education. METHODS: Bivariate and multivariate analyses of data on 99,268 children from the 1989-91 National Health Interview Surveys were conducted. RESULTS: Native American, Black, and Hispanic children are poorest (35%, 41% below poverty level vs 10% of Whites), least healthy (66%-74% in excellent or very good health vs 85% of Whites), and have the least well educated parents. Compared with Whites, non-White children average fewer doctor visits and are more likely to have excessive intervals between visits. Hispanic subgroup differences in demographics, health, and use of services equal or surpass differences among major ethnic groups. In multivariate analyses, almost all ethnic group disparities persisted after adjustment for family income, parental education, and other relevant covariates. CONCLUSIONS: Major ethnic groups and subgroups of children differ strikingly in demographics, health, and use of services; subgroup differences are easily overlooked; and most disparities persist even after adjustment for family income and parental education. PMID:10394317

Understanding Xeroderma Pigmentosum Complementation Groups Using Gene Expression Profiling after UV-Light Exposure.

PubMed

Bowden, Nikola A; Beveridge, Natalie J; Ashton, Katie A; Baines, Katherine J; Scott, Rodney J

2015-07-14

Children with the recessive genetic disorder Xeroderma Pigmentosum (XP) have extreme sensitivity to UV-light, a 10,000-fold increase in skin cancers from age 2 and rarely live beyond 30 years. There are seven genetic subgroups of XP, which are all resultant of pathogenic mutations in genes in the nucleotide excision repair (NER) pathway and a XP variant resultant of a mutation in translesion synthesis, POLH. The clinical symptoms and severity of the disease is varied across the subgroups, which does not correlate with the functional position of the affected protein in the NER pathway. The aim of this study was to further understand the biology of XP subgroups, particularly those that manifest with neurological symptoms. Whole genome gene expression profiling of fibroblasts from each XP complementation group was assessed before and after UV-light exposure. The biological pathways with altered gene expression after UV-light exposure were distinct for each subtype and contained oncogenic related functions such as perturbation of cell cycle, apoptosis, proliferation and differentiation. Patients from the subgroups XP-B and XP-F were the only subgroups to have transcripts associated with neuronal activity altered after UV-light exposure. This study will assist in furthering our understanding of the different subtypes of XP which will lead to better diagnosis, treatment and management of the disease.

Understanding Xeroderma Pigmentosum Complementation Groups Using Gene Expression Profiling after UV-Light Exposure

PubMed Central

Bowden, Nikola A.; Beveridge, Natalie J.; Ashton, Katie A.; Baines, Katherine J.; Scott, Rodney J.

2015-01-01

Children with the recessive genetic disorder Xeroderma Pigmentosum (XP) have extreme sensitivity to UV-light, a 10,000-fold increase in skin cancers from age 2 and rarely live beyond 30 years. There are seven genetic subgroups of XP, which are all resultant of pathogenic mutations in genes in the nucleotide excision repair (NER) pathway and a XP variant resultant of a mutation in translesion synthesis, POLH. The clinical symptoms and severity of the disease is varied across the subgroups, which does not correlate with the functional position of the affected protein in the NER pathway. The aim of this study was to further understand the biology of XP subgroups, particularly those that manifest with neurological symptoms. Whole genome gene expression profiling of fibroblasts from each XP complementation group was assessed before and after UV-light exposure. The biological pathways with altered gene expression after UV-light exposure were distinct for each subtype and contained oncogenic related functions such as perturbation of cell cycle, apoptosis, proliferation and differentiation. Patients from the subgroups XP-B and XP-F were the only subgroups to have transcripts associated with neuronal activity altered after UV-light exposure. This study will assist in furthering our understanding of the different subtypes of XP which will lead to better diagnosis, treatment and management of the disease. PMID:26184184

Gender differences in legal outcomes of filicide in Austria and Finland.

PubMed

Amon, S; Putkonen, H; Weizmann-Henelius, G; Fernandez Arias, P; Klier, C M

2018-06-01

Female offenders of filicide have been found to receive more lenient legal handling than male offenders. We aimed to discover these possible gender differences in the legal outcome of filicide cases. This was a binational register-based study covering all filicide offenders in Austria and Finland 1995-2005. We examined the legal outcomes of the crimes of all living offenders (64 mothers and 26 fathers). Mothers received a conviction of murder and life imprisonment less often than fathers. Within psychotic and personality-disordered offenders, infanticides, and offenders convicted for life, gender differences were less evident. Even though there seems to be some gender differences within the legal outcomes of filicide, ruling seemed more consistent than expected within distinct subgroups of offenders. Gender-based assumptions should not hinder equal and just handling of filicide cases.

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

PubMed Central

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, as much as possible that well-defined clinical and biological subgroups of ME and CFS patients are investigated in more detail, and that patients are monitored before, during and after interventions with objective measures and biomarkers. PMID:24734022

Methylation-based classification of benign and malignant peripheral nerve sheath tumors.

PubMed

Röhrich, Manuel; Koelsche, Christian; Schrimpf, Daniel; Capper, David; Sahm, Felix; Kratz, Annekathrin; Reuss, Jana; Hovestadt, Volker; Jones, David T W; Bewerunge-Hudler, Melanie; Becker, Albert; Weis, Joachim; Mawrin, Christian; Mittelbronn, Michel; Perry, Arie; Mautner, Victor-Felix; Mechtersheimer, Gunhild; Hartmann, Christian; Okuducu, Ali Fuat; Arp, Mirko; Seiz-Rosenhagen, Marcel; Hänggi, Daniel; Heim, Stefanie; Paulus, Werner; Schittenhelm, Jens; Ahmadi, Rezvan; Herold-Mende, Christel; Unterberg, Andreas; Pfister, Stefan M; von Deimling, Andreas; Reuss, David E

2016-06-01

The vast majority of peripheral nerve sheath tumors derive from the Schwann cell lineage and comprise diverse histological entities ranging from benign schwannomas and neurofibromas to high-grade malignant peripheral nerve sheath tumors (MPNST), each with several variants. There is increasing evidence for methylation profiling being able to delineate biologically relevant tumor groups even within the same cellular lineage. Therefore, we used DNA methylation arrays for methylome- and chromosomal profile-based characterization of 171 peripheral nerve sheath tumors. We analyzed 28 conventional high-grade MPNST, three malignant Triton tumors, six low-grade MPNST, four epithelioid MPNST, 33 neurofibromas (15 dermal, 8 intraneural, 10 plexiform), six atypical neurofibromas, 43 schwannomas (including 5 NF2 and 5 schwannomatosis associated cases), 11 cellular schwannomas, 10 melanotic schwannomas, 7 neurofibroma/schwannoma hybrid tumors, 10 nerve sheath myxomas and 10 ganglioneuromas. Schwannomas formed different epigenomic subgroups including a vestibular schwannoma subgroup. Cellular schwannomas were not distinct from conventional schwannomas. Nerve sheath myxomas and neurofibroma/schwannoma hybrid tumors were most similar to schwannomas. Dermal, intraneural and plexiform neurofibromas as well as ganglioneuromas all showed distinct methylation profiles. Atypical neurofibromas and low-grade MPNST were indistinguishable with a common methylation profile and frequent losses of CDKN2A. Epigenomic analysis finds two groups of conventional high-grade MPNST sharing a frequent loss of neurofibromin. The larger of the two groups shows an additional loss of trimethylation of histone H3 at lysine 27 (H3K27me3). The smaller one retains H3K27me3 and is found in spinal locations. Sporadic MPNST with retained neurofibromin expression did not form an epigenetic group and most cases could be reclassified as cellular schwannomas or soft tissue sarcomas. Widespread immunohistochemical loss of H3K27me3 was exclusively seen in MPNST of the main methylation cluster, which defines it as an additional useful marker for the differentiation of cellular schwannoma and MPNST.

Lineage diversification of pigeon paramyxovirus effect re-emergence potential in chickens.

PubMed

Chong, Yee Ling; Kim, Oekyung; Poss, Mary

2014-08-01

Genotype VI-paramyxovirus (GVI-PMV1) is a major cause of epidemic Newcastle-like disease in Columbiformes. This genotype of avian paramyxovirus type 1 has diversified rapidly since its introduction into the US in 1982 resulting in two extant lineages, which have different population growth properties. Although some GVI-PMV1s replicate poorly in chickens, it is possible that variants with different replicative or pathogenic potential in chickens exist among the genetically-diverse GVI-PMV1s strains. To determine if variants of Columbiform GVI-PMV1 with different phylogenetic affiliations have distinct phenotypic properties in chickens, we investigated the replicative properties of 10 naturally circulating pigeon-derived isolates representing four subgroups of GVI-PMV1 in primary chicken lung epithelial cells and in chicken embryos. Our data demonstrate that GVI-PMV1 variants have different infection phenotypes in their chicken source host and that properties reflect subgroup affiliation. These subgroup replicative properties are consistent with observed dynamics of viral population growth. Copyright © 2014 Elsevier Inc. All rights reserved.

Neural Biomarkers for Dyslexia, ADHD, and ADD in the Auditory Cortex of Children.

PubMed

Serrallach, Bettina; Groß, Christine; Bernhofs, Valdis; Engelmann, Dorte; Benner, Jan; Gündert, Nadine; Blatow, Maria; Wengenroth, Martina; Seitz, Angelika; Brunner, Monika; Seither, Stefan; Parncutt, Richard; Schneider, Peter; Seither-Preisler, Annemarie

2016-01-01

Dyslexia, attention deficit hyperactivity disorder (ADHD), and attention deficit disorder (ADD) show distinct clinical profiles that may include auditory and language-related impairments. Currently, an objective brain-based diagnosis of these developmental disorders is still unavailable. We investigated the neuro-auditory systems of dyslexic, ADHD, ADD, and age-matched control children (N = 147) using neuroimaging, magnetencephalography and psychoacoustics. All disorder subgroups exhibited an oversized left planum temporale and an abnormal interhemispheric asynchrony (10-40 ms) of the primary auditory evoked P1-response. Considering right auditory cortex morphology, bilateral P1 source waveform shapes, and auditory performance, the three disorder subgroups could be reliably differentiated with outstanding accuracies of 89-98%. We therefore for the first time provide differential biomarkers for a brain-based diagnosis of dyslexia, ADHD, and ADD. The method allowed not only allowed for clear discrimination between two subtypes of attentional disorders (ADHD and ADD), a topic controversially discussed for decades in the scientific community, but also revealed the potential for objectively identifying comorbid cases. Noteworthy, in children playing a musical instrument, after three and a half years of training the observed interhemispheric asynchronies were reduced by about 2/3, thus suggesting a strong beneficial influence of music experience on brain development. These findings might have far-reaching implications for both research and practice and enable a profound understanding of the brain-related etiology, diagnosis, and musically based therapy of common auditory-related developmental disorders and learning disabilities.

Neural Biomarkers for Dyslexia, ADHD, and ADD in the Auditory Cortex of Children

PubMed Central

Serrallach, Bettina; Groß, Christine; Bernhofs, Valdis; Engelmann, Dorte; Benner, Jan; Gündert, Nadine; Blatow, Maria; Wengenroth, Martina; Seitz, Angelika; Brunner, Monika; Seither, Stefan; Parncutt, Richard; Schneider, Peter; Seither-Preisler, Annemarie

2016-01-01

Dyslexia, attention deficit hyperactivity disorder (ADHD), and attention deficit disorder (ADD) show distinct clinical profiles that may include auditory and language-related impairments. Currently, an objective brain-based diagnosis of these developmental disorders is still unavailable. We investigated the neuro-auditory systems of dyslexic, ADHD, ADD, and age-matched control children (N = 147) using neuroimaging, magnetencephalography and psychoacoustics. All disorder subgroups exhibited an oversized left planum temporale and an abnormal interhemispheric asynchrony (10–40 ms) of the primary auditory evoked P1-response. Considering right auditory cortex morphology, bilateral P1 source waveform shapes, and auditory performance, the three disorder subgroups could be reliably differentiated with outstanding accuracies of 89–98%. We therefore for the first time provide differential biomarkers for a brain-based diagnosis of dyslexia, ADHD, and ADD. The method allowed not only allowed for clear discrimination between two subtypes of attentional disorders (ADHD and ADD), a topic controversially discussed for decades in the scientific community, but also revealed the potential for objectively identifying comorbid cases. Noteworthy, in children playing a musical instrument, after three and a half years of training the observed interhemispheric asynchronies were reduced by about 2/3, thus suggesting a strong beneficial influence of music experience on brain development. These findings might have far-reaching implications for both research and practice and enable a profound understanding of the brain-related etiology, diagnosis, and musically based therapy of common auditory-related developmental disorders and learning disabilities. PMID:27471442

Transcription Factors of Lotus: Regulation of Isoflavonoid Biosynthesis Requires Coordinated Changes in Transcription Factor Activity1[W][OA

PubMed Central

Shelton, Dale; Stranne, Maria; Mikkelsen, Lisbeth; Pakseresht, Nima; Welham, Tracey; Hiraka, Hideki; Tabata, Satoshi; Sato, Shusei; Paquette, Suzanne; Wang, Trevor L.; Martin, Cathie; Bailey, Paul

2012-01-01

Isoflavonoids are a class of phenylpropanoids made by legumes, and consumption of dietary isoflavonoids confers benefits to human health. Our aim is to understand the regulation of isoflavonoid biosynthesis. Many studies have shown the importance of transcription factors in regulating the transcription of one or more genes encoding enzymes in phenylpropanoid metabolism. In this study, we coupled bioinformatics and coexpression analysis to identify candidate genes encoding transcription factors involved in regulating isoflavonoid biosynthesis in Lotus (Lotus japonicus). Genes encoding proteins belonging to 39 of the main transcription factor families were examined by microarray analysis of RNA from leaf tissue that had been elicited with glutathione. Phylogenetic analyses of each transcription factor family were used to identify subgroups of proteins that were specific to L. japonicus or closely related to known regulators of the phenylpropanoid pathway in other species. R2R3MYB subgroup 2 genes showed increased expression after treatment with glutathione. One member of this subgroup, LjMYB14, was constitutively overexpressed in L. japonicus and induced the expression of at least 12 genes that encoded enzymes in the general phenylpropanoid and isoflavonoid pathways. A distinct set of six R2R3MYB subgroup 2-like genes was identified. We suggest that these subgroup 2 sister group proteins and those belonging to the main subgroup 2 have roles in inducing isoflavonoid biosynthesis. The induction of isoflavonoid production in L. japonicus also involves the coordinated down-regulation of competing biosynthetic pathways by changing the expression of other transcription factors. PMID:22529285

Novel clustering of items from the Autism Diagnostic Interview-Revised to define phenotypes within autism spectrum disorders

PubMed Central

Hu, Valerie W.; Steinberg, Mara E.

2009-01-01

Heterogeneity in phenotypic presentation of ASD has been cited as one explanation for the difficulty in pinpointing specific genes involved in autism. Recent studies have attempted to reduce the “noise” in genetic and other biological data by reducing the phenotypic heterogeneity of the sample population. The current study employs multiple clustering algorithms on 123 item scores from the Autism Diagnostic Interview-Revised (ADI-R) diagnostic instrument of nearly 2000 autistic individuals to identify subgroups of autistic probands with clinically relevant behavioral phenotypes in order to isolate more homogeneous groups of subjects for gene expression analyses. Our combined cluster analyses suggest optimal division of the autistic probands into 4 phenotypic clusters based on similarity of symptom severity across the 123 selected item scores. One cluster is characterized by severe language deficits, while another exhibits milder symptoms across the domains. A third group possesses a higher frequency of savant skills while the fourth group exhibited intermediate severity across all domains. Grouping autistic individuals by multivariate cluster analysis of ADI-R scores reveals meaningful phenotypes of subgroups within the autistic spectrum which we show, in a related (accompanying) study, to be associated with distinct gene expression profiles. PMID:19455643

Introduction to the CEA family: structure, function and secretion.

PubMed

Von Kleist, S

1992-01-01

Due to the phenomenal progress in the field of tumor immunology that took place during the last twenty years, we dispose today of highly specific and sensitive techniques and reagents like monoclonal antibodies (MAbs). In this context the discovery in human carcinomas of tumor-associated antigens, such as CEA, was of primary importance, especially since the latter was found to have clinical relevance as a tumor marker. Based on animal models, a new in vivo technology for the detection of tumors and metastases was developed in recent years, that uses anti-CEA MAbs, or fragments of them, coupled to radio-isotopes. This technique, called radio-immunodetection (RAID), also paved the way for immunotherapeutic procedures, where again CEA served as the target-antigen. This new technique holds great promise, provided the epitope-specificity of the MAbs is well-controlled: it has been shown that CEA belongs to a large gene-family of at least 22 members, which can be subdivided into two subgroups (i.e., the CEA- and the PSG-subgroup) and which in turn belongs to the immunoglobulin-supergene family. Great structural similarities render the distinction of the various cross-reactive molecules by immunological means rather difficult.

The Peculiar Characteristics of Fish Type I Interferons

PubMed Central

Boudinot, Pierre; Langevin, Christelle; Secombes, Christopher J.; Levraud, Jean-Pierre

2016-01-01

Antiviral type I interferons (IFNs) have been discovered in fish. Genomic studies revealed their considerable number in many species; some genes encode secreted and non-secreted isoforms. Based on cysteine motifs, fish type I IFNs fall in two subgroups, which use two different receptors. Mammalian type I IFN genes are intronless while type III have introns; in fish, all have introns, but structurally, both subgroups belong to type I. Type I IFNs likely appeared early in vertebrates as intron containing genes, and evolved in parallel in tetrapods and fishes. The diversity of their repertoires in fish and mammals is likely a convergent feature, selected as a response to the variety of viral strategies. Several alternative nomenclatures have been established for different taxonomic fish groups, calling for a unified system. The specific functions of each type I gene remains poorly understood, as well as their interactions in antiviral responses. However, distinct induction pathways, kinetics of response, and tissue specificity indicate that fish type I likely are highly specialized, especially in groups where they are numerous such as salmonids or cyprinids. Unravelling their functional integration constitutes the next challenge to understand how these cytokines evolved to orchestrate antiviral innate immunity in vertebrates. PMID:27827855

Psychological Features and Their Relationship to Movement-Based Subgroups in People Living With Low Back Pain.

PubMed

Karayannis, Nicholas V; Jull, Gwendolen A; Nicholas, Michael K; Hodges, Paul W

2018-01-01

To determine the distribution of higher psychological risk features within movement-based subgroups for people with low back pain (LBP). Cross-sectional observational study. Participants were recruited from physiotherapy clinics and community advertisements. Measures were collected at a university outpatient-based physiotherapy clinic. People (N=102) seeking treatment for LBP. Participants were subgrouped according to 3 classification schemes: Mechanical Diagnosis and Treatment (MDT), Treatment-Based Classification (TBC), and O'Sullivan Classification (OSC). Questionnaires were used to categorize low-, medium-, and high-risk features based on depression, anxiety, and stress (Depression, Anxiety, and Stress Scale-21 Items); fear avoidance (Fear-Avoidance Beliefs Questionnaire); catastrophizing and coping (Pain-Related Self-Symptoms Scale); and self-efficacy (Pain Self-Efficacy Questionnaire). Psychological risk profiles were compared between movement-based subgroups within each scheme. Scores across all questionnaires revealed that most patients had low psychological risk profiles, but there were instances of higher (range, 1%-25%) risk profiles within questionnaire components. The small proportion of individuals with higher psychological risk scores were distributed between subgroups across TBC, MDT, and OSC schemes. Movement-based subgrouping alone cannot inform on individuals with higher psychological risk features. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Occasional Smoking in Adolescence: Constructing an Identity of Control

ERIC Educational Resources Information Center

Scheffels, Janne; Lund, Karl Erik

2005-01-01

This study discusses whether adolescent occasional smokers form a distinct subgroup in comparison with daily smokers, in terms of smoking motivation, confidence in ability to quit and social and cultural characteristics. In a sample of 2484 adolescents aged 16-19, 22 per cent (n = 552) were daily smokers and 20 per cent (n = 495) were occasional…

Evidence for Distinct Cognitive Profiles in Autism Spectrum Disorders and Specific Language Impairment

ERIC Educational Resources Information Center

Taylor, Lauren J.; Maybery, Murray T.; Grayndler, Luke; Whitehouse, Andrew J. O.

2014-01-01

Findings that a subgroup of children with an autism spectrum disorder (ASD) have linguistic capabilities that resemble specific language impairment (SLI) have led some authors to hypothesise that ASD and SLI have a shared aetiology. While considerable research has explored overlap in the language phenotypes of the two conditions, little research…

Distinct Subgroups of Former Foster Youth during Young Adulthood: Implications for Policy and Practice

ERIC Educational Resources Information Center

Courtney, Mark E.; Hook, Jennifer L.; Lee, JoAnn S.

2012-01-01

The Fostering Connections to Success and Increasing Adoptions Act of 2008 ("Fostering Connections Act") fundamentally changed the nature of federal support for young people in state care by extending entitlement funding under Title IV-E of the Social Security Act to age 21 beginning in FY2011. While the Fostering Connections Act provides…

Investigation of Profiles of Risk Factors for Adolescent Psychopathology: A Person-Centered Approach

ERIC Educational Resources Information Center

Parra, Gilbert R.; DuBois, David L.; Sher, Kenneth J.

2006-01-01

Latent variable mixture modeling was used to identify subgroups of adolescents with distinct profiles of risk factors from individual, family, peer, and broader contextual domains. Data were drawn from the National Longitudinal Study of Adolescent Health. Four-class models provided the most theoretically meaningful solutions for both 7th (n = 907;…

A utility-based design for randomized comparative trials with ordinal outcomes and prognostic subgroups.

PubMed

Murray, Thomas A; Yuan, Ying; Thall, Peter F; Elizondo, Joan H; Hofstetter, Wayne L

2018-01-22

A design is proposed for randomized comparative trials with ordinal outcomes and prognostic subgroups. The design accounts for patient heterogeneity by allowing possibly different comparative conclusions within subgroups. The comparative testing criterion is based on utilities for the levels of the ordinal outcome and a Bayesian probability model. Designs based on two alternative models that include treatment-subgroup interactions are considered, the proportional odds model and a non-proportional odds model with a hierarchical prior that shrinks toward the proportional odds model. A third design that assumes homogeneity and ignores possible treatment-subgroup interactions also is considered. The three approaches are applied to construct group sequential designs for a trial of nutritional prehabilitation versus standard of care for esophageal cancer patients undergoing chemoradiation and surgery, including both untreated patients and salvage patients whose disease has recurred following previous therapy. A simulation study is presented that compares the three designs, including evaluation of within-subgroup type I and II error probabilities under a variety of scenarios including different combinations of treatment-subgroup interactions. © 2018, The International Biometric Society.

Improving Virus Taxonomy by Recontextualizing Sequence-Based Classification with Biologically Relevant Data: the Case of the Alphacoronavirus 1 Species

PubMed Central

André, Nicole M.

2018-01-01

ABSTRACT The difficulties related to virus taxonomy have been amplified by recent advances in next-generation sequencing and metagenomics, prompting the field to revisit the question of what constitutes a useful viral classification. Here, taking a challenging classification found in coronaviruses, we argue that consideration of biological properties in addition to sequence-based demarcations is critical for generating useful taxonomy that recapitulates complex evolutionary histories. Within the Alphacoronavirus genus, the Alphacoronavirus 1 species encompasses several biologically distinct viruses. We carried out functionally based phylogenetic analysis, centered on the spike gene, which encodes the main surface antigen and primary driver of tropism and pathogenesis. Within the Alphacoronavirus 1 species, we identify clade A (encompassing serotype I feline coronavirus [FCoV] and canine coronavirus [CCoV]) and clade B (grouping serotype II FCoV and CCoV and transmissible gastroenteritis virus [TGEV]-like viruses). We propose this clade designation, along with the newly proposed Alphacoronavirus 2 species, as an improved way to classify the Alphacoronavirus genus. IMPORTANCE Our work focuses on improving the classification of the Alphacoronavirus genus. The Alphacoronavirus 1 species groups viruses of veterinary importance that infect distinct mammalian hosts and includes canine and feline coronaviruses and transmissible gastroenteritis virus. It is the prototype species of the Alphacoronavirus genus; however, it encompasses biologically distinct viruses. To better characterize this prototypical species, we performed phylogenetic analyses based on the sequences of the spike protein, one of the main determinants of tropism and pathogenesis, and reveal the existence of two subgroups or clades that fit with previously established serotype demarcations. We propose a new clade designation to better classify Alphacoronavirus 1 members. PMID:29299531

Improving Virus Taxonomy by Recontextualizing Sequence-Based Classification with Biologically Relevant Data: the Case of the Alphacoronavirus 1 Species.

PubMed

Whittaker, Gary R; André, Nicole M; Millet, Jean Kaoru

2018-01-01

The difficulties related to virus taxonomy have been amplified by recent advances in next-generation sequencing and metagenomics, prompting the field to revisit the question of what constitutes a useful viral classification. Here, taking a challenging classification found in coronaviruses, we argue that consideration of biological properties in addition to sequence-based demarcations is critical for generating useful taxonomy that recapitulates complex evolutionary histories. Within the Alphacoronavirus genus, the Alphacoronavirus 1 species encompasses several biologically distinct viruses. We carried out functionally based phylogenetic analysis, centered on the spike gene, which encodes the main surface antigen and primary driver of tropism and pathogenesis. Within the Alphacoronavirus 1 species, we identify clade A (encompassing serotype I feline coronavirus [FCoV] and canine coronavirus [CCoV]) and clade B (grouping serotype II FCoV and CCoV and transmissible gastroenteritis virus [TGEV]-like viruses). We propose this clade designation, along with the newly proposed Alphacoronavirus 2 species, as an improved way to classify the Alphacoronavirus genus. IMPORTANCE Our work focuses on improving the classification of the Alphacoronavirus genus. The Alphacoronavirus 1 species groups viruses of veterinary importance that infect distinct mammalian hosts and includes canine and feline coronaviruses and transmissible gastroenteritis virus. It is the prototype species of the Alphacoronavirus genus; however, it encompasses biologically distinct viruses. To better characterize this prototypical species, we performed phylogenetic analyses based on the sequences of the spike protein, one of the main determinants of tropism and pathogenesis, and reveal the existence of two subgroups or clades that fit with previously established serotype demarcations. We propose a new clade designation to better classify Alphacoronavirus 1 members.

Psychometric properties and a latent class analysis of the 12-item World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) in a pooled dataset of community samples.

PubMed

MacLeod, Melissa A; Tremblay, Paul F; Graham, Kathryn; Bernards, Sharon; Rehm, Jürgen; Wells, Samantha

2016-12-01

The 12-item World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) is a brief measurement tool used cross-culturally to capture the multi-dimensional nature of disablement through six domains, including: understanding and interacting with the world; moving and getting around; self-care; getting on with people; life activities; and participation in society. Previous psychometric research supports that the WHODAS 2.0 functions as a general factor of disablement. In a pooled dataset from community samples of adults (N = 447) we used confirmatory factor analysis to confirm a one-factor structure. Latent class analysis was used to identify subgroups of individuals based on their patterns of responses. We identified four distinct classes, or patterns of disablement: (1) pervasive disability; (2) physical disability; (3) emotional, cognitive, or interpersonal disability; (4) no/low disability. Convergent validity of the latent class subgroups was found with respect to socio-demographic characteristics, number of days affected by disabilities, stress, mental health, and substance use. These classes offer a simple and meaningful way to classify people with disabilities based on the 12-item WHODAS 2.0. Focusing on individuals with a high probability of being in the first three classes may help guide interventions. Copyright © 2016 John Wiley & Sons, Ltd.

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

PubMed

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.

Typology of religiosity/spirituality in relation to perceived health, depression, and life satisfaction among older Korean immigrants.

PubMed

Roh, Soonhee; Lee, Yeon-Shim; Lee, Jae Hoon; Martin, James I

2014-05-01

The objectives of this study were (1) to identify distinct subtypes of older Korean immigrants based on their levels of religiosity/spirituality (R/S) and (2) to determine if the identified subtypes differed by demographic characteristics, perceived health, depression, and life satisfaction. Factor mixture models were evaluated with a nonprobability sample of older Korean immigrants (N=200) residing in the New York City area in 2009 to classify typologies of R/S. Multiple regression was used to test the associations between the R/S subtypes and outcomes (perceived health, depression, and life satisfaction) while controlling for demographics. Two substantively distinct latent profiles were identified: normally religious/spiritual ('average R/S') and minimally religious/spiritual ('low R/S'). The average R/S subgroup (74.4%) showed higher means than those in the low R/S subgroup (25.6%) on all six R/S class indicators. Subtypes did not differ on age, education, income, marital status, living arrangements, or years in the USA. However, males were more likely than females to be 'average R/S.' The 'average R/S' subtype had significantly greater life satisfaction than their 'low R/S' counterpart. No differences between the two subtypes were found on perceived health or depression. Findings highlight the importance of the classifications of R/S for mental health outcomes, and they indicate that relationships among R/S, various demographic characteristics, and physical/mental health are complex. Future research should validate and refine this classification of R/S in order to help identify particular sources of health risks/behaviors, relevant treatments, and health-promoting interventions within homogenous subtypes of older Korean immigrants.

Comprehensive Molecular Characterization of Papillary Renal-Cell Carcinoma.

PubMed

Linehan, W Marston; Spellman, Paul T; Ricketts, Christopher J; Creighton, Chad J; Fei, Suzanne S; Davis, Caleb; Wheeler, David A; Murray, Bradley A; Schmidt, Laura; Vocke, Cathy D; Peto, Myron; Al Mamun, Abu Amar M; Shinbrot, Eve; Sethi, Anurag; Brooks, Samira; Rathmell, W Kimryn; Brooks, Angela N; Hoadley, Katherine A; Robertson, A Gordon; Brooks, Denise; Bowlby, Reanne; Sadeghi, Sara; Shen, Hui; Weisenberger, Daniel J; Bootwalla, Moiz; Baylin, Stephen B; Laird, Peter W; Cherniack, Andrew D; Saksena, Gordon; Haake, Scott; Li, Jun; Liang, Han; Lu, Yiling; Mills, Gordon B; Akbani, Rehan; Leiserson, Mark D M; Raphael, Benjamin J; Anur, Pavana; Bottaro, Donald; Albiges, Laurence; Barnabas, Nandita; Choueiri, Toni K; Czerniak, Bogdan; Godwin, Andrew K; Hakimi, A Ari; Ho, Thai H; Hsieh, James; Ittmann, Michael; Kim, William Y; Krishnan, Bhavani; Merino, Maria J; Mills Shaw, Kenna R; Reuter, Victor E; Reznik, Ed; Shelley, Carl S; Shuch, Brian; Signoretti, Sabina; Srinivasan, Ramaprasad; Tamboli, Pheroze; Thomas, George; Tickoo, Satish; Burnett, Kenneth; Crain, Daniel; Gardner, Johanna; Lau, Kevin; Mallery, David; Morris, Scott; Paulauskis, Joseph D; Penny, Robert J; Shelton, Candace; Shelton, W Troy; Sherman, Mark; Thompson, Eric; Yena, Peggy; Avedon, Melissa T; Bowen, Jay; Gastier-Foster, Julie M; Gerken, Mark; Leraas, Kristen M; Lichtenberg, Tara M; Ramirez, Nilsa C; Santos, Tracie; Wise, Lisa; Zmuda, Erik; Demchok, John A; Felau, Ina; Hutter, Carolyn M; Sheth, Margi; Sofia, Heidi J; Tarnuzzer, Roy; Wang, Zhining; Yang, Liming; Zenklusen, Jean C; Zhang, Jiashan; Ayala, Brenda; Baboud, Julien; Chudamani, Sudha; Liu, Jia; Lolla, Laxmi; Naresh, Rashi; Pihl, Todd; Sun, Qiang; Wan, Yunhu; Wu, Ye; Ally, Adrian; Balasundaram, Miruna; Balu, Saianand; Beroukhim, Rameen; Bodenheimer, Tom; Buhay, Christian; Butterfield, Yaron S N; Carlsen, Rebecca; Carter, Scott L; Chao, Hsu; Chuah, Eric; Clarke, Amanda; Covington, Kyle R; Dahdouli, Mahmoud; Dewal, Ninad; Dhalla, Noreen; Doddapaneni, Harsha V; Drummond, Jennifer A; Gabriel, Stacey B; Gibbs, Richard A; Guin, Ranabir; Hale, Walker; Hawes, Alicia; Hayes, D Neil; Holt, Robert A; Hoyle, Alan P; Jefferys, Stuart R; Jones, Steven J M; Jones, Corbin D; Kalra, Divya; Kovar, Christie; Lewis, Lora; Li, Jie; Ma, Yussanne; Marra, Marco A; Mayo, Michael; Meng, Shaowu; Meyerson, Matthew; Mieczkowski, Piotr A; Moore, Richard A; Morton, Donna; Mose, Lisle E; Mungall, Andrew J; Muzny, Donna; Parker, Joel S; Perou, Charles M; Roach, Jeffrey; Schein, Jacqueline E; Schumacher, Steven E; Shi, Yan; Simons, Janae V; Sipahimalani, Payal; Skelly, Tara; Soloway, Matthew G; Sougnez, Carrie; Tam, Angela; Tan, Donghui; Thiessen, Nina; Veluvolu, Umadevi; Wang, Min; Wilkerson, Matthew D; Wong, Tina; Wu, Junyuan; Xi, Liu; Zhou, Jane; Bedford, Jason; Chen, Fengju; Fu, Yao; Gerstein, Mark; Haussler, David; Kasaian, Katayoon; Lai, Phillip; Ling, Shiyun; Radenbaugh, Amie; Van Den Berg, David; Weinstein, John N; Zhu, Jingchun; Albert, Monique; Alexopoulou, Iakovina; Andersen, Jeremiah J; Auman, J Todd; Bartlett, John; Bastacky, Sheldon; Bergsten, Julie; Blute, Michael L; Boice, Lori; Bollag, Roni J; Boyd, Jeff; Castle, Erik; Chen, Ying-Bei; Cheville, John C; Curley, Erin; Davies, Benjamin; DeVolk, April; Dhir, Rajiv; Dike, Laura; Eckman, John; Engel, Jay; Harr, Jodi; Hrebinko, Ronald; Huang, Mei; Huelsenbeck-Dill, Lori; Iacocca, Mary; Jacobs, Bruce; Lobis, Michael; Maranchie, Jodi K; McMeekin, Scott; Myers, Jerome; Nelson, Joel; Parfitt, Jeremy; Parwani, Anil; Petrelli, Nicholas; Rabeno, Brenda; Roy, Somak; Salner, Andrew L; Slaton, Joel; Stanton, Melissa; Thompson, R Houston; Thorne, Leigh; Tucker, Kelinda; Weinberger, Paul M; Winemiller, Cynthia; Zach, Leigh Anne; Zuna, Rosemary

2016-01-14

Papillary renal-cell carcinoma, which accounts for 15 to 20% of renal-cell carcinomas, is a heterogeneous disease that consists of various types of renal cancer, including tumors with indolent, multifocal presentation and solitary tumors with an aggressive, highly lethal phenotype. Little is known about the genetic basis of sporadic papillary renal-cell carcinoma, and no effective forms of therapy for advanced disease exist. We performed comprehensive molecular characterization of 161 primary papillary renal-cell carcinomas, using whole-exome sequencing, copy-number analysis, messenger RNA and microRNA sequencing, DNA-methylation analysis, and proteomic analysis. Type 1 and type 2 papillary renal-cell carcinomas were shown to be different types of renal cancer characterized by specific genetic alterations, with type 2 further classified into three individual subgroups on the basis of molecular differences associated with patient survival. Type 1 tumors were associated with MET alterations, whereas type 2 tumors were characterized by CDKN2A silencing, SETD2 mutations, TFE3 fusions, and increased expression of the NRF2-antioxidant response element (ARE) pathway. A CpG island methylator phenotype (CIMP) was observed in a distinct subgroup of type 2 papillary renal-cell carcinomas that was characterized by poor survival and mutation of the gene encoding fumarate hydratase (FH). Type 1 and type 2 papillary renal-cell carcinomas were shown to be clinically and biologically distinct. Alterations in the MET pathway were associated with type 1, and activation of the NRF2-ARE pathway was associated with type 2; CDKN2A loss and CIMP in type 2 conveyed a poor prognosis. Furthermore, type 2 papillary renal-cell carcinoma consisted of at least three subtypes based on molecular and phenotypic features. (Funded by the National Institutes of Health.).

Number of Patients Eligible for PCSK9 Inhibitors Based on Real-world Data From 2.5 Million Patients.

PubMed

Zamora, Alberto; Masana, Luís; Comas-Cufi, Marc; Plana, Núria; Vila, Àlex; García-Gil, Maria; Alves-Cabratosa, Lia; Elosua, Roberto; Marrugat, Jaume; Ramos, Rafel

2018-03-29

PCSK9 inhibitors (PCSK9i) are safe and effective lipid-lowering drugs. Their main limitation is their high cost. The aim of this study was to estimate the number of patients eligible for treatment with PCSK9i according to distinct published criteria. Data were obtained from the Information System for the Development of Research in Primary Care. Included patients were equal to or older than 18 years and had at least 1 low-density lipoprotein cholesterol measurement recorded between 2006 and 2014 (n = 2 500 907). An indication for treatment with PCSK9i was assigned according to the following guidelines: National Health System, Spanish Society of Arteriosclerosis, Spanish Society of Cardiology, National Institute for Health and Care Excellence, and the European Society of Cardiology/European Atherosclerosis Society Task Force. Lipid-lowering treatment was defined as optimized if it reduced low-density lipoprotein levels by ≥ 50% and adherence was > 80%. Among the Spanish population aged 18 years or older, the number of possible candidates to receive PCSK9i in an optimal lipid-lowering treatment scenario ranged from 0.1% to 1.7%, depending on the guideline considered. The subgroup of patients with the highest proportion of potential candidates consisted of patients with familial hypercholesterolemia, and the subgroup with the highest absolute number consisted of patients in secondary cardiovascular prevention. The number of candidates to receive PCSK9i in conditions of real-world clinical practice is high and varies widely depending on the recommendations of distinct scientific societies. Copyright © 2017 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Subgroups of Dutch homeless young adults based on risk- and protective factors for quality of life: Results of a latent class analysis.

PubMed

Altena, Astrid M; Beijersbergen, Mariëlle D; Vermunt, Jeroen K; Wolf, Judith R L M

2018-04-17

It is important to gain more insight into specific subgroups of homeless young adults (HYA) to enable the development of tailored interventions that adequately meet their diverse needs and to improve their quality of life. Within a heterogeneous sample of HYA, we investigated whether subgroups are distinguishable based on risk- and protective factors for quality of life. In addition, differences between subgroups were examined regarding the socio-demographic characteristics, the use of cognitive coping strategies and quality of life. A total of 393 HYA using shelter facilities in the Netherlands were approached to participate, between December 2011 and March 2013. Structured face-to-face interviews were administered approximately 2 weeks after shelter admission by trained research assistants. A latent class analysis was conducted to empirically distinguish 251 HYA in subgroups based on common risk factors (former abuse, victimisation, psychological symptoms and substance use) and protective factors (resilience, family and social support and perceived health status). Additional analysis of variance and chi-square tests were used to compare subgroups on socio-demographic characteristics, the use of cognitive coping strategies and quality of life. The latent class analysis yielded four highly interpretable subgroups: the at-risk subgroup, the high-risk and least protected subgroup, the low-risk subgroup and the higher functioning and protected subgroup. Subgroups of HYA with lower scores in risk factors showed higher scores in protective factors, the adaptive cognitive coping strategies and quality of life. Our findings confirm the need for targeted and tailored interventions for specific subgroups of HYA. Social workers need to be attentive to the pattern of risk- and protective factors in each individual to determine which risk factors are prominent and need to be targeted and which protective factors need to be enhanced to improve the quality of life of HYA. © 2018 John Wiley & Sons Ltd.

A Comparison of Rule-based Analysis with Regression Methods in Understanding the Risk Factors for Study Withdrawal in a Pediatric Study.

PubMed

Haghighi, Mona; Johnson, Suzanne Bennett; Qian, Xiaoning; Lynch, Kristian F; Vehik, Kendra; Huang, Shuai

2016-08-26

Regression models are extensively used in many epidemiological studies to understand the linkage between specific outcomes of interest and their risk factors. However, regression models in general examine the average effects of the risk factors and ignore subgroups with different risk profiles. As a result, interventions are often geared towards the average member of the population, without consideration of the special health needs of different subgroups within the population. This paper demonstrates the value of using rule-based analysis methods that can identify subgroups with heterogeneous risk profiles in a population without imposing assumptions on the subgroups or method. The rules define the risk pattern of subsets of individuals by not only considering the interactions between the risk factors but also their ranges. We compared the rule-based analysis results with the results from a logistic regression model in The Environmental Determinants of Diabetes in the Young (TEDDY) study. Both methods detected a similar suite of risk factors, but the rule-based analysis was superior at detecting multiple interactions between the risk factors that characterize the subgroups. A further investigation of the particular characteristics of each subgroup may detect the special health needs of the subgroup and lead to tailored interventions.

Influence of birth cohort on age of onset cluster analysis in bipolar I disorder.

PubMed

Bauer, M; Glenn, T; Alda, M; Andreassen, O A; Angelopoulos, E; Ardau, R; Baethge, C; Bauer, R; Bellivier, F; Belmaker, R H; Berk, M; Bjella, T D; Bossini, L; Bersudsky, Y; Cheung, E Y W; Conell, J; Del Zompo, M; Dodd, S; Etain, B; Fagiolini, A; Frye, M A; Fountoulakis, K N; Garneau-Fournier, J; Gonzalez-Pinto, A; Harima, H; Hassel, S; Henry, C; Iacovides, A; Isometsä, E T; Kapczinski, F; Kliwicki, S; König, B; Krogh, R; Kunz, M; Lafer, B; Larsen, E R; Lewitzka, U; Lopez-Jaramillo, C; MacQueen, G; Manchia, M; Marsh, W; Martinez-Cengotitabengoa, M; Melle, I; Monteith, S; Morken, G; Munoz, R; Nery, F G; O'Donovan, C; Osher, Y; Pfennig, A; Quiroz, D; Ramesar, R; Rasgon, N; Reif, A; Ritter, P; Rybakowski, J K; Sagduyu, K; Scippa, A M; Severus, E; Simhandl, C; Stein, D J; Strejilevich, S; Hatim Sulaiman, A; Suominen, K; Tagata, H; Tatebayashi, Y; Torrent, C; Vieta, E; Viswanath, B; Wanchoo, M J; Zetin, M; Whybrow, P C

2015-01-01

Two common approaches to identify subgroups of patients with bipolar disorder are clustering methodology (mixture analysis) based on the age of onset, and a birth cohort analysis. This study investigates if a birth cohort effect will influence the results of clustering on the age of onset, using a large, international database. The database includes 4037 patients with a diagnosis of bipolar I disorder, previously collected at 36 collection sites in 23 countries. Generalized estimating equations (GEE) were used to adjust the data for country median age, and in some models, birth cohort. Model-based clustering (mixture analysis) was then performed on the age of onset data using the residuals. Clinical variables in subgroups were compared. There was a strong birth cohort effect. Without adjusting for the birth cohort, three subgroups were found by clustering. After adjusting for the birth cohort or when considering only those born after 1959, two subgroups were found. With results of either two or three subgroups, the youngest subgroup was more likely to have a family history of mood disorders and a first episode with depressed polarity. However, without adjusting for birth cohort (three subgroups), family history and polarity of the first episode could not be distinguished between the middle and oldest subgroups. These results using international data confirm prior findings using single country data, that there are subgroups of bipolar I disorder based on the age of onset, and that there is a birth cohort effect. Including the birth cohort adjustment altered the number and characteristics of subgroups detected when clustering by age of onset. Further investigation is needed to determine if combining both approaches will identify subgroups that are more useful for research. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Parsing Heterogeneity in the Brain Connectivity of Depressed and Healthy Adults During Positive Mood.

PubMed

Price, Rebecca B; Lane, Stephanie; Gates, Kathleen; Kraynak, Thomas E; Horner, Michelle S; Thase, Michael E; Siegle, Greg J

2017-02-15

There is well-known heterogeneity in affective mechanisms in depression that may extend to positive affect. We used data-driven parsing of neural connectivity to reveal subgroups present across depressed and healthy individuals during positive processing, informing targets for mechanistic intervention. Ninety-two individuals (68 depressed patients, 24 never-depressed control subjects) completed a sustained positive mood induction during functional magnetic resonance imaging. Directed functional connectivity paths within a depression-relevant network were characterized using Group Iterative Multiple Model Estimation (GIMME), a method shown to accurately recover the direction and presence of connectivity paths in individual participants. During model selection, individuals were clustered using community detection on neural connectivity estimates. Subgroups were externally tested across multiple levels of analysis. Two connectivity-based subgroups emerged: subgroup A, characterized by weaker connectivity overall, and subgroup B, exhibiting hyperconnectivity (relative to subgroup A), particularly among ventral affective regions. Subgroup predicted diagnostic status (subgroup B contained 81% of patients; 50% of control subjects; χ 2 = 8.6, p = .003) and default mode network connectivity during a separate resting-state task. Among patients, subgroup B members had higher self-reported symptoms, lower sustained positive mood during the induction, and higher negative bias on a reaction-time task. Symptom-based depression subgroups did not predict these external variables. Neural connectivity-based categorization travels with diagnostic category and is clinically predictive, but not clinically deterministic. Both patients and control subjects showed heterogeneous, and overlapping, profiles. The larger and more severely affected patient subgroup was characterized by ventrally driven hyperconnectivity during positive processing. Data-driven parsing suggests heterogeneous substrates of depression and possible resilience in control subjects in spite of biological overlap. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Distinctive pattern of expression of spermatogenic molecular markers in testes of azoospermic men with non-mosaic Klinefelter syndrome.

PubMed

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.

Genetic diversity in the feline leukemia virus gag gene.

PubMed

Kawamura, Maki; Watanabe, Shinya; Odahara, Yuka; Nakagawa, So; Endo, Yasuyuki; Tsujimoto, Hajime; Nishigaki, Kazuo

2015-06-02

Feline leukemia virus (FeLV) belongs to the Gammaretrovirus genus and is horizontally transmitted among cats. FeLV is known to undergo recombination with endogenous retroviruses already present in the host during FeLV-subgroup A infection. Such recombinant FeLVs, designated FeLV-subgroup B or FeLV-subgroup D, can be generated by transduced endogenous retroviral env sequences encoding the viral envelope. These recombinant viruses have biologically distinct properties and may mediate different disease outcomes. The generation of such recombinant viruses resulted in structural diversity of the FeLV particle and genetic diversity of the virus itself. FeLV env diversity through mutation and recombination has been studied, while gag diversity and its possible effects are less well understood. In this study, we investigated recombination events in the gag genes of FeLVs isolated from naturally infected cats and reference isolates. Recombination and phylogenetic analyses indicated that the gag genes often contain endogenous FeLV sequences and were occasionally replaced by entire endogenous FeLV gag genes. Phylogenetic reconstructions of FeLV gag sequences allowed for classification into three distinct clusters, similar to those previously established for the env gene. Analysis of the recombination junctions in FeLV gag indicated that these variants have similar recombination patterns within the same genotypes, indicating that the recombinant viruses were horizontally transmitted among cats. It remains to be investigated whether the recombinant sequences affect the molecular mechanism of FeLV transmission. These findings extend our understanding of gammaretrovirus evolutionary patterns in the field. Copyright © 2015 Elsevier B.V. All rights reserved.

ICGC PedBrain: Dissecting the genomic complexity underlying medulloblastoma

PubMed Central

Jones, David TW; Jäger, Natalie; Kool, Marcel; Zichner, Thomas; Hutter, Barbara; Sultan, Marc; Cho, Yoon-Jae; Pugh, Trevor J; Hovestadt, Volker; Stütz, Adrian M; Rausch, Tobias; Warnatz, Hans-Jörg; Ryzhova, Marina; Bender, Sebastian; Sturm, Dominik; Pleier, Sabrina; Cin, Huriye; Pfaff, Elke; Sieber, Laura; Wittmann, Andrea; Remke, Marc; Witt, Hendrik; Hutter, Sonja; Tzaridis, Theophilos; Weischenfeldt, Joachim; Raeder, Benjamin; Avci, Meryem; Amstislavskiy, Vyacheslav; Zapatka, Marc; Weber, Ursula D; Wang, Qi; Lasitschka, Bärbel; Bartholomae, Cynthia C; Schmidt, Manfred; von Kalle, Christof; Ast, Volker; Lawerenz, Chris; Eils, Jürgen; Kabbe, Rolf; Benes, Vladimir; van Sluis, Peter; Koster, Jan; Volckmann, Richard; Shih, David; Betts, Matthew J; Russell, Robert B; Coco, Simona; Tonini, Gian Paolo; Schüller, Ulrich; Hans, Volkmar; Graf, Norbert; Kim, Yoo-Jin; Monoranu, Camelia; Roggendorf, Wolfgang; Unterberg, Andreas; Herold-Mende, Christel; Milde, Till; Kulozik, Andreas E; von Deimling, Andreas; Witt, Olaf; Maass, Eberhard; Rössler, Jochen; Ebinger, Martin; Schuhmann, Martin U; Frühwald, Michael C; Hasselblatt, Martin; Jabado, Nada; Rutkowski, Stefan; von Bueren, André O; Williamson, Dan; Clifford, Steven C; McCabe, Martin G; Collins, V. Peter; Wolf, Stephan; Wiemann, Stefan; Lehrach, Hans; Brors, Benedikt; Scheurlen, Wolfram; Felsberg, Jörg; Reifenberger, Guido; Northcott, Paul A; Taylor, Michael D; Meyerson, Matthew; Pomeroy, Scott L; Yaspo, Marie-Laure; Korbel, Jan O; Korshunov, Andrey; Eils, Roland; Pfister, Stefan M; Lichter, Peter

2013-01-01

Summary Medulloblastoma is an aggressively-growing tumour, arising in the cerebellum or medulla/brain stem. It is the most common malignant brain tumour in children, and displays tremendous biological and clinical heterogeneity1. Despite recent treatment advances, approximately 40% of children experience tumour recurrence, and 30% will die from their disease. Those who survive often have a significantly reduced quality of life. Four tumour subgroups with distinct clinical, biological and genetic profiles are currently discriminated2,3. WNT tumours, displaying activated wingless pathway signalling, carry a favourable prognosis under current treatment regimens4. SHH tumours show hedgehog pathway activation, and have an intermediate prognosis2. Group 3 & 4 tumours are molecularly less well-characterised, and also present the greatest clinical challenges2,3,5. The full repertoire of genetic events driving this distinction, however, remains unclear. Here we describe an integrative deep-sequencing analysis of 125 tumour-normal pairs. Tetraploidy was identified as a frequent early event in Group 3 & 4 tumours, and a positive correlation between patient age and mutation rate was observed. Several recurrent mutations were identified, both in known medulloblastoma-related genes (CTNNB1, PTCH1, MLL2, SMARCA4) and in genes not previously linked to this tumour (DDX3X, CTDNEP1, KDM6A, TBR1), often in subgroup-specific patterns. RNA-sequencing confirmed these alterations, and revealed the expression of the first medulloblastoma fusion genes. Chromatin modifiers were frequently altered across all subgroups. These findings enhance our understanding of the genomic complexity and heterogeneity underlying medulloblastoma, and provide several potential targets for new therapeutics, especially for Group 3 & 4 patients. PMID:22832583

Memory for self-generated narration in the elderly.

PubMed

Drevenstedt, J; Bellezza, F S

1993-06-01

The story mnemonic technique, an effective encoding and retrieval strategy for young adults, was used as a procedure to study encoding and recall in elderly women. Experiment 1 (15 undergraduate and 14 elderly women) showed the technique to be reliable over 3 weeks and without practice effects in both age groups. In Experiment 2, 67 elderly women (mean age = 72 years) were found to make up 3 distinctive subgroupings in patterns of narration cohesiveness and recall accuracy, consistent with pilot data on the technique. A stepwise multiple regression equation found narration cohesiveness, an adaptation of the Daneman-Carpenter (1980) working-memory measure and vocabulary to predict word recall. Results suggested that a general memory factor differentiated the 3 elderly subgroups.

Characterizing severe and enduring anorexia nervosa: An empirical approach.

PubMed

Wildes, Jennifer E; Forbush, Kelsie T; Hagan, Kelsey E; Marcus, Marsha D; Attia, Evelyn; Gianini, Loren M; Wu, Wei

2017-04-01

Targeted approaches for the treatment of severe and enduring anorexia nervosa (SE-AN) have been recommended, but there is no consensus definition of SE-AN to inform research and clinical practice. This study aimed to take initial steps toward developing an empirically based definition of SE-AN by characterizing associations among putative indicators of severity and chronicity in eating disorders. Patients with AN (N = 355) completed interviews and questionnaires at treatment admission and discharge; height and weight were assessed to calculate body mass index (BMI). Structural equation mixture modeling was used to test whether associations among potential indicators of SE-AN (illness duration, treatment history, BMI, binge eating, purging, quality-of-life) formed distinct subgroups, a single group with one or more dimensions, or a combination of subgroups and dimensions. A three-factor (dimensional), two-profile (categorical) mixture model provided the best fit to the data. Factor 1 included eating disorder behaviors; Factor 2 comprised quality-of-life domains; Factor 3 was characterized by illness duration, number of hospitalizations, and admission BMI. Profiles differed on eating disorder behaviors and quality-of-life, but not on indicators of chronicity or BMI. Factor scores, but not profile membership, predicted outcome at discharge from treatment. Data suggest that patients with AN can be classified on the basis of eating disorder behaviors and quality-of-life, but there was no evidence for a chronic subgroup of AN. Rather, indices of chronicity varied dimensionally within each class. Given that current definitions of SE-AN rely on illness duration, these findings have implications for research and clinical practice. © 2016 Wiley Periodicals, Inc.

The relationship among psychological and psychophysiological characteristics of fibromyalgia patients.

PubMed

Thieme, Kati; Turk, Dennis C; Gracely, Richard H; Maixner, William; Flor, Herta

2015-02-01

This study examined the relationship of psychophysiological response patterns in fibromyalgia with psychological characteristics and comorbid mental disorders. Surface electromyographic data, systolic and diastolic blood pressure, heart rate (HR), and skin conductance levels were recorded continuously during baseline, stress, and relaxation tasks. Cluster analysis revealed 4 subgroups of patients who differed on pain characteristics and cognitive, affective, and behavioral responses to pain and stress. The largest group (46.7%) was characterized by elevated blood pressure levels and stress reactivity (a disposition assumed to be a vulnerability factor for the development of diseases) associated with pain, anxiety, physical interference, low activity, and pain behaviors. A second group (41.6%) showed low baseline blood pressure and reactivity, and high activity and stress. A third group (9.2%) displayed high baseline skin conductance level, reactivity, and depression, and a fourth small group (2.5%) displayed elevated baseline electromyographic response and reactivity with high levels of anxiety and depression. These data suggest that unique psychophysiological response patterns are associated with psychological coping and mental disorders in fibromyalgia patients. The identification of the mechanisms that contribute to these group differences will further our understanding of the mechanisms involved in the development and maintenance of fibromyalgia and suggest differential treatment strategies. This article presents psychological characteristics and comorbidity with mental disorders of psychophysiological subgroups of fibromyalgia patients. This mechanistic analysis will assist scientific identification of systems-based pathways that contribute to autonomic and stress mechanisms that mediate chronic pain. Demonstration of distinct, homogeneous subgroups is an important step towards personalized, mechanism-oriented treatments. Copyright © 2015 American Pain Society. All rights reserved.

Decreased dietary fiber intake and structural alteration of gut microbiota in patients with advanced colorectal adenoma.

PubMed

Chen, Hui-Min; Yu, Ya-Nan; Wang, Ji-Lin; Lin, Yan-Wei; Kong, Xuan; Yang, Chang-Qing; Yang, Li; Liu, Zhan-Ju; Yuan, Yao-Zong; Liu, Fei; Wu, Jian-Xin; Zhong, Liang; Fang, Dian-Chun; Zou, Weiping; Fang, Jing-Yuan

2013-05-01

Accumulating evidence indicates that diet is one of the most important environmental factors involved in the progression from advanced colorectal adenoma (A-CRA) to colorectal cancer. We evaluated the possible effects of dietary fiber on the fecal microbiota of patients with A-CRA. Patients with a diagnosis of A-CRA by pathological examination were enrolled in the A-CRA group. Patients with no obvious abnormalities or histopathological changes were enrolled in the healthy control (HC) group. Dietary fiber intake was assessed in all patients. Short-chain fatty acids (SCFAs) in feces were detected by gas chromatography. The fecal microbiota community was analyzed by 454 pyrosequencing based on 16S ribosomal RNA. Lower dietary fiber patterns and consistently lower SCFA production were observed in the A-CRA group (n = 344). Principal component analysis showed distinct differences in the fecal microbiota communities of the 2 groups. Clostridium, Roseburia, and Eubacterium spp. were significantly less prevalent in the A-CRA group (n = 47) than in the HC group (n = 47), whereas Enterococcus and Streptococcus spp. were more prevalent in the A-CRA group (n = 47) (all P < 0.05). Butyrate and butyrate-producing bacteria were more prevalent in a subgroup of HC subjects with a high fiber intake than in those in both the low-fiber HC subgroup and the high-fiber A-CRA subgroup (all P < 0.05). A high-fiber dietary pattern and subsequent consistent production of SCFAs and healthy gut microbiota are associated with a reduced risk of A-CRA. This trial was registered at www.chictr.org as ChiCTR-TRC-00000123.

A 6-gene signature identifies four molecular subgroups of neuroblastoma

PubMed Central

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 < 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. PMID:21492432

Use of 3-dimensional surface acquisition to study facial morphology in 5 populations.

PubMed

Kau, Chung How; Richmond, Stephen; Zhurov, Alexei; Ovsenik, Maja; Tawfik, Wael; Borbely, Peter; English, Jeryl D

2010-04-01

The aim of this study was to assess the use of 3-dimensional facial averages for determining morphologic differences from various population groups. We recruited 473 subjects from 5 populations. Three-dimensional images of the subjects were obtained in a reproducible and controlled environment with a commercially available stereo-photogrammetric camera capture system. Minolta VI-900 (Konica Minolta, Tokyo, Japan) and 3dMDface (3dMD LLC, Atlanta, Ga) systems were used. Each image was obtained as a facial mesh and orientated along a triangulated axis. All faces were overlaid, one on top of the other, and a complex mathematical algorithm was performed until average composite faces of 1 man and 1 woman were achieved for each subgroup. These average facial composites were superimposed based on a previously validated superimposition method, and the facial differences were quantified. Distinct facial differences were observed among the groups. The linear differences between surface shells ranged from 0.37 to 1.00 mm for the male groups. The linear differences ranged from 0.28 and 0.87 mm for the women. The color histograms showed that the similarities in facial shells between the subgroups by sex ranged from 26.70% to 70.39% for men and 36.09% to 79.83% for women. The average linear distance from the signed color histograms for the male subgroups ranged from -6.30 to 4.44 mm. The female subgroups ranged from -6.32 to 4.25 mm. Average faces can be efficiently and effectively created from a sample of 3-dimensional faces. Average faces can be used to compare differences in facial morphologies for various populations and sexes. Facial morphologic differences were greatest when totally different ethnic variations were compared. Facial morphologic similarities were present in comparable groups, but there were large variations in concentrated areas of the face. Copyright 2010 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

Taxonomy of Individual Variations in Aesthetic Responses to Fractal Patterns

PubMed Central

Spehar, Branka; Walker, Nicholas; Taylor, Richard P.

2016-01-01

In two experiments, we investigate group and individual preferences in a range of different types of patterns with varying fractal-like scaling characteristics. In Experiment 1, we used 1/f filtered grayscale images as well as their thresholded (black and white) and edges only counterparts. Separate groups of observers viewed different types of images varying in slope of their amplitude spectra. Although with each image type, the groups exhibited the “universal” pattern of preference for intermediate amplitude spectrum slopes, we identified 4 distinct sub-groups in each case. Sub-group 1 exhibited a typical peak preference for intermediate amplitude spectrum slopes (“intermediate”; approx. 50%); sub-group 2 exhibited a linear increase in preference with increasing amplitude spectrum slope (“smooth”; approx. 20%), while sub-group 3 exhibited a linear decrease in preference as a function of the amplitude spectrum slope (“sharp”; approx. 20%). Sub-group 4 revealed no significant preference (“other”; approx. 10%). In Experiment 2, we extended the range of different image types and investigated preferences within the same observers. We replicate the results of our first experiment and show that individual participants exhibit stable patterns of preference across a wide range of image types. In both experiments, Q-mode factor analysis identified two principal factors that were able to explain more than 80% of interindividual variations in preference across all types of images, suggesting a highly similar dimensional structure of interindividual variations in preference for fractal-like scaling characteristics. PMID:27458365

Sample heterogeneity in unipolar depression as assessed by functional connectivity analyses is dominated by general disease effects.

PubMed

Feder, Stephan; Sundermann, Benedikt; Wersching, Heike; Teuber, Anja; Kugel, Harald; Teismann, Henning; Heindel, Walter; Berger, Klaus; Pfleiderer, Bettina

2017-11-01

Combinations of resting-state fMRI and machine-learning techniques are increasingly employed to develop diagnostic models for mental disorders. However, little is known about the neurobiological heterogeneity of depression and diagnostic machine learning has mainly been tested in homogeneous samples. Our main objective was to explore the inherent structure of a diverse unipolar depression sample. The secondary objective was to assess, if such information can improve diagnostic classification. We analyzed data from 360 patients with unipolar depression and 360 non-depressed population controls, who were subdivided into two independent subsets. Cluster analyses (unsupervised learning) of functional connectivity were used to generate hypotheses about potential patient subgroups from the first subset. The relationship of clusters with demographical and clinical measures was assessed. Subsequently, diagnostic classifiers (supervised learning), which incorporated information about these putative depression subgroups, were trained. Exploratory cluster analyses revealed two weakly separable subgroups of depressed patients. These subgroups differed in the average duration of depression and in the proportion of patients with concurrently severe depression and anxiety symptoms. The diagnostic classification models performed at chance level. It remains unresolved, if subgroups represent distinct biological subtypes, variability of continuous clinical variables or in part an overfitting of sparsely structured data. Functional connectivity in unipolar depression is associated with general disease effects. Cluster analyses provide hypotheses about potential depression subtypes. Diagnostic models did not benefit from this additional information regarding heterogeneity. Copyright © 2017 Elsevier B.V. All rights reserved.

Cardiovascular Disease Mortality in Asian Americans (2003–2010)

PubMed Central

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

2014-01-01

Background Asian Americans are a rapidly growing racial/ethnic group in the United States. Our current understanding of Asian-American cardiovascular disease mortality patterns is distorted by the aggregation of distinct subgroups. Objectives To examine heart disease and stroke mortality rates in Asian-American subgroups to determine racial/ethnic differences in cardiovascular disease mortality within the United States. Methods We examined heart disease and stroke mortality rates for the 6 largest Asian-American subgroups (Asian Indian, Chinese, Filipino, Japanese, Korean, and Vietnamese) from 2003–2010. U.S. death records were used to identify race/ethnicity and cause of death by ICD-10 coding. Using both U.S. Census and death record data, standardized mortality ratios (SMR), relative SMRs (rSMR), and proportional mortality ratios (PMR) were calculated for each sex and ethnic group relative to Non-Hispanic Whites (NHW). Results 10,442,034 death records were examined. While NHW men and women had the highest overall mortality rates, Asian Indian men and women and Filipino men had greater proportionate mortality burden from ischemic heart disease. The proportionate mortality burden of hypertensive heart disease and cerebrovascular disease, especially hemorrhagic stroke, was higher in every Asian-American subgroup compared to NHWs. Conclusions The heterogeneity in cardiovascular disease mortality patterns among diverse Asian-American subgroups calls attention to the need for more research to help direct more specific treatment and prevention efforts, in particular with hypertension and stroke, to reduce health disparities for this growing population. PMID:25500233

Determinants of Poverty among Rural and Urban Women Who Live Alone.

ERIC Educational Resources Information Center

Slesinger, Doris P.; Cautley, Eleanor

Using data from the 1980 Census Public Use Microdata Sample, this paper examines characteristics of women who live alone and incidence of poverty in this group. Results show there are two distinct subgroups among women who live alone: the elderly, most of whom are widowed; and the young, many of whom are single or divorced. For both groups, about…

Diagnosis of intrachromosomal amplification of chromosome 21 (iAMP21) by molecular cytogenetics in pediatric acute lymphoblastic leukemia.

PubMed

Duployez, Nicolas; Boudry-Labis, Elise; Decool, Gauthier; Grzych, Guillaume; Grardel, Nathalie; Abou Chahla, Wadih; Preudhomme, Claude; Roche-Lestienne, Catherine

2015-10-01

Intrachromosomal amplification of chromosome 21 (iAMP21) defines a distinct cytogenetic subgroup of B-cell precursor acute lymphoblastic leukemia (BCP-ALL) with poor prognosis that should be investigated in routine practice. Single-nucleotide polymorphism (SNP)-array provides a useful method to detect such cases showing a highly characteristic profile.

Dyadic Taxonomy of Delinquent Youth: Exploring Risks and Outcomes Associated With Maternal-Youth Reporting Discrepancies of Delinquent Behavior

ERIC Educational Resources Information Center

Reid, Joan A.; Sullivan, Christopher J.

2016-01-01

Using latent class analysis (LCA), this study identified a dyadic taxonomy of delinquent youth categorized by varying types of maternal-youth reporting discrepancies (i.e., youth < maternal, youth > maternal) within a sample of 764 14-year-old high-risk youth. Four distinctive subgroups of youth were identified, two of which reported more…

Cognition and Lobar Morphology in Full Mutation Boys with Fragile X Syndrome

ERIC Educational Resources Information Center

Meguid, Nagwa A.; Fahim, Cherine; Sami, Rasha; Nashaat, Neveen H.; Yoon, Uicheul; Anwar, Mona; El-Dessouky, Hosam M.; Shahine, Elham A.; Ibrahim, Ahmed Samir; Mancini-Marie, Adham; Evans, Alan C.

2012-01-01

The aims of the present study are twofold: (1) to examine cortical morphology (CM) associated with alterations in cognition in fragile X syndrome (FXS); (2) to characterize the CM profile of FXS versus FXS with an autism diagnosis (FXS+Aut) as a preliminary attempt to further elucidate the behavioral distinctions between the two sub-groups. We…

Consumer preferences for food allergen labeling.

PubMed

Marra, Carlo A; Harvard, Stephanie; Grubisic, Maja; Galo, Jessica; Clarke, Ann; Elliott, Susan; Lynd, Larry D

2017-01-01

Food allergen labeling is an important tool to reduce risk of exposure and prevent anaphylaxis for individuals with food allergies. Health Canada released a Canadian food allergen labeling regulation (2008) and subsequent update (2012) suggesting that research is needed to guide further iterations of the regulation to improve food allergen labeling and reduce risk of exposure. The primary objective of this study was to examine consumer preferences in food labeling for allergy avoidance and anaphylaxis prevention. A secondary objective was to identify whether different subgroups within the consumer population emerged. A discrete choice experiment using a fractional factorial design divided into ten different versions with 18 choice-sets per version was developed to examine consumer preferences for different attributes of food labeling. Three distinct subgroups of Canadian consumers with different allergen considerations and food allergen labeling needs were identified. Overall, preferences for standardized precautionary and safety symbols at little or no increased cost emerged. While three distinct groups with different preferences were identified, in general the results revealed that the current Canadian food allergen labeling regulation can be improved by enforcing the use of standardized precautionary and safety symbols and educating the public on the use of these symbols.

CD30 expression defines a novel subgroup of diffuse large B-cell lymphoma with favorable prognosis and distinct gene expression signature: a report from the International DLBCL Rituximab-CHOP Consortium Program Study

PubMed Central

Hu, Shimin; Xu-Monette, Zijun Y.; Balasubramanyam, Aarthi; Manyam, Ganiraju C.; Visco, Carlo; Tzankov, Alexander; Liu, Wei-min; Miranda, Roberto N.; Zhang, Li; Montes-Moreno, Santiago; Dybkær, Karen; Chiu, April; Orazi, Attilio; Zu, Youli; Bhagat, Govind; Richards, Kristy L.; Hsi, Eric D.; Choi, William W. L.; Han van Krieken, J.; Huang, Qin; Huh, Jooryung; Ai, Weiyun; Ponzoni, Maurilio; Ferreri, Andrés J. M.; Zhao, Xiaoying; Winter, Jane N.; Zhang, Mingzhi; Li, Ling; Møller, Michael B.; Piris, Miguel A.; Li, Yong; Go, Ronald S.; Wu, Lin; Medeiros, L. Jeffrey; Young, Ken H.

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 CD30 expression in DLBCL is unknown. Here we report that CD30 expression is a favorable prognostic factor in a cohort of 903 de novo DLBCL patients. CD30 was expressed in ∼14% of DLBCL patients. Patients with CD30+ DLBCL had superior 5-year overall survival (CD30+, 79% vs CD30–, 59%; P = .001) and progression-free survival (P = .003). The favorable outcome of CD30 expression was maintained in both the germinal center B-cell and activated B-cell subtypes. Gene expression profiling revealed the upregulation of genes encoding negative regulators of nuclear factor κB activation and lymphocyte survival, and downregulation of genes encoding B-cell receptor signaling and proliferation, as well as prominent cytokine and stromal signatures in CD30+ DLBCL patients, suggesting a distinct molecular basis for its favorable outcome. Given the superior prognostic value, unique gene expression signature, and significant 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. PMID:23343832

Is there a role for conventional MRI and MR diffusion-weighted imaging for distinction of skull base chordoma and chondrosarcoma?

PubMed

Müller, Uta; Kubik-Huch, Rahel A; Ares, Carmen; Hug, Eugen B; Löw, Roland; Valavanis, Antonios; Ahlhelm, Frank J

2016-02-01

Chordoma and chondrosarcoma are locally invasive skull base tumors with similar clinical symptoms and anatomic imaging features as reported in the literature. To determine differentiation of chordoma and chondrosarcoma of the skull base with conventional magnetic resonance imaging (cMRI) and diffusion-weighted MR imaging (DWI) in comparison to histopathological diagnosis. This retrospective study comprised 96 (chordoma, n = 64; chondrosarcoma, n = 32) patients with skull base tumors referred to the Paul Scherrer Institute (PSI) for proton therapy. cMRI signal intensities of all tumors were investigated. In addition, median apparent diffusion coefficient (ADC) values were measured in a subgroup of 19 patients (chordoma, n = 11; chondrosarcoma, n = 8). The majority 81.2% (26/32) of chondrosarcomas displayed an off-midline growth pattern, 18.8% (6/32) showed clival invasion, 18.8% (6/32) were located more centrally. Only 4.7% (3/64) of chordomas revealed a lateral clival origin. Using cMRI no significant differences in MR signal intensities were observed in contrast to significantly different ADC values (subgroup of 19/96 patients examined by DWI), with the highest mean value of 2017.2 × 10(-6 )mm(2)/s (SD, 139.9( )mm(2)/s) for chondrosarcoma and significantly lower value of 1263.5 × 10(-6 )mm(2)/s (SD, 100.2 × 10(-6 )mm(2)/s) for chordoma (P = 0.001/median test). An off-midline growth pattern can differentiate chondrosarcoma from chordoma on cMRI in a majority of patients. Additional DWI is a promising tool for the differentiation of these skull base tumors. © The Foundation Acta Radiologica 2015.

Evaluation of a treatment-based classification algorithm for low back pain: a cross-sectional study.

PubMed

Stanton, Tasha R; Fritz, Julie M; Hancock, Mark J; Latimer, Jane; Maher, Christopher G; Wand, Benedict M; Parent, Eric C

2011-04-01

Several studies have investigated criteria for classifying patients with low back pain (LBP) into treatment-based subgroups. A comprehensive algorithm was created to translate these criteria into a clinical decision-making guide. This study investigated the translation of the individual subgroup criteria into a comprehensive algorithm by studying the prevalence of patients meeting the criteria for each treatment subgroup and the reliability of the classification. This was a cross-sectional, observational study. Two hundred fifty patients with acute or subacute LBP were recruited from the United States and Australia to participate in the study. Trained physical therapists performed standardized assessments on all participants. The researchers used these findings to classify participants into subgroups. Thirty-one participants were reassessed to determine interrater reliability of the algorithm decision. Based on individual subgroup criteria, 25.2% (95% confidence interval [CI]=19.8%-30.6%) of the participants did not meet the criteria for any subgroup, 49.6% (95% CI=43.4%-55.8%) of the participants met the criteria for only one subgroup, and 25.2% (95% CI=19.8%-30.6%) of the participants met the criteria for more than one subgroup. The most common combination of subgroups was manipulation + specific exercise (68.4% of the participants who met the criteria for 2 subgroups). Reliability of the algorithm decision was moderate (kappa=0.52, 95% CI=0.27-0.77, percentage of agreement=67%). Due to a relatively small patient sample, reliability estimates are somewhat imprecise. These findings provide important clinical data to guide future research and revisions to the algorithm. The finding that 25% of the participants met the criteria for more than one subgroup has important implications for the sequencing of treatments in the algorithm. Likewise, the finding that 25% of the participants did not meet the criteria for any subgroup provides important information regarding potential revisions to the algorithm's bottom table (which guides unclear classifications). Reliability of the algorithm is sufficient for clinical use.

Radiographic hand osteoarthritis: patterns and associations with hand pain and function in a community-dwelling sample.

PubMed

Marshall, M; van der Windt, D; Nicholls, E; Myers, H; Hay, E; Dziedzic, K

2009-11-01

Patterns of radiographic osteoarthritis (ROA) of the hand are often examined by row, with the four joints of the thumb studied inconsistently. The objectives of this study were to determine relationships of ROA at different hand joints, use the findings to define radiographic sub-groups and investigate their associations with pain and function. Sixteen joints in each hand were scored for the presence of ROA in a community-dwelling cohort of adults, 50-years-and-over, with self-reported hand pain or problems. Principal components analysis (PCA) with varimax rotation was used to study patterns of ROA in the hand joints and identify distinct sub-groups. Differences in pain and function between these sub-groups were assessed using Australian/Canadian Osteoarthritis Index (AUSCAN), Grip Ability Test (GAT) and grip and pinch strength. PCA was undertaken on data from 592 participants and identified four components: distal interphalangeal joints (DIPs), proximal interphalangeal joints (PIPs), metacarpophalangeal joints (MCPs), thumb joints. However, the left thumb interphalangeal (IP) joint cross-loaded with the PIP and thumb groups. On this basis, participants were categorised into four radiographic sub-groups: no osteoarthritis (OA), finger only OA, thumb only OA and combined thumb and finger OA. Statistically significant differences were found between the sub-groups for AUSCAN function, and in women alone for grip and pinch strength. Participants with combined thumb and finger OA had the worst scores. Individual thumb joints can be clustered together as a joint group in ROA. Four radiographic sub-groups of hand OA can be distinguished. Pain and functional difficulties were highest in participants with both thumb and finger OA.

Identification of a neuronal transcription factor network involved in medulloblastoma development.

PubMed

Lastowska, Maria; Al-Afghani, Hani; Al-Balool, Haya H; Sheth, Harsh; Mercer, Emma; Coxhead, Jonathan M; Redfern, Chris P F; Peters, Heiko; Burt, Alastair D; Santibanez-Koref, Mauro; Bacon, Chris M; Chesler, Louis; Rust, Alistair G; Adams, David J; Williamson, Daniel; Clifford, Steven C; Jackson, Michael S

2013-07-11

Medulloblastomas, the most frequent malignant brain tumours affecting children, comprise at least 4 distinct clinicogenetic subgroups. Aberrant sonic hedgehog (SHH) signalling is observed in approximately 25% of tumours and defines one subgroup. Although alterations in SHH pathway genes (e.g. PTCH1, SUFU) are observed in many of these tumours, high throughput genomic analyses have identified few other recurring mutations. Here, we have mutagenised the Ptch+/- murine tumour model using the Sleeping Beauty transposon system to identify additional genes and pathways involved in SHH subgroup medulloblastoma development. Mutagenesis significantly increased medulloblastoma frequency and identified 17 candidate cancer genes, including orthologs of genes somatically mutated (PTEN, CREBBP) or associated with poor outcome (PTEN, MYT1L) in the human disease. Strikingly, these candidate genes were enriched for transcription factors (p=2x10-5), the majority of which (6/7; Crebbp, Myt1L, Nfia, Nfib, Tead1 and Tgif2) were linked within a single regulatory network enriched for genes associated with a differentiated neuronal phenotype. Furthermore, activity of this network varied significantly between the human subgroups, was associated with metastatic disease, and predicted poor survival specifically within the SHH subgroup of tumours. Igf2, previously implicated in medulloblastoma, was the most differentially expressed gene in murine tumours with network perturbation, and network activity in both mouse and human tumours was characterised by enrichment for multiple gene-sets indicating increased cell proliferation, IGF signalling, MYC target upregulation, and decreased neuronal differentiation. Collectively, our data support a model of medulloblastoma development in SB-mutagenised Ptch+/- mice which involves disruption of a novel transcription factor network leading to Igf2 upregulation, proliferation of GNPs, and tumour formation. Moreover, our results identify rational therapeutic targets for SHH subgroup tumours, alongside prognostic biomarkers for the identification of poor-risk SHH patients.

An investigation of young girls' responses to sexualized images.

PubMed

Jongenelis, Michelle I; Pettigrew, Simone; Byrne, Susan M; Biagioni, Nicole

2016-12-01

Evidence suggests that the sexualization of girls has increased and become more explicit in recent years. However, most of the research conducted to date has focused on sexualization in adults. To address this research gap, this study explored how young Australian girls respond to and describe sexualized and non-sexualized depictions of their peers. Results from 42 girls aged 6-11 years revealed that sexualization was a perceptually salient attribute, with participants readily classifying sexualized girls as a subgroup. Participants also made distinct trait attributions based on the differences between sexualized and non-sexualized girls. The results suggest that young girls respond differently to sexualized and non-sexualized depictions of their peers and are beginning to develop stereotypes based on these depictions. As such, the implementation of media literacy programs in adolescence may be too late and efforts may be required to address this issue among younger children. Copyright © 2016 Elsevier Ltd. All rights reserved.

BRAF Mutation and CDKN2A Deletion Define a Clinically Distinct Subgroup of Childhood Secondary High-Grade Glioma

PubMed Central

Mistry, Matthew; Zhukova, Nataliya; Merico, Daniele; Rakopoulos, Patricia; Krishnatry, Rahul; Shago, Mary; Stavropoulos, James; Alon, Noa; Pole, Jason D.; Ray, Peter N.; Navickiene, Vilma; Mangerel, Joshua; Remke, Marc; Buczkowicz, Pawel; Ramaswamy, Vijay; Guerreiro Stucklin, Ana; Li, Martin; Young, Edwin J.; Zhang, Cindy; Castelo-Branco, Pedro; Bakry, Doua; Laughlin, Suzanne; Shlien, Adam; Chan, Jennifer; Ligon, Keith L.; Rutka, James T.; Dirks, Peter B.; Taylor, Michael D.; Greenberg, Mark; Malkin, David; Huang, Annie; Bouffet, Eric; Hawkins, Cynthia E.; Tabori, Uri

2015-01-01

Purpose To uncover the genetic events leading to transformation of pediatric low-grade glioma (PLGG) to secondary high-grade glioma (sHGG). Patients and Methods We retrospectively identified patients with sHGG from a population-based cohort of 886 patients with PLGG with long clinical follow-up. Exome sequencing and array CGH were performed on available samples followed by detailed genetic analysis of the entire sHGG cohort. Clinical and outcome data of genetically distinct subgroups were obtained. Results sHGG was observed in 2.9% of PLGGs (26 of 886 patients). Patients with sHGG had a high frequency of nonsilent somatic mutations compared with patients with primary pediatric high-grade glioma (HGG; median, 25 mutations per exome; P = .0042). Alterations in chromatin-modifying genes and telomere-maintenance pathways were commonly observed, whereas no sHGG harbored the BRAF-KIAA1549 fusion. The most recurrent alterations were BRAF V600E and CDKN2A deletion in 39% and 57% of sHGGs, respectively. Importantly, all BRAF V600E and 80% of CDKN2A alterations could be traced back to their PLGG counterparts. BRAF V600E distinguished sHGG from primary HGG (P = .0023), whereas BRAF and CDKN2A alterations were less commonly observed in PLGG that did not transform (P < .001 and P < .001 respectively). PLGGs with BRAF mutations had longer latency to transformation than wild-type PLGG (median, 6.65 years [range, 3.5 to 20.3 years] v 1.59 years [range, 0.32 to 15.9 years], respectively; P = .0389). Furthermore, 5-year overall survival was 75% ± 15% and 29% ± 12% for children with BRAF mutant and wild-type tumors, respectively (P = .024). Conclusion BRAF V600E mutations and CDKN2A deletions constitute a clinically distinct subtype of sHGG. The prolonged course to transformation for BRAF V600E PLGGs provides an opportunity for surgical interventions, surveillance, and targeted therapies to mitigate the outcome of sHGG. PMID:25667294

Patient characteristics in low back pain subgroups based on an existing classification system. A descriptive cohort study in chiropractic practice.

PubMed

Eirikstoft, Heidi; Kongsted, Alice

2014-02-01

Sub-grouping of low back pain (LBP) is believed to improve prediction of prognosis and treatment effects. The objectives of this study were: (1) to examine whether chiropractic patients could be sub-grouped according to an existing pathoanatomically-based classification system, (2) to describe patient characteristics within each subgroup, and (3) to determine the proportion of patients in whom clinicians considered the classification to be unchanged after approximately 10 days. A cohort of 923 LBP patients was included during their first consultation. Patients completed an extensive questionnaire and were examined according to a standardised protocol. Based on the clinical examination, patients were classified into diagnostic subgroups. After approximately 10 days, chiropractors reported whether they considered the subgroup had changed. The most frequent subgroups were reducible and partly reducible disc syndromes followed by facet joint pain, dysfunction and sacroiliac (SI)-joint pain. Classification was inconclusive in 5% of the patients. Differences in pain, activity limitation, and psychological factors were small across subgroups. Within 10 days, 82% were reported to belong to the same subgroup as at the first visit. In conclusion, LBP patients could be classified according to a standardised protocol, and chiropractors considered most patient classifications to be unchanged within 10 days. Differences in patient characteristics between subgroups were very small, and the clinical relevance of the classification system should be investigated by testing its value as a prognostic factor or a treatment effect modifier. It is recommended that this classification system be combined with psychological and social factors if it is to be useful. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

PubMed

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.

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

PubMed

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.

Differentiation of respiratory syncytial virus subgroups with cDNA probes in a nucleic acid hybridization assay.

PubMed Central

Sullender, W M; Anderson, L J; Anderson, K; Wertz, G W

1990-01-01

A new approach to respiratory syncytial (RS) virus subgroup determination was developed by using a simple nucleic acid filter hybridization technique. By this method, virus-infected cells are bound and fixed in a single step, and the viral RNA in the fixed-cell preparation is characterized directly by its ability to hybridize to cDNA probes specific for either the A or B subgroups of RS virus. The subgroup-specific probes were constructed from cDNA clones that corresponded to a portion of the extracellular domain of the RS virus G protein of either a subgroup B RS virus (8/60) or a subgroup A RS virus (A2). The cDNA probes were labeled with 32P and used to analyze RS virus isolates collected over a period of three decades. Replicate templates of infected cell preparations were hybridized with either the subgroup A or B probe. The subgroup assignments of 40 viruses tested by nucleic acid hybridization were in agreement with the results of subgroup determinations based on their reactivities with monoclonal antibodies, which previously has been the only method available for determining the subgroup classification of RS virus isolates. The nucleic acid hybridization assay has the advantage of providing broad-based discrimination of the two subgroups on the basis of nucleic acid homology, irrespective of minor antigenic differences that are detected in assays in which monoclonal antibodies are used. The nucleic acid hybridization technique provides a reliable method for RS virus subgroup characterization. Images PMID:2118548

Improvement of selective screening strategy for gestational diabetes through a more accurate definition of high-risk groups.

PubMed

Pintaudi, Basilio; Di Vieste, Giacoma; Corrado, Francesco; Lucisano, Giuseppe; Pellegrini, Fabio; Giunta, Loretta; Nicolucci, Antonio; D'Anna, Rosario; Di Benedetto, Antonino

2014-01-01

This study aimed to assess the predictive value of risk factors (RFs) for gestational diabetes mellitus (GDM) established by selective screening (SS) and to identify subgroups of women at a higher risk of developing GDM. A retrospective, single-center study design was employed. Data of 1015 women screened for GDM at 24-28 weeks of gestation and diagnosed according to the International Association of Diabetes and Pregnancy Study Groups criteria were evaluated. Information on RFs established by SS was also collected and their association with GDM was determined. To identify distinct and homogeneous subgroups of patients at a higher risk, the RECursive Partitioning and AMalgamation (RECPAM) method was used. Overall, 113 (11.1%) women were diagnosed as having GDM. The application of the SS criteria would result in the execution of an oral glucose tolerance test (OGTT) in 58.3% of women and 26 (23.0%) cases of GDM would not be detected due to the absence of any RF. The RECPAM analysis identified high-risk subgroups characterized by fasting plasma glucose values >5.1 mmol/l (odds ratio (OR)=26.5; 95% CI 14.3-49.0) and pre-pregnancy BMI (OR=7.0; 95% CI 3.9-12.8 for overweight women). In a final logistic model including RECPAM classes, previous macrosomia (OR=3.6; 95% CI 1.1-11.6), and family history of diabetes (OR=1.8; 95% CI 1.1-2.8), but not maternal age, were also found to be associated with an increased risk of developing GDM. A screening approach based on the RECPAM model would reduce by over 50% (23.0 vs 10.6%) the number of undiagnosed GDM cases when compared with the current SS approach, at the expense of 50 additional OGTTs required. A screening approach based on our RECPAM model results in a significant reduction in the number of undetected GDM cases compared with the current SS procedure.

Plasma Metabolomic Profiling Suggests Early Indications for Predisposition to Latent Insulin Resistance in Children Conceived by ICSI

PubMed Central

Margeli, Alexandra; Mantzou, Emilia; Konsta, Maria; Loutradis, Dimitrios; Mastorakos, George; Papassotiriou, Ioannis; Klapa, Maria I.; Kanaka-Gantenbein, Christina; Chrousos, George P.

2014-01-01

Background There have been increasing indications about an epigenetically-based elevated predisposition of assisted reproductive technology (ART) offspring to insulin resistance, which can lead to an unfavorable cardio-metabolic profile in adult life. However, the relevant long-term systematic molecular studies are limited, especially for the IntraCytoplasmic Sperm Injection (ICSI) method, introduced in 1992. In this study, we carefully defined a group of 42 prepubertal ICSI and 42 naturally conceived (NC) children. We assessed differences in their metabolic profile based on biochemical measurements, while, for a subgroup, plasma metabolomic analysis was also performed, investigating any relevant insulin resistance indices. Methods & Results Auxological and biochemical parameters of 42 6.8±2.1 yrs old ICSI-conceived and 42 age-matched controls were measured. Significant differences between the groups were determined using univariate and multivariate statistics, indicating low urea and low-grade inflammation markers (YKL-40, hsCRP) and high triiodothyronine (T3) in ICSI-children compared to controls. Moreover, plasma metabolomic analysis carried out for a subgroup of 10 ICSI- and 10 NC girls using Gas Chromatography-Mass Spectrometry (GC-MS) indicated clear differences between the two groups, characterized by 36 metabolites linked to obesity, insulin resistance and metabolic syndrome. Notably, the distinction between the two girl subgroups was accentuated when both their biochemical and metabolomic measurements were employed. Conclusions The present study contributes a large auxological and biochemical dataset of a well-defined group of pre-pubertal ICSI-conceived subjects to the research of the ART effect to the offspring's health. Moreover, it is the first time that the relevant usefulness of metabolomics was investigated. The acquired results are consistent with early insulin resistance in ICSI-offspring, paving the way for further systematic investigations. These data support that metabolomics may unravel metabolic differences before they become clinically or biochemically evident, underlining its utility in the ART research. PMID:24728198

"Where do auditory hallucinations come from?"--a brain morphometry study of schizophrenia patients with inner or outer space hallucinations.

PubMed

Plaze, Marion; Paillère-Martinot, Marie-Laure; Penttilä, Jani; Januel, Dominique; de Beaurepaire, Renaud; Bellivier, Franck; Andoh, Jamila; Galinowski, André; Gallarda, Thierry; Artiges, Eric; Olié, Jean-Pierre; Mangin, Jean-François; Martinot, Jean-Luc; Cachia, Arnaud

2011-01-01

Auditory verbal hallucinations are a cardinal symptom of schizophrenia. Bleuler and Kraepelin distinguished 2 main classes of hallucinations: hallucinations heard outside the head (outer space, or external, hallucinations) and hallucinations heard inside the head (inner space, or internal, hallucinations). This distinction has been confirmed by recent phenomenological studies that identified 3 independent dimensions in auditory hallucinations: language complexity, self-other misattribution, and spatial location. Brain imaging studies in schizophrenia patients with auditory hallucinations have already investigated language complexity and self-other misattribution, but the neural substrate of hallucination spatial location remains unknown. Magnetic resonance images of 45 right-handed patients with schizophrenia and persistent auditory hallucinations and 20 healthy right-handed subjects were acquired. Two homogeneous subgroups of patients were defined based on the hallucination spatial location: patients with only outer space hallucinations (N=12) and patients with only inner space hallucinations (N=15). Between-group differences were then assessed using 2 complementary brain morphometry approaches: voxel-based morphometry and sulcus-based morphometry. Convergent anatomical differences were detected between the patient subgroups in the right temporoparietal junction (rTPJ). In comparison to healthy subjects, opposite deviations in white matter volumes and sulcus displacements were found in patients with inner space hallucination and patients with outer space hallucination. The current results indicate that spatial location of auditory hallucinations is associated with the rTPJ anatomy, a key region of the "where" auditory pathway. The detected tilt in the sulcal junction suggests deviations during early brain maturation, when the superior temporal sulcus and its anterior terminal branch appear and merge.

Curidium Medica, plc.

PubMed

Caffo, Nathan A

2008-05-01

Curidium Medica, plc is a personalized medicine company intent on developing targeted medicines and their associated companion diagnostics to treat patients more effectively and safely. Through the use of its proprietary gene-expression analysis tool, Homomatrix ® , Curidium aims to reveal different patient subgroups characterized by distinct underlying disease mechanisms. This is anticipated to lead to the identification of diagnostics to subclassify patients within heterogeneous disease populations and improved therapies for different patient subgroups, ultimately resulting in the development of personalized medicines using companion diagnostics and targeted treatments. The company's initial focus on diseases of the CNS has resulted in the identification of a blood diagnostic tool, PsychINDx™, which classifies patients with schizophrenia/bipolar disorder into four subgroups. PsychINDx may have the potential to improve the treatment of patients with schizophrenia/bipolar disorder. Curidium aims to continue to use this approach to improve patient treatments in a variety of therapeutic areas and heterogeneous diseases. The first such additional application using Homomatrix has been initiated within a strategic research alliance with Takeda (Osaka, Japan) in the area of major depressive disorder.

TCR gamma chain diversity in the spleen of the duckbill platypus (Ornithorhynchus anatinus).

PubMed

Parra, Zuly E; Arnold, Tamara; Nowak, Melissa A; Hellman, Lars; Miller, Robert D

2006-01-01

TCR gamma (TRG) chain diversity in splenic gammadelta T cells was determined for an egg-laying mammal (or monotreme), the duckbill platypus. Three distinct V subgroups were found in the expressed TRG chains and these three subgroups are members of a clade not found so far in eutherian mammals or birds. Each subgroup contains approximately five V gene segments, and their overall divergence is much less than is found in eutherians and birds, consistent with their recent evolution from an ancestral V gene segment. The platypus TRG locus also contains three C region genes and many of the residues involved in TCR function, such as interactions with CD3, were conserved in the monotreme C regions. All non-eutherian mammals (monotremes and marsupials) lacked the second cysteine residue necessary to form the intradomain disulfide bond in the C region, a loss apparently due to independent mutations in marsupials and monotremes. Monotreme TRGC regions also had among the most variation in the length of the connecting peptide region described for any species due to repeated motifs.

Early Size Distributions of Chondrule Subgroups Overprinted by the Final Accumulation Process of Particle Components in Allende

NASA Technical Reports Server (NTRS)

McCain, K. A.; Simon, J. I.; Cuzzi, J. N

2015-01-01

Populations of compositionally distinct particles are fundamental components of undifferentiated chondritic meteorites. Many theories explain the formation of chondrites, one class of which includes mechanisms for sorting the component particles in the solar nebula prior to their accretion. Mechanisms include sorting by mass, turbulent concentration, X-winds, and photophoresis, which will produce characteristic distributions of observable properties such as particle size. Distinguishing processes that occur in specific astrophysical environments requires characterization of particle types, which include refractory Ca-Al-rich Inclusions (CAIs) and less-refractory chondrules. Previous investigations of modal abundances of CAIs and chondrules exist, but differences within and between these two groups, both of which are made up of diverse subgroups with different thermal histories and chemical compositions, remain mostly unstudied. The presence of rims, a significant event occurring after the formation of at least some chondrules, have also yet to be considered with respect to sorting. Here we present the sizes of CAIs and chondrules in Allende with attention to the smallest sizes, subgroups, and particle rims.

Distribution and Features of the Six Classes of Peroxiredoxins

PubMed Central

Poole, Leslie B.; Nelson, Kimberly J.

2016-01-01

Peroxiredoxins are cysteine-dependent peroxide reductases that group into 6 different, structurally discernable classes. In 2011, our research team reported the application of a bioinformatic approach called active site profiling to extract active site-proximal sequence segments from the 29 distinct, structurally-characterized peroxiredoxins available at the time. These extracted sequences were then used to create unique profiles for the six groups which were subsequently used to search GenBank(nr), allowing identification of ∼3500 peroxiredoxin sequences and their respective subgroups. Summarized in this minireview are the features and phylogenetic distributions of each of these peroxiredoxin subgroups; an example is also provided illustrating the use of the web accessible, searchable database known as PREX to identify subfamily-specific peroxiredoxin sequences for the organism Vitis vinifera (grape). PMID:26810075

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

PubMed

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

2015-01-01

Recognition of homogeneous subgroups of patients can usefully improve prediction of their outcomes and the targeting of treatment. There are a number of research approaches that have been used to recognise homogeneity in such subgroups and to test their implications. One approach is to use statistical clustering techniques, such as Cluster Analysis or Latent Class Analysis, to detect latent relationships between patient characteristics. Influential patient characteristics can come from diverse domains of health, such as pain, activity limitation, physical impairment, social role 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 improve the clinical interpretability of derived subgroups and reduce sample size requirements. This approach involves clustering in two sequential stages. The first stage involves clustering within health domains and therefore requires creating as many clustering models as there are health domains in the available data. This first stage produces scoring patterns within each domain. The second stage involves clustering using the scoring patterns from each health domain (from the first stage) to identify subgroups across all domains. We illustrate this using chest pain data from the baseline presentation of 580 patients. The new two-stage clustering resulted in two subgroups that approximated the classic textbook descriptions of musculoskeletal chest pain and atypical angina chest pain. The traditional single-stage clustering resulted in five clusters that were also clinically recognisable but displayed less distinct differences. In this paper, a new approach to using clustering techniques to identify clinically useful subgroups of patients is suggested. Research designs, statistical methods and outcome metrics suitable for performing that testing are also described. This approach has 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.

Diagnosis of intrachromosomal amplification of chromosome 21 (iAMP21) by molecular cytogenetics in pediatric acute lymphoblastic leukemia

PubMed Central

Duployez, Nicolas; Boudry-Labis, Elise; Decool, Gauthier; Grzych, Guillaume; Grardel, Nathalie; Abou Chahla, Wadih; Preudhomme, Claude; Roche-Lestienne, Catherine

2015-01-01

Key Clinical Message Intrachromosomal amplification of chromosome 21 (iAMP21) defines a distinct cytogenetic subgroup of B-cell precursor acute lymphoblastic leukemia (BCP-ALL) with poor prognosis that should be investigated in routine practice. Single-nucleotide polymorphism (SNP)-array provides a useful method to detect such cases showing a highly characteristic profile. PMID:26509013

Current Proceedings in the Molecular Dissection of Hepatocellular Adenomas: Review and Hands-on Guide for Diagnosis

PubMed Central

Goltz, Diane; Fischer, Hans-Peter

2015-01-01

Molecular dissection of hepatocellular adenomas has brought forward a diversity of well-defined entities. Their distinction is important for routine practice, since prognosis is tightly related to the individual subgroup. Very recent activity has generated new details on the molecular background of hepatocellular adenoma, which this article aims to integrate into the current concepts of taxonomy. PMID:26404250

Current Proceedings in the Molecular Dissection of Hepatocellular Adenomas: Review and Hands-on Guide for Diagnosis.

PubMed

Goltz, Diane; Fischer, Hans-Peter

2015-09-02

Molecular dissection of hepatocellular adenomas has brought forward a diversity of well-defined entities. Their distinction is important for routine practice, since prognosis is tightly related to the individual subgroup. Very recent activity has generated new details on the molecular background of hepatocellular adenoma, which this article aims to integrate into the current concepts of taxonomy.

Acceptance of pain, self-compassion and psychopathology: using the chronic pain acceptance questionnaire to identify patients' subgroups.

PubMed

Costa, Joana; Pinto-Gouveia, José

2011-01-01

The present study explores whether specific subgroups of patients could be identified based on Chronic Pain Acceptance Questionnaire scores. A battery of self-report questionnaire was used to assess acceptance of pain, self-compassion and psychopathology in 103 participants with chronic pain, from Portuguese health care units. K-Means cluster were performed and the results supported three subgroups of patients (low acceptance subgroup; high acceptance subgroup; intermediate subgroup with activity engagement near to the mean and low willingness to pain). One-way ANOVA's showed that the three subgroups identified differed significantly from each other on psychopathology and self-compassion. Results indicated that the intermediate subgroup presented less depression and stress, compared with the low acceptance subgroup. In what concerns self-compassion, the low acceptance subgroup reported higher self-judgment, isolation and over identification, compared with the intermediate subgroup. These subgroups also differed from each other in common humanity and mindfulness. Implications and clinical utility of the results were discussed, suggesting the increase of willingness to pain as an important key in chronic pain interventions.  Copyright © 2010 John Wiley & Sons, Ltd.

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

PubMed

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.

Fibromyalgia and neuropathic pain - differences and similarities. A comparison of 3057 patients with diabetic painful neuropathy and fibromyalgia

PubMed Central

2011-01-01

Background Patients with diabetic neuropathy (DPN) and fibromyalgia differ substantially in pathogenetic factors and the spatial distribution of the perceived pain. We questioned whether, despite these obvious differences, similar abnormal sensory complaints and pain qualities exist in both entities. We hypothesized that similar sensory symptoms might be associated with similar mechanisms of pain generation. The aims were (1) to compare epidemiological features and co-morbidities and (2) to identify similarities and differences of sensory symptoms in both entities. Methods The present multi-center study compares epidemiological data and sensory symptoms of a large cohort of 1434 fibromyalgia patients and 1623 patients with painful diabetic neuropathy. Data acquisition included standard demographic questions and self-report questionnaires (MOS sleep scale, PHQ-9, PainDETECT). To identify subgroups of patients with characteristic combinations of symptoms (sensory profiles) a cluster analysis was performed using all patients in both cohorts. Results Significant differences in co-morbidities (depression, sleep disturbance) were found between both disorders. Patients of both aetiologies chose very similar descriptors to characterize their sensory perceptions. Burning pain, prickling and touch-evoked allodynia were present in the same frequency. Five subgroups with distinct symptom profiles could be detected. Two of the subgroups were characteristic for fibromyalgia whereas one profile occurred predominantly in DPN patients. Two profiles were found frequently in patients of both entities (20-35%). Conclusions DPN and fibromyalgia patients experience very similar sensory phenomena. The combination of sensory symptoms - the sensory profile - is in most cases distinct and almost unique for each one of the two entities indicating aetiology-specific mechanisms of symptom generation. Beside the unique aetiology-specific sensory profiles an overlap of sensory profiles can be found in 20-35% of patients of both aetiologies. PMID:21612589

How have researchers studied multiracial populations? A content and methodological review of 20 years of research.

PubMed

Charmaraman, Linda; Woo, Meghan; Quach, Ashley; Erkut, Sumru

2014-07-01

The U.S. Census shows that the racial-ethnic makeup of over 9 million people (2.9% of the total population) who self-identified as multiracial is extremely diverse. Each multiracial subgroup has unique social and political histories that may lead to distinct societal perceptions, economic situations, and health outcomes. Despite the increasing academic and media interest in multiracial individuals, there are methodological and definitional challenges in studying the population, resulting in conflicting representations in the literature. This content and methods review of articles on multiracial populations provides a comprehensive understanding of which multiracial populations have been included in research and how they have been studied, both to recognize emerging research and to identify gaps for guiding future research on this complex but increasingly visible population. We examine 125 U.S.-based peer-reviewed journal articles published over the past 20 years (1990 to 2009) containing 133 separate studies focused on multiracial individuals, primarily from the fields of psychology, sociology, social work, education, and public health. Findings include (a) descriptive data regarding the sampling strategies, methodologies, and demographic characteristics of studies, including which multiracial subgroups are most studied, gender, age range, region of country, and socioeconomic status; (b) major thematic trends in research topics concerning multiracial populations; and (c) implications and recommendations for future studies.

Internal working models and adjustment of physically abused children: the mediating role of self-regulatory abilities.

PubMed

Hawkins, Amy L; Haskett, Mary E

2014-01-01

Abused children's internal working models (IWM) of relationships are known to relate to their socioemotional adjustment, but mechanisms through which negative representations increase vulnerability to maladjustment have not been explored. We sought to expand the understanding of individual differences in IWM of abused children and investigate the mediating role of self-regulation in links between IWM and adjustment. Cluster analysis was used to subgroup 74 physically abused children based on their IWM. Internal working models were identified by children's representations, as measured by a narrative story stem task. Self-regulation was assessed by teacher report and a behavioral task, and adjustment was measured by teacher report. Cluster analyses indicated two subgroups of abused children with distinct patterns of IWMs. Cluster membership predicted internalizing and externalizing problems. Associations between cluster membership and adjustment were mediated by children's regulation, as measured by teacher reports of many aspects of regulation. There was no support for mediation when regulation was measured by a behavioral task that tapped more narrow facets of regulation. Abused children exhibit clinically relevant individual differences in their IWMs; these models are linked to adjustment in the school setting, possibly through children's self-regulation. © 2013 The Authors. Journal of Child Psychology and Psychiatry © 2013 Association for Child and Adolescent Mental Health.

Horizontal Hostility among Non-Meat Eaters

PubMed Central

Rothgerber, Hank

2014-01-01

The present study examined intergroup judgments made between four groups of non-meat eaters: health vegetarians; ethical vegetarians; health vegans, and ethical vegans. Consistent with hypotheses based on horizontal hostility and the need to maintain ingroup distinctiveness, ethical vegetarians gave unfavorable evaluations to health vegetarians relative to vegans, especially when the mainstream omnivore group was made salient. Contrary to expectations, vegans gave relatively more favorable evaluations to ethical vegetarians than health vegetarians when mainstream salience was low. This was especially true for vegans who were motivated primarily by ethical concerns. When mainstream salience was high, vegans did not distinguish between the vegetarian subgroups. Results suggest that one’s motives for abstaining from meat often play a larger role in this type of intergroup perceptions than one’s dietary practices. PMID:24809342

Development of remote sensing techniques capable of delineating soils as an aid to soil survey

NASA Technical Reports Server (NTRS)

Coleman, T. L.; Montgomery, O. L.

1988-01-01

Eighty-one benchmark soils from Alabama, Georgia, Florida, Tennessee, and Mississippi were evaluated to determine the feasibility of spectrally differentiating among soil categories. Relationships among spectral properties that occur between soils and within soils were examined, using discriminant analysis. Soil spectral data were obtained from air-dried samples using an Exotech Model 20C field spectroradiometer (0.37 to 2.36 microns). Differentiating among the orders, suborders, great groups, and subgroups using reflectance spectra achieved varying percentages of accuracy. Six distinct reflectance curve forms were developed from the air-dried samples based on the shape and presence or absence of adsorption bands. Iron oxide and organic matter content were the dominant soil parameters affecting the spectral characteristics for differentiating among and between these soils.

A taxonomy of adolescent health: development of the adolescent health profile-types.

PubMed

Riley, A W; Green, B F; Forrest, C B; Starfield, B; Kang, M; Ensminger, M E

1998-08-01

The aim of this study was to develop a taxonomy of health profile-types that describe adolescents' patterns of health as self-reported on a health status questionnaire. The intent was to be able to assign individuals to mutually exclusive and exhaustive groups that characterize the important aspects of their health and need for health services. Cluster analytic empirical methods and clinically based conceptual methods were used to identify patterns of health in samples of adolescents from schools and from clinics that serve adolescents with chronic conditions and acute illnesses. Individuals with similar patterns of scores across multiple domains were assigned to the same profile-type. Results from the empirical and conceptually based methods were integrated to produce a practical system for assigning youths to profile-types. Four domains of health (Satisfaction, Discomfort, Risks and Resilience) were used to group individuals into 13 distinct profile-types. The profile-types were characterized primarily by the number of domains in which health is poor, identifying the unique combinations of problems that characterize different subgroups of adolescents. This method of reporting the information available on health status surveys is potentially a more informative way of identifying and classifying the health needs of subgroups in the population than is available from global scores or multiple scale scores. The reliability and validity of this taxonomy of health profile-types for the purposes of planning and evaluating health services must be demonstrated. That is the purpose of the accompanying study.

Typology of patients with fibromyalgia: cluster analysis of duloxetine study patients.

PubMed

Lipkovich, Ilya A; Choy, Ernest H; Van Wambeke, Peter; Deberdt, Walter; Sagman, Doron

2014-12-23

To identify distinct groups of patients with fibromyalgia (FM) with respect to multiple outcome measures. Data from 631 duloxetine-treated women in 4 randomized, placebo-controlled trials were included in a cluster analysis based on outcomes after up to 12 weeks of treatment. Corresponding classification rules were constructed using a classification tree method. Probabilities for transitioning from baseline to Week 12 category were estimated for placebo and duloxetine patients (Ntotal = 1188) using logistic regression. Five clusters were identified, from "worst" (high pain levels and severe mental/physical impairment) to "best" (low pain levels and nearly normal mental/physical function). For patients with moderate overall severity, mental and physical symptoms were less correlated, resulting in 2 distinct clusters based on these 2 symptom domains. Three key variables with threshold values were identified for classification of patients: Brief Pain Inventory (BPI) pain interference overall scores of <3.29 and <7.14, respectively, a Fibromyalgia Impact Questionnaire (FIQ) interference with work score of <2, and an FIQ depression score of ≥5. Patient characteristics and frequencies per baseline category were similar between treatments; >80% of patients were in the 3 worst categories. Duloxetine patients were significantly more likely to improve after 12 weeks than placebo patients. A sustained effect was seen with continued duloxetine treatment. FM patients are heterogeneous and can be classified into distinct subgroups by simple descriptive rules derived from only 3 variables, which may guide individual patient management. Duloxetine showed higher improvement rates than placebo and had a sustained effect beyond 12 weeks.

Molecular subtypes of Alzheimer's disease.

PubMed

Di Fede, Giuseppe; Catania, Marcella; Maderna, Emanuela; Ghidoni, Roberta; Benussi, Luisa; Tonoli, Elisa; Giaccone, Giorgio; Moda, Fabio; Paterlini, Anna; Campagnani, Ilaria; Sorrentino, Stefano; Colombo, Laura; Kubis, Adriana; Bistaffa, Edoardo; Ghetti, Bernardino; Tagliavini, Fabrizio

2018-02-19

Protein misfolding and aggregation is a central feature of several neurodegenerative disorders including Alzheimer's disease (AD), in which assemblies of amyloid β (Aβ) peptides accumulate in the brain in the form of parenchymal and/or vascular amyloid. A widely accepted concept is that AD is characterized by distinct clinical and neuropathological phenotypes. Recent studies revealed that Aβ assemblies might have structural differences among AD brains and that such pleomorphic assemblies can correlate with distinct disease phenotypes. We found that in both sporadic and inherited forms of AD, amyloid aggregates differ in the biochemical composition of Aβ species. These differences affect the physicochemical properties of Aβ assemblies including aggregation kinetics, resistance to degradation by proteases and seeding ability. Aβ-amyloidosis can be induced and propagated in animal models by inoculation of brain extracts containing aggregated Aβ. We found that brain homogenates from AD patients with different molecular profiles of Aβ are able to induce distinct patterns of Aβ-amyloidosis when injected into mice. Overall these data suggest that the assembly of mixtures of Aβ peptides into different Aβ seeds leads to the formation of distinct subtypes of amyloid having distinctive physicochemical and biological properties which result in the generation of distinct AD molecular subgroups.

Long-term type 1 diabetes alters the deposition of collagens and proteoglycans in the early pregnant myometrium of mice.

PubMed

Favaro, Rodolfo R; Raspantini, Priscila R; Salgado, Renato M; Fortes, Zuleica B; Zorn, Telma M T

2015-04-01

We have previously shown that long-term type 1 diabetes affects the structural organization, contractile apparatus and extracellular matrix (ECM) of the myometrium during early pregnancy in mice. This study aimed to identify which myometrial ECM components are affected by diabetes, including fibril-forming collagen types I, III and V, as well as proteoglycans, decorin, lumican, fibromodulin and biglycan. Alloxan-induced type 1 diabetic female mice were divided into subgroups D1 and D2, formed by females that bred 90-100 and 100-110 days after diabetes induction, respectively. The deposition of ECM components in the myometrium was evaluated by immunohistochemistry/immunofluorescence. The subgroup D1 showed decreased deposition of collagen types I and III in the external muscle layer (EML) and decreased collagen types III and V in the internal muscle layer (IML). Collagen types I and III were decreased in both muscle layers of the subgroup D2. In addition, increased deposition of collagen types I and III and lumican as well as decreased collagen type V were observed in the connective tissue between muscle layers of D2. Lumican was decreased in the EML of the subgroups D1 and D2. Fibromodulin was repressed in the IML and EML of both D1 and D2. In contrast, decorin deposition diminished only in muscle layers of D2. No changes were noticed for biglycan. Subgroups D1 and D2 showed distinct stages of progression of diabetic complications in the myometrium, characterized by both common and specific sets of changes in the ECM composition.

A global view of structure–function relationships in the tautomerase superfamily

PubMed Central

Davidson, Rebecca; Baas, Bert-Jan; Akiva, Eyal; Holliday, Gemma L.; Polacco, Benjamin J.; LeVieux, Jake A.; Pullara, Collin R.; Zhang, Yan Jessie; Whitman, Christian P.

2018-01-01

The tautomerase superfamily (TSF) consists of more than 11,000 nonredundant sequences present throughout the biosphere. Characterized members have attracted much attention because of the unusual and key catalytic role of an N-terminal proline. These few characterized members catalyze a diverse range of chemical reactions, but the full scale of their chemical capabilities and biological functions remains unknown. To gain new insight into TSF structure–function relationships, we performed a global analysis of similarities across the entire superfamily and computed a sequence similarity network to guide classification into distinct subgroups. Our results indicate that TSF members are found in all domains of life, with most being present in bacteria. The eukaryotic members of the cis-3-chloroacrylic acid dehalogenase subgroup are limited to fungal species, whereas the macrophage migration inhibitory factor subgroup has wide eukaryotic representation (including mammals). Unexpectedly, we found that 346 TSF sequences lack Pro-1, of which 85% are present in the malonate semialdehyde decarboxylase subgroup. The computed network also enabled the identification of similarity paths, namely sequences that link functionally diverse subgroups and exhibit transitional structural features that may help explain reaction divergence. A structure-guided comparison of these linker proteins identified conserved transitions between them, and kinetic analysis paralleled these observations. Phylogenetic reconstruction of the linker set was consistent with these findings. Our results also suggest that contemporary TSF members may have evolved from a short 4-oxalocrotonate tautomerase–like ancestor followed by gene duplication and fusion. Our new linker-guided strategy can be used to enrich the discovery of sequence/structure/function transitions in other enzyme superfamilies. PMID:29184004

Gene expression profiles of metabolic aggressiveness and tumor recurrence in benign meningioma.

PubMed

Serna, Eva; Morales, José Manuel; Mata, Manuel; Gonzalez-Darder, José; San Miguel, Teresa; Gil-Benso, Rosario; Lopez-Gines, Concha; Cerda-Nicolas, Miguel; Monleon, Daniel

2013-01-01

Around 20% of meningiomas histologically benign may be clinically aggressive and recur. This strongly affects management of meningioma patients. There is a need to evaluate the potential aggressiveness of an individual meningioma. Additional criteria for better classification of meningiomas will improve clinical decisions as well as patient follow up strategy after surgery. The aim of this study was to determine the relationship between gene expression profiles and new metabolic subgroups of benign meningioma with potential clinical relevance. Forty benign and fourteen atypical meningioma tissue samples were included in the study. We obtained metabolic profiles by NMR and recurrence after surgery information for all of them. We measured gene expression by oligonucleotide microarray measurements on 19 of them. To our knowledge, this is the first time that distinct gene expression profiles are reported for benign meningioma molecular subgroups with clinical correlation. Our results show that metabolic aggressiveness in otherwise histological benign meningioma proceeds mostly through alterations in the expression of genes involved in the regulation of transcription, mainly the LMO3 gene. Genes involved in tumor metabolism, like IGF1R, are also differentially expressed in those meningioma subgroups with higher rates of membrane turnover, higher energy demand and increased resistance to apoptosis. These new subgroups of benign meningiomas exhibit different rates of recurrence. This work shows that benign meningioma with metabolic aggressiveness constitute a subgroup of potentially recurrent tumors in which alterations in genes regulating critical features of aggressiveness, like increased angiogenesis or cell invasion, are still no predominant. The determination of these gene expression biosignatures may allow the early detection of clinically aggressive tumors.

Cardiovascular disease mortality in Asian Americans.

PubMed

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

2014-12-16

Asian Americans are a rapidly growing racial/ethnic group in the United States. Our current understanding of Asian-American cardiovascular disease mortality patterns is distorted by the aggregation of distinct subgroups. The purpose of the study was to examine heart disease and stroke mortality rates in Asian-American subgroups to determine racial/ethnic differences in cardiovascular disease mortality within the United States. We examined heart disease and stroke mortality rates for the 6 largest Asian-American subgroups (Asian Indian, Chinese, Filipino, Japanese, Korean, and Vietnamese) from 2003 to 2010. U.S. death records were used to identify race/ethnicity and cause of death by International Classification of Diseases-10th revision coding. Using both U.S. Census data and death record data, standardized mortality ratios (SMRs), relative SMRs (rSMRs), and proportional mortality ratios were calculated for each sex and ethnic group relative to non-Hispanic whites (NHWs). In this study, 10,442,034 death records were examined. Whereas NHW men and women had the highest overall mortality rates, Asian Indian men and women and Filipino men had greater proportionate mortality burden from ischemic heart disease. The proportionate mortality burden of hypertensive heart disease and cerebrovascular disease, especially hemorrhagic stroke, was higher in every Asian-American subgroup compared with NHWs. The heterogeneity in cardiovascular disease mortality patterns among diverse Asian-American subgroups calls attention to the need for more research to help direct more specific treatment and prevention efforts, in particular with hypertension and stroke, to reduce health disparities for this growing population. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Genotypes and phylogeographical relationships of infectious hematopoietic necrosis virus in California, USA

USGS Publications Warehouse

Kelley, G.O.; Bendorf, C.M.; Yun, S.C.; Kurath, G.; Hedrick, R.P.

2007-01-01

Infectious hematopoietic necrosis virus (IHNV) contains 3 major genogroups in North America with discreet geographic ranges designated as upper (U), middle (M), and lower (L). A comprehensive genotyping of 237 IHNV isolates from hatchery and wild salmonids in California revealed 25 different sequence types (a to y) all in the L genogroup; specifically, the genogroup contained 14 sequence types that were unique to individual isolates as well as 11 sequence types representing 2 or more identical isolates. The most evident trend was the phylogenetic and geographical division of the L genogroup into 2 distinct subgroups designated as LI and LII. Isolates within Subgroup LI were primarily found within waterways linked to southern Oregon and northern California coastal rivers. Isolates in Subgroup LII were concentrated within inland valley watersheds that included the Sacramento River, San Joaquin River, and their tributaries. The temporal and spatial patterns of virus occurrence suggested that infections among adult Chinook salmon in the hatchery or that spawn in the river are a major source of virus potentially infecting other migrating or resident salmonids in California. Serum neutralization results of the California isolates of IHNV corroborated a temporal trend of sequence divergence; specifically, 2 progressive shifts in which more recent virus isolates represent new serotypes. A comparison of the estimates of divergence rates for Subgroup LI (1 ?? ICT5 mutations per nucleotide site per year) indicated stasis similar to that observed in the U genogroup, while the Subgroup LII rate (1 ?? 10 3 mutations per nucleotide site per year) suggested a more active evolution similar to that of the M genogroup. ?? Inter-Research 2007.

Distinct types of primary cutaneous large B-cell lymphoma identified by gene expression profiling.

PubMed

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.

Novel molecular subgroups for clinical classification and outcome prediction in childhood medulloblastoma: a cohort study.

PubMed

Schwalbe, Edward C; Lindsey, Janet C; Nakjang, Sirintra; Crosier, Stephen; Smith, Amanda J; Hicks, Debbie; Rafiee, Gholamreza; Hill, Rebecca M; Iliasova, Alice; Stone, Thomas; Pizer, Barry; Michalski, Antony; Joshi, Abhijit; Wharton, Stephen B; Jacques, Thomas S; Bailey, Simon; Williamson, Daniel; Clifford, Steven C

2017-07-01

International consensus recognises four medulloblastoma molecular subgroups: WNT (MB WNT ), SHH (MB SHH ), group 3 (MB Grp3 ), and group 4 (MB Grp4 ), each defined by their characteristic genome-wide transcriptomic and DNA methylomic profiles. These subgroups have distinct clinicopathological and molecular features, and underpin current disease subclassification and initial subgroup-directed therapies that are underway in clinical trials. However, substantial biological heterogeneity and differences in survival are apparent within each subgroup, which remain to be resolved. We aimed to investigate whether additional molecular subgroups exist within childhood medulloblastoma and whether these could be used to improve disease subclassification and prognosis predictions. In this retrospective cohort study, we assessed 428 primary medulloblastoma samples collected from UK Children's Cancer and Leukaemia Group (CCLG) treatment centres (UK), collaborating European institutions, and the UKCCSG-SIOP-PNET3 European clinical trial. An independent validation cohort (n=276) of archival tumour samples was also analysed. We analysed samples from patients with childhood medulloblastoma who were aged 0-16 years at diagnosis, and had central review of pathology and comprehensive clinical data. We did comprehensive molecular profiling, including DNA methylation microarray analysis, and did unsupervised class discovery of test and validation cohorts to identify consensus primary molecular subgroups and characterise their clinical and biological significance. We modelled survival of patients aged 3-16 years in patients (n=215) who had craniospinal irradiation and had been treated with a curative intent. Seven robust and reproducible primary molecular subgroups of childhood medulloblastoma were identified. MB WNT remained unchanged and each remaining consensus subgroup was split in two. MB SHH was split into age-dependent subgroups corresponding to infant (<4·3 years; MB SHH-Infant ; n=65) and childhood patients (≥4·3 years; MB SHH-Child ; n=38). MB Grp3 and MB Grp4 were each split into high-risk (MB Grp3-HR [n=65] and MB Grp4-HR [n=85]) and low-risk (MB Grp3-LR [n=50] and MB Grp4-LR [n=73]) subgroups. These biological subgroups were validated in the independent cohort. We identified features of the seven subgroups that were predictive of outcome. Cross-validated subgroup-dependent survival models, incorporating these novel subgroups along with secondary clinicopathological and molecular features and established disease risk-factors, outperformed existing disease risk-stratification schemes. These subgroup-dependent models stratified patients into four clinical risk groups for 5-year progression-free survival: favourable risk (54 [25%] of 215 patients; 91% survival [95% CI 82-100]); standard risk (50 [23%] patients; 81% survival [70-94]); high-risk (82 [38%] patients; 42% survival [31-56]); and very high-risk (29 [13%] patients; 28% survival [14-56]). The discovery of seven novel, clinically significant subgroups improves disease risk-stratification and could inform treatment decisions. These data provide a new foundation for future research and clinical investigations. Cancer Research UK, The Tom Grahame Trust, Star for Harris, Action Medical Research, SPARKS, The JGW Patterson Foundation, The INSTINCT network (co-funded by The Brain Tumour Charity, Great Ormond Street Children's Charity, and Children with Cancer UK). Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Epigenetic deregulation in chronic lymphocytic leukemia: Clinical and biological impact.

PubMed

Mansouri, Larry; Wierzbinska, Justyna Anna; Plass, Christoph; Rosenquist, Richard

2018-02-07

Deregulated transcriptional control caused by aberrant DNA methylation and/or histone modifications is a hallmark of cancer cells. In chronic lymphocytic leukemia (CLL), the most common adult leukemia, the epigenetic 'landscape' has added a new layer of complexity to our understanding of this clinically and biologically heterogeneous disease. Early studies identified aberrant DNA methylation, often based on single gene promoter analysis with both biological and clinical impact. Subsequent genome-wide profiling studies revealed differential DNA methylation between CLLs and controls and in prognostics subgroups of the disease. From these studies, it became apparent that DNA methylation in regions outside of promoters, such as enhancers, is important for the regulation of coding genes as well as for the regulation of non-coding RNAs. Although DNA methylation profiles are reportedly stable over time and in relation to therapy, a higher epigenetic heterogeneity or 'burden' is seen in more aggressive CLL subgroups, albeit as non-recurrent 'passenger' events. More recently, DNA methylation profiles in CLL analyzed in relation to differentiating normal B-cell populations revealed that the majority of the CLL epigenome reflects the epigenomes present in the cell of origin and that only a small fraction of the epigenetic alterations represents truly CLL-specific changes. Furthermore, CLL patients can be grouped into at least three clinically relevant epigenetic subgroups, potentially originating from different cells at various stages of differentiation and associated with distinct outcomes. In this review, we summarize the current understanding of the DNA methylome in CLL, the role of histone modifying enzymes, highlight insights derived from animal models and attempts made to target epigenetic regulators in CLL along with the future directions of this rapidly advancing field. Copyright © 2018 Elsevier Ltd. All rights reserved.

Analysis of human herpesvirus-6 IE1 sequence variation in clinical samples.

PubMed

Stanton, Richard; Wilkinson, Gavin W G; Fox, Julie D

2003-12-01

Herpesvirus immediate early (IE) proteins are known to play key roles in establishing productive infections, regulating reactivation from latency, and creating a cellular environment favourable to viral replication. Human herpesvirus-6 (HHV-6) IE genes have not been studied as intensively as their homologues in the prototype betaherpesvirus human cytomegalovirus (HCMV). Whilst the HCMV IE1 gene is relatively conserved, early studies indicated that HHV-6 IE1 exhibited a high level of sequence variation between HHV-6A and HHV-6B isolates, although the observation was based primarily on virus stocks that had been isolated and propagated in vitro. In this study, we investigated the level of HHV-6 IE1 sequence variation in vivo by direct sequencing of circulating virus in clinical samples without prior in vitro culture. Sequences exactly matching those reported for reference HHV-6 isolates were identified in clinical samples, thus the HHV-6 laboratory strains used in the majority of in vitro studies appear to be representative of virus circulating in vivo with respect to the IE1 gene. The HHV-6 IE1 sequence is also conserved in reference strains that had been passaged extensively in vitro. The high degree of divergence between variant A and B type IE1 sequences was confirmed, but interestingly HHV-6B IE1 sequences were observed to further segregate into two distinct subgroups, with the laboratory strains Z29 and HST representative of these two subgroups. Within each HHV-6B subgroup, a remarkably high level of homology was observed. Thus the HHV-6 IE1 sequence appears highly stable, underlining its potential importance to the viral life cycle. Copyright 2003 Wiley-Liss, Inc.

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

PubMed

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 from 6.8%-20.3% for disability, and highest at the 2 weeks follow-up. Latent Class-derived subgroups provided additional prognostic information when compared to a range of variables, but the improvements were not substantial enough to warrant further development into a new prognostic tool. Further research could investigate if these novel subgrouping approaches may help to improve existing tools that subgroup low back pain patients.

Consolidation of glycosyl hydrolase family 30 : a dual domain 4/7 hydrolase family consisting of two structurally distinct groups

Treesearch

Franz J. St John; Javier M. Gonzalez; Edwin Pozharski

2010-01-01

In this work glycosyl hydrolase (GH) family 30 (GH30) is analyzed and shown to consist of its currently classified member sequences as well as several homologous sequence groups currently assigned within family GH5. A large scale amino acid sequence alignment and a phylogenetic tree were generated and GH30 groups and subgroups were designated. A partial rearrangement...

Identification of an Amino Acid Domain Encoded by the Capsid Protein Gene of Porcine Circovirus Type 2 that Modulates Viral Protein Distribution During Replication

USDA-ARS?s Scientific Manuscript database

Previous work showed that distinct amino acid motifs are encoded by the Rep, Cap and ORF3 genes of two subgroups of porcine circoviruses (PCV), PCV2a and PCV2b. At a specific location of the gene, a certain amino acid residue or sequence is preferred. Specifically, two amino acid domains located in ...

A Systematic Approach to Subgroup Classification in Intellectual Disability

ERIC Educational Resources Information Center

Schalock, Robert L.; Luckasson, Ruth

2015-01-01

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

Treatment effect heterogeneity for univariate subgroups in clinical trials: Shrinkage, standardization, or else

PubMed Central

Varadhan, Ravi; Wang, Sue-Jane

2016-01-01

Treatment effect heterogeneity is a well-recognized phenomenon in randomized controlled clinical trials. In this paper, we discuss subgroup analyses with prespecified subgroups of clinical or biological importance. We explore various alternatives to the naive (the traditional univariate) subgroup analyses to address the issues of multiplicity and confounding. Specifically, we consider a model-based Bayesian shrinkage (Bayes-DS) and a nonparametric, empirical Bayes shrinkage approach (Emp-Bayes) to temper the optimism of traditional univariate subgroup analyses; a standardization approach (standardization) that accounts for correlation between baseline covariates; and a model-based maximum likelihood estimation (MLE) approach. The Bayes-DS and Emp-Bayes methods model the variation in subgroup-specific treatment effect rather than testing the null hypothesis of no difference between subgroups. The standardization approach addresses the issue of confounding in subgroup analyses. The MLE approach is considered only for comparison in simulation studies as the “truth” since the data were generated from the same model. Using the characteristics of a hypothetical large outcome trial, we perform simulation studies and articulate the utilities and potential limitations of these estimators. Simulation results indicate that Bayes-DS and Emp-Bayes can protect against optimism present in the naïve approach. Due to its simplicity, the naïve approach should be the reference for reporting univariate subgroup-specific treatment effect estimates from exploratory subgroup analyses. Standardization, although it tends to have a larger variance, is suggested when it is important to address the confounding of univariate subgroup effects due to correlation between baseline covariates. The Bayes-DS approach is available as an R package (DSBayes). PMID:26485117

Power of an Adaptive Trial Design for Endovascular Stroke Studies: Simulations Using IMS (Interventional Management of Stroke) III Data.

PubMed

Lansberg, Maarten G; Bhat, Ninad S; Yeatts, Sharon D; Palesch, Yuko Y; Broderick, Joseph P; Albers, Gregory W; Lai, Tze L; Lavori, Philip W

2016-12-01

Adaptive trial designs that allow enrichment of the study population through subgroup selection can increase the chance of a positive trial when there is a differential treatment effect among patient subgroups. The goal of this study is to illustrate the potential benefit of adaptive subgroup selection in endovascular stroke studies. We simulated the performance of a trial design with adaptive subgroup selection and compared it with that of a traditional design. Outcome data were based on 90-day modified Rankin Scale scores, observed in IMS III (Interventional Management of Stroke III), among patients with a vessel occlusion on baseline computed tomographic angiography (n=382). Patients were categorized based on 2 methods: (1) according to location of the arterial occlusive lesion and onset-to-randomization time and (2) according to onset-to-randomization time alone. The power to demonstrate a treatment benefit was based on 10 000 trial simulations for each design. The treatment effect was relatively homogeneous across categories when patients were categorized based on arterial occlusive lesion and time. Consequently, the adaptive design had similar power (47%) compared with the fixed trial design (45%). There was a differential treatment effect when patients were categorized based on time alone, resulting in greater power with the adaptive design (82%) than with the fixed design (57%). These simulations, based on real-world patient data, indicate that adaptive subgroup selection has merit in endovascular stroke trials as it substantially increases power when the treatment effect differs among subgroups in a predicted pattern. © 2016 American Heart Association, Inc.

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

PubMed Central

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 major subgroups A and B, and one atypical subgroup D serving as a link between L. monocytogenes and L. innocua in the evolutionary chain. Although subgroups A and B appeared at approximately the same time, subgroup A seems to have experienced a recent expansion of the population size with higher recombination frequency and effect than those of subgroup B, and might represent the possible evolutionary direction towards adaptation to enviroments. The evolutionary history in the L. monocytogenes-L. innocua clade represents a rare example of evolution towards reduced virulence of pathogens. PMID:20356375

A comparison of subgroup analyses in grant applications and publications.

PubMed

Boonacker, Chantal W B; Hoes, Arno W; van Liere-Visser, Karen; Schilder, Anne G M; Rovers, Maroeska M

2011-07-15

In this paper, the authors compare subgroup analyses as outlined in grant applications and their related publications. Grants awarded by the Netherlands Organization for Health Research and Development (ZonMw) from 2001 onward that were finalized before March 1, 2010, were studied. Of the 79 grant proposals, 50 (63%) were intervention studies, 18 (23%) were diagnostic studies, and 6 (8%) were prognostic studies. Subgroups were mentioned in 49 (62%) grant applications and in 53 (67%) publications. In 20 of the 79 projects (25%), the publications were completely in agreement with the grant proposal; that is, subgroups that were prespecified in the grant proposal were reported and no new subgroup analyses were introduced in the publications. Of the 149 prespecified subgroups, 46 (31%) were reported in the final report or scientific publications, and 143 of the 189 (76%) reported subgroups were based on post-hoc findings. For 77% of the subgroup analyses in the publications, there was no mention of whether these were prespecified or post hoc. Justification for subgroup analysis and methods to study subgroups were rarely reported. The authors conclude that there is a large discrepancy between grant applications and final publications regarding subgroup analyses. Both nonreporting prespecified subgroup analyses and reporting post-hoc subgroup analyses are common. More guidance is clearly needed.

The medical genetics workforce: an analysis of clinical geneticist subgroups.

PubMed

Cooksey, Judith A; Forte, Gaetano; Flanagan, Patricia A; Benkendorf, Judith; Blitzer, Miriam G

2006-10-01

Clinical geneticists with a Doctor of Medicine degree face challenges to meet the growing population demand for genetic services. This study was designed to assist the profession with workforce planning by identifying clinically relevant subgroups of geneticists and describing their professional characteristics and clinical practices. Geneticists' patient care productivity is compared across subgroups and other medical specialists. Part of a comprehensive national study of genetic services and the health workforce, this study uses data from a 2003 survey of geneticists certified by the American Board of Medical Genetics. This study includes 610 clinical geneticists who spend at least 5% of their time in direct patient-care services. An iterative approach was used to identify five subgroups based on the types of new patients seen. We conducted a descriptive analysis of subgroups by demographic, training, professional, and practice characteristics. The subgroups include general (36%), pediatric (28%), reproductive (15%), metabolic (14%), and adult (7%) geneticists. Clinically relevant variations across subgroups were noted in training, professional, and practice parameters. Subgroups vary across patient care hours (median, 15-33 hours/week) and total weekly work hours (52-60 hours). New patient visits (mean, 222-900/year) are higher than follow-up patient visits (mean, 155-405) for all subgroups except metabolic geneticists. Although many geneticists practice as generalist geneticists, this study provides an evidence base for distinguishing clinically relevant subgroups of geneticists. Geneticists provide similar numbers of new patient visits and far fewer follow-up visits than other medical specialists. These findings are relevant to geneticist workforce planning.

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

PubMed

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.

Anti-adhesive effect of poloxamer-based thermo-sensitive sol-gel in rabbit laminectomy model.

PubMed

Shin, Sung Joon; Lee, Jae Hyup; So, Jungwon; Min, Kyungdan

2016-11-01

Poloxamer-based thermo-sensitive sol-gel has been developed to reduce the incidence of postoperative scar formation at the laminectomy site. The purpose of this study was to evaluate the anti-adhesive effect of poloxamer based thermo-sensitive sol-gel compared to hyaluronate based solution after laminectomy, using a rabbit model. A thermo-sensitive anti-adhesive with a property of sol-gel transition was manufactured by a physical mixture of Poloxamer188/407, Chitosan and Gelatin. The viscosity in different temperatures was assessed. 72 adult New Zealand rabbits underwent lumbar laminectomy and were randomly divided into experimental (treated with the newly developed agent), positive (treated with hyaluronate based solution), and negative control groups. Each group was subdivided into 1 and 4-week subgroups. Gross and histological evaluations were performed to assess the extent of epidural adhesion. The experimental group showed significantly higher viscosity compared to the positive control group and showed a significant increase of viscosity as the temperature increased. Gross evaluation showed no statistically significant differences between the 1- and 4-week subgroups. However, histologic evaluation showed significant differences both in 1- and 4-week subgroups. Although the 4-week histologic results of the experimental and the positive control subgroups showed no significant difference, both subgroups revealed higher value compared to the negative control subgroup with regard to the ratio of adhesion less than 50 %. The new poloxamer based thermo-sensitive agent showed superior efficacy over the hyaluronate based agent at 1 week postoperatively. At 4 weeks postoperatively, there were no statistically significant differences between the two agents, although both showed efficacy over the sham group.

SiglecF+Gr1hi eosinophils are a distinct subpopulation within the lungs of allergen-challenged mice

PubMed Central

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+Gr1hi). SiglecF+Gr1hi 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+Gr1hi 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+Gr1hi eosinophil population (at 3.9 and 4.8 pg/106 cells, respectively), as was the prominent proinflammatory mediator IL-13 (72 pg/106 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+Gr1hi eosinophil subset in lungs of allergen-challenged, wild-type and granule protein-deficient mice. SiglecF+Gr1hi 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. PMID:27531929

SiglecF+Gr1hi eosinophils are a distinct subpopulation within the lungs of allergen-challenged mice.

PubMed

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.

Historical HIV incidence modelling in regional subgroups: use of flexible discrete models with penalized splines based on prior curves.

PubMed

Greenland, S

1996-03-15

This paper presents an approach to back-projection (back-calculation) of human immunodeficiency virus (HIV) person-year infection rates in regional subgroups based on combining a log-linear model for subgroup differences with a penalized spline model for trends. The penalized spline approach allows flexible trend estimation but requires far fewer parameters than fully non-parametric smoothers, thus saving parameters that can be used in estimating subgroup effects. Use of reasonable prior curve to construct the penalty function minimizes the degree of smoothing needed beyond model specification. The approach is illustrated in application to acquired immunodeficiency syndrome (AIDS) surveillance data from Los Angeles County.

The direct assignment option as a modular design component: an example for the setting of two predefined subgroups.

PubMed

An, Ming-Wen; Lu, Xin; Sargent, Daniel J; Mandrekar, Sumithra J

2015-01-01

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. 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. 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. 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.

Identification of a neuronal transcription factor network involved in medulloblastoma development

PubMed Central

2013-01-01

Background Medulloblastomas, the most frequent malignant brain tumours affecting children, comprise at least 4 distinct clinicogenetic subgroups. Aberrant sonic hedgehog (SHH) signalling is observed in approximately 25% of tumours and defines one subgroup. Although alterations in SHH pathway genes (e.g. PTCH1, SUFU) are observed in many of these tumours, high throughput genomic analyses have identified few other recurring mutations. Here, we have mutagenised the Ptch+/- murine tumour model using the Sleeping Beauty transposon system to identify additional genes and pathways involved in SHH subgroup medulloblastoma development. Results Mutagenesis significantly increased medulloblastoma frequency and identified 17 candidate cancer genes, including orthologs of genes somatically mutated (PTEN, CREBBP) or associated with poor outcome (PTEN, MYT1L) in the human disease. Strikingly, these candidate genes were enriched for transcription factors (p=2x10-5), the majority of which (6/7; Crebbp, Myt1L, Nfia, Nfib, Tead1 and Tgif2) were linked within a single regulatory network enriched for genes associated with a differentiated neuronal phenotype. Furthermore, activity of this network varied significantly between the human subgroups, was associated with metastatic disease, and predicted poor survival specifically within the SHH subgroup of tumours. Igf2, previously implicated in medulloblastoma, was the most differentially expressed gene in murine tumours with network perturbation, and network activity in both mouse and human tumours was characterised by enrichment for multiple gene-sets indicating increased cell proliferation, IGF signalling, MYC target upregulation, and decreased neuronal differentiation. Conclusions Collectively, our data support a model of medulloblastoma development in SB-mutagenised Ptch+/- mice which involves disruption of a novel transcription factor network leading to Igf2 upregulation, proliferation of GNPs, and tumour formation. Moreover, our results identify rational therapeutic targets for SHH subgroup tumours, alongside prognostic biomarkers for the identification of poor-risk SHH patients. PMID:24252690

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

PubMed

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.

Longitudinal cognitive trajectories and associated clinical variables in youth with bipolar disorder.

PubMed

Frías, Álvaro; Dickstein, Daniel P; Merranko, John; Gill, Mary Kay; Goldstein, Tina R; Goldstein, Benjamin I; Hower, Heather; Yen, Shirley; Hafeman, Danella M; Liao, Fangzi; Diler, Rasim; Axelson, David; Strober, Michael; Hunt, Jeffrey I; Ryan, Neal D; Keller, Martin B; Birmaher, Boris

2017-06-01

There is substantial interest in delineating the course of cognitive functioning in bipolar (BP) youth. However, there are no longitudinal studies aimed at defining subgroups of BP youth based on their distinctive cognitive trajectories and their associated clinical variables. Cognitive functioning was measured in 135 participants from the Course and Outcome of BP Youth (COBY) study using several subtests of the Cambridge Neuropsychological Test Automated Battery (CANTAB). Youth were prospectively evaluated three times on average every 13.75 months over 2.5 years. Clinical and functional outcomes were assessed using the Longitudinal Interval Follow-Up Evaluation (LIFE). Latent class growth analysis identified three longitudinal patterns of cognitive functioning based on a general cognitive index: class 1, "persistently high" (N=21; 15.6%); class 2, "persistently moderate" (N=82; 60.74%); and class 3, "persistently low" (N=32; 23.7%). All classes showed normal cognitive functioning when compared with the CANTAB normative data. After adjustment for confounders, youth from class 3 had a significantly greater percentage of time with overall, manic, and depressive syndromal symptoms than youth in the other two classes. Also, after adjustment for confounders, youth from class 3 had significantly poorer global, academic, and social functioning than youth from class 1. BP youth showed normal overall cognitive functioning that remained stable during the follow-up within each class. However, 24% of BP youth showed poorer cognitive functioning than the other BP youth. This subgroup had poorer mood course and functioning, and may benefit from cognitive remediation and early management with evidence-based pharmacological treatments. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

PubMed Central

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

Population Neuroscience: Dementia Epidemiology Serving Precision Medicine and Population Health.

PubMed

Ganguli, Mary; Albanese, Emiliano; Seshadri, Sudha; Bennett, David A; Lyketsos, Constantine; Kukull, Walter A; Skoog, Ingmar; Hendrie, Hugh C

2018-01-01

Over recent decades, epidemiology has made significant contributions to our understanding of dementia, translating scientific discoveries into population health. Here, we propose reframing dementia epidemiology as "population neuroscience," blending techniques and models from contemporary neuroscience with those of epidemiology and biostatistics. On the basis of emerging evidence and newer paradigms and methods, population neuroscience will minimize the bias typical of traditional clinical research, identify the relatively homogenous subgroups that comprise the general population, and investigate broader and denser phenotypes of dementia and cognitive impairment. Long-term follow-up of sufficiently large study cohorts will allow the identification of cohort effects and critical windows of exposure. Molecular epidemiology and omics will allow us to unravel the key distinctions within and among subgroups and better understand individuals' risk profiles. Interventional epidemiology will allow us to identify the different subgroups that respond to different treatment/prevention strategies. These strategies will inform precision medicine. In addition, insights into interactions between disease biology, personal and environmental factors, and social determinants of health will allow us to measure and track disease in communities and improve population health. By placing neuroscience within a real-world context, population neuroscience can fulfill its potential to serve both precision medicine and population health.

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

PubMed

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.

Lexical Variation and Change in British Sign Language

PubMed Central

Stamp, Rose; Schembri, Adam; Fenlon, Jordan; Rentelis, Ramas; Woll, Bencie; Cormier, Kearsy

2014-01-01

This paper presents results from a corpus-based study investigating lexical variation in BSL. An earlier study investigating variation in BSL numeral signs found that younger signers were using a decreasing variety of regionally distinct variants, suggesting that levelling may be taking place. Here, we report findings from a larger investigation looking at regional lexical variants for colours, countries, numbers and UK placenames elicited as part of the BSL Corpus Project. Age, school location and language background were significant predictors of lexical variation, with younger signers using a more levelled variety. This change appears to be happening faster in particular sub-groups of the deaf community (e.g., signers from hearing families). Also, we find that for the names of some UK cities, signers from outside the region use a different sign than those who live in the region. PMID:24759673

Uneven Expressive Language Development in Mandarin-Exposed Preschool Children with ASD: Comparing Vocabulary, Grammar, and the Decontextualized Use of Language via the PCDI-Toddler Form.

PubMed

Su, Yi Esther; Naigles, Letitia R; Su, Lin-Yan

2018-05-21

Data from children with ASD who are learning Indo-European languages indicate that (a) they vary hugely in their expressive language skills and (b) their pragmatic/socially-based language is more impaired than their structural language. We investigate whether similar patterns of language development exist for Mandarin-exposed children with ASD. Parent report data of the Putonghua Communicative Development Inventory-Toddler Form were collected from 160 17-83-month-old children with ASD. These children with ASD demonstrated similar levels of variability as Western children with ASD. In particular, they could be divided into three distinct subgroups (high verbal, middle verbal, low verbal), all of which manifested relative strengths in lexical and grammatical language compared to pragmatic usage of decontextualized language.

Cognition and the Brain

DTIC Science & Technology

1992-05-25

by a by the distinctions between short-term and long-term sensory event. As evidence they shom that %khen the ISI memory ’. episodic , semantic and...Patterson. J.V. and Starr. A. I 19S9a) ams .1 function of variations in semantic citaceori,’itions. In: D. Brain potentials in a memory scanning task. 1...number) FIELD GROUP SUB-GROUP L ocalization of cognitive processes; alpha-band suppression; memory scanning for tones; silent speech; visual image

Sibling rivalry in the E2F family.

PubMed

Trimarchi, Jeffrey M; Lees, Jacqueline A

2002-01-01

The E2F transcription factor family determines whether or not a cell will divide by controlling the expression of key cell-cycle regulators. The individual E2Fs can be divided into distinct subgroups that act in direct opposition to one another to promote either cellular proliferation or cell-cycle exit and terminal differentiation. What is the underlying molecular basis of this 'push-me-pull-you' regulation, and what are its biological consequences?

Profiles of Cyberpornography Use and Sexual Well-Being in Adults.

PubMed

Vaillancourt-Morel, Marie-Pier; Blais-Lecours, Sarah; Labadie, Chloé; Bergeron, Sophie; Sabourin, Stéphane; Godbout, Natacha

2017-01-01

Although findings concerning sexual outcomes associated with cyberpornography use are mixed, viewing explicit sexual content online is becoming a common activity for an increasing number of individuals. To investigate heterogeneity in cyberpornography-related sexual outcomes by examining a theoretically and clinically based model suggesting that individuals who spend time viewing online pornography form three distinct profiles (recreational, at-risk, and compulsive) and to examine whether these profiles were associated with sexual well-being, sex, and interpersonal context of pornography use. The present cluster-analytic study was conducted using a convenience sample of 830 adults who completed online self-reported measurements of cyberpornography use and sexual well-being, which included sexual satisfaction, compulsivity, avoidance, and dysfunction. Dimensions of cyberpornography use were assessed using the Cyber Pornography Use Inventory. Sexual well-being measurements included the Global Measure of Sexual Satisfaction, the Sexual Compulsivity Scale, the Sexual Avoidance Subscale, and the Arizona Sexual Experiences Scale. Cluster analyses indicated three distinct profiles: recreational (75.5%), highly distressed non-compulsive (12.7%), and compulsive (11.8%). Recreational users reported higher sexual satisfaction and lower sexual compulsivity, avoidance, and dysfunction, whereas users with a compulsive profile presented lower sexual satisfaction and dysfunction and higher sexual compulsivity and avoidance. Highly distressed less active users were sexually less satisfied and reported less sexual compulsivity and more sexual dysfunction and avoidance. A larger proportion of women and of dyadic users was found among recreational users, whereas solitary users were more likely to be in the highly distressed less active profile and men were more likely to be in the compulsive profile. This pattern of results confirms the existence of recreational and compulsive profiles but also demonstrates the existence of an important subgroup of not particularly active, yet highly distressed consumers. Cyberpornography users represent a heterogeneous population, in which each subgroup is associated with specific sexual outcomes. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Integrating Colon Cancer Microarray Data: Associating Locus-Specific Methylation Groups to Gene Expression-Based Classifications.

PubMed

Barat, Ana; Ruskin, Heather J; Byrne, Annette T; Prehn, Jochen H M

2015-11-23

Recently, considerable attention has been paid to gene expression-based classifications of colorectal cancers (CRC) and their association with patient prognosis. In addition to changes in gene expression, abnormal DNA-methylation is known to play an important role in cancer onset and development, and colon cancer is no exception to this rule. Large-scale technologies, such as methylation microarray assays and specific sequencing of methylated DNA, have been used to determine whole genome profiles of CpG island methylation in tissue samples. In this article, publicly available microarray-based gene expression and methylation data sets are used to characterize expression subtypes with respect to locus-specific methylation. A major objective was to determine whether integration of these data types improves previously characterized subtypes, or provides evidence for additional subtypes. We used unsupervised clustering techniques to determine methylation-based subgroups, which are subsequently annotated with three published expression-based classifications, comprising from three to six subtypes. Our results showed that, while methylation profiles provide a further basis for segregation of certain (Inflammatory and Goblet-like) finer-grained expression-based subtypes, they also suggest that other finer-grained subtypes are not distinctive and can be considered as a single subtype.

Integrating Colon Cancer Microarray Data: Associating Locus-Specific Methylation Groups to Gene Expression-Based Classifications

PubMed Central

Barat, Ana; Ruskin, Heather J.; Byrne, Annette T.; Prehn, Jochen H. M.

2015-01-01

Recently, considerable attention has been paid to gene expression-based classifications of colorectal cancers (CRC) and their association with patient prognosis. In addition to changes in gene expression, abnormal DNA-methylation is known to play an important role in cancer onset and development, and colon cancer is no exception to this rule. Large-scale technologies, such as methylation microarray assays and specific sequencing of methylated DNA, have been used to determine whole genome profiles of CpG island methylation in tissue samples. In this article, publicly available microarray-based gene expression and methylation data sets are used to characterize expression subtypes with respect to locus-specific methylation. A major objective was to determine whether integration of these data types improves previously characterized subtypes, or provides evidence for additional subtypes. We used unsupervised clustering techniques to determine methylation-based subgroups, which are subsequently annotated with three published expression-based classifications, comprising from three to six subtypes. Our results showed that, while methylation profiles provide a further basis for segregation of certain (Inflammatory and Goblet-like) finer-grained expression-based subtypes, they also suggest that other finer-grained subtypes are not distinctive and can be considered as a single subtype. PMID:27600244

Genomic Tools for Evolution and Conservation in the Chimpanzee: Pan troglodytes ellioti Is a Genetically Distinct Population

PubMed Central

Myers, Simon; Hellenthal, Garrett; Nerrienet, Eric; Bontrop, Ronald E.; Freeman, Colin; Donnelly, Peter; Mundy, Nicholas I.

2012-01-01

In spite of its evolutionary significance and conservation importance, the population structure of the common chimpanzee, Pan troglodytes, is still poorly understood. An issue of particular controversy is whether the proposed fourth subspecies of chimpanzee, Pan troglodytes ellioti, from parts of Nigeria and Cameroon, is genetically distinct. Although modern high-throughput SNP genotyping has had a major impact on our understanding of human population structure and demographic history, its application to ecological, demographic, or conservation questions in non-human species has been extremely limited. Here we apply these tools to chimpanzee population structure, using ∼700 autosomal SNPs derived from chimpanzee genomic data and a further ∼100 SNPs from targeted re-sequencing. We demonstrate conclusively the existence of P. t. ellioti as a genetically distinct subgroup. We show that there is clear differentiation between the verus, troglodytes, and ellioti populations at the SNP and haplotype level, on a scale that is greater than that separating continental human populations. Further, we show that only a small set of SNPs (10–20) is needed to successfully assign individuals to these populations. Tellingly, use of only mitochondrial DNA variation to classify individuals is erroneous in 4 of 54 cases, reinforcing the dangers of basing demographic inference on a single locus and implying that the demographic history of the species is more complicated than that suggested analyses based solely on mtDNA. In this study we demonstrate the feasibility of developing economical and robust tests of individual chimpanzee origin as well as in-depth studies of population structure. These findings have important implications for conservation strategies and our understanding of the evolution of chimpanzees. They also act as a proof-of-principle for the use of cheap high-throughput genomic methods for ecological questions. PMID:22396655

Genomic tools for evolution and conservation in the chimpanzee: Pan troglodytes ellioti is a genetically distinct population.

PubMed

Bowden, Rory; MacFie, Tammie S; Myers, Simon; Hellenthal, Garrett; Nerrienet, Eric; Bontrop, Ronald E; Freeman, Colin; Donnelly, Peter; Mundy, Nicholas I

2012-01-01

In spite of its evolutionary significance and conservation importance, the population structure of the common chimpanzee, Pan troglodytes, is still poorly understood. An issue of particular controversy is whether the proposed fourth subspecies of chimpanzee, Pan troglodytes ellioti, from parts of Nigeria and Cameroon, is genetically distinct. Although modern high-throughput SNP genotyping has had a major impact on our understanding of human population structure and demographic history, its application to ecological, demographic, or conservation questions in non-human species has been extremely limited. Here we apply these tools to chimpanzee population structure, using ∼700 autosomal SNPs derived from chimpanzee genomic data and a further ∼100 SNPs from targeted re-sequencing. We demonstrate conclusively the existence of P. t. ellioti as a genetically distinct subgroup. We show that there is clear differentiation between the verus, troglodytes, and ellioti populations at the SNP and haplotype level, on a scale that is greater than that separating continental human populations. Further, we show that only a small set of SNPs (10-20) is needed to successfully assign individuals to these populations. Tellingly, use of only mitochondrial DNA variation to classify individuals is erroneous in 4 of 54 cases, reinforcing the dangers of basing demographic inference on a single locus and implying that the demographic history of the species is more complicated than that suggested analyses based solely on mtDNA. In this study we demonstrate the feasibility of developing economical and robust tests of individual chimpanzee origin as well as in-depth studies of population structure. These findings have important implications for conservation strategies and our understanding of the evolution of chimpanzees. They also act as a proof-of-principle for the use of cheap high-throughput genomic methods for ecological questions.

Identifying subgroups of patients using latent class analysis: should we use a single-stage or a two-stage approach? A methodological study using a cohort of patients with low back pain.

PubMed

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

2017-02-01

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. From 928 LBP patients consulting a chiropractor, baseline data were used as input to the statistical subgrouping. In a single-stage LCA, all variables were modelled simultaneously to identify patient subgroups. In a two-stage LCA, we used the latent class membership from our previously published LCA within each of six domains of health (activity, contextual factors, pain, participation, physical impairment and psychology) (first stage) as the variables entered into the second stage of the two-stage LCA to identify patient subgroups. The description of the results of the single-stage and two-stage LCA was based on a combination of statistical performance measures, qualitative evaluation of clinical interpretability (face validity) and a subgroup membership comparison. 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 identified similar, but not identical, patient subgroups characterised by (i) mild intermittent LBP, (ii) recent severe LBP and activity limitations, (iii) very recent severe LBP with both activity and participation limitations, (iv) work-related LBP, (v) LBP and several negative consequences and (vi) LBP with nerve root involvement. Both approaches identified clinically interpretable patient subgroups. The potential importance of these subgroups needs to be investigated by exploring whether they can be identified in other cohorts and by examining their possible association with patient outcomes. This may inform the selection of a preferred LCA approach.

Dissociative Experiences are Associated with Obsessive-Compulsive Symptoms in a Non-clinical Sample: A Latent Profile Analysis

PubMed Central

BOYSAN, Murat

2014-01-01

Introduction There has been a burgeoning literature considering the significant associations between obsessive-compulsive symptoms and dissociative experiences. In this study, the relationsips between dissociative symtomotology and dimensions of obsessive-compulsive symptoms were examined in homogeneous sub-groups obtained with latent class algorithm in an undergraduate Turkish sample. Method Latent profile analysis, a recently developed classification method based on latent class analysis, was applied to the Dissociative Experiences Scale (DES) item-response data from 2976 undergraduates. Differences in severity of obsessive-compulsive symptoms, anxiety and depression across groups were evaluated by running multinomial logistic regression analyses. Associations between latent class probabilities and psychological variables in terms of obsessive-compulsive sub-types, anxiety, and depression were assessed by computing Pearson’s product-moment correlation coefficients. Results The findings of the latent profile analysis supported further evidence for discontinuity model of dissociative experiences. The analysis empirically justified the distinction among three sub-groups based on the DES items. A marked proportion of the sample (42%) was assigned to the high dissociative class. In the further analyses, all sub-types of obsessive-compulsive symptoms significantly differed across latent classes. Regarding the relationships between obsessive-compulsive symptoms and dissociative symptomatology, low dissociation appeared to be a buffering factor dealing with obsessive-compulsive symptoms; whereas high dissociation appeared to be significantly associated with high levels of obsessive-compulsive symptoms. Conclusion It is concluded that the concept of dissociation can be best understood in a typological approach that dissociative symptomatology not only exacerbates obsessive-compulsive symptoms but also serves as an adaptive coping mechanism. PMID:28360635

Dissociative Experiences are Associated with Obsessive-Compulsive Symptoms in a Non-clinical Sample: A Latent Profile Analysis.

PubMed

Boysan, Murat

2014-09-01

There has been a burgeoning literature considering the significant associations between obsessive-compulsive symptoms and dissociative experiences. In this study, the relationsips between dissociative symtomotology and dimensions of obsessive-compulsive symptoms were examined in homogeneous sub-groups obtained with latent class algorithm in an undergraduate Turkish sample. Latent profile analysis, a recently developed classification method based on latent class analysis, was applied to the Dissociative Experiences Scale (DES) item-response data from 2976 undergraduates. Differences in severity of obsessive-compulsive symptoms, anxiety and depression across groups were evaluated by running multinomial logistic regression analyses. Associations between latent class probabilities and psychological variables in terms of obsessive-compulsive sub-types, anxiety, and depression were assessed by computing Pearson's product-moment correlation coefficients. The findings of the latent profile analysis supported further evidence for discontinuity model of dissociative experiences. The analysis empirically justified the distinction among three sub-groups based on the DES items. A marked proportion of the sample (42%) was assigned to the high dissociative class. In the further analyses, all sub-types of obsessive-compulsive symptoms significantly differed across latent classes. Regarding the relationships between obsessive-compulsive symptoms and dissociative symptomatology, low dissociation appeared to be a buffering factor dealing with obsessive-compulsive symptoms; whereas high dissociation appeared to be significantly associated with high levels of obsessive-compulsive symptoms. It is concluded that the concept of dissociation can be best understood in a typological approach that dissociative symptomatology not only exacerbates obsessive-compulsive symptoms but also serves as an adaptive coping mechanism.

SELF-CONCEPT DIFFERENTIATION AND SELF-CONCEPT CLARITY ACROSS ADULTHOOD: ASSOCIATIONS WITH AGE AND PSYCHOLOGICAL WELL-BEING*

PubMed Central

DIEHL, MANFRED; HAY, ELIZABETH L.

2011-01-01

This study focused on the identification of conceptually meaningful groups of individuals based on their joint self-concept differentiation (SCD) and self-concept clarity (SCC) scores. Notably, we examined whether membership in different SCD-SCC groups differed by age and also was associated with differences in psychological well-being (PWB). Cluster analysis revealed five distinct SCD-SCC groups: a self-assured, unencumbered, fragmented-only, confused-only, and fragmented and confused group. Individuals in the self-assured group had the highest mean scores for positive PWB and the lowest mean scores for negative PWB, whereas individuals in the fragmented and confused group showed the inverse pattern. Findings showed that it was psychologically advantageous to belong to the self-assured group at all ages. As hypothesized, older adults were more likely than young adults to be in the self-assured cluster, whereas young adults were more likely to be in the fragmented and confused cluster. Thus, consistent with extant theorizing, age was positively associated with psychologically adaptive self-concept profiles. This study examined whether conceptually meaningful subgroups of individuals can be identified based on their joint scores on self-concept differentiation (SCD) and self-concept clarity (SCC). Specifically, we considered whether individuals within such subgroups differed systematically from one another on measures of positive and negative psychological well-being (PWB). Of interest to us was also whether there were age differences in the distribution of adults across the SCD-SCC groups and whether age moderated the association between PWB and SCD-SCC grouping. PMID:22010361

Clinical and Biological Relevance of Genomic Heterogeneity in Chronic Lymphocytic Leukemia

PubMed Central

Friedman, Daphne R.; Lucas, Joseph E.; Weinberg, J. Brice

2013-01-01

Background Chronic lymphocytic leukemia (CLL) is typically regarded as an indolent B-cell malignancy. However, there is wide variability with regards to need for therapy, time to progressive disease, and treatment response. This clinical variability is due, in part, to biological heterogeneity between individual patients’ leukemias. While much has been learned about this biological variation using genomic approaches, it is unclear whether such efforts have sufficiently evaluated biological and clinical heterogeneity in CLL. Methods To study the extent of genomic variability in CLL and the biological and clinical attributes of genomic classification in CLL, we evaluated 893 unique CLL samples from fifteen publicly available gene expression profiling datasets. We used unsupervised approaches to divide the data into subgroups, evaluated the biological pathways and genetic aberrations that were associated with the subgroups, and compared prognostic and clinical outcome data between the subgroups. Results Using an unsupervised approach, we determined that approximately 600 CLL samples are needed to define the spectrum of diversity in CLL genomic expression. We identified seven genomically-defined CLL subgroups that have distinct biological properties, are associated with specific chromosomal deletions and amplifications, and have marked differences in molecular prognostic markers and clinical outcomes. Conclusions Our results indicate that investigations focusing on small numbers of patient samples likely provide a biased outlook on CLL biology. These findings may have important implications in identifying patients who should be treated with specific targeted therapies, which could have efficacy against CLL cells that rely on specific biological pathways. PMID:23468975

Gene Expression Analyses of the Spatio-Temporal Relationships of Human Medulloblastoma Subgroups during Early Human Neurogenesis

PubMed Central

Hooper, Cornelia M.; Hawes, Susan M.; Kees, Ursula R.; Gottardo, Nicholas G.; Dallas, Peter B.

2014-01-01

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. PMID:25412507

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

PubMed

Hooper, Cornelia M; Hawes, Susan M; Kees, Ursula R; Gottardo, Nicholas G; Dallas, Peter B

2014-01-01

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.

Clinical and biological relevance of genomic heterogeneity in chronic lymphocytic leukemia.

PubMed

Friedman, Daphne R; Lucas, Joseph E; Weinberg, J Brice

2013-01-01

Chronic lymphocytic leukemia (CLL) is typically regarded as an indolent B-cell malignancy. However, there is wide variability with regards to need for therapy, time to progressive disease, and treatment response. This clinical variability is due, in part, to biological heterogeneity between individual patients' leukemias. While much has been learned about this biological variation using genomic approaches, it is unclear whether such efforts have sufficiently evaluated biological and clinical heterogeneity in CLL. To study the extent of genomic variability in CLL and the biological and clinical attributes of genomic classification in CLL, we evaluated 893 unique CLL samples from fifteen publicly available gene expression profiling datasets. We used unsupervised approaches to divide the data into subgroups, evaluated the biological pathways and genetic aberrations that were associated with the subgroups, and compared prognostic and clinical outcome data between the subgroups. Using an unsupervised approach, we determined that approximately 600 CLL samples are needed to define the spectrum of diversity in CLL genomic expression. We identified seven genomically-defined CLL subgroups that have distinct biological properties, are associated with specific chromosomal deletions and amplifications, and have marked differences in molecular prognostic markers and clinical outcomes. Our results indicate that investigations focusing on small numbers of patient samples likely provide a biased outlook on CLL biology. These findings may have important implications in identifying patients who should be treated with specific targeted therapies, which could have efficacy against CLL cells that rely on specific biological pathways.

Rapid visual perception of interracial crowds: Racial category learning from emotional segregation.

PubMed

Lamer, Sarah Ariel; Sweeny, Timothy D; Dyer, Michael Louis; Weisbuch, Max

2018-05-01

Drawing from research on social identity and ensemble coding, we theorize that crowd perception provides a powerful mechanism for social category learning. Crowds include allegiances that may be distinguished by visual cues to shared behavior and mental states, providing perceivers with direct information about social groups and thus a basis for learning social categories. Here, emotion expressions signaled group membership: to the extent that a crowd exhibited emotional segregation (i.e., was segregated into emotional subgroups), a visible characteristic (race) that incidentally distinguished emotional subgroups was expected to support categorical distinctions. Participants were randomly assigned to view interracial crowds in which emotion differences between (black vs. white) subgroups were either small (control condition) or large (emotional segregation condition). On each trial, participants saw crowds of 12 faces (6 black, 6 white) for roughly 300 ms and were asked to estimate the average emotion of the entire crowd. After all trials, participants completed a racial categorization task and self-report measure of race essentialism. As predicted, participants exposed to emotional segregation (vs. control) exhibited stronger racial category boundaries and stronger race essentialism. Furthermore, such effects accrued via ensemble coding, a visual mechanism that summarizes perceptual information: emotional segregation strengthened participants' racial category boundaries to the extent that segregation limited participants' abilities to integrate emotion across racial subgroups. Together with evidence that people observe emotional segregation in natural environments, these findings suggest that crowd perception mechanisms support racial category boundaries and race essentialism. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Identification of Gene Networks Associated with Acute Myeloid Leukemia by Comparative Molecular Methylation and Expression Profiling

PubMed Central

Dellett, Margaret; O’Hagan, Kathleen Ann; Colyer, Hilary Ann Alexandra; Mills, Ken I.

2010-01-01

Around 80% of acute myeloid leukemia (AML) patients achieve a complete remission, however many will relapse and ultimately die of their disease. The association between karyotype and prognosis has been studied extensively and identified patient cohorts as having favourable [e.g. t(8; 21), inv (16)/t(16; 16), t(15; 17)], intermediate [e.g. cytogenetically normal (NK-AML)] or adverse risk [e.g. complex karyotypes]. Previous studies have shown that gene expression profiling signatures can classify the sub-types of AML, although few reports have shown a similar feature by using methylation markers. The global methylation patterns in 19 diagnostic AML samples were investigated using the Methylated CpG Island Amplification Microarray (MCAM) method and CpG island microarrays containing 12,000 CpG sites. The first analysis, comparing favourable and intermediate cytogenetic risk groups, revealed significantly differentially methylated CpG sites (594 CpG islands) between the two subgroups. Mutations in the NPM1 gene occur at a high frequency (40%) within the NK-AML subgroup and are associated with a more favourable prognosis in these patients. A second analysis comparing the NPM1 mutant and wild-type research study subjects again identified distinct methylation profiles between these two subgroups. Network and pathway analysis revealed possible molecular mechanisms associated with the different risk and/or mutation sub-groups. This may result in a better classification of the risk groups, improved monitoring targets, or the identification of novel molecular therapies. PMID:24179384

Protective and risk factors for toxocariasis in children from two different social classes of Brazil.

PubMed

Santarém, Vamilton Alvares; Leli, Flávia Noris Chagas; Rubinsky-Elefant, Guita; Giuffrida, Rogério

2011-01-01

The aim of this study was to analyze the prevalence of Toxocara spp. antibodies in children from two different socioeconomic classes in the Presidente Prudente municipality, São Paulo State, Brazil, and the protective and risk factors associated with toxocariasis. One hundred and twenty-six middle-class (MC) and 126 disadvantaged children (DC) were included in this study. Anti-Toxocara ELISA test was performed in order to evaluate seroprevalence. A survey was applied to the children's guardians/parents in order to analyze the protective and risk factors. The overall prevalence was 11.1%, and of 9.5% (12/126) and 12.7% (16/126) for MC and DC subgroups, respectively. Toxocara seropositivity was inversely proportional to the family income. A high household income was considered a protective factor for toxocariasis in the total population and in both MC and DC subgroups. Being a girl was considered a protective factor for the total population and for both subgroups. Whilst being an owner of cat was a risk factor for children belonging to the total and for both MC and DC subgroups, having dog was considered as a risk factor for only the MC. Epidemiologic protective/factor risks can be distinct depending on the strata of the same population. Thus, it is relevant to evaluate these factors independently for different socioeconomic classes in order to design future investigations and programs for preventing the infection of human beings by Toxocara spp. and other geohelminths.

Genomic profiling using array comparative genomic hybridization define distinct subtypes of diffuse large b-cell lymphoma: a review of the literature

PubMed Central

2012-01-01

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 as Karyotypes and FISH have played a major role in classification schemes of lymphomas, better classification models are clearly needed to further understanding the biology, disease outcome and therapeutic management of DLBCL. In summary, microarray data reviewed here can provide better subtype specific classifications models for DLBCL. PMID:22967872

The crystal structures of the tri-functional Chloroflexus aurantiacus and bi-functional Rhodobacter sphaeroides malyl-CoA lyases and comparison with CitE-like superfamily enzymes and malate synthases.

PubMed

Zarzycki, Jan; Kerfeld, Cheryl A

2013-11-09

Malyl-CoA lyase (MCL) is a promiscuous carbon-carbon bond lyase that catalyzes the reversible cleavage of structurally related Coenzyme A (CoA) thioesters. This enzyme plays a crucial, multifunctional role in the 3-hydroxypropionate bi-cycle for autotrophic CO2 fixation in Chloroflexus aurantiacus. A second, phylogenetically distinct MCL from Rhodobacter sphaeroides is involved in the ethylmalonyl-CoA pathway for acetate assimilation. Both MCLs belong to the large superfamily of CitE-like enzymes, which includes the name-giving β-subunit of citrate lyase (CitE), malyl-CoA thioesterases and other enzymes of unknown physiological function. The CitE-like enzyme superfamily also bears sequence and structural resemblance to the malate synthases. All of these different enzymes share highly conserved catalytic residues, although they catalyze distinctly different reactions: C-C bond formation and cleavage, thioester hydrolysis, or both (the malate synthases). Here we report the first crystal structures of MCLs from two different phylogenetic subgroups in apo- and substrate-bound forms. Both the C. aurantiacus and the R. sphaeroides MCL contain elaborations on the canonical β8/α8 TIM barrel fold and form hexameric assemblies. Upon ligand binding, changes in the C-terminal domains of the MCLs result in closing of the active site, with the C-terminal domain of one monomer forming a lid over and contributing side chains to the active site of the adjacent monomer. The distinctive features of the two MCL subgroups were compared to known structures of other CitE-like superfamily enzymes and to malate synthases, providing insight into the structural subtleties that underlie the functional versatility of these enzymes. Although the C. aurantiacus and the R. sphaeroides MCLs have divergent primary structures (~37% identical), their tertiary and quaternary structures are very similar. It can be assumed that the C-C bond formation catalyzed by the MCLs occurs as proposed for malate synthases. However, a comparison of the two MCL structures with known malate synthases raised the question why the MCLs are not also able to hydrolyze CoA thioester bonds. Our results suggest the previously proposed reaction mechanism for malate synthases may be incomplete or not entirely correct. Further studies involving site-directed mutagenesis based on these structures may be required to solve this puzzling question.

The New Classification of Seizures by the International League Against Epilepsy 2017.

PubMed

Fisher, Robert S

2017-06-01

This review presents the newly developed International League Against Epilepsy (ILAE) 2017 classification of seizure types. The fundamental distinction is between seizures that begin focally in one hemisphere of the brain, generalized onset seizures that apparently originate in both hemispheres, and seizures of unknown onset. Focal seizures optionally can be subclassified according to whether awareness (a surrogate marker for consciousness) is intact or impaired. The next level of classification for focal seizures is motor (with subgroups automatisms, atonic, clonic, epileptic spasms, hyperkinetic, myoclonic, tonic), non-motor (with subgroups autonomic, behavior arrest, cognitive, emotional, sensory), and focal to bilateral tonic-clonic. Generalized seizures are categorized as motor (tonic-clonic, clonic, tonic, myoclonic, myoclonic-tonic-clonic, myoclonic-atonic, atonic, epileptic spasms) and non-motor/absence (typical, atypical, myoclonic, eyelid myoclonia). The classification allows new types of focal seizures and a few new generalized seizures, and clarifies terms used to name seizures.

Developmental dyspraxia by any other name: are they all just clumsy children?

PubMed

Missiuna, C; Polatajko, H

1995-01-01

The recent introduction of the diagnostic category developmental coordination disorder (DCD) (American Psychiatric Association [APA], 1987, 1994), has generated confusion among researchers and clinicians in many fields, including occupational therapy. Although the diagnostic criteria appear to be similar to those used to define clumsy children, children with developmental dyspraxia, or children with sensory integrative dysfunction, we are left with the question: Are children who receive the diagnosis of DCD the same as those who receive the other diagnoses, a subgroup, or an entirely distinct group of children? This article will examine the theoretical and empirical literature and use the results to support the thesis that these terms are not interchangeable and yet are not being used in the literature in a way that clearly defines each subgroup of children. Clear definitions and characteristic features need to be identified and associated with each term to guide occupational therapy assessment and intervention and clinical research.

Evolutionary relationships among pathogenic Candida species and relatives.

PubMed Central

Barns, S M; Lane, D J; Sogin, M L; Bibeau, C; Weisburg, W G

1991-01-01

Small subunit rRNA sequences have been determined for 10 of the most clinically important pathogenic species of the yeast genus Candida (including Torulopsis [Candida] glabrata and Yarrowia [Candida] lipolytica) and for Hansenula polymorpha. Phylogenetic analyses of these sequences and those of Saccharomyces cerevisiae, Kluyveromyces marxianus var. lactis, and Aspergillus fumigatus indicate that Candida albicans, C. tropicalis, C. parapsilosis, and C. viswanathii form a subgroup within the genus. The remaining significant pathogen, T. glabrata, falls into a second, distinct subgroup and is specifically related to S. cerevisiae and more distantly related to C. kefyr (psuedotropicalis) and K. marxianus var. lactis. The 18S rRNA sequence of Y. lipolytica has evolved rapidly in relation to the other Candida sequences examined and appears to be only distantly related to them. As anticipated, species of several other genera appear to bear specific relationships to members of the genus Candida. PMID:2007550

Inference of Functionally-Relevant N-acetyltransferase Residues Based on Statistical Correlations.

PubMed

Neuwald, Andrew F; Altschul, Stephen F

2016-12-01

Over evolutionary time, members of a superfamily of homologous proteins sharing a common structural core diverge into subgroups filling various functional niches. At the sequence level, such divergence appears as correlations that arise from residue patterns distinct to each subgroup. Such a superfamily may be viewed as a population of sequences corresponding to a complex, high-dimensional probability distribution. Here we model this distribution as hierarchical interrelated hidden Markov models (hiHMMs), which describe these sequence correlations implicitly. By characterizing such correlations one may hope to obtain information regarding functionally-relevant properties that have thus far evaded detection. To do so, we infer a hiHMM distribution from sequence data using Bayes' theorem and Markov chain Monte Carlo (MCMC) sampling, which is widely recognized as the most effective approach for characterizing a complex, high dimensional distribution. Other routines then map correlated residue patterns to available structures with a view to hypothesis generation. When applied to N-acetyltransferases, this reveals sequence and structural features indicative of functionally important, yet generally unknown biochemical properties. Even for sets of proteins for which nothing is known beyond unannotated sequences and structures, this can lead to helpful insights. We describe, for example, a putative coenzyme-A-induced-fit substrate binding mechanism mediated by arginine residue switching between salt bridge and π-π stacking interactions. A suite of programs implementing this approach is available (psed.igs.umaryland.edu).

Host range diversification within the IncP-1 plasmid group

PubMed Central

Yano, Hirokazu; Rogers, Linda M.; Knox, Molly G.; Heuer, Holger; Smalla, Kornelia; Brown, Celeste J.

2013-01-01

Broad-host-range plasmids play a critical role in the spread of antibiotic resistance and other traits. In spite of increasing information about the genomic diversity of closely related plasmids, the relationship between sequence divergence and host range remains unclear. IncP-1 plasmids are currently classified into six subgroups based on the genetic distance of backbone genes. We investigated whether plasmids from two subgroups exhibit a different host range, using two IncP-1γ plasmids, an IncP-1β plasmid and their minireplicons. Efficiencies of plasmid establishment and maintenance were compared using five species that belong to the Alphaproteobacteria, Betaproteobacteria and Gammaproteobacteria. The IncP-1β plasmid replicated and persisted in all five hosts in the absence of selection. Of the two IncP-1γ plasmids, both were unable to replicate in alphaproteobacterial host Sphingobium japonicum, and one established itself in Agrobacterium tumefaciens but was very unstable. In contrast, both IncP-1γ minireplicons, which produced higher levels of replication initiation protein than the wild-type plasmids, replicated in all strains, suggesting that poor establishment of the native plasmids is in part due to suboptimal replication initiation gene regulation. The findings suggest that host ranges of distinct IncP-1 plasmids only partially overlap, which may limit plasmid recombination and thus result in further genome divergence. PMID:24002747

Aggressive surgery for borderline resectable pancreatic cancer: evaluation of National Comprehensive Cancer Network guidelines.

PubMed

Yamada, Suguru; Fujii, Tsutomu; Sugimoto, Hiroyuki; Nomoto, Shuji; Takeda, Shin; Kodera, Yasuhiro; Nakao, Akimasa

2013-08-01

The objective of this study was to evaluate the relevance of defining borderline resectable (BR) pancreatic cancer as a distinct entity in the treatment scheme of pancreatic cancer as proposed by the National Comprehensive Cancer Network. Among 375 patients with pancreatic cancer, 137 patients were deemed to have resectable disease (R) by preoperative imaging studies, whereas 96 were found to have an unresectable disease during surgery. The remaining 142 patients fulfilled the definition of BR and were further classified into 3 subgroups based on the National Comprehensive Cancer Network guidelines: portal vein invasion (PV[+]), common hepatic artery invasion (CHA[+]), and superior mesenteric artery invasion (SMA[+]). PV(+) was subdivided into types B, C, and D according to the degree of portal vein invasion. Patients in the R group had significantly better survival than those in the PV(+) group (P = 0.0038), who in turn survived significantly longer than those classified as SMA(+) (P = 0.041). Type B patients survived significantly longer than did types C and D patients (P = 0.013 and P = 0.030, respectively). In PV(+) patients, compliance with postoperative chemotherapy at 3 and 6 months was 56.9% and 44.6%, respectively, substantially inferior to patients with resectable disease (72.6% and 54.7%, respectively). The optimal treatment strategy may differ among various subgroups within the BR category.

Longitudinal Patterns of Glycemic Control and Blood Pressure in Pregnant Women with Type 1 Diabetes Mellitus: Phenotypes from Functional Data Analysis.

PubMed

Szczesniak, Rhonda D; Li, Dan; Duan, Leo L; Altaye, Mekibib; Miodovnik, Menachem; Khoury, Jane C

2016-11-01

Objective  To identify phenotypes of type 1 diabetes control and associations with maternal/neonatal characteristics based on blood pressure (BP), glucose, and insulin curves during gestation, using a novel functional data analysis approach that accounts for sparse longitudinal patterns of medical monitoring during pregnancy. Methods  We performed a retrospective longitudinal cohort study of women with type 1 diabetes whose BP, glucose, and insulin requirements were monitored throughout gestation as part of a program-project grant. Scores from sparse functional principal component analysis (fPCA) were used to classify gestational profiles according to the degree of control for each monitored measure. Phenotypes created using fPCA were compared with respect to maternal and neonatal characteristics and outcome. Results  Most of the gestational profile variation in the monitored measures was explained by the first principal component (82-94%). Profiles clustered into three subgroups of high, moderate, or low heterogeneity, relative to the overall mean response. Phenotypes were associated with baseline characteristics, longitudinal changes in glycohemoglobin A1 and weight, and to pregnancy-related outcomes. Conclusion  Three distinct longitudinal patterns of glucose, insulin, and BP control were found. By identifying these phenotypes, interventions can be targeted for subgroups at highest risk for compromised outcome, to optimize diabetes management during pregnancy. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Comparison of the clinicopathological features of flat and polypoid colorectal adenomas that are smaller than or equal to five millimeters.

PubMed

Yener, Neşe Arzu; Midi, Ahmet; Ataizi Çelikel, Ciğdem

2014-02-01

Colorectal flat adenomas (FAs) may represent a different histogenesis, since their malignant potential is thought to be higher than polypoid adenomas of the same size. In this study, we classified FAs of ≤5 mm into three subgroups-superficially elevated adenomas (SEAs), completely flat adenomas (CFAs), and depressed adenomas (DAs)-based on their low microscopic shapes and compared their clinicopathological features with polypoid tubular adenomas (pTAs) with the same size. One hundred one pTAs and 46 FAs with tubular morphology with the same size (≤5 mm) were studied. The percentages of high-grade dysplasia in FAs and pTAs were 19.56% and 12.87%, respectively. The percentages of the high-grade dysplasia were 28.57%, 13.63%, and 20.00% in the DA, SEA, and CFA subgroups, respectively. FAs had a significantly higher number of normal epithelium at the basal crypts of the lesion than the pTAs (p=0.001). The presence of pericryptal mesenchymal cells was higher in pTAs than the FAs (78.21% vs 10.86%) (p<0.001). Flat adenoma represents a distinct type of colorectal adenoma with special histopathological properties-existence of a normal epithelium at the basal crypts, lack of pericryptal mesenchymal cells, and a high percentage of high-grade dysplasia-especially when it has a depressed shape at low magnification.

Cluster analysis and subgrouping to investigate inter-individual variability to non-invasive brain stimulation: a systematic review.

PubMed

Pellegrini, Michael; Zoghi, Maryam; Jaberzadeh, Shapour

2018-01-12

Cluster analysis and other subgrouping techniques have risen in popularity in recent years in non-invasive brain stimulation research in the attempt to investigate the issue of inter-individual variability - the issue of why some individuals respond, as traditionally expected, to non-invasive brain stimulation protocols and others do not. Cluster analysis and subgrouping techniques have been used to categorise individuals, based on their response patterns, as responder or non-responders. There is, however, a lack of consensus and consistency on the most appropriate technique to use. This systematic review aimed to provide a systematic summary of the cluster analysis and subgrouping techniques used to date and suggest recommendations moving forward. Twenty studies were included that utilised subgrouping techniques, while seven of these additionally utilised cluster analysis techniques. The results of this systematic review appear to indicate that statistical cluster analysis techniques are effective in identifying subgroups of individuals based on response patterns to non-invasive brain stimulation. This systematic review also reports a lack of consensus amongst researchers on the most effective subgrouping technique and the criteria used to determine whether an individual is categorised as a responder or a non-responder. This systematic review provides a step-by-step guide to carrying out statistical cluster analyses and subgrouping techniques to provide a framework for analysis when developing further insights into the contributing factors of inter-individual variability in response to non-invasive brain stimulation.

Longitudinal Examination of Symptom Profiles among Breast Cancer Survivors

PubMed Central

Avis, Nancy E.; Levine, Beverly; Marshall, Sarah A.; Ip, Edward H.

2017-01-01

Context Identification of cancer patients with similar symptom profiles may facilitate targeted symptom management. Objectives To identify subgroups of breast cancer survivors based on differential experience of symptoms, examine change in subgroup membership over time, and identify relevant characteristics and quality of life (QOL) among subgroups. Methods Secondary analyses of data from 653 breast cancer survivors recruited within 8 months of diagnosis who completed questionnaires at five timepoints. Hidden Markov modeling was used to: 1) formulate symptom profiles based on prevalence and severity of eight symptoms commonly associated with breast cancer, and 2) estimate probabilities of changing subgroup membership over 18 months of follow-up. Ordinal repeated measures were used to: 3) identify patient characteristics related to subgroup membership, and 4) evaluate the relationship between symptom subgroup and QOL. Results A seven-subgroup model provided the best fit: 1) low symptom burden, 2) mild fatigue, 3) mild fatigue and mild pain, 4) moderate fatigue and moderate pain, 5) moderate fatigue and moderate psychological, 6) moderate fatigue, mild pain, mild psychological; and 7) high symptom burden. Seventy percent of survivors remained in the same subgroup over time. In multivariable analyses, chemotherapy and greater illness intrusiveness were significantly related to greater symptom burden, while not being married or partnered, no difficulty paying for basics, and greater social support were protective. Higher symptom burden was associated with lower QOL. Survivors who reported psychological symptoms had significantly lower QOL than did survivors with pain symptoms. Conclusion Cancer survivors can be differentiated by their symptom profiles. PMID:28042076

The differences between sex offenders who victimise older women and sex offenders who offend against children.

PubMed

Browne, K D; Hines, Morag; Tully, Ruth J

2018-01-01

Within the literature on sex offending, much attention is paid to the distinction between those sex offenders who offend against adults and those who offend against children. In contrast, there is a paucity of research into sex offenders who offend specifically against elderly or older victims. A detailed interview and psychometric tests were conducted with a sample of 28 sex offenders who had been convicted of a sexually motivated offence against an older female. These data were compared to a sample of 23 child sex offenders. Results indicate that amongst other significant differences between these sub-groups, men who offend against older women are generally younger, are more violent, and are more likely to use a weapon and cause injury and death compared to child sex offenders. The men who offended against children were more likely to think about and plan their offending, spend more time with the victim pre and post offence, admit sexual arousal during the offence, and admit to a sexual motivation for the offence. This study suggests that men who sexually offend against older women and men who sexually offend against children are distinct groups. Treatment and risk management strategies should take this into account. Further exploration of this sub-group of offenders is recommended to help inform treatment and risk management strategies for sex offenders who offend against older people.

Using Symmetric Predication of Endogenous Subgroups for Causal Inferences about Program Effects under Robust Assumptions: Part Two of a Method Note in Three Parts

ERIC Educational Resources Information Center

Bell, Stephen H.; Peck, Laura R.

2013-01-01

To answer "what works?" questions about policy interventions based on an experimental design, Peck (2003) proposes to use baseline characteristics to symmetrically divide treatment and control group members into subgroups defined by endogenously determined postrandom assignment events. Symmetric prediction of these subgroups in both…

Analysis of the Drosophila Clock promoter reveals heterogeneity in expression between subgroups of central oscillator cells and identifies a novel enhancer region.

PubMed

Gummadova, Jennet Orazmuradovna; Coutts, Graham Andrew; Glossop, Nicholas Robert John

2009-10-01

The CLOCK-CYCLE (CLK-CYC) heterodimer lies at the heart of the circadian oscillator mechanism in Drosophila, yet little is known about the identity of transcription factors that regulate the expression of Clk and/or cyc. Here, the authors have used a transgenic approach to isolate regions of the Clk locus that are necessary for expression in central oscillator neurons in the adult fly brain. This analysis shows that central clock cells can be subdivided into 2 distinct groups based on Clk gene regulation. Expression in the lateral neuron (LN), dorsal neuron 1 anterior (DN1a) and 2 (DN2) clusters requires cis-elements located in a 122 base-pair (bp) region (-206 to -84) of the Clk promoter. Expression in the remaining dorsal neurons, 1 posterior (DN1p) and 3 (DN3) and the lateral posterior neurons (LPN), requires regulatory elements located in the -856 to -206 region. In addition, expression in photoreceptors of the compound eye is enhanced by cis-elements located in a 3rd region of the Clk locus (-1982 to -856). This region also enhances expression in nonoscillator cells in the brain including the Kenyon cells, but expression in these neurons is suppressed by regulatory sites located further upstream of -1982. The authors' analysis reveals clear heterogeneity in Clk gene expression in the adult brain and provides a necessary focus to isolate novel transcription factors that bind at the Clk locus to regulate expression in different oscillator neuron subgroups. These results also suggest that the DN1a/DN2 neurons may have more molecular commonality with the LNs than they do with the DN1p/DN3/LPN neurons. Finally, this analysis has generated new transgenic lines that will enable genes to be misexpressed in subgroups of central oscillator cells that have previously been resistant to discrete genetic manipulation. Hence, these lines provide important new tools to facilitate a more complete dissection of the neural network that regulates output rhythms in physiology and behavior.

Identifying profiles of service users in housing services and exploring their quality of life and care needs.

PubMed

Bitter, Neis A; Roeg, Diana P K; van Nieuwenhuizen, Chijs; van Weeghel, Jaap

2016-11-23

Housing services aim to support people with mental illness in their daily life and recovery. As the level of recovery differs between service users, the quality of life and care needs also might vary. However, the type and amount of care and support that service users receive do not always match their recovery. In order to improve the quality of care, this study aims to explore whether subgroups of service users exist based on three dimensions of recovery and to examine and compare the quality of life and care needs of the persons in these subgroups. Latent class analysis was performed with data from 263 service users of housing services in the Netherlands. Classes were based on three variables: personal recovery (Mental Health Recovery Measure), social recovery (Social Functioning Scale), and clinical recovery (Brief Symptom Inventory). Subsequently, the quality of life (MANSA) and care needs (CANSAS) of the different classes were analysed by the use of descriptive and inferential statistics. Three classes could be distinguished. Class 1 (45%) comprised of people who score the highest of the three classes in terms of personal and social recovery and who experience the least number of symptoms. People in class 2 (44%) and class 3 (11%) score significantly lower on personal and social recovery, and they experience significantly more symptoms compared to class 1. The distinction between class 2 and 3 can be made on the significantly higher number of symptoms in class 3. All three classes differ significantly on quality of life and unmet needs. The quality of life of service users of housing services needs improvement, as even persons in the best-recovered subgroup have a lower quality of life than the average population. Workers of housing services need to be aware of the recovery of a client and what his or her individual needs and goals are. Furthermore, better care (allocation) concerning mental and physical health and rehabilitation is needed. Care should be provided on all dimensions of recovery at the same time, therefore mental health care organisations should work together and integrate their services. ISRCTN registry ISRCTN77355880 retrospectively registered 05/07/2013.

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

PubMed Central

Rai, Richa; Chauhan, Sudhir Kumar; Singh, Vikas Vikram; Rai, Madhukar; Rai, Geeta

2016-01-01

Systemic lupus erythematosus (SLE) patients exhibit immense heterogeneity which is challenging from the diagnostic perspective. Emerging high throughput sequencing technologies have been proved to be a useful platform to understand the complex and dynamic disease processes. SLE patients categorised based on autoantibody specificities are reported to have differential immuno-regulatory mechanisms. Therefore, we performed RNA-seq analysis to identify transcriptomics of SLE patients with distinguished autoantibody specificities. The SLE patients were segregated into three subsets based on the type of autoantibodies present in their sera (anti-dsDNA+ group with anti-dsDNA autoantibody alone; anti-ENA+ group having autoantibodies against extractable nuclear antigens (ENA) only, and anti-dsDNA+ENA+ group having autoantibodies to both dsDNA and ENA). Global transcriptome profiling for each SLE patients subsets was performed using Illumina® Hiseq-2000 platform. The biological relevance of dysregulated transcripts in each SLE subsets was assessed by ingenuity pathway analysis (IPA) software. We observed that dysregulation in the transcriptome expression pattern was clearly distinct in each SLE patients subsets. IPA analysis of transcripts uniquely expressed in different SLE groups revealed specific biological pathways to be affected in each SLE subsets. Multiple cytokine signaling pathways were specifically dysregulated in anti-dsDNA+ patients whereas Interferon signaling was predominantly dysregulated in anti-ENA+ patients. In anti-dsDNA+ENA+ patients regulation of actin based motility by Rho pathway was significantly affected. The granulocyte gene signature was a common feature to all SLE subsets; however, anti-dsDNA+ group showed relatively predominant expression of these genes. Dysregulation of Plasma cell related transcripts were higher in anti-dsDNA+ and anti-ENA+ patients as compared to anti-dsDNA+ ENA+. Association of specific canonical pathways with the uniquely expressed transcripts in each SLE subgroup indicates that specific immunological disease mechanisms are operative in distinct SLE patients’ subsets. This ‘sub-grouping’ approach could further be useful for clinical evaluation of SLE patients and devising targeted therapeutics. PMID:27835693

"Disorganized in time": impact of bottom-up and top-down negative emotion generation on memory formation among healthy and traumatized adolescents.

PubMed

Guillery-Girard, Bérengère; Clochon, Patrice; Giffard, Bénédicte; Viard, Armelle; Egler, Pierre-Jean; Baleyte, Jean-Marc; Eustache, Francis; Dayan, Jacques

2013-09-01

"Travelling in time," a central feature of episodic memory is severely affected among individuals with Post Traumatic Stress Disorder (PTSD) with two opposite effects: vivid traumatic memories are unorganized in temporality (bottom-up processes), non-traumatic personal memories tend to lack spatio-temporal details and false recognitions occur more frequently that in the general population (top-down processes). To test the effect of these two types of processes (i.e. bottom-up and top-down) on emotional memory, we conducted two studies in healthy and traumatized adolescents, a period of life in which vulnerability to emotion is particularly high. Using negative and neutral images selected from the international affective picture system (IAPS), stimuli were divided into perceptual images (emotion generated by perceptual details) and conceptual images (emotion generated by the general meaning of the material). Both categories of stimuli were then used, along with neutral pictures, in a memory task with two phases (encoding and recognition). In both populations, we reported a differential effect of the emotional material on encoding and recognition. Negative perceptual scenes induced an attentional capture effect during encoding and enhanced the recollective distinctiveness. Conversely, the encoding of conceptual scenes was similar to neutral ones, but the conceptual relatedness induced false memories at retrieval. However, among individuals with PTSD, two subgroups of patients were identified. The first subgroup processed the scenes faster than controls, except for the perceptual scenes, and obtained similar performances to controls in the recognition task. The second subgroup group desmonstrated an attentional deficit in the encoding task with no benefit from the distinctiveness associated with negative perceptual scenes on memory performances. These findings provide a new perspective on how negative emotional information may have opposite influences on memory in normal and traumatized individuals. It also gives clues to understand how intrusive memories and overgeneralization takes place in PTSD. Copyright © 2013 Elsevier Ltd. All rights reserved.

Methylation profiling of choroid plexus tumors reveals 3 clinically distinct subgroups.

PubMed

Thomas, Christian; Sill, Martin; Ruland, Vincent; Witten, Anika; Hartung, Stefan; Kordes, Uwe; Jeibmann, Astrid; Beschorner, Rudi; Keyvani, Kathy; Bergmann, Markus; Mittelbronn, Michel; Pietsch, Torsten; Felsberg, Jörg; Monoranu, Camelia M; Varlet, Pascale; Hauser, Peter; Olar, Adriana; Grundy, Richard G; Wolff, Johannes E; Korshunov, Andrey; Jones, David T; Bewerunge-Hudler, Melanie; Hovestadt, Volker; von Deimling, Andreas; Pfister, Stefan M; Paulus, Werner; Capper, David; Hasselblatt, Martin

2016-06-01

Choroid plexus tumors are intraventricular neoplasms derived from the choroid plexus epithelium. A better knowledge of molecular factors involved in choroid plexus tumor biology may aid in identifying patients at risk for recurrence. Methylation profiles were examined in 29 choroid plexus papillomas (CPPs, WHO grade I), 32 atypical choroid plexus papillomas (aCPPs, WHO grade II), and 31 choroid plexus carcinomas (CPCs, WHO grade III) by Illumina Infinium HumanMethylation450 Bead Chip Array. Unsupervised hierarchical clustering identified 3 subgroups: methylation cluster 1 (pediatric CPP and aCPP of mainly supratentorial location), methylation cluster 2 (adult CPP and aCPP of mainly infratentorial location), and methylation cluster 3 (pediatric CPP, aCPP, and CPC of supratentorial location). In methylation cluster 3, progression-free survival (PFS) accounted for a mean of 72 months (CI, 55-89 mo), whereas only 1 of 42 tumors of methylation clusters 1 and 2 progressed (P< .001). On stratification of outcome data according to WHO grade, all CPCs clustered within cluster 3 and were associated with shorter overall survival (mean, 105 mo [CI, 81-128 mo]) and PFS (mean, 55 mo [CI, 36-73 mo]). The aCPP of methylation cluster 3 also progressed frequently (mean, 69 mo [CI, 44-93 mo]), whereas no tumor progression was observed in aCPP of methylation clusters 1 and 2 (P< .05). Only 1 of 29 CPPs recurred. Methylation profiling of choroid plexus tumors reveals 3 distinct subgroups (ie, pediatric low-risk choroid plexus tumors [cluster 1], adult low-risk choroid plexus tumors [cluster 2], and pediatric high-risk choroid plexus tumors [cluster 3]) and may provide useful prognostic information in addition to histopathology. Published by Oxford University Press on behalf of the Society for Neuro-Oncology 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Identification of two poorly prognosed ovarian carcinoma subtypes associated with CHEK2 germ-line mutation and non-CHEK2 somatic mutation gene signatures.

PubMed

Ow, Ghim Siong; Ivshina, Anna V; Fuentes, Gloria; Kuznetsov, Vladimir A

2014-01-01

High-grade serous ovarian cancer (HG-SOC), a major histologic type of epithelial ovarian cancer (EOC), is a poorly-characterized, heterogeneous and lethal disease where somatic mutations of TP53 are common and inherited loss-of-function mutations in BRCA1/2 predispose to cancer in 9.5-13% of EOC patients. However, the overall burden of disease due to either inherited or sporadic mutations is not known. We performed bioinformatics analyses of mutational and clinical data of 334 HG-SOC tumor samples from The Cancer Genome Atlas to identify novel tumor-driving mutations, survival-significant patient subgroups and tumor subtypes potentially driven by either hereditary or sporadic factors. We identified a sub-cluster of high-frequency mutations in 22 patients and 58 genes associated with DNA damage repair, apoptosis and cell cycle. Mutations of CHEK2, observed with the highest intensity, were associated with poor therapy response and overall survival (OS) of these patients (P = 8.00e-05), possibly due to detrimental effect of mutations at the nuclear localization signal. A 21-gene mutational prognostic signature significantly stratifies patients into relatively low or high-risk subgroups with 5-y OS of 37% or 6%, respectively (P = 7.31e-08). Further analysis of these genes and high-risk subgroup revealed 2 distinct classes of tumors characterized by either germline mutations of genes such as CHEK2, RPS6KA2 and MLL4, or somatic mutations of other genes in the signature. Our results could provide improvement in prediction and clinical management of HG-SOC, facilitate our understanding of this complex disease, guide the design of targeted therapeutics and improve screening efforts to identify women at high-risk of hereditary ovarian cancers distinct from those associated with BRCA1/2 mutations.

Identification of two poorly prognosed ovarian carcinoma subtypes associated with CHEK2 germ-line mutation and non-CHEK2 somatic mutation gene signatures

PubMed Central

Ow, Ghim Siong; Ivshina, Anna V; Fuentes, Gloria; Kuznetsov, Vladimir A

2014-01-01

High-grade serous ovarian cancer (HG-SOC), a major histologic type of epithelial ovarian cancer (EOC), is a poorly-characterized, heterogeneous and lethal disease where somatic mutations of TP53 are common and inherited loss-of-function mutations in BRCA1/2 predispose to cancer in 9.5–13% of EOC patients. However, the overall burden of disease due to either inherited or sporadic mutations is not known.     We performed bioinformatics analyses of mutational and clinical data of 334 HG-SOC tumor samples from The Cancer Genome Atlas to identify novel tumor-driving mutations, survival-significant patient subgroups and tumor subtypes potentially driven by either hereditary or sporadic factors. We identified a sub-cluster of high-frequency mutations in 22 patients and 58 genes associated with DNA damage repair, apoptosis and cell cycle. Mutations of CHEK2, observed with the highest intensity, were associated with poor therapy response and overall survival (OS) of these patients (P = 8.00e-05), possibly due to detrimental effect of mutations at the nuclear localization signal. A 21-gene mutational prognostic signature significantly stratifies patients into relatively low or high-risk subgroups with 5-y OS of 37% or 6%, respectively (P = 7.31e-08). Further analysis of these genes and high-risk subgroup revealed 2 distinct classes of tumors characterized by either germline mutations of genes such as CHEK2, RPS6KA2 and MLL4, or somatic mutations of other genes in the signature. Our results could provide improvement in prediction and clinical management of HG-SOC, facilitate our understanding of this complex disease, guide the design of targeted therapeutics and improve screening efforts to identify women at high-risk of hereditary ovarian cancers distinct from those associated with BRCA1/2 mutations. PMID:24879340

Identification and characterization of HPA-axis reactivity endophenotypes in a cohort of female PTSD patients.

PubMed

Zaba, Monika; Kirmeier, Thomas; Ionescu, Irina A; Wollweber, Bastian; Buell, Dominik R; Gall-Kleebach, Dominique J; Schubert, Christine F; Novak, Bozidar; Huber, Christine; Köhler, Katharina; Holsboer, Florian; Pütz, Benno; Müller-Myhsok, Bertram; Höhne, Nina; Uhr, Manfred; Ising, Marcus; Herrmann, Leonie; Schmidt, Ulrike

2015-05-01

Analysis of the function of the hypothalamic-pituitary-adrenal (HPA)-axis in patients suffering from posttraumatic stress disorder (PTSD) has hitherto produced inconsistent findings, inter alia in the Trier Social Stress Test (TSST). To address these inconsistencies, we compared a sample of 23 female PTSD patients with either early life trauma (ELT) or adult trauma (AT) or combined ELT and AT to 18 age-matched non-traumatized female healthy controls in the TSST which was preceded by intensive baseline assessments. During the TSST, we determined a variety of clinical, psychological, endocrine and cardiovascular parameters as well as expression levels of four HPA-axis related genes. Using a previously reported definition of HPA-axis responsive versus non-responsive phenotypes, we identified for the first time two clinically and biologically distinct HPA-axis reactivity subgroups of PTSD. One subgroup ("non-responders") showed a blunted HPA-axis response and distinct clinical and biological characteristics such as a higher prevalence of trauma-related dissociative symptoms and of combined AT and ELT as well as alterations in the expression kinetics of the genes encoding for the mineralocorticoid receptor (MR) and for FK506 binding protein 51 (FKBP51). Interestingly, this non-responder subgroup largely drove the relatively diminished HPA axis response of the total cohort of PTSD patients. These findings are limited by the facts that the majority of patients was medicated, by the lack of traumatized controls and by the relatively small sample size. The here for the first time identified and characterized HPA-axis reactivity endophenotypes offer an explanation for the inconsistent reports on HPA-axis function in PTSD and, moreover, suggest that most likely other factors than HPA-axis reactivity play a decisive role in determination of PTSD core symptom severity. Copyright © 2015 Elsevier Ltd. All rights reserved.

High proportion of subgroup A' (genotype A) among Brazilian isolates of Hepatitis B virus.

PubMed

Araujo, N M; Mello, F C A; Yoshida, C F T; Niel, C; Gomes, S A

2004-07-01

Hepatitis B virus (HBV) genotype A has been divided recently into two subgroups, designated A-A' (genotype A excluding A') and A'. Isolates belonging to subgroup A' have been identified in Africa. A new genotyping method, based on PCR amplification of the pre-S/S genome region and subsequent restriction fragment length polymorphism (RFLP) analysis, was developed, that established a correlation between RFLP subtypes and subgroups within genotype A. To investigate the occurrence of subgroup A' in South America, 119 Brazilian HBV isolates were analyzed. Ninety-three (78%) of them belonged to genotype A, with three predominating RFLP subtypes: 44 (37%) isolates were classified as AI, 30 (25%) were AII, and 18 (15%) were AIII. Pre-S/S nucleotide sequences of 15 genotype A isolates were determined. Phylogenetic analysis performed with these 15 and an additional 41 sequences revealed that isolates AI and AII clustered in subgroup A', whereas isolates AIII were classified into subgroup A-A'. The correlation RFLP subtypes-subgroups was confirmed by the presence of amino acid residues specific for subgroup A' in the surface antigens and polymerase of isolates AI and AII. The high proportion (63%) of isolates from subgroup A' suggested an African origin for a large number of Brazilian HBVs.

Change in surface roughness of esthetic restorative materials after exposure to different immersion regimes in a cola drink.

PubMed

Bajwa, Navroop Kaur; Pathak, Anuradha

2014-01-01

Context. An in vitro study carried out to evaluate and compare the effect of Cola drink on surface roughness of esthetic restorative materials. Purpose. To compare the effect of different immersion regimes in a Cola drink on surface roughness of esthetic restorative materials. Method. Two hundred samples were grouped into 4 equal groups of 50 samples each: Group I: conventional glass ionomer, Group II: resin modified glass ionomer, Group III: polyacid-modified resin composite, Group IV: Composite resin. Each group was further subdivided into 5 subgroups of 10 samples each. Subgroup A (Control Subgroup). Samples were kept immersed in artificial saliva. Subgroup B. Samples were immersed in Cola drink once a day. Subgroup C. Samples were immersed in Cola drink, 3 times a day. Subgroup D. Samples were immersed in Cola drink 5 times a day. Subgroup E. Samples were immersed in Cola drink 10 times a day. Each immersion lasted 5 minutes. The immersion protocol was repeated for 7 days. Results. Maximum surface roughness was seen in Group I conventional glass ionomer cement, followed by Group II resin modified glass ionomer, Group III polyacid modified resin composite, and Group IV composite resin samples. Conclusion. Resistance to change in surface roughness is more in resin based restorative materials as compared to glass ionomer based materials.

Change in Surface Roughness of Esthetic Restorative Materials after Exposure to Different Immersion Regimes in a Cola Drink

PubMed Central

Bajwa, Navroop Kaur; Pathak, Anuradha

2014-01-01

Context. An in vitro study carried out to evaluate and compare the effect of Cola drink on surface roughness of esthetic restorative materials. Purpose. To compare the effect of different immersion regimes in a Cola drink on surface roughness of esthetic restorative materials. Method. Two hundred samples were grouped into 4 equal groups of 50 samples each: Group I: conventional glass ionomer, Group II: resin modified glass ionomer, Group III: polyacid-modified resin composite, Group IV: Composite resin. Each group was further subdivided into 5 subgroups of 10 samples each. Subgroup A (Control Subgroup). Samples were kept immersed in artificial saliva. Subgroup B. Samples were immersed in Cola drink once a day. Subgroup C. Samples were immersed in Cola drink, 3 times a day. Subgroup D. Samples were immersed in Cola drink 5 times a day. Subgroup E. Samples were immersed in Cola drink 10 times a day. Each immersion lasted 5 minutes. The immersion protocol was repeated for 7 days. Results. Maximum surface roughness was seen in Group I conventional glass ionomer cement, followed by Group II resin modified glass ionomer, Group III polyacid modified resin composite, and Group IV composite resin samples. Conclusion. Resistance to change in surface roughness is more in resin based restorative materials as compared to glass ionomer based materials. PMID:25006464

[Prognostication of immunological reactivity and the choice of the variant of reflexotherapy for a newborn infant].

PubMed

Filonenko, A V; Sergeeva, A I; Filonenko, V A

2014-01-01

The objective of the present study was to determine the classification differences in immunological reactivity and to identify its predictors in the newborn infants. The study involved 115 full-term newborn infants presenting with grade 3 prenatal hypoxic ischemic encephalopathy in the late neonatal period. The features of immunological reactivity under the influence of acupuncture were examined. Statistical processing was carried out by means of discriminant analysis. The assessment and prediction of the effectiveness of acupuncture in the neonates suffering from cerebral ischemia are based on the index of immunological reactivity and the leukocyte index of intoxication, as well as on the ratio of monocytes to band neutrophils content. For generation of the group classifier of immunological predictors in a newborn infant and development of indications for reflex therapy, nine parameters of interest were measured. The group specificity of the child was determined by three variables, viz. leukocyte index of intoxication, monocyte and band neutrophil counts with values of the Fisher's exact test (F) and reliability (Wilks Lambda 0.90894; approximation F (3.144) = 4.809; p < 0.0032). The partial Wilks Lambda values showed that the greatest contribution was provided by the leukocyte index of intoxication and monocytes. Prediction accuracy of the classification matrix in the standard treatment group reached 30.8% and 91.7% respectively when reflex therapy was included in the combined rehabilitation treatment. Overall, classification accuracy amounted to 70.3%. The presence of distinctive changes in the subgroups preconditioned a personalized approach to the prescription of reflex therapy to the newborn infants and the choice of the treatment modality on an individual basis (parent, child, or both) in the "mother-newborn" system. The variant of treatment was determined by comparing the values of the results of the formulas. The newborns were referred to the subgroup with the highest value of the classification function. The predictors made it possible to reliably distinguished the second (p = 0.032) and the third (p = 0.022) subgroups from the first one, with some degree of overlapping between the edge zones of centroids of the second and third subgroups (p = 0.073). Therefore, the sensitivity of classification in the individual subgroups was lower than in the group model and was estimated at 34.4, 71.9, and 65.6% for the first, second and third groups, respectively. The mathematical models can discriminatebetween the immunological characteristics and predict them in individual newborn infants; also, they can be helpful for preventing the disruption of their adaptation process.

Breast Cancer Subtypes: Two decades of Journey from Cell Culture to Patients

PubMed Central

Zhao, Xiangshan; Gurumurthy, Channabasavaiah Basavaraju; Malhotra, Gautam; Mirza, Sameer; Mohibi, Shakur; Bele, Aditya; Quinn, Meghan G; Band, Hamid; Band, Vimla

2014-01-01

Breast cancer remains the second leading cause of cancer-related deaths among women. Clinically breast cancer patients present with distinct diseases with vastly different outcomes. Recent molecular profiling has identified five major subtypes of breast cancers. Importantly, survival analyses have shown significantly different outcomes for patients belonging to various subgroups. These studies strongly support the idea that breast tumor subtypes may represent malignancies of biologically distinct cell types producing distinct disease entities that may also require different treatment strategies. Alternatively, different types of breast cancers may arise from a common precursor based on oncogene-driven reprogramming. Experimental systems that clearly define cancer cell heterogeneity and link this process to cancer stem/progenitor cells have not been developed. It is also unclear if oncogenic transformation of committed progenitors drives them along their committed pathway, and hence the cell of origin determines the histological features of breast cancer, or if different oncogenic pathways can transform the same precursor along distinct phenotypes. One major hurdle to addressing these fundamental questions about the origin and heterogeneity of human breast cancer is the lack of immortal human stem/progenitor cells that could be interrogated with breast cancer-relevant oncogenesis protocols. We have now identified, isolated and immortalized (using hTERT) such mammary stem/progenitor cells that are immortal and still maintain their progenitor/stem cell properties (self-renewal and differentiation into myoepithelial and luminal cells). Our research using these progenitor/stem cells that are highly susceptible to oncogenesis and various models of mammary cell immortalization has allowed us to define several novel cellular pathways and demonstration of their involvement in oncogenesis and breast cancer progression. Given the emerging evidence that stem/progenitor cells are precursors of cancers and distinct subtypes of breast cancer have different survival outcome, these studies are timely and carry the potential of developing novel therapeutics in the future as well as provide potentially novel markers for diagnostic/prognostic use in breast cancer. PMID:21901624

Identification of Heterogeneous Cognitive Subgroups in Community-Dwelling Older Adults: A Latent Class Analysis of the Einstein Aging Study.

PubMed

Zammit, Andrea R; Hall, Charles B; Lipton, Richard B; Katz, Mindy J; Muniz-Terrera, Graciela

2018-05-01

The aim of this study was to identify natural subgroups of older adults based on cognitive performance, and to establish each subgroup's characteristics based on demographic factors, physical function, psychosocial well-being, and comorbidity. We applied latent class (LC) modeling to identify subgroups in baseline assessments of 1345 Einstein Aging Study (EAS) participants free of dementia. The EAS is a community-dwelling cohort study of 70+ year-old adults living in the Bronx, NY. We used 10 neurocognitive tests and 3 covariates (age, sex, education) to identify latent subgroups. We used goodness-of-fit statistics to identify the optimal class solution and assess model adequacy. We also validated our model using two-fold split-half cross-validation. The sample had a mean age of 78.0 (SD=5.4) and a mean of 13.6 years of education (SD=3.5). A 9-class solution based on cognitive performance at baseline was the best-fitting model. We characterized the 9 identified classes as (i) disadvantaged, (ii) poor language, (iii) poor episodic memory and fluency, (iv) poor processing speed and executive function, (v) low average, (vi) high average, (vii) average, (viii) poor executive and poor working memory, (ix) elite. The cross validation indicated stable class assignment with the exception of the average and high average classes. LC modeling in a community sample of older adults revealed 9 cognitive subgroups. Assignment of subgroups was reliable and associated with external validators. Future work will test the predictive validity of these groups for outcomes such as Alzheimer's disease, vascular dementia and death, as well as markers of biological pathways that contribute to cognitive decline. (JINS, 2018, 24, 511-523).

Genotypic and phenotypic diversity in tropical strains of Aspergillus spp. (section Circumdati) isolated from insects.

PubMed

Moraes, Aurea; Holanda, Veronica; Zahner, Viviane

2006-04-01

The morphology, multilocus enzyme electrophoresis (MLEE), and RAPD-PCR profiles of a panel of 63 strains of Aspergilus section Circumdati, all isoloated from Brazilian insects, were examined. When compared to the descriptions reported in the literature, differences were observed in terms of colony diameter for the representatives studies. Numerical taxonomy based on data generated by MLEE identified two distinct subgroups among the A. ochraceus isolates. In addition, phosphoglucose isomerase (GPI-1) was detected only in A. sclerotiorum, while phosphofructokinase (FK-1) and acid phosphatase (ACP-2) were present only in strains of A. sulphureus, suggesting that these alleles (bands) could be used for species-specific detection. Using RAPD-PCR, species-specific molecular markers were identified for both A. petrakii and A. sulphureus. These results are important from the taxonomic viewpoint and may also be used in the design of screening programs for the isoloation of new strains.

Heterogeneity among violence-exposed women: applying person-oriented research methods.

PubMed

Nurius, Paula S; Macy, Rebecca J

2008-03-01

Variability of experience and outcomes among violence-exposed people pose considerable challenges toward developing effective prevention and treatment protocols. To address these needs, the authors present an approach to research and a class of methodologies referred to as person oriented. Person-oriented tools support assessment of meaningful patterns among people that distinguish one group from another, subgroups for whom different interventions are indicated. The authors review the conceptual base of person-oriented methods, outline their distinction from more familiar variable-oriented methods, present descriptions of selected methods as well as empirical applications of person-oriented methods germane to violence exposure, and conclude with discussion of implications for future research and translation between research and practice. The authors focus on violence against women as a population, drawing on stress and coping theory as a theoretical framework. However, person-oriented methods hold utility for investigating diversity among violence-exposed people's experiences and needs across populations and theoretical foundations.

Longitudinal Examination of Symptom Profiles Among Breast Cancer Survivors.

PubMed

Avis, Nancy E; Levine, Beverly; Marshall, Sarah A; Ip, Edward H

2017-04-01

Identification of cancer patients with similar symptom profiles may facilitate targeted symptom management. To identify subgroups of breast cancer survivors based on differential experience of symptoms, examine change in subgroup membership over time, and identify relevant characteristics and quality of life (QOL) among subgroups. Secondary analyses of data from 653 breast cancer survivors recruited within eight months of diagnosis who completed questionnaires at five time points. Hidden Markov modeling was used to 1) formulate symptom profiles based on prevalence and severity of eight symptoms commonly associated with breast cancer and 2) estimate probabilities of changing subgroup membership over 18 months of follow-up. Ordinal repeated measures were used to 3) identify patient characteristics related to subgroup membership and 4) evaluate the relationship between symptom subgroup and QOL. A seven-subgroup model provided the best fit: 1) low symptom burden, 2) mild fatigue, 3) mild fatigue and mild pain, 4) moderate fatigue and moderate pain, 5) moderate fatigue and moderate psychological, 6) moderate fatigue, mild pain, mild psychological, and 7) high symptom burden. Seventy percent of survivors remained in the same subgroup over time. In multivariable analyses, chemotherapy and greater illness intrusiveness were significantly related to greater symptom burden, while not being married or partnered, no difficulty paying for basics, and greater social support were protective. Higher symptom burden was associated with lower QOL. Survivors who reported psychological symptoms had significantly lower QOL than did survivors with pain symptoms. Cancer survivors can be differentiated by their symptom profiles. Copyright © 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Characterisation of vitamin and mineral supplement users differentiated according to their motives for using supplements: results of the German National Nutrition Monitoring (NEMONIT).

PubMed

Frey, Anne; Hoffmann, Ingrid; Heuer, Thorsten

2017-08-01

To characterise German vitamin and mineral supplement users differentiated by their motives for supplement use. Data were obtained from the German National Nutrition Monitoring (2010/11) via two 24 h dietary recalls and a telephone interview. Motive-based subgroups of supplement users were identified by factor and cluster analysis. Sociodemographic, lifestyle, health and dietary characteristics and supplement use were examined. Differences were analysed using χ 2 tests, logistic and linear regression models. Germany, nationwide. Individuals (n 1589) aged 18-80 years. Three motive-based subgroups were identified: a 'Prevention' subgroup (n 324), characterised by the motive to prevent nutrient deficiencies; a 'Prevention and additional benefits' subgroup (n 166), characterised by motives to prevent health problems and improve well-being and performance; and a 'Treatment' subgroup (n 136), characterised by motives to treat nutrient deficiencies or diseases. Members of the two prevention subgroups had a higher Healthy Eating Index score and tended to be more physically active than non-users. Those in the 'Prevention and additional benefits' subgroup supplemented with a greater number of micronutrients. Members of the 'Treatment' subgroup tended to be older and have a lower self-reported health status than non-users, and supplemented with a smaller number of micronutrients. The majority of supplement users take supplements for preventive purposes and they are more health conscious than non-users of supplements due to their concerns about developing health problems. Those supplementing for treatment purposes may have underlying health indications and may be more likely to benefit from supplementation than those supplementing for preventive purposes.

Emotional impact of a video-based suicide prevention program on suicidal viewers and suicide survivors.

PubMed

Bryan, Craig J; Dhillon-Davis, Luther E; Dhillon-Davis, Kieran K

2009-12-01

In light of continuing concerns about iatrogenic effects associated with suicide prevention efforts utilizing video-based media, the impact of emotionally-charged videos on two vulnerable subgroups--suicidal viewers and suicide survivors--was explored. Following participation in routine suicide education as a part of the U.S. Air Force Suicide Prevention Program's video-based community briefing, a sample of young active duty airmen demonstrated small decreases in positive emotional states and larger decreases in negative emotional states, especially among suicidal females. No evidence of iatrogenic effects were observed among suicidal or survivor subgroups when compared to controls. Results support the use of video-based media as a safe educational strategy that might actually serve to decrease emotional distress among vulnerable subgroups.

Sub-grouping patients with non-specific low back pain based on cluster analysis of discriminatory clinical items.

PubMed

Billis, Evdokia; McCarthy, Christopher J; Roberts, Chris; Gliatis, John; Papandreou, Maria; Gioftsos, George; Oldham, Jacqueline A

2013-02-01

To identify potential subgroups amongst patients with non-specific low back pain based on a consensus list of potentially discriminatory examination items. Exploratory study. A convenience sample of 106 patients with non-specific low back pain (43 males, 63 females, mean age 36 years, standard deviation 15.9 years) and 7 physiotherapists. Based on 3 focus groups and a two-round Delphi involving 23 health professionals and a random stratified sample of 150 physiotherapists, respectively, a comprehensive examination list comprising the most "discriminatory" items was compiled. Following reliability analysis, the most reliable clinical items were assessed with a sample of patients with non-specific low back pain. K-means cluster analysis was conducted for 2-, 3- and 4-cluster options to explore for meaningful homogenous subgroups. The most clinically meaningful cluster was a two-subgroup option, comprising a small group (n = 24) with more severe clinical presentation (i.e. more widespread pain, functional and sleeping problems, other symptoms, increased investigations undertaken, more severe clinical signs, etc.) and a larger less dysfunctional group (n = 80). A number of potentially discriminatory clinical items were identified by health professionals and sub-classified, based on a sample of patients with non-specific low back pain, into two subgroups. However, further work is needed to validate this classification process.

The heterogeneity of antipsychotic response in the treatment of schizophrenia

PubMed Central

Case, M.; Stauffer, V. L.; Ascher-Svanum, H.; Conley, R.; Kapur, S.; Kane, J. M.; Kollack-Walker, S.; Jacob, J.; Kinon, B. J.

2011-01-01

Background Schizophrenia is a heterogeneous disorder in terms of patient response to antipsychotic treatment. Understanding the heterogeneity of treatment response may help to guide treatment decisions. This study was undertaken to capture inherent patterns of response to antipsychotic treatment in patients with schizophrenia, characterize the subgroups of patients with similar courses of response, and examine illness characteristics at baseline as possible predictors of response. Method Growth mixture modeling (GMM) was applied to data from a randomized, double-blind, 12-week study of 628 patients with schizophrenia or schizo-affective disorder treated with risperidone or olanzapine. Results Four distinct response trajectories based on Positive and Negative Syndrome Scale (PANSS) total score over 12 weeks were identified: Class 1 (420 patients, 80.6%) with moderate average baseline PANSS total score showing gradual symptom improvement; Class 2 (65 patients, 12.5%) showing rapid symptom improvement; Class 3 (24 patients, 4.6%) with high average baseline PANSS total score showing gradual symptom improvement; and Class 4 (12 patients, 2.3%) showing unsustained symptom improvement. Latent class membership of early responders (ER) and early non-responders (ENR) was determined based on 20% symptom improvement criteria at 2 weeks and ultimate responders (UR) and ultimate non-responders (UNR) based on 40% symptom improvement criteria at 12 weeks. Baseline factors with potential influence on latent class membership were identified. Conclusions This study identified four distinct treatment response patterns with predominant representation of responders or non-responders to treatment in these classes. This heterogeneity may represent discrete endophenotypes of response to treatment with different etiologic underpinnings. PMID:20925971

Customized oligonucleotide microarray gene expression-based classification of neuroblastoma patients outperforms current clinical risk stratification.

PubMed

Oberthuer, André; Berthold, Frank; Warnat, Patrick; Hero, Barbara; Kahlert, Yvonne; Spitz, Rüdiger; Ernestus, Karen; König, Rainer; Haas, Stefan; Eils, Roland; Schwab, Manfred; Brors, Benedikt; Westermann, Frank; Fischer, Matthias

2006-11-01

To develop a gene expression-based classifier for neuroblastoma patients that reliably predicts courses of the disease. Two hundred fifty-one neuroblastoma specimens were analyzed using a customized oligonucleotide microarray comprising 10,163 probes for transcripts with differential expression in clinical subgroups of the disease. Subsequently, the prediction analysis for microarrays (PAM) was applied to a first set of patients with maximally divergent clinical courses (n = 77). The classification accuracy was estimated by a complete 10-times-repeated 10-fold cross validation, and a 144-gene predictor was constructed from this set. This classifier's predictive power was evaluated in an independent second set (n = 174) by comparing results of the gene expression-based classification with those of risk stratification systems of current trials from Germany, Japan, and the United States. The first set of patients was accurately predicted by PAM (cross-validated accuracy, 99%). Within the second set, the PAM classifier significantly separated cohorts with distinct courses (3-year event-free survival [EFS] 0.86 +/- 0.03 [favorable; n = 115] v 0.52 +/- 0.07 [unfavorable; n = 59] and 3-year overall survival 0.99 +/- 0.01 v 0.84 +/- 0.05; both P < .0001) and separated risk groups of current neuroblastoma trials into subgroups with divergent outcome (NB2004: low-risk 3-year EFS 0.86 +/- 0.04 v 0.25 +/- 0.15, P < .0001; intermediate-risk 1.00 v 0.57 +/- 0.19, P = .018; high-risk 0.81 +/- 0.10 v 0.56 +/- 0.08, P = .06). In a multivariate Cox regression model, the PAM predictor classified patients of the second set more accurately than risk stratification of current trials from Germany, Japan, and the United States (P < .001; hazard ratio, 4.756 [95% CI, 2.544 to 8.893]). Integration of gene expression-based class prediction of neuroblastoma patients may improve risk estimation of current neuroblastoma trials.

Groupwise connectivity-based parcellation of the whole human cortical surface using watershed-driven dimension reduction.

PubMed

Lefranc, Sandrine; Roca, Pauline; Perrot, Matthieu; Poupon, Cyril; Le Bihan, Denis; Mangin, Jean-François; Rivière, Denis

2016-05-01

Segregating the human cortex into distinct areas based on structural connectivity criteria is of widespread interest in neuroscience. This paper presents a groupwise connectivity-based parcellation framework for the whole cortical surface using a new high quality diffusion dataset of 79 healthy subjects. Our approach performs gyrus by gyrus to parcellate the whole human cortex. The main originality of the method is to compress for each gyrus the connectivity profiles used for the clustering without any anatomical prior information. This step takes into account the interindividual cortical and connectivity variability. To this end, we consider intersubject high density connectivity areas extracted using a surface-based watershed algorithm. A wide validation study has led to a fully automatic pipeline which is robust to variations in data preprocessing (tracking type, cortical mesh characteristics and boundaries of initial gyri), data characteristics (including number of subjects), and the main algorithmic parameters. A remarkable reproducibility is achieved in parcellation results for the whole cortex, leading to clear and stable cortical patterns. This reproducibility has been tested across non-overlapping subgroups and the validation is presented mainly on the pre- and postcentral gyri. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

African American women and men at high and low risk for hypertension: a signal detection analysis of NHANES III, 1988-1994.

PubMed

Collins, Rakale; Winkleby, Marilyn A

2002-10-01

African Americans have some of the highest rates of hypertension in the world. This study identified subgroups of U.S. African American women and men with particularly high and low rates of hypertension. Data are presented for 1,911 Black women and 1,657 Black men, ages 25-84 from the Third National Health and Nutrition Examination Survey, 1988-1994. Signal detection methodology identified high and low risk subgroups; stratified analyses characterized the population of hypertensives. We identified 12 distinct subgroups with highly variable rates of hypertension (11-78%). The two groups with the highest rates of hypertension (>70% hypertensive) were more likely to be middle aged or older, less educated, overweight or obese (>80%), physically inactive (50%), and to have diabetes (28 and 100% diabetic). The two groups with the lowest hypertension rates (<18% hypertensive) were more likely to be younger, but were also overweight or obese (>50%). Among hypertensives, those who were uncontrolled and not on antihypertensive medications were distinguished by their male gender, younger age, and infrequent contact with a physician. Hypertension rates vary substantially within African Americans, illustrating the need for effective weight management, diabetes control, and increased access to health care for those at highest risk. Copyright 2002 American Health Foundation and Elsevier Science (USA)

Prevalence of Tobacco mosaic virus in Iran and Evolutionary Analyses of the Coat Protein Gene

PubMed Central

Alishiri, Athar; Rakhshandehroo, Farshad; Zamanizadeh, Hamid-Reza; Palukaitis, Peter

2013-01-01

The incidence and distribution of Tobacco mosaic virus (TMV) and related tobamoviruses was determined using an enzyme-linked immunosorbent assay on 1,926 symptomatic horticultural crops and 107 asymptomatic weed samples collected from 78 highly infected fields in the major horticultural crop-producing areas in 17 provinces throughout Iran. The results were confirmed by host range studies and reverse transcription-polymerase chain reaction. The overall incidence of infection by these viruses in symptomatic plants was 11.3%. The coat protein (CP) gene sequences of a number of isolates were determined and disclosed to be a high identity (up to 100%) among the Iranian isolates. Phylogenetic analysis of all known TMV CP genes showed three clades on the basis of nucleotide sequences with all Iranian isolates distinctly clustered in clade II. Analysis using the complete CP amino acid sequence showed one clade with two subgroups, IA and IB, with Iranian isolates in both subgroups. The nucleotide diversity within each sub-group was very low, but higher between the two clades. No correlation was found between genetic distance and geographical origin or host species of isolation. Statistical analyses suggested a negative selection and demonstrated the occurrence of gene flow from the isolates in other clades to the Iranian population. PMID:25288953

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

NASA Astrophysics Data System (ADS)

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).

Digital Citizenship and Health Promotion Programs: The Power of Knowing.

PubMed

Hicks, Elaine R

2016-11-03

Patterns of Internet access and use among disadvantaged subgroups of Americans reveal that not all disparities are the same, a distinction crucial for appropriate public policies and health promotion program planning. In their book, Digital Citizenship: The Internet, Society, and Participation, authors Karen Mossberger, Caroline Tolbert, and Ramona McNeal deconstructed national opinion surveys and used multivariate methods of data analysis to demonstrate the impact of exclusion from online society economically, socially, and politically among disadvantaged Americans. © 2016 Society for Public Health Education.

The interdigitating loop of the enolase superfamily as a specificity binding determinant or 'flying buttress'.

PubMed

Bearne, Stephen L

2017-05-01

Enzymes of the enolase superfamily (ENS) are mechanistically diverse, yet share a common partial reaction (abstraction of the α-proton from a carboxylate substrate). While the catalytic machinery responsible for the deprotonation reaction has been conserved, divergent evolution has led to numerous ENS members that catalyze different overall reactions. This rich functional diversity has made the ENS an excellent model system for developing the approaches necessary to validate enzyme function. However, enzymes of the ENS also share a common bidomain structure ((β/α) 7 β-barrel domain and α+β capping domain) which makes validation of function from structural information challenging. This review presents a comparative survey of the structural data obtained over the past decade for enzymes from all seven subgroups that comprise the ENS. Of the seven ENS subgroups (enolase, mandelate racemase (MR), muconate lactonizing enzyme, β-methylaspartate ammonia lyase, d-glucarate dehydratase, d-mannonate dehydratase (ManD), and galactarate dehydratase 2), only enzymes of the MR and ManD subgroups exhibit an additional feature of structural complexity-an interdigitating loop. This loop emanates from one protomer of a homodimeric pair and penetrates into the adjacent, symmetry-related protomer to either contribute a binding determinant to the active site of the adjacent protomer, or act as a 'flying buttress' to support residues of the active site. The analysis presented in this review suggests that the interdigitating loop is the only gross structural element that permits functional distinction between ENS subgroups at the tertiary level of protein structure. Copyright © 2017 Elsevier B.V. All rights reserved.

Sim1 is required for the migration and axonal projections of V3 interneurons in the developing mouse spinal cord.

PubMed

Blacklaws, Jake; Deska-Gauthier, Dylan; Jones, Christopher T; Petracca, Yanina L; Liu, Mingwei; Zhang, Han; Fawcett, James P; Glover, Joel C; Lanuza, Guillermo M; Zhang, Ying

2015-09-01

V3 spinal interneurons (INs) are a group of excitatory INs that play a crucial role in producing balanced and stable gaits in vertebrate animals. In the developing mouse spinal cord, V3 INs arise from the most ventral progenitor domain and form anatomically distinctive subpopulations in adult spinal cords. They are marked by the expression of transcription factor Sim1 postmitotically, but the function of Sim1 in V3 development remains unknown. Here, we used Sim1(Cre) ;tdTomato mice to trace the fate of V3 INs in a Sim1 mutant versus control genetic background during development. In Sim1 mutants, V3 INs are produced normally and maintain a similar position and organization as in wild types before E12.5. Further temporal analysis revealed that the V3 INs in the mutants failed to migrate properly to form V3 subgroups along the dorsoventral axis of the spinal cord. At birth, in the Sim1 mutant the number of V3 INs in the ventral subgroup was normal, but they were significantly reduced in the dorsal subgroup with a concomitant increase in the intermediate subgroup. Retrograde labeling at lumbar level revealed that loss of Sim1 led to a reduction in extension of contralateral axon projections both at E14.5 and P0 without affecting ipsilateral axon projections. These results demonstrate that Sim1 is essential for proper migration and the guidance of commissural axons of the spinal V3 INs. © 2015 Wiley Periodicals, Inc.

Hierarchical Bayes approach for subgroup analysis.

PubMed

Hsu, Yu-Yi; Zalkikar, Jyoti; Tiwari, Ram C

2017-01-01

In clinical data analysis, both treatment effect estimation and consistency assessment are important for a better understanding of the drug efficacy for the benefit of subjects in individual subgroups. The linear mixed-effects model has been used for subgroup analysis to describe treatment differences among subgroups with great flexibility. The hierarchical Bayes approach has been applied to linear mixed-effects model to derive the posterior distributions of overall and subgroup treatment effects. In this article, we discuss the prior selection for variance components in hierarchical Bayes, estimation and decision making of the overall treatment effect, as well as consistency assessment of the treatment effects across the subgroups based on the posterior predictive p-value. Decision procedures are suggested using either the posterior probability or the Bayes factor. These decision procedures and their properties are illustrated using a simulated example with normally distributed response and repeated measurements.

Novel Feline Leukemia Virus Interference Group Based on the env Gene.

PubMed

Miyake, Ariko; Watanabe, Shinya; Hiratsuka, Takahiro; Ito, Jumpei; Ngo, Minh Ha; Makundi, Isaac; Kawasaki, Junna; Endo, Yasuyuki; Tsujimoto, Hajime; Nishigaki, Kazuo

2016-05-01

Feline leukemia virus (FeLV) subgroups have emerged in infected cats via the mutation or recombination of the env gene of subgroup A FeLV (FeLV-A), the primary virus. We report the isolation and characterization of a novel env gene, TG35-2, and report that the TG35-2 pseudotype can be categorized as a novel FeLV subgroup. The TG35-2 envelope protein displays strong sequence identity to FeLV-A Env, suggesting that selection pressure in cats causes novel FeLV subgroups to emerge. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Profiles of Community Violence Exposure Among African American Youth: An Examination of Desensitization to Violence Using Latent Class Analysis.

PubMed

Gaylord-Harden, Noni K; Dickson, Daniel; Pierre, Cynthia

2016-07-01

The current study employed latent class analysis (LCA) to identify distinct profiles of community violence exposure and their associations to desensitization outcomes in 241 African American early adolescents (M age = 12.86, SD = 1.28) in the sixth through eighth grade from under-resourced urban communities. Participants self-reported on their exposure to community violence, as well as on depressive and anxiety symptoms. The LCA revealed three distinct classes: a class exposed to low levels of violence (low exposure class), a class exposed to moderately high levels of victimization (victimization class), and a class exposed to high levels of all types of violence (high exposure class). Consistent with predictions, the high exposure class showed the lowest levels of depressive symptoms, suggesting a desensitization outcome. Gender and age were also examined in relation to the classes, and age was significantly associated with an increased risk of being a member of the high exposure class relative to the low exposure class. Using person-based analyses to examine desensitization outcomes provides useful information for prevention and intervention efforts, as it helps to identify a specific subgroup of youth that may be more likely to show desensitization outcomes in the context of community violence. © The Author(s) 2015.

Aerodynamic profiles of women with muscle tension dysphonia/aphonia.

PubMed

Gillespie, Amanda I; Gartner-Schmidt, Jackie; Rubinstein, Elaine N; Abbott, Katherine Verdolini

2013-04-01

In this study, the authors aimed to (a) determine whether phonatory airflows and estimated subglottal pressures (est-Psub) for women with primary muscle tension dysphonia/aphonia (MTD/A) differ from those for healthy speakers; (b) identify different aerodynamic profile patterns within the MTD/A subject group; and (c) determine whether results suggest new understanding of pathogenesis in MTD/A. Retrospective review of aerodynamic data collected from 90 women at the time of primary MTD/A diagnosis. Aerodynamic profiles were significantly different for women with MTD/A as compared with healthy speakers. Five distinct profiles were identified: (a) normal flow, normal est-Psub; (b) high flow, high est-Psub; (c) low flow, normal est-Psub; (d) normal flow, high est-Psub; and (e) high flow, normal est-Psub. This study is the first to identify distinct subgroups of aerodynamic profiles in women with MTD/A and to quantitatively identify a clinical phenomenon sometimes described in association with it-"breath holding"-that is shown by low airflow with normal est-Psub. Results were consistent with clinical claims that diverse respiratory and laryngeal functions may underlie phonatory patterns associated with MTD/A. One potential mechanism, based in psychobiological theory, is introduced to explain some of the variability in aerodynamic profiles of women with MTD/A.

A novel prognostic six-CpG signature in glioblastomas.

PubMed

Yin, An-An; Lu, Nan; Etcheverry, Amandine; Aubry, Marc; Barnholtz-Sloan, Jill; Zhang, Lu-Hua; Mosser, Jean; Zhang, Wei; Zhang, Xiang; Liu, Yu-He; He, Ya-Long

2018-03-01

We aimed to identify a clinically useful biomarker using DNA methylation-based information to optimize individual treatment of patients with glioblastoma (GBM). A six-CpG panel was identified by incorporating genome-wide DNA methylation data and clinical information of three distinct discovery sets and was combined using a risk-score model. Different validation sets of GBMs and lower-grade gliomas and different statistical methods were implemented for prognostic evaluation. An integrative analysis of multidimensional TCGA data was performed to molecularly characterize different risk tumors. The six-CpG risk-score signature robustly predicted overall survival (OS) in all discovery and validation cohorts and in a treatment-independent manner. It also predicted progression-free survival (PFS) in available patients. The multimarker epigenetic signature was demonstrated as an independent prognosticator and had better performance than known molecular indicators such as glioma-CpG island methylator phenotype (G-CIMP) and proneural subtype. The defined risk subgroups were molecularly distinct; high-risk tumors were biologically more aggressive with concordant activation of proangiogenic signaling at multimolecular levels. Accordingly, we observed better OS benefits of bevacizumab-contained therapy to high-risk patients in independent sets, supporting its implication in guiding usage of antiangiogenic therapy. Finally, the six-CpG signature refined the risk classification based on G-CIMP and MGMT methylation status. The novel six-CpG signature is a robust and independent prognostic indicator for GBMs and is of promising value to improve personalized management. © 2018 John Wiley & Sons Ltd.

Correlation between Serum Calcineurin Activity and Left Ventricular Hypertrophy in Hypertensive Patients and Its Clinical Significance.

PubMed

Cao, Jia-Li; Yang, Yu-Qing; Nabeel, Dookhun Muhammad; Sun, Ya-Li; Zou, Hua-Yi-Yang; Kong, Xiang-Qing; Lu, Xin-Zheng

The aim of this study is to investigate the correlation between calcineurin (CaN) and hypertension with left ventricular hypertrophy (HLVH) and to evaluate its potential clinical significance. The study involved 160 patients diagnosed with hypertension and 42 controls. Based on the exclusion criteria, 42 were not eligible for this study. The remaining 118 hypertensive patients were categorized into 2 subgroups based on left ventricular mass index and relative ventricular wall thickness: a normal model subgroup with hypertension (HNM) and an HLVH subgroup. Serum CaN levels were determined by enzyme-linked immunosorbent assay, while serum CaN activity was determined by malachite green colorimetric assay. Among the HNM and HLVH subgroups, a positive correlation was demonstrated between serum CaN activity, but not serum CaN level, and HLVH. Moreover, the HLVH subgroup displayed a remarkable increase in the levels of brain natriuretic peptide, cystatin C, urinary albumin/creatinine ratio, and left atrium diameter compared to the HNM subgroup and controls. There was a positive correlation between serum CaN activity and LVH in hypertensive patients. Activated CaN could play an important role in the pathophysiologic mechanism of HLVH. Serum CaN activity could be a clinically useful diagnostic and prognostic biomarker for LVH. © 2018 S. Karger AG, Basel.

A Simple and Reliable Strategy for BK Virus Subtyping and Subgrouping

PubMed Central

Morel, Virginie; Martin, Elodie; François, Catherine; Helle, François; Faucher, Justine; Mourez, Thomas; Choukroun, Gabriel; Duverlie, Gilles; Castelain, Sandrine

2017-01-01

ABSTRACT BK virus (BKV)-associated diseases in transplant recipients are an emerging issue. However, identification of the various BK virus subtypes/subgroups is a long and delicate process on the basis of currently available data. Therefore, we wanted to define a simple and effective one-step strategy for characterizing all BK virus strains from the VP1 gene sequence. Based on the analysis of 199 available complete DNA VP1 sequences, phylogenetic trees, alignments, and isolated polymorphisms were used to define an effective strategy for distinguishing the 12 different BK virus subtypes/subgroups. Based on the 12 subtypes identified from the 199 complete BKV VP1 sequences (1,089 bp), 60 mutations that can be used to differentiate these various subtypes/subgroups were identified. Some genomic areas were more variable and comprised mutational hot spots. From a subregion of only 100 bp in the VP1 region (1977 through 2076), we therefore constructed an algorithm that enabled rapid determination of all BKV subtypes/subgroups with 99% agreement (197/199) relative to the complete VP1 sequence. We called this domain of the BK viral genome the BK typing and grouping region (BKTGR). Finally, we validated our viral subtype identification process in a population of 100 transplant recipients with 100% efficiency. The new simpler method of BKV subtyping/subgrouping reported here constitutes a useful tool for future studies that will help us to more clearly understand the impact of BKV subtypes/subgroups on diagnosis, infection, and BK virus-associated diseases. PMID:28151406

Symptom-specific course trajectories and their determinants in primary care patients with Major Depressive Disorder: Evidence for two etiologically distinct prototypes.

PubMed

Wardenaar, K J; Monden, R; Conradi, H J; de Jonge, P

2015-07-01

The course-heterogeneity of Major Depressive Disorder (MDD) hampers development of better prognostic models. Although latent class growth analyses (LCGA) have been used to explain course-heterogeneity, such analyses have failed to also account for symptom-heterogeneity of depressive symptoms. Therefore, the aim was to identify more specific data-driven subgroups based on patterns of course-trajectories on different depressive symptom domains. In primary care MDD patients (n=205), the presence of the MDD criterion symptoms was determined for each week during a year. Weekly 'mood/cognition' (MC) and 'somatic' (SOM) scores were computed and parallel processes-LCGA (PP-LCGA) was used to identify subgroups based on the course on these domains. The classes׳ associations with baseline predictors and 2-/3-year outcomes were investigated. PP-LCGA identified four classes: quick recovery, persisting SOM, persisting MC, and persisting SOM+MC (chronic). Persisting SOM was specifically predicted by higher baseline somatic symptomatology and somatization, and was associated with more somatic depressive symptomatology at long-term follow-up. Persisting MC was specifically predicted by higher depressive severity, thinking insufficiencies, neuroticism, loneliness and lower self-esteem, and was associated with lower mental health related quality of life and more mood/cognitive depressive symptomatology at follow-up. The sample was small and contained only primary care MDD patients. The weekly depression assessments were collected retrospectively at 3-month intervals. The results indicate that there are two specific prototypes of depression, characterized by either persisting MC or persisting SOM, which have different sets of associated prognostic factors and long-term outcomes, and could have different etiological mechanisms. Copyright © 2015 Elsevier B.V. All rights reserved.

Functional Abdominal Pain Patient Subtypes in Childhood Predict Functional Gastrointestinal Disorders with Chronic Pain and Psychiatric Comorbidities in Adolescence and Adulthood

PubMed Central

Walker, Lynn S.; Sherman, Amanda L.; Bruehl, Stephen; Garber, Judy; Smith, Craig A.

2012-01-01

Although pediatric functional abdominal pain (FAP) has been linked to abdominal pain later in life, childhood predictors of long-term outcomes have not been identified. This study evaluated whether distinct FAP profiles based on patterns of pain and adaptation in childhood could be identified and whether these profiles predicted differences in clinical outcomes and central sensitization (wind-up) on average 9 years later. In 843 pediatric FAP patients, cluster analysis was used to identify subgroups at initial FAP evaluation based on profiles of pain severity, gastrointestinal (GI) and non-GI symptoms, pain threat appraisal, pain coping efficacy, catastrophizing, negative affect, and activity impairment. Three profiles were identified: High Pain Dysfunctional, High Pain Adaptive, and Low Pain Adaptive. Logistic regression analyses controlling for age and sex showed that, compared to pediatric patients with the Low Pain Adaptive profile, those with the High Pain Dysfunctional profile were significantly more likely at long-term follow-up to meet criteria for pain-related functional gastrointestinal disorder (FGID) (OR: 3.45; CI: 1.95–6.11), FGID with comorbid non-abdominal chronic pain (OR: 2.6; CI:1.45–4.66), and FGID with comorbid anxiety or depressive psychiatric disorder (OR: 2.84; CI: 1.35–6.00). Pediatric patients with the High Pain Adaptive profile had baseline pain severity comparable to the High Pain Dysfunctional profile, but had outcomes as favorable as the Low Pain Adaptive profile. In laboratory pain testing at follow-up, High Pain Dysfunctional patients exhibited significantly greater thermal wind-up than Low Pain Adaptive patients, suggesting that a subgroup of FAP patients has outcomes consistent with widespread effects of heightened central sensitization. PMID:22721910

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

PubMed

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.

Differentiation of Alcaligenes-like bacteria of avian origin and comparison with Alcaligenes spp. reference strains.

PubMed Central

Berkhoff, H A; Riddle, G D

1984-01-01

Although standard biochemical tests used for the identification of Alcaligenes spp. revealed only minor differences, the oxidative low-peptone technique clearly differentiated between Alcaligenes-like bacteria of avian origin and Alcaligenes spp. reference strains. Based on their colonial morphology, biochemical profiles, and hemagglutination, the Alcaligenes-like bacteria of avian origin were further divided into two subgroups, C1-T1 and C2-T2. Colonies of subgroup C1-T1 were nondescript, round, raised, glistening, translucent, greyish, and about 2 mm in diameter. Colonies of subgroup C2-T2 were off-white, flat, dry and wrinkled, generally round, and resembled tiny lily pads. Biochemical profiles by the oxidative low-peptone method showed the C1-T1 subgroup alkalinizing only three substrates (citrate, acetate, and succinate), whereas the C2-T2 subgroup alkalinized eight substrates (citrate, acetate, butyrate, itaconate, malonate, saccharate, succinate, and M-tartrate). Subgroup C1-T1 agglutinated human, chicken, and turkey erythrocytes, whereas subgroup C2-T2 did not. The recognition of these two subgroups within the Alcaligenes-like bacteria of avian origin is important, since it may explain the differences seen in pathogenicity among isolates. Images PMID:6715517

Differentiation of Alcaligenes-like bacteria of avian origin and comparison with Alcaligenes spp. reference strains.

PubMed

Berkhoff, H A; Riddle, G D

1984-04-01

Although standard biochemical tests used for the identification of Alcaligenes spp. revealed only minor differences, the oxidative low-peptone technique clearly differentiated between Alcaligenes-like bacteria of avian origin and Alcaligenes spp. reference strains. Based on their colonial morphology, biochemical profiles, and hemagglutination, the Alcaligenes-like bacteria of avian origin were further divided into two subgroups, C1-T1 and C2-T2. Colonies of subgroup C1-T1 were nondescript, round, raised, glistening, translucent, greyish, and about 2 mm in diameter. Colonies of subgroup C2-T2 were off-white, flat, dry and wrinkled, generally round, and resembled tiny lily pads. Biochemical profiles by the oxidative low-peptone method showed the C1-T1 subgroup alkalinizing only three substrates (citrate, acetate, and succinate), whereas the C2-T2 subgroup alkalinized eight substrates (citrate, acetate, butyrate, itaconate, malonate, saccharate, succinate, and M-tartrate). Subgroup C1-T1 agglutinated human, chicken, and turkey erythrocytes, whereas subgroup C2-T2 did not. The recognition of these two subgroups within the Alcaligenes-like bacteria of avian origin is important, since it may explain the differences seen in pathogenicity among isolates.

Characterising the latent structure and organisation of self-reported thoughts, feelings and behaviours in adolescents and young adults

PubMed Central

Neufeld, Sharon; Jones, Peter B.; Fonagy, Peter; Bullmore, Edward T.; Dolan, Raymond J.; Moutoussis, Michael; Toseeb, Umar; Goodyer, Ian M.

2017-01-01

Little is known about the underlying relationships between self-reported mental health items measuring both positive and negative emotional and behavioural symptoms at the population level in young people. Improved measurement of the full range of mental well-being and mental illness may aid in understanding the aetiological substrates underlying the development of both mental wellness as well as specific psychiatric diagnoses. A general population sample aged 14 to 24 years completed self-report questionnaires on anxiety, depression, psychotic-like symptoms, obsessionality and well-being. Exploratory and confirmatory factor models for categorical data and latent profile analyses were used to evaluate the structure of both mental wellness and illness items. First order, second order and bifactor structures were evaluated on 118 self-reported items obtained from 2228 participants. A bifactor solution was the best fitting latent variable model with one general latent factor termed ‘distress’ and five ‘distress independent’ specific factors defined as self-confidence, antisocial behaviour, worry, aberrant thinking, and mood. Next, six distinct subgroups were derived from a person-centred latent profile analysis of the factor scores. Finally, concurrent validity was assessed using information on hazardous behaviours (alcohol use, substance misuse, self-harm) and treatment for mental ill health: both discriminated between the latent traits and latent profile subgroups. The findings suggest a complex, multidimensional mental health structure in the youth population rather than the previously assumed first or second order factor structure. Additionally, the analysis revealed a low hazardous behaviour/low mental illness risk subgroup not previously described. Population sub-groups show greater validity over single variable factors in revealing mental illness risks. In conclusion, our findings indicate that the structure of self reported mental health is multidimensional in nature and uniquely finds improved prediction to mental illness risk within person-centred subgroups derived from the multidimensional latent traits. PMID:28403164

Characterising the latent structure and organisation of self-reported thoughts, feelings and behaviours in adolescents and young adults.

PubMed

St Clair, Michelle C; Neufeld, Sharon; Jones, Peter B; Fonagy, Peter; Bullmore, Edward T; Dolan, Raymond J; Moutoussis, Michael; Toseeb, Umar; Goodyer, Ian M

2017-01-01

Little is known about the underlying relationships between self-reported mental health items measuring both positive and negative emotional and behavioural symptoms at the population level in young people. Improved measurement of the full range of mental well-being and mental illness may aid in understanding the aetiological substrates underlying the development of both mental wellness as well as specific psychiatric diagnoses. A general population sample aged 14 to 24 years completed self-report questionnaires on anxiety, depression, psychotic-like symptoms, obsessionality and well-being. Exploratory and confirmatory factor models for categorical data and latent profile analyses were used to evaluate the structure of both mental wellness and illness items. First order, second order and bifactor structures were evaluated on 118 self-reported items obtained from 2228 participants. A bifactor solution was the best fitting latent variable model with one general latent factor termed 'distress' and five 'distress independent' specific factors defined as self-confidence, antisocial behaviour, worry, aberrant thinking, and mood. Next, six distinct subgroups were derived from a person-centred latent profile analysis of the factor scores. Finally, concurrent validity was assessed using information on hazardous behaviours (alcohol use, substance misuse, self-harm) and treatment for mental ill health: both discriminated between the latent traits and latent profile subgroups. The findings suggest a complex, multidimensional mental health structure in the youth population rather than the previously assumed first or second order factor structure. Additionally, the analysis revealed a low hazardous behaviour/low mental illness risk subgroup not previously described. Population sub-groups show greater validity over single variable factors in revealing mental illness risks. In conclusion, our findings indicate that the structure of self reported mental health is multidimensional in nature and uniquely finds improved prediction to mental illness risk within person-centred subgroups derived from the multidimensional latent traits.

Breast and cervical cancer screening among Hispanic subgroups in the USA: estimates from the National Health Interview Survey 2008, 2010, and 2013.

PubMed

Shoemaker, Meredith L; White, Mary C

2016-03-01

This study examined patterns in mammography and Pap test use across and within subpopulations of Hispanic women. Based on data from the National Health Interview Survey (2008, 2010, and 2013), we estimated the proportion of Hispanic women reporting testing for breast and cervical cancer for specific subgroups. We examined test use by demographic characteristics using Chi-square tests. Overall, the proportion of women aged 50-74 years who reported a mammogram within the past 2 years did not differ significantly across Hispanic subgroups. Among publically and uninsured women, however, proportions of mammography utilization varied significantly across Hispanic subgroups. The proportion of women aged 21-65 years who received a Pap test within the past 3 years differed significantly across Hispanic subgroups. Among subgroups of Hispanic women, patterns in mammography and Pap test use vary by insurance status, length of US residency, and type of screening. Certain subgroups of Hispanic women may benefit from culturally tailored efforts to promote breast and cervical cancer screening.

Reclassification of Mixed Oligoastrocytic Tumors Using a Genetically Integrated Diagnostic Approach

PubMed Central

Kim, Seong-Ik; Lee, Yujin; Won, Jae-Kyung; Park, Chul-Kee; Choi, Seung Hong; Park, Sung-Hye

2018-01-01

Background Mixed gliomas, such as oligoastrocytomas (OA), anaplastic oligoastrocytomas, and glioblastomas (GBMs) with an oligodendroglial component (GBMO) are defined as tumors composed of a mixture of two distinct neoplastic cell types, astrocytic and oligodendroglial. Recently, mutations ATRX and TP53, and codeletion of 1p/19q are shown to be genetic hallmarks of astrocytic and oligodendroglial tumors, respectively. Subsequent molecular analyses of mixed gliomas preferred the reclassification to either oligodendroglioma or astrocytoma. This study was designed to apply genetically integrated diagnostic criteria to mixed gliomas and determine usefulness and prognostic value of new classification in Korean patients. Methods Fifty-eight cases of mixed OAs and GBMOs were retrieved from the pathology archives of Seoul National University Hospital from 2004 to 2015. Reclassification was performed according to genetic and immunohistochemical properties. Clinicopathological characteristics of each subgroup were evaluated. Overall survival was assessed and compared between subgroups. Results We could reclassify all mixed OAs and GBMOs into either astrocytic or oligodendroglial tumors. Notably, 29 GBMOs could be reclassified into 11 cases of GBM, IDH-mutant, 16 cases of GBM, IDH-wildtype, and two cases of anaplastic oligodendroglioma, IDH mutant. Overall survival was significantly different among these new groups (p<.001). Overall survival and progression-free survival were statistically better in gliomas with IDH mutation, ATRX mutation, no microscopic necrosis, and young patient age (cut off, 45 years old). Conclusions Our results strongly suggest that a genetically integrated diagnosis of glioma better reflects prognosis than former morphology-based methods. PMID:28958143

Surface defect detection in tiling Industries using digital image processing methods: analysis and evaluation.

PubMed

Karimi, Mohammad H; Asemani, Davud

2014-05-01

Ceramic and tile industries should indispensably include a grading stage to quantify the quality of products. Actually, human control systems are often used for grading purposes. An automatic grading system is essential to enhance the quality control and marketing of the products. Since there generally exist six different types of defects originating from various stages of tile manufacturing lines with distinct textures and morphologies, many image processing techniques have been proposed for defect detection. In this paper, a survey has been made on the pattern recognition and image processing algorithms which have been used to detect surface defects. Each method appears to be limited for detecting some subgroup of defects. The detection techniques may be divided into three main groups: statistical pattern recognition, feature vector extraction and texture/image classification. The methods such as wavelet transform, filtering, morphology and contourlet transform are more effective for pre-processing tasks. Others including statistical methods, neural networks and model-based algorithms can be applied to extract the surface defects. Although, statistical methods are often appropriate for identification of large defects such as Spots, but techniques such as wavelet processing provide an acceptable response for detection of small defects such as Pinhole. A thorough survey is made in this paper on the existing algorithms in each subgroup. Also, the evaluation parameters are discussed including supervised and unsupervised parameters. Using various performance parameters, different defect detection algorithms are compared and evaluated. Copyright © 2013 ISA. Published by Elsevier Ltd. All rights reserved.

Comparative genomic analysis of coffee-infecting Xylella fastidiosa strains isolated from Brazil.

PubMed

Barbosa, Deibs; Alencar, Valquíria Campos; Santos, Daiene Souza; de Freitas Oliveira, Ana Cláudia; de Souza, Alessandra A; Coletta-Filho, Helvecio D; de Oliveira, Regina Souza; Nunes, Luiz R

2015-05-01

Strains of Xylella fastidiosa constitute a complex group of bacteria that develop within the xylem of many plant hosts, causing diseases of significant economic importance, such as Pierce's disease in North American grapevines and citrus variegated chlorosis in Brazil. X. fastidiosa has also been obtained from other host plants, in direct correlation with the development of diseases, as in the case of coffee leaf scorch (CLS)--a disease with potential to cause severe economic losses to the Brazilian coffee industry. This paper describes a thorough genomic characterization of coffee-infecting X. fastidiosa strains, initially performed through a microarray-based approach, which demonstrated that CLS strains could be subdivided in two phylogenetically distinct subgroups. Whole-genomic sequencing of two of these bacteria (one from each subgroup) allowed identification of ORFs and horizontally transferred elements (HTEs) that were specific to CLS-related X. fastidiosa strains. Such analyses confirmed the size and importance of HTEs as major mediators of chromosomal evolution amongst these bacteria, and allowed identification of differences in gene content, after comparisons were made with previously sequenced X. fastidiosa strains, isolated from alternative hosts. Although direct experimentation still needs to be performed to elucidate the biological consequences associated with such differences, it was interesting to verify that CLS-related bacteria display variations in genes that produce toxins, as well as surface-related factors (such as fimbrial adhesins and LPS) that have been shown to be involved with recognition of specific host factors in different pathogenic bacteria. © 2015 The Authors.

PERSISTENT ARM PAIN IS DISTINCT FROM PERSISTENT BREAST PAIN FOLLOWING BREAST CANCER SURGERY

PubMed Central

Langford, Dale J.; Paul, Steven M.; West, Claudia; Abrams, Gary; Elboim, Charles; Levine, Jon D.; Hamolsky, Deborah; Luce, Judith A.; Kober, Kord M.; Neuhaus, John M.; Cooper, Bruce A.; Aouizerat, Bradley E.; Miaskowski, Christine

2014-01-01

Persistent pain following breast cancer surgery is well-documented. However, it is not well characterized in terms of the anatomic site effected (i.e., breast, arm). In two separate growth mixture modeling analyses, we identified subgroups of women (n=398) with distinct breast pain and arm pain trajectories. Based on the fact that these latent classes differed by anatomic site, types if tissue affected, and neural innervation patterns suggests the need for separate evaluations of these distinct persistent pain conditions. Purposes of this companion study were to identify demographic and clinical characteristics that differed between the two arm pain classes and determine if differences existed over time in sensitivity in the upper inner arm and axillary lymph node dissection (ALND) sites, pain qualities, pain interference, and hand and arm function; as well as to compare findings with persistent breast pain. Higher occurrence rates for depression and lymphedema were found in the Moderate Arm pain class. Regardless of pain group membership, sensory loss was observed in the upper inner arm and ALND site. Arm pain was described similarly to neuropathic pain and interfered with daily functioning. Persistent arm pain was associated with sustained impairments in shoulder mobility. Perspective: For persistent breast and arm pain, changes in sensation following breast cancer surgery were notable. Persistent arm pain was associated with sustained interference with daily functioning and upper body mobility impairments. Long-term management of persistent pain following breast cancer surgery is warranted to improve the quality of survivorship for these women. PMID:25439319

Local sparse bump hunting reveals molecular heterogeneity of colon tumors‡

PubMed Central

Dazard, Jean-Eudes; Rao, J. Sunil; Markowitz, Sanford

2013-01-01

The question of molecular heterogeneity and of tumoral phenotype in cancer remains unresolved. To understand the underlying molecular basis of this phenomenon, we analyzed genome-wide expression data of colon cancer metastasis samples, as these tumors are the most advanced and hence would be anticipated to be the most likely heterogeneous group of tumors, potentially exhibiting the maximum amount of genetic heterogeneity. Casting a statistical net around such a complex problem proves difficult because of the high dimensionality and multi-collinearity of the gene expression space, combined with the fact that genes act in concert with one another and that not all genes surveyed might be involved. We devise a strategy to identify distinct subgroups of samples and determine the genetic/molecular signature that defines them. This involves use of the local sparse bump hunting algorithm, which provides a much more optimal and biologically faithful transformed space within which to search for bumps. In addition, thanks to the variable selection feature of the algorithm, we derived a novel sparse gene expression signature, which appears to divide all colon cancer patients into two populations: a population whose expression pattern can be molecularly encompassed within the bump and an outlier population that cannot be. Although all patients within any given stage of the disease, including the metastatic group, appear clinically homogeneous, our procedure revealed two subgroups in each stage with distinct genetic/molecular profiles. We also discuss implications of such a finding in terms of early detection, diagnosis and prognosis. PMID:22052459

Heterogeneity of subclinical autistic traits among parents of children with autism spectrum disorder: Identifying the broader autism phenotype with a data-driven method.

PubMed

Bora, Emre; Aydın, Aydan; Saraç, Tuğba; Kadak, Muhammed Tayyib; Köse, Sezen

2017-02-01

Clinical diagnosis of autism spectrum disorder (ASD) can be conceptualized as the extreme end of the distribution of subclinical autistic traits related to genetic susceptibility factors (broad autism phenotype (BAP)) in the general population. Subclinical autistic traits are significantly more common among unaffected first-degree relatives of probands with autism. However, there is a significant heterogeneity of autistic traits in family members of individuals with ASD and severity of autistic traits are not significantly different from controls in the majority of these relatives. The current study investigated the heterogeneity of autistic traits using latent class analysis (LCA) of the Autism Spectrum Quotient (AQ) ratings of 673 parents of children with ASD and 147 parents of typically developing children. Two distinct subgroups, including a "low-scoring" and a "high-scorer (BAP)" groups, were found. In comparison to control parents, a significantly larger proportion (21.1% vs. 7.5%) of parents of ASD were members of BAP group. Communication subscale made a distinctive contribution to the separation of high and low-scoring groups (d = 2.77). Further studies investigating neurobiological and genetic biomarkers and stability of these two subgroups over time are important for understanding the nature of autistic traits in the general population. Autism Res 2017, 10: 321-326. © 2016 International Society for Autism Research, Wiley Periodicals, Inc. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

Single-cell RNA sequencing reveals developmental heterogeneity among early lymphoid progenitors.

PubMed

Alberti-Servera, Llucia; von Muenchow, Lilly; Tsapogas, Panagiotis; Capoferri, Giuseppina; Eschbach, Katja; Beisel, Christian; Ceredig, Rhodri; Ivanek, Robert; Rolink, Antonius

2017-12-15

Single-cell RNA sequencing is a powerful technology for assessing heterogeneity within defined cell populations. Here, we describe the heterogeneity of a B220 + CD117 int CD19 - NK1.1 - uncommitted hematopoietic progenitor having combined lymphoid and myeloid potential. Phenotypic and functional assays revealed four subpopulations within the progenitor with distinct lineage developmental potentials. Among them, the Ly6D + SiglecH - CD11c - fraction was lymphoid-restricted exhibiting strong B-cell potential, whereas the Ly6D - SiglecH - CD11c - fraction showed mixed lympho-myeloid potential. Single-cell RNA sequencing of these subsets revealed that the latter population comprised a mixture of cells with distinct lymphoid and myeloid transcriptional signatures and identified a subgroup as the potential precursor of Ly6D + SiglecH - CD11c - Subsequent functional assays confirmed that B220 + CD117 int CD19 - NK1.1 - single cells are, with rare exceptions, not bipotent for lymphoid and myeloid lineages. A B-cell priming gradient was observed within the Ly6D + SiglecH - CD11c - subset and we propose a herein newly identified subgroup as the direct precursor of the first B-cell committed stage. Therefore, the apparent multipotency of B220 + CD117 int CD19 - NK1.1 - progenitors results from underlying heterogeneity at the single-cell level and highlights the validity of single-cell transcriptomics for resolving cellular heterogeneity and developmental relationships among hematopoietic progenitors. © 2017 The Authors.

Theory-Driven Longitudinal Study Exploring Indoor Tanning Initiation in Teens Using a Person-Centered Approach

PubMed Central

Hillhouse, Joel; Turrisi, Rob; Cleveland, Michael J.; Scaglione, Nichole M.; Baker, Katie; Florence, L. Carter

2015-01-01

Background Younger indoor tanning initiation leads to greater melanoma risk due to more frequent and persistent behavior. Despite this, there are no published studies exploring the predictors of indoor tanning initiation in teen populations. Purpose This longitudinal study uses latent profile analysis to examine indoor tanning initiation in indoor tanning risk subgroups from a national sample of female adolescents. Methods Latent profile analysis used indoor tanning beliefs and perceptions to identify indoor tanning initiation risk subgroups. The teens in each subgroup were reassessed on indoor tanning initiation after a year. Results Three subgroups were identified: a low-risk, Anti-Tanning subgroup (18.6%) characterized by low scores on positive indoor tanning belief scales and high scores on beliefs about indoor tanning dangers; a moderate-risk Aware Social Tanner subgroup (47.2%) characterized by high scores on positive indoor tanning belief scales but also high scores on beliefs about indoor tanning dangers; and a high-risk Risky Relaxation Tanner subgroup (34.2%) characterized by high scores on positive indoor tanning belief scales and low scores on beliefs about indoor tanning dangers. Teens in the Aware Social Tanner and Risky Relaxation Tanner subgroups were significantly more likely to initiate indoor tanning in the following year. Conclusions These findings highlight the need to identify teens at risk for indoor tanning initiation and develop tailored interventions that will move them to the lowest risk subgroup. Subgroup correlates suggest parent and peer-based interventions may be successful. PMID:26370893

Theory-Driven Longitudinal Study Exploring Indoor Tanning Initiation in Teens Using a Person-Centered Approach.

PubMed

Hillhouse, Joel; Turrisi, Rob; Cleveland, Michael J; Scaglione, Nichole M; Baker, Katie; Florence, L Carter

2016-02-01

Younger indoor tanning initiation leads to greater melanoma risk due to more frequent and persistent behavior. Despite this, there are no published studies exploring the predictors of indoor tanning initiation in teen populations. This longitudinal study uses latent profile analysis to examine indoor tanning initiation in indoor tanning risk subgroups from a national sample of female adolescents. Latent profile analysis used indoor tanning beliefs and perceptions to identify indoor tanning initiation risk subgroups. The teens in each subgroup were reassessed on indoor tanning initiation after a year. Three subgroups were identified: a low risk, anti-tanning subgroup (18.6 %) characterized by low scores on positive indoor tanning belief scales and high scores on beliefs about indoor tanning dangers; a moderate risk aware social tanner subgroup (47.2 %) characterized by high scores on positive indoor tanning belief scales but also high scores on beliefs about indoor tanning dangers; and a high risk risky relaxation tanner subgroup (34.2 %) characterized by high scores on positive indoor tanning belief scales and low scores on beliefs about indoor tanning dangers. Teens in the aware social tanner and risky relaxation tanner subgroups were significantly more likely to initiate indoor tanning in the following year. These findings highlight the need to identify teens at risk for indoor tanning initiation and develop tailored interventions that will move them to the lowest risk subgroup. Subgroup correlates suggest parent and peer-based interventions may be successful.

Effect of Dimethyl Sulfoxide on Bond Strength of a Self-Etch Primer and an Etch and Rinse Adhesive to Surface and Deep Dentin.

PubMed

Sharafeddin, Farahnaz; Salehi, Raha; Feizi, Negar

2016-09-01

Composite bond to dentin is crucial in many clinical conditions particularly in deep cavities without enamel margins due to insufficient penetration of adhesive into demineralized dentin. The aim of this study was to assess the shear bond strength (SBS) of a methacrylate-based and a silorane-based composite resin to surface and deep dentin after pretreatment with dimethyl sulfoxide (DMSO). Eighty extracted human premolars were randomly divided into two groups of flat occlusal dentin with different cuts as A: surface group (sections just below the dentinoenamel junction (DEJ) and B: deep group (2 mm below DEJ). Each group was randomly assigned to 4 subgroups and their samples were restored with Adper Single bond (ASB) and Filtek Z350 or Silorane system Adhesive (SA) and Filtek P90 composite resins, using a 3×3mm cylindrical plastic mold. following these steps , the subgroups were assigned as SubgroupA 1 : surface dentin+ Silorane System Primer (SSP)+ Silorane System Bonding (SSB)+ P90; Subgroup A 2 : surface dentin+ 37% etchant (E37%) + Adper Single Bond (ASB)+ Z350; Subgroup A 3 : surface dentin+ DMSO+ SSP+ SSB+ P90; Subgroup A 4 : surface dentin+ E37%+ DMSO+ ASB+ Z350; Subgroup B 1 : deep dentin+ SSP+ SSB+ P90; Subgroup B 2 : deep dentin+ E37%+ ASB+ Z350; Subgroup B 3 : deep dentin+ DMSO+ SSP+ SSB+ P90; Subgroup B 4 :dentin +E37% +DMSO +ASB +Z350. The specimens were thermocycled at 5± 2/55± 2°C for 1000 cycles and then tested for SBS. Using DMSO as dentin conditioner increased SBS of ASB to deep dentin (p< 0.001) and SBS of SA to surface dentin (p= 0.003) but had no effect on SBS of SA to deep dentin (p= 1.00). The ability of DMSO to increase SBS of ASB to deep dentin provides a basis for improving bonding of this composite resin in deep cavities.

Morphological changes in human melanoma cells following irradiation with thermal neutrons.

PubMed

Barkla, D H; Allen, B J; Brown, J K; Mountford, M; Mishima, Y; Ichihashi, M

1989-01-01

Morphological changes in two human melanoma cell lines, MM96 and MM418, following irradiation with thermal neutrons, were studied using light and electron microscopy. The results show that the response of human malignant melanoma cells to neutron irradiation is both cell line dependent and dose dependent, and that in any given cell line, some cells are more resistant to irradiation than others, thus demonstrating heterogeneity in respect to radiosensitivity. Cells repopulating MM96 flasks after irradiation were morphologically similar to the cells of origin whereas in MM418 flasks cells differentiated into five morphologically distinct subgroups and showed increased melanization. The results also show that radiation causes distinctive morphological patterns of damage although ultrastructural changes unique to the high LET particles released from boron 10 neutron capture are yet to be identified.

The Distinction of Amyloid-β Protein Precursor (AβPP) Ratio in Platelet Between Alzheimer's Disease Patients and Controls: A Systematic Review and Meta-Analysis.

PubMed

Shi, Yachen; Gu, Lihua; Alsharif, Abdul Azeez; Zhang, Zhijun

2017-01-01

To systematically assess the clinical significance of platelet amyloid-β protein precursor (AβPP) ratio between Alzheimer's disease (AD) patients and controls. 14 articles were selected in this analysis by search of databases including PubMed and Web of Science up to December 2016. Random effects models were used to calculate the standardized mean difference (SMD). Subgroup analyses were used to detect the cause of heterogeneity. The result showed a significant drop in platelet AβPP ratio in AD patients compared to controls [SMD: -1.871; 95% CI: (-2.33, -1.41); p < 0.001; I2 = 88.0% ]. Subgroup analysis revealed races or the quality of studies may be the cause of high heterogeneity. This meta-analysis concluded that there is a close association between platelet AβPP ratio and AD. It is necessary to design a sizable sample study to further support that platelet AβPP ratio can be a biomarker of AD.

The Florida manatee (Trichechus manatus latirostris) T cell receptor loci exhibit V subgroup synteny and chain-specific evolution

USGS Publications Warehouse

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.

Differences in cortisol response affect the distinction of observed reactive and proactive aggression in children with aggressive behaviour disorders.

PubMed

Kempes, M; de Vries, H; Matthys, W; van Engeland, H; van Hooff, J

2008-01-01

Various researchers distinguished two categories of aggressive behaviour, namely reactive and proactive aggression. Reactive aggression is an aggressive response to a perceived threat or provocation, whereas proactive aggression is behaviour that anticipates a reward. In the present study, including both a sample of disruptive behaviour disordered (DBD) and normal control (NC) children, we observed reactive and proactive aggressive behaviour during an experimental dyadic play session. DBD children showed more observed reactive and proactive aggression. Subsequently, we investigated whether the observed measures correlated with parent-rated measures of reactive and proactive aggression in. We distinguished in both NC and DBD children a subgroup showing a rise in cortisol level, i.e. responders, and a subgroup who did not show a rise in cortisol, i.e. non-responders. Results suggest that differences in the cortisol response affects the correspondence between observed and parent-rated reactive and proactive aggression since only DBD non-responders showed the expected correlations.

Verbal, facial and autonomic responses to empathy-eliciting film clips by disruptive male adolescents with high versus low callous-unemotional traits.

PubMed

de Wied, Minet; van Boxtel, Anton; Matthys, Walter; Meeus, Wim

2012-02-01

This study examined empathy-related responding in male adolescents with disruptive behavior disorder (DBD), high or low on callous-unemotional (CU) traits. Facial electromyographic (EMG) and heart rate (HR) responses were monitored during exposure to empathy-inducing film clips portraying sadness, anger or happiness. Self-reports were assessed afterward. In agreement with expectations, DBD adolescents with high CU traits showed significantly lower levels of empathic sadness than healthy controls across all response systems. Between DBD subgroups significant differences emerged at the level of autonomic (not verbal or facial) reactions to sadness, with high CU respondents showing less HR change from baseline than low CU respondents. The study also examined basal patterns of autonomic function. Resting HR was not different between groups, but resting respiratory sinus arrhythmia (RSA) was significantly lower in DBD adolescents with high CU traits compared to controls. Results support the notion that CU traits designate a distinct subgroup of DBD individuals.

Incidence of cognitively defined late-onset Alzheimer's dementia subgroups from a prospective cohort study.

PubMed

Crane, Paul K; Trittschuh, Emily; Mukherjee, Shubhabrata; Saykin, Andrew J; Sanders, R Elizabeth; Larson, Eric B; McCurry, Susan M; McCormick, Wayne; Bowen, James D; Grabowski, Thomas; Moore, Mackenzie; Bauman, Julianna; Gross, Alden L; Keene, C Dirk; Bird, Thomas D; Gibbons, Laura E; Mez, Jesse

2017-12-01

There may be biologically relevant heterogeneity within typical late-onset Alzheimer's dementia. We analyzed cognitive data from people with incident late-onset Alzheimer's dementia from a prospective cohort study. We determined individual averages across memory, visuospatial functioning, language, and executive functioning. We identified domains with substantial impairments relative to that average. We compared demographic, neuropathology, and genetic findings across groups defined by relative impairments. During 32,286 person-years of follow-up, 869 people developed Alzheimer's dementia. There were 393 (48%) with no domain with substantial relative impairments. Some participants had isolated relative impairments in memory (148, 18%), visuospatial functioning (117, 14%), language (71, 9%), and executive functioning (66, 8%). The group with isolated relative memory impairments had higher proportions with ≥ APOE ε4 allele, more extensive Alzheimer's-related neuropathology, and higher proportions with other Alzheimer's dementia genetic risk variants. A cognitive subgrouping strategy may identify biologically distinct subsets of people with Alzheimer's dementia. Copyright © 2017 the Alzheimer's Association. All rights reserved.

Modification of levels of depression in mother-bereaved women by parental and marital relationships.

PubMed

Parker, G; Hadzi-Pavlovic, D

1984-02-01

A sample of 79 young women whose mothers had died in the subjects' childhood, and whose fathers had remarried, was studied to determine any effects on state and trait depression associated with modification of high and low risk parental style. Lack of care from fathers and lack of care from step-mothers were the parental variables most strongly associated with high trait depression, and almost all subjects scoring both these parents as uncaring affirmed a distinct life-time episode of depression. In a married sub-group of 63 subjects, low marital affection and low stepmother care accounted for 33% of the variance in trait depression scores, while low paternal care was no longer a significant predictor. Data for the married sub-group suggested that an affectionate husband largely corrected any diathesis to greater depression exerted by uncaring parenting, while the protective effects of caring parenting on adult depressive experience were largely undone by marriage to an unaffectionate husband.

Life Expectancy Among U.S.-born and Foreign-born Older Adults in the United States: Estimates From Linked Social Security and Medicare Data.

PubMed

Mehta, Neil K; Elo, Irma T; Engelman, Michal; Lauderdale, Diane S; Kestenbaum, Bert M

2016-08-01

In recent decades, the geographic origins of America's foreign-born population have become increasingly diverse. The sending countries of the U.S. foreign-born vary substantially in levels of health and economic development, and immigrants have arrived with distinct distributions of socioeconomic status, visa type, year of immigration, and age at immigration. We use high-quality linked Social Security and Medicare records to estimate life tables for the older U.S. population over the full range of birth regions. In 2000-2009, the foreign-born had a 2.4-year advantage in life expectancy at age 65 relative to the U.S.-born, with Asian-born subgroups displaying exceptionally high longevity. Foreign-born individuals who migrated more recently had lower mortality compared with those who migrated earlier. Nonetheless, we also find remarkable similarities in life expectancy among many foreign-born subgroups that were born in very different geographic and socioeconomic contexts (e.g., Central America, western/eastern Europe, and Africa).

The Florida manatee (Trichechus manatus latirostris) T cell receptor loci exhibit V subgroup synteny and chain-specific evolution.

PubMed

Breaux, Breanna; Hunter, Margaret E; Cruz-Schneider, Maria Paula; Sena, Leonardo; Bonde, Robert K; Criscitiello, Michael F

2018-08-01

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. latirostris and 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. Copyright © 2018. Published by Elsevier Ltd.

Image-based RNA interference screening reveals an individual dependence of acute lymphoblastic leukemia on stromal cysteine support

PubMed Central

Marovca, Blerim; Vonderheit, Andreas; Grotzer, Michael A.; Eckert, Cornelia; Cario, Gunnar; Wollscheid, Bernd; Horvath, Peter

2014-01-01

Interactions with the bone marrow microenvironment are essential for leukemia survival and disease progression. We developed an imaging-based RNAi platform to identify protective cues from bone marrow derived mesenchymal stromal cells (MSC) that promote survival of primary acute lymphoblastic leukemia (ALL) cells. Using a candidate gene approach, we detected distinct responses of individual ALL cases to RNA interference with stromal targets. The strongest effects were observed when interfering with solute carrier family 3 member 2 (SLC3A2) expression, which forms the cystine transporter xc− when associated with SLC7A11. Import of cystine and metabolism to cysteine by stromal cells provides the limiting substrate to generate and maintain glutathione in ALL. This metabolic interaction reduces oxidative stress in ALL cells that depend on stromal xc−. Indeed, cysteine depletion using cysteine dioxygenase resulted in leukemia cell death. Thus, functional evaluation of intercellular interactions between leukemia cells and their microenvironment identifies a selective dependency of ALL cells on stromal metabolism for a relevant subgroup of cases, providing new opportunities to develop more personalized approaches to leukemia treatment. PMID:25415224

Factorial invariance of child self-report across age subgroups: a confirmatory factor analysis of ages 5 to 16 years utilizing the PedsQL 4.0 Generic Core Scales.

PubMed

Limbers, Christine A; Newman, Daniel A; Varni, James W

2008-01-01

The utilization of health-related quality of life (HRQOL) measurement in an effort to improve pediatric health and well-being and determine the value of health care services has grown dramatically over the past decade. The paradigm shift toward patient-reported outcomes (PROs) in clinical trials has provided the opportunity to emphasize the value and essential need for pediatric patient self-report. In order for HRQOL/PRO comparisons to be meaningful for subgroup analyses, it is essential to demonstrate factorial invariance. This study examined age subgroup factorial invariance of child self-report for ages 5 to 16 years on more than 8,500 children utilizing the PedsQL 4.0 Generic Core Scales. Multigroup Confirmatory Factor Analysis (MGCFA) was performed specifying a five-factor model. Two multigroup structural equation models, one with constrained parameters and the other with unconstrained parameters, were proposed to compare the factor loadings across the age subgroups. Metric invariance (i.e., equal factor loadings) across the age subgroups was demonstrated based on stability of the Comparative Fit Index between the two models, and several additional indices of practical fit including the Root Mean Squared Error of Approximation, the Non-Normed Fit Index, and the Parsimony Normed Fit Index. The findings support an equivalent five-factor structure across the age subgroups. Based on these data, it can be concluded that children across the age subgroups in this study interpreted items on the PedsQL 4.0 Generic Core Scales in a similar manner regardless of their age.

Daily happiness and stock returns: Some international evidence

NASA Astrophysics Data System (ADS)

Zhang, Wei; Li, Xiao; Shen, Dehua; Teglio, Andrea

2016-10-01

In this paper, we examine the relations between the daily happiness sentiment extracted from Twitter and the stock market performance in 11 international stock markets. By partitioning this happiness sentiment into quintiles from the least to the happiest days, we first show that the contemporary correlation coefficients between happiness sentiment and index return in the 4 and most-happiness subgroups are higher than that in least, 2 and 3-happiness subgroups. Secondly, the happiness sentiment can provide additional explanatory power for index return in the most-happiness subgroup. Thirdly, the daily happiness can granger-cause the changes in index return for the majority of stock markets. Fourthly, we find that the index return and the range-based volatility of the most-happiness subgroup are larger than those of other subgroups. These results highlight the important role of social media in stock market.

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

PubMed

Verra, Martin L; Angst, Felix; Staal, J Bart; Brioschi, Roberto; Lehmann, Susanne; Aeschlimann, André; de Bie, Rob A

2011-06-30

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

Uncovering precision phenotype-biomarker associations in traumatic brain injury using topological data analysis

PubMed Central

Nielson, Jessica L.; Cooper, Shelly R.; Sorani, Marco D.; Inoue, Tomoo; Yuh, Esther L.; Mukherjee, Pratik; Petrossian, Tanya C.; Lum, Pek Y.; Lingsma, Hester F.; Gordon, Wayne A.; Okonkwo, David O.; Manley, Geoffrey T.

2017-01-01

Background Traumatic brain injury (TBI) is a complex disorder that is traditionally stratified based on clinical signs and symptoms. Recent imaging and molecular biomarker innovations provide unprecedented opportunities for improved TBI precision medicine, incorporating patho-anatomical and molecular mechanisms. Complete integration of these diverse data for TBI diagnosis and patient stratification remains an unmet challenge. Methods and findings The Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Pilot multicenter study enrolled 586 acute TBI patients and collected diverse common data elements (TBI-CDEs) across the study population, including imaging, genetics, and clinical outcomes. We then applied topology-based data-driven discovery to identify natural subgroups of patients, based on the TBI-CDEs collected. Our hypothesis was two-fold: 1) A machine learning tool known as topological data analysis (TDA) would reveal data-driven patterns in patient outcomes to identify candidate biomarkers of recovery, and 2) TDA-identified biomarkers would significantly predict patient outcome recovery after TBI using more traditional methods of univariate statistical tests. TDA algorithms organized and mapped the data of TBI patients in multidimensional space, identifying a subset of mild TBI patients with a specific multivariate phenotype associated with unfavorable outcome at 3 and 6 months after injury. Further analyses revealed that this patient subset had high rates of post-traumatic stress disorder (PTSD), and enrichment in several distinct genetic polymorphisms associated with cellular responses to stress and DNA damage (PARP1), and in striatal dopamine processing (ANKK1, COMT, DRD2). Conclusions TDA identified a unique diagnostic subgroup of patients with unfavorable outcome after mild TBI that were significantly predicted by the presence of specific genetic polymorphisms. Machine learning methods such as TDA may provide a robust method for patient stratification and treatment planning targeting identified biomarkers in future clinical trials in TBI patients. Trial Registration ClinicalTrials.gov Identifier NCT01565551 PMID:28257413

Proteomic analysis of secreted proteins in early rheumatoid arthritis: anti‐citrulline autoreactivity is associated with up regulation of proinflammatory cytokines

PubMed Central

Hueber, Wolfgang; Tomooka, Beren H; Zhao, Xiaoyan; Kidd, Brian A; Drijfhout, Jan W; Fries, James F; van Venrooij, Walther J; Metzger, Allan L; Genovese, Mark C; Robinson, William H

2007-01-01

Objectives To identify peripheral blood autoantibody and cytokine profiles that characterise clinically relevant subgroups of patients with early rheumatoid arthritis using arthritis antigen microarrays and a multiplex cytokine assay. Methods Serum samples from 56 patients with a diagnosis of rheumatoid arthritis of <6 months' duration were tested. Cytokine profiles were also determined in samples from patients with psoriatic arthritis (PsA) and ankylosing spondylitis (n = 21), and from healthy individuals (n = 19). Data were analysed using Kruskal–Wallis test with Dunn's adjustment for multiple comparisons, linear correlation tests, significance analysis of microarrays (SAM) and hierarchical clustering software. Results Distinct antibody profiles were associated with subgroups of patients who exhibited high serum levels of tumour necrosis factor (TNF)α, interleukin (IL)1β, IL6, IL13, IL15 and granulocyte macrophage colony‐stimulating factor. Significantly increased autoantibody reactivity against citrullinated epitopes was observed in patients within the cytokine “high” subgroup. Increased levels of TNFα, IL1α, IL12p40 and IL13, and the chemokines eotaxin/CCL11, monocyte chemoattractant protein‐1 and interferon‐inducible protein 10, were present in early rheumatoid arthritis as compared with controls (p<0.001). Chemokines showed some of the most impressive differences. Only IL8/CXCL8 concentrations were higher in patients with PsA/ankylosing spondylitis (p = 0.02). Conclusions Increased blood levels of proinflammatory cytokines are associated with autoantibody targeting of citrullinated antigens and surrogate markers of disease activity in patients with early rheumatoid arthritis. Proteomic analysis of serum autoantibodies, cytokines and chemokines enables stratification of patients with early rheumatoid arthritis into molecular subgroups. PMID:16901957

Dissociation between two subgroups of the suprachiasmatic nucleus affected by the number of damped oscillated neurons

NASA Astrophysics Data System (ADS)

Gu, Changgui; Yang, Huijie; Rohling, Jos HT

2017-03-01

In mammals, the main clock located in the suprachiasmatic nucleus (SCN) of the brain synchronizes the body rhythms to the environmental light-dark cycle. The SCN is composed of about 2 ×104 neurons which can be classified into three oscillatory phenotypes: self-sustained oscillators, damped oscillators, and arrhythmic neurons. Exposed to an artificial external light-dark cycle with a period of 22 h instead of 24 h , two subgroups of the SCN can become desynchronized (dissociated). The ventrolateral (VL) subgroup receives photic input and is entrained to the external cycle and a dorsomedial (DM) subgroup oscillates with its endogenous (i.e., free running) period and is synchronized to the external light-dark cycle through coupling from the VL. In the present study, we examined the effects of damped oscillatory neurons on the dissociation between VL and DM under an external 22 h cycle. We found that, with increasing numbers of damped oscillatory neurons located in the VL, the dissociation between the VL and DM emerges, but if these neurons are increasingly present in the DM the dissociation disappears. Hence, the damped oscillatory neurons in different subregions of the SCN play distinct roles in the dissociation between the two subregions of the SCN. This shows that synchrony between SCN subregions is affected by the number of damped oscillatory neurons and the location of these cells. We suggest that more knowledge on the number and the location of these cells may explain why some species do show a dissociation between the subregions and others do not, as the distribution of oscillatory types of neurons offers a plausible and novel candidate mechanism to explain heterogeneity.

A latent class analysis of dissociation and posttraumatic stress disorder: evidence for a dissociative subtype.

PubMed

Wolf, Erika J; Miller, Mark W; Reardon, Annemarie F; Ryabchenko, Karen A; Castillo, Diane; Freund, Rachel

2012-07-01

The nature of the relationship of dissociation to posttraumatic stress disorder (PTSD) is controversial and of considerable clinical and nosologic importance. To examine evidence for a dissociative subtype of PTSD and to examine its association with different types of trauma. A latent profile analysis of cross-sectional data from structured clinical interviews indexing DSM-IV symptoms of current PTSD and dissociation. The VA Boston Healthcare System and the New Mexico VA Health Care System. A total of 492 veterans and their intimate partners, all of whom had a history of trauma. Participants reported exposure to a variety of traumatic events, including combat, childhood physical and sexual abuse, partner abuse, motor vehicle accidents, and natural disasters, with most participants reporting exposure to multiple types of traumatic events. Forty-two percent of the sample met the criteria for a current diagnosis of PTSD. Item-level scores on the Clinician-Administered PTSD Scale. A latent profile analysis suggested a 3-class solution: a low PTSD severity subgroup, a high PTSD severity subgroup characterized by elevations across the 17 core symptoms of the disorder, and a small but distinctly dissociative subgroup that composed 12% of individuals with a current diagnosis of PTSD. The latter group was characterized by severe PTSD symptoms combined with marked elevations on items assessing flashbacks, derealization, and depersonalization. Individuals in this subgroup also endorsed greater exposure to childhood and adult sexual trauma compared with the other 2 groups, suggesting a possible etiologic link with the experience of repeated sexual trauma. These results support the subtype hypothesis of the association between PTSD and dissociation and suggest that dissociation is a highly salient facet of posttraumatic psychopathology in a subset of individuals with the disorder.

Occurrence and distribution of Giardia species in wild rodents in Germany.

PubMed

Helmy, Yosra A; Spierling, Nastasja G; Schmidt, Sabrina; Rosenfeld, Ulrike M; Reil, Daniela; Imholt, Christian; Jacob, Jens; Ulrich, Rainer G; Aebischer, Toni; Klotz, Christian

2018-03-27

Giardiasis is an important gastrointestinal parasitic disease in humans and other mammals caused by the protozoan Giardia duodenalis. This species complex is represented by genetically distinct groups (assemblages A-H) with varying zoonotic potential and host preferences. Wild rodents can harbor potentially zoonotic assemblages A and B, and the rodent-specific assemblage G. Other Giardia spp. found in these animals are Giardia muris and Giardia microti. For the latter, only limited information on genetic typing is available. It has been speculated that wild rodents might represent an important reservoir for parasites causing human giardiasis. The aim of this study was to investigate the occurrence and distribution of Giardia spp. and assemblage types in wild rodents from different study sites in Germany. Screening of 577 wild rodents of the genera Apodemus, Microtus and Myodes, sampled at eleven study sites in Germany, revealed a high overall Giardia prevalence. Giardia species determination at the SSU rDNA gene locus revealed that Apodemus mice, depending on species, were predominantly infected with one of two distinct G. muris sequence types. Giardia microti was the predominant parasite species found in voles of the genera Microtus and Myodes. Only a few animals were positive for potentially zoonotic G. duodenalis. Subtyping at the beta-giardin (bg) and glutamine dehydrogenase (gdh) genes strongly supported the existence of different phylogenetic subgroups of G. microti that are preferentially harbored by distinct host species. The present study highlights the preference of G. muris for Apodemus, and G. microti for Microtus and Myodes hosts and argues for a very low prevalence of zoonotic G. duodenalis assemblages in wild rodents in Germany. It also provides evidence that G. muris and G. microti subdivide into several phylogenetically distinguishable subgroups, each of which appears to be preferentially harbored by species of a particular rodent host genus. Finally, the study expands the database of sequences relevant for sequence typing of G. muris and G. microti isolates which will greatly help future analyses of these parasites' population structure.

der(11)t(11;17): a distinct cytogenetic pathway of advanced stage neuroblastoma (NBL) - detected by spectral karyotyping (SKY).

PubMed

Stark, Batia; Jeison, Marta; Glaser-Gabay, Leticia; Bar-Am, Irit; Mardoukh, Jacques; Ash, Shifra; Atias, Dina; Stein, Jerry; Zaizov, Rina; Yaniv, Isaac

2003-07-18

Conventional cytogenetic, molecular cytogenic and genetic methods disclosed a broad spectrum of genetic abnormalities leading to gain and loss of chromosomal segments in advanced stage neuroblastoma (NBL). Specific correlation between the genetic findings could delineate distinct genetic pathways, of which the biology and prognostic significance is as yet undetermined. Using spectral karyotyping (SKY) and fluorescence in situ hybridization (FISH) on metaphases from 16 patients with advanced stage NBL, it was possible to explore the whole spectrum of rearrangement within complex karyotypes and to detect hidden recurrent translocations. All translocations were unbalanced. The most prevalent recurrent unbalanced translocations resulted in 17q gain in 12 patients (75%), 11q loss in nine patients (56%), and 1p deletion/imbalance in eight patients (50%). The most frequent recurrent translocation was der(11)t(11;17) in six patients. Three cytogenetic pathways could be delineated. The first, with six patients, was characterized by the unbalanced translocation der(11)t(11;17), detected only by SKY, resulting in the concomitant 17q gain and 11q loss. No MYCN amplification or 1p deletion (except one patient with 1p imbalance) were found, while 3p deletion, and complex karyotypes were common. The second subgroup, with four patients, had 17q gain and 1p deletion, and in two patients 11q loss, that was apparent only by FISH. 1p deletion occurred through der(1)t(1;17) or del(1p). The third subgroup of four patients was characterized by MYCN amplification with 17q gain and 1p deletion, very rarely with 11q loss (one patient) through a translocation with a non-17q partner. The SKY subclassifications were in accordance with the findings reported by molecular genetic techniques, and may indicate that distinct oncogenes and suppressor genes are involved in the der(11)t(11;17) pathway of advanced stage NBL.

Evaluation of the 8th TNM classification on p16-positive oropharyngeal squamous cell carcinomas in the Netherlands, and the importance of additional HPV DNA-testing.

PubMed

Nauta, I H; Rietbergen, M M; van Bokhoven, A A J D; Bloemena, E; Witte, B I; Heideman, D A M; Baatenburg de Jong, R J; Brakenhoff, R H; Leemans, C R

2018-02-09

Oropharyngeal squamous cell carcinomas (OPSCCs) are traditionally caused by smoking and excessive alcohol consumption. However, in the last decades high-risk human papillomavirus (HR-HPV) infections play an increasingly important role in tumorigenesis. HPV-driven OPSCCs are known to have a more favorable prognosis, which has led to important and marked changes in the recently released TNM-8. In this edition, OPSCCs are divided based on p16-immunostaining, with p16-overexpression as surrogate marker for the presence of HPV. The aims of this study are to evaluate TNM-8 on a Dutch consecutive cohort of patients with p16-positive OPSCC and to determine the relevance of additional HPV DNA-testing. All OPSCC patients without distant metastases at diagnosis and treated with curative intent at VU University Medical Center (2000-2015) and Erasmus Medical Center (2000-2006) were included (N = 1,204). HPV-status was established by p16-immunostaining followed by HPV DNA-PCR on the p16-immunopositive cases. We compared TNM-7 and TNM-8 using the Harrell's C index. In total, 388 of 1,204 (32.2%) patients were p16-immunopositive. In these patients, TNM-8 had a markedly better predictive prognostic power than TNM-7 (Harrell's C index 0.63 versus 0.53). Of the 388 p16-positive OPSCCs, 48 tumors (12.4%) were HPV DNA-negative. This subgroup had distinct demographic, clinical and morphologic characteristics and showed a significantly worse five-year overall survival compared to the HPV DNA-positive tumors (P < 0.001). TNM-8 has a better predictive prognostic power than TNM-7 in patients with p16-positive OPSCC. However, within p16-positive OPSCCs there is an HPV DNA-negative subgroup with distinct features and a worse overall survival, indicating the importance to perform additional HPV DNA-testing when predicting prognosis and particularly for selecting patients for de-intensified treatment regimens. © The Author 2018. 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.

New evidence of heterogeneity in social anxiety disorder: defining two qualitatively different personality profiles taking into account clinical, environmental and genetic factors.

PubMed

Binelli, C; Muñiz, A; Sanches, S; Ortiz, A; Navines, R; Egmond, E; Udina, M; Batalla, A; López-Sola, C; Crippa, J A; Subirà, S; Martín-Santos, R

2015-01-01

To study qualitatively different subgroups of social anxiety disorder (SAD) based on harm avoidance (HA) and novelty seeking (NS) dimensions. One hundred and forty-two university students with SAD (SCID-DSM-IV) were included in the study. The temperament dimensions HA and NS from the Cloninger's Temperament and Character Inventory were subjected to cluster analysis to identify meaningful subgroups. The identified subgroups were compared for sociodemographics, SAD severity, substance use, history of suicide and self-harm attempts, early life events, and two serotonin transporter gene polymorphisms (5-HTTLPR and STin2.VNTR). Two subgroups of SAD were identified by cluster analysis: a larger (61% of the sample) inhibited subgroup of subjects with "high-HA/low-NS", and a smaller (39%) atypical impulsive subgroup with high-moderate HA and NS. The two groups did not differ in social anxiety severity, but did differ in history of lifetime impulsive-related-problems. History of suicide attempts and self-harm were as twice as frequent in the impulsive subgroup. Significant differences were observed in the pattern of substance misuse. Whereas subjects in the inhibited subgroup showed a greater use of alcohol (P=0.002), subjects in the impulsive subgroup showed a greater use of substances with a high-sensation-seeking profile (P<0.001). The STin2.VNTR genotype frequency showed an inverse distribution between subgroups (P=0.005). Our study provides further evidence for the presence of qualitatively different SAD subgroups and the propensity of a subset of people with SAD to exhibit impulsive, high-risk behaviors. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

How indicative is a self-reported driving behaviour profile of police registered traffic law offences?

PubMed

Martinussen, L M; Møller, M; Prato, C G; Haustein, S

2017-02-01

Although most motorised countries have experienced massive improvements in road safety over the last decades, human behaviour and differences in accident risk across sub-groups of drivers remains a key issue in the area of road safety. The identification of risk groups requires the identification of reliable predictors of safe or unsafe driving behaviour. Given this background, the aim of this study was to test whether driver sub-groups identified based on self-reported driving behaviour and skill differed in registered traffic law offences and accidents, and whether group membership was predictive of having traffic law offences. Sub-groups of drivers were identified based on the Driver Behaviour Questionnaire (DBQ) and the Driver Skill Inventory (DSI), while traffic offences and accidents were register-based (Statistics Denmark). The participants (N=3683) were aged 18-84 years and randomly selected from the Danish Driving License Register. Results show that the driver sub-groups differed significantly in registered traffic offences but not in registered accidents. In a logistic regression analysis, the sub-group "Violating unsafe drivers" was found predictive of having a traffic offence, even when socio-demographic variables and exposure were controlled for. The most important predictive factor, however, was having a criminal record for non-traffic offences, while gender, living without a partner, and being self-employed also had a significant effect. The study confirms the use of the DBQ and DSI as suitable instruments for predicting traffic offences while also confirming previous results on accumulation of problematic behaviours across life contexts. The finding that driver sub-groups did not differ in registered accidents supports the recent research activities in finding and modelling surrogate safety measures. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

PubMed Central

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

2014-01-01

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

Adult and juvenile dermatomyositis: are the distinct clinical features explained by our current understanding of serological subgroups and pathogenic mechanisms?

PubMed Central

2013-01-01

Adult and juvenile dermatomyositis share the hallmark features of pathognomic skin rash and muscle inflammation, but are heterogeneous disorders with a range of additional disease features and complications. The frequency of important clinical features such as calcinosis, interstitial lung disease and malignancy varies markedly between adult and juvenile disease. These differences may reflect different disease triggers between children and adults, but whilst various viral and other environmental triggers have been implicated, results are so far conflicting. Myositis-specific autoantibodies can be detected in both adults and children with idiopathic inflammatory myopathies. They are associated with specific disease phenotypes and complications, and divide patients into clinically homogenous subgroups. Interestingly, whilst the same autoantibodies are found in both adults and children, the disease features remain different within autoantibody subgroups, particularly with regard to life-threatening disease associations, such as malignancy and rapidly progressive interstitial lung disease. Our understanding of the mechanisms that underlie these differences is limited by a lack of studies directly comparing adults and children. Dermatomyositis is an autoimmune disease, which is believed to develop as a result of an environmental trigger in a genetically predisposed individual. Age-specific host immune responses and muscle physiology may be additional complicating factors that have significant impact on disease presentation. Further study into this area may produce new insights into disease pathogenesis. PMID:23566358

Subgroup of ADNI Normal Controls Characterized by Atrophy and Cognitive Decline Associated With Vascular Damage

PubMed Central

Nettiksimmons, Jasmine; Beckett, Laurel; Schwarz, Christopher; Carmichael, Owen; Fletcher, Evan; DeCarli, Charles

2013-01-01

Previous work examining Alzheimer’s Disease Neuroimaging Initiative (ADNI) normal controls using cluster analysis identified a subgroup characterized by substantial brain atrophy and white matter hyperintensities (WMH). We hypothesized that these effects could be related to vascular damage. Fifty-three individuals in the suspected vascular cluster (Normal 2) were compared with 31 individuals from the cluster characterized as healthy/typical (Normal 1) on a variety of outcomes, including magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) biomarkers, vascular risk factors and outcomes, cognitive trajectory, and medications for vascular conditions. Normal 2 was significantly older but did not differ on ApoE4+ prevalence. Normal 2 differed significantly from Normal 1 on all MRI measures but not on Amyloid-Beta1-42 or total tau protein. Normal 2 had significantly higher body mass index (BMI), Hachinksi score, and creatinine levels, and took significantly more medications for vascular conditions. Normal 2 had marginally significantly higher triglycerides and blood glucose. Normal 2 had a worse cognitive trajectory on the Rey’s Auditory Verbal Learning Test (RAVLT) 30-min delay test and the Functional Activity Questionnaire (FAQ). Cerebral atrophy associated with multiple vascular risks is common among cognitively normal individuals, forming a distinct subgroup with significantly increased cognitive decline. Further studies are needed to determine the clinical impact of these findings. PMID:23527743

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

PubMed

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.

Single-Domain Parvulins Constitute a Specific Marker for Recently Proposed Deep-Branching Archaeal Subgroups

PubMed Central

Lederer, Christoph; Heider, Dominik; van den Boom, Johannes; Hoffmann, Daniel; Mueller, Jonathan W.; Bayer, Peter

2011-01-01

Peptidyl-prolyl cis/trans isomerases (PPIases) are enzymes assisting protein folding and protein quality control in organisms of all kingdoms of life. In contrast to the other sub-classes of PPIases, the cyclophilins and the FK-506 binding proteins, little was formerly known about the parvulin type of PPIase in Archaea. Recently, the first solution structure of an archaeal parvulin, the PinA protein from Cenarchaeum symbiosum, was reported. Investigation of occurrence and frequency of PPIase sequences in numerous archaeal genomes now revealed a strong tendency for thermophilic microorganisms to reduce the number of PPIases. Single-domain parvulins were mostly found in the genomes of recently proposed deep-branching archaeal subgroups, the Thaumarchaeota and the ARMANs (archaeal Richmond Mine acidophilic nanoorganisms). Hence, we used the parvulin sequence to reclassify available archaeal metagenomic contigs, thereby, adding new members to these subgroups. A combination of genomic background analysis and phylogenetic approaches of parvulin sequences suggested that the assigned sequences belong to at least two distinct groups of Thaumarchaeota. Finally, machine learning approaches were applied to identify amino acid residues that separate archaeal and bacterial parvulin proteins from each other. When mapped onto the recent PinA solution structure, most of these positions form a cluster at one site of the protein possibly indicating a different functionality of the two groups of parvulin proteins. PMID:22065628

What is your patient’s cognitive profile? Three distinct subgroups of cognitive function in persons with heart failure

PubMed Central

Hawkins, Misty A.W.; Schaefer, Julie T.; Gunstad, John; Dolansky, Mary A.; Redle, Joseph D.; Josephson, Richard; Moore, Shirley M.; Hughes, Joel W.

2014-01-01

Purpose To determine whether patients with heart failure (HF) have distinct profiles of cognitive impairment. Background Cognitive impairment is common in HF. Recent work found three cognitive profiles in HF patients— (1) intact, (2) impaired, and (3) memory-impaired. We examined the reproducibility of these profiles and clarified mechanisms. Methods HF patients (68.6±9.7years; N=329) completed neuropsychological testing. Composite scores were created for cognitive domains and used to identify clusters via agglomerative-hierarchical cluster analysis. Results A 3-cluster solution emerged. Cluster 1 (n=109) had intact cognition. Cluster 2 (n=123) was impaired across all domains. Cluster 3 (n=97) had impaired memory only. Clusters differed in age, race, education, SES, IQ, BMI, and diabetes (ps ≤.026) but not in mood, anxiety, cardiovascular, or pulmonary disease (ps≥.118). Conclusions We replicated three distinct patterns of cognitive function in persons with HF. These profiles may help providers offer tailored care to patients with different cognitive and clinical needs. PMID:25510559

The Impact of Epithelial Stromal Interactions on Human Breast Tumor Heterogeneity

DTIC Science & Technology

2016-12-01

Heterogeneity plays a substantial role in the variability of patient response to treatment , especially in triple-negative (TN) breast cancer. A fuller...understanding of the molecularly distinct TN subgroups linked to outcome is essential to promote the development of more personalized treatment strategies...factor underlying the variability in patient response to  treatment , especially in  TN cases. There is a need for a fuller understanding of the

A Data Mining Approach to Identify Sexuality Patterns in a Brazilian University Population.

PubMed

Waleska Simões, Priscyla; Cesconetto, Samuel; Toniazzo de Abreu, Larissa Letieli; Côrtes de Mattos Garcia, Merisandra; Cassettari Junior, José Márcio; Comunello, Eros; Bisognin Ceretta, Luciane; Aparecida Manenti, Sandra

2015-01-01

This paper presents the profile and experience of sexuality generated from a data mining classification task. We used a database about sexuality and gender violence performed on a university population in southern Brazil. The data mining task identified two relationships between the variables, which enabled the distinction of subgroups that better detail the profile and experience of sexuality. The identification of the relationships between the variables define behavioral models and factors of risk that will help define the algorithms being implemented in the data mining classification task.

Complete Genome Sequences of Newcastle Disease Virus Strains Circulating in Chicken Populations of Indonesia

PubMed Central

Xiao, Sa; Paldurai, Anandan; Nayak, Baibaswata; Samuel, Arthur; Bharoto, Eny E.; Prajitno, Teguh Y.; Collins, Peter L.

2012-01-01

Eight highly virulent Newcastle disease virus (NDV) strains were isolated from vaccinated commercial chickens in Indonesia during outbreaks in 2009 and 2010. The complete genome sequences of two NDV strains and the sequences of the surface protein genes (F and HN) of six other strains were determined. Phylogenetic analysis classified them into two new subgroups of genotype VII in the class II cluster that were genetically distinct from vaccine strains. This is the first report of complete genome sequences of NDV strains isolated from chickens in Indonesia. PMID:22532534

Identification of subgroups among fibromyalgia patients.

PubMed

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.

Job Demand and Job Satisfaction in Latent Groups of Turnover Intention Among Licensed Nurses in Taiwan Nursing Homes.

PubMed

Chen, I-Hui; Brown, Roger; Bowers, Barbara J; Chang, Wen-Yin

2015-10-01

Nurses' turnover intention is not dichotomous; it may reflect intent to leave the profession, intent to leave a type of facility, or intent to leave a specific workplace. In a latent class analysis (LCA) of data from 186 licensed nurses (RNs and LPNs) recruited from 25 nursing homes (NHs) in Taiwan, we classified nurses into turnover intention subgroups based on seven questionnaire items and used a multilevel contrast analysis to characterize the subgroups according to demographic and facility factors, job demand, and job satisfaction. A multilevel probit model was used to examine how job demand and job satisfaction influenced subgroup membership. Three turnover subgroups were identified: high turnover intention (12%), middle turnover intention (57%), and low turnover intention (31%). The high turnover intention subgroup comprised the youngest nurses and had the lowest percentage of registered nurses (RNs); nurses in this subgroup had worked the longest at the current NH and had the greatest likelihood of working at a for-profit facility. Nurses in the middle turnover intention subgroup had the lowest likelihood of working at a for-profit facility. Nurses in the low turnover intention subgroup were primarily RNs and had the shortest work experience in the current facility. Nurses in the high and middle turnover intention subgroups reported lower intrinsic job satisfaction than those with low turnover intention. Extrinsic job satisfaction mediated the relationship between job demand and turnover intention subgroup assignment. The results of this LCA can help target interventions to address heterogeneity of turnover intention and ultimately lessen turnover. © 2015 Wiley Periodicals, Inc.

The myositis autoantibody phenotypes of the juvenile idiopathic inflammatory myopathies.

PubMed

Rider, Lisa G; Shah, Mona; Mamyrova, Gulnara; Huber, Adam M; Rice, Madeline Murguia; Targoff, Ira N; Miller, Frederick W

2013-07-01

The juvenile idiopathic inflammatory myopathies (JIIM) are systemic autoimmune diseases characterized by skeletal muscle weakness, characteristic rashes, and other systemic features. In follow-up to our study defining the major clinical subgroup phenotypes of JIIM, we compared demographics, clinical features, laboratory measures, and outcomes among myositis-specific autoantibody (MSA) subgroups, as well as with published data on adult idiopathic inflammatory myopathy patients enrolled in a separate natural history study. In the present study, of 430 patients enrolled in a nationwide registry study who had serum tested for myositis autoantibodies, 374 had either a single specific MSA (n = 253) or no identified MSA (n = 121) and were the subject of the present report. Following univariate analysis, we used random forest classification and exact logistic regression modeling to compare autoantibody subgroups. Anti-p155/140 autoantibodies were the most frequent subgroup, present in 32% of patients with juvenile dermatomyositis (JDM) or overlap myositis with JDM, followed by anti-MJ autoantibodies, which were seen in 20% of JIIM patients, primarily in JDM. Other MSAs, including anti-synthetase, anti-signal recognition particle (SRP), and anti-Mi-2, were present in only 10% of JIIM patients. Features that characterized the anti-p155/140 autoantibody subgroup included Gottron papules, malar rash, "shawl-sign" rash, photosensitivity, cuticular overgrowth, lowest creatine kinase (CK) levels, and a predominantly chronic illness course. The features that differed for patients with anti-MJ antibodies included muscle cramps, dysphonia, intermediate CK levels, a high frequency of hospitalization, and a monocyclic disease course. Patients with anti-synthetase antibodies had higher frequencies of interstitial lung disease, arthralgia, and "mechanic's hands," and had an older age at diagnosis. The anti-SRP group, which had exclusively juvenile polymyositis, was characterized by high frequencies of black race, severe onset, distal weakness, falling episodes, Raynaud phenomenon, cardiac involvement, high CK levels, chronic disease course, frequent hospitalization, and wheelchair use. Characteristic features of the anti-Mi-2 subgroup included Hispanic ethnicity, classic dermatomyositis and malar rashes, high CK levels, and very low mortality. Finally, the most common features of patients without any currently defined MSA or myositis-associated autoantibodies included linear extensor erythema, arthralgia, and a monocyclic disease course. Several demographic and clinical features were shared between juvenile and adult idiopathic inflammatory myopathy subgroups, but with several important differences. We conclude that juvenile myositis is a heterogeneous group of illnesses with distinct autoantibody phenotypes defined by varying clinical and demographic characteristics, laboratory features, and outcomes.

The Myositis Autoantibody Phenotypes of the Juvenile Idiopathic Inflammatory Myopathies

PubMed Central

Shah, Mona; Mamyrova, Gulnara; Huber, Adam M.; Rice, Madeline Murguia; Targoff, Ira N.; Miller, Frederick W.

2013-01-01

Abstract The juvenile idiopathic inflammatory myopathies (JIIM) are systemic autoimmune diseases characterized by skeletal muscle weakness, characteristic rashes, and other systemic features. In follow-up to our study defining the major clinical subgroup phenotypes of JIIM, we compared demographics, clinical features, laboratory measures, and outcomes among myositis-specific autoantibody (MSA) subgroups, as well as with published data on adult idiopathic inflammatory myopathy patients enrolled in a separate natural history study. In the present study, of 430 patients enrolled in a nationwide registry study who had serum tested for myositis autoantibodies, 374 had either a single specific MSA (n = 253) or no identified MSA (n = 121) and were the subject of the present report. Following univariate analysis, we used random forest classification and exact logistic regression modeling to compare autoantibody subgroups. Anti-p155/140 autoantibodies were the most frequent subgroup, present in 32% of patients with juvenile dermatomyositis (JDM) or overlap myositis with JDM, followed by anti-MJ autoantibodies, which were seen in 20% of JIIM patients, primarily in JDM. Other MSAs, including anti-synthetase, anti-signal recognition particle (SRP), and anti-Mi-2, were present in only 10% of JIIM patients. Features that characterized the anti-p155/140 autoantibody subgroup included Gottron papules, malar rash, “shawl-sign” rash, photosensitivity, cuticular overgrowth, lowest creatine kinase (CK) levels, and a predominantly chronic illness course. The features that differed for patients with anti-MJ antibodies included muscle cramps, dysphonia, intermediate CK levels, a high frequency of hospitalization, and a monocyclic disease course. Patients with anti-synthetase antibodies had higher frequencies of interstitial lung disease, arthralgia, and “mechanic’s hands,” and had an older age at diagnosis. The anti-SRP group, which had exclusively juvenile polymyositis, was characterized by high frequencies of black race, severe onset, distal weakness, falling episodes, Raynaud phenomenon, cardiac involvement, high CK levels, chronic disease course, frequent hospitalization, and wheelchair use. Characteristic features of the anti-Mi-2 subgroup included Hispanic ethnicity, classic dermatomyositis and malar rashes, high CK levels, and very low mortality. Finally, the most common features of patients without any currently defined MSA or myositis-associated autoantibodies included linear extensor erythema, arthralgia, and a monocyclic disease course. Several demographic and clinical features were shared between juvenile and adult idiopathic inflammatory myopathy subgroups, but with several important differences. We conclude that juvenile myositis is a heterogeneous group of illnesses with distinct autoantibody phenotypes defined by varying clinical and demographic characteristics, laboratory features, and outcomes. PMID:23877355

Lithospheric convective removal related post-collisional middle Eocene magmatism along the Izmir-Ankara-Erzincan suture zone (NE Turkey).

NASA Astrophysics Data System (ADS)

Göçmengil, Gönenç; Karacık, Zekiye; Genç, Ş. Can

2017-04-01

Obliteration of the Mesozoic Neo-Tethyan Ocean and succeeding collision of the micro plates along the northern part of Turkey lead the development of the İzmir-Ankara-Erzincan suture zone (IAESZ). The suturing and collision stages terminate with the amalgamation of the three different crustal blocks (Pontides, Central Anatolian Crystalline Complex and Anatolide-Tauride Block) in the Paleocene-Early Eocene period. After the collisional stage; a new phase of extension and magmatism concomitantly developed at the both sides and as well as along the IAESZ during the Middle Eocene period. However, the origin, mechanism and driving force of the post-collisional magmatism is still enigmatic. To understand and better constrain the syn-to post collisional evolutionary stages, we have carried out volcano-stratigraphy and geochemistry based study on the middle Eocene magmatic associations along a transect ( 100 km) from Pontides to the Central Anatolian Crystalline Complex (CACC) at the NE part of the Turkey. Middle Eocene magmatic activity in the region has been represented by calc-alkaline, alkaline, shoshonitic volcanic and granitic rocks together with scarce gabbroic intrusions. We particularly focused on middle Eocene volcano-sedimentary successions (MEVSS) to constrain the tectono-magmatic evolution of the abovementioned transect. The volcano-sedimentary succsessions are coevally developed and cover the crustal blocks (Pontides and CACC) and the IAESZ with a region wide unconformity. We have differentiated three lava series (V1-V2-V3) and their sub-groups (V1a-V1b; V2a-V2b) in MEVSS. Generally, all lava series have middle-K to shoshonitic composition with distinct subduction characteristics. V1 series is marked by presence of hydrous phenocrysts such as amphibole+biotite. V1a sub-group constitute the first volcanic product and characterized by the high Mg# (42-69); alkaline basaltic andesite, and hawaiites. V1b sub-group is represented by calc-alkaline, low Mg# (24-57) andesite and dacites. V2 series made up of the olivine+pyroxene rich anhydrous lavas. V2a sub-group displays calc-alkaline/mildly alkaline character, moderate Mg# (33-54) and represented by basaltic andesites. Furthermore, V2b sub-group has mildly alkaline/alkaline in character and represented by more Mg# rich (40-62) basalt and trachy-basalt lavas. Final products, V3 series, cut the older units and made up of high-K - shoshonitic trachyte and trachy-andesites. The V1a sub-group, showing the alkali nature and high Mg#, is probably derived from the partial melting of a hydrous spinel lherzolitic source with minor garnet and amphibole while the V1b sub-group is a fractionated (FC) derivative of them. The V2 series are mixed products of varying amounts of magma sources similar to V1b type with a high Mg#, deep-seated magma source and their fractionated assemblages. The V3 series developed independently from the other series in shallow magma chambers, displaying the large amounts of crustal assimilation and constitutes the final product of the Middle Eocene volcanism. The data presented above shown that volcanic units; (i) are rich in potassium, (ii) have subduction-related signatures, (iii) display fluctuant alkalinity and Mg# during the course of volcanism, (iv) coevally developed on both amalgamated continental blocks after the cessation of subduction. These characteristics imply that, lithospheric convective removal related processes can be the most plausible driving mechanism of the middle Eocene magmatism.

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

PubMed

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 clinically significant subgroups of CaPts. Moreover, regression analyses indicate the following association: Nurses and physicians seem to be able to reduce CaPts' unmet information needs by establishing a relationship with the patient, which is trusting, caring and empathic.

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

PubMed

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.

Methodologic issues in terminating enrollment of a subgroup of patients in a multicenter randomized trial.

PubMed

Lee, Shing M; Wise, Robert; Sternberg, Alice L; Tonascia, James; Piantadosi, Steven

2004-01-01

The National Emphysema Treatment Trial (NETT) was a multicenter randomized controlled trial comparing medical treatment plus lung-volume-reduction surgery (LVRS) to medical treatment alone for the treatment of severe emphysema. The primary outcomes specified for the trial were mortality from all causes and change in functional status as indicated by the change in maximum exercise capacity measured two years after randomization. A secondary objective of the trial was to define criteria to identify subgroups of patients at risk of harm or benefit from LVRS. Stopping guidelines for safety and efficacy based on 30-day mortality and a combination of overall mortality and functional status at two years were specified at the inception of the trial. Although specific subgroups of patients likely to benefit were not identified in advance, several clinical factors were specified as likely to be important in defining subgroups with differential outcome. In May 2001, with 40% of expected deaths accrued, the Data and Safety Monitoring Board determined that a subgroup of patients was at significantly higher risk of 30-day mortality from LVRS without counterbalancing evidence of functional benefit, and recommended that the protocol be modified to exclude further randomization of such patients. The trial's sponsor, the National Heart, Lung and Blood Institute, accepted the recommendation, which was rapidly communicated to participating clinics. This paper describes the operational aspects of identification of the subgroup and implementation of the recommendation to continue the trial, but to terminate enrollment of new patients in the subgroup. These aspects include notification of the investigators, the institutional review boards, the Research Group, the patients and the medical community. We also describe the repercussions of the publication and the misinterpretations of the results based on media coverage.

Primary somatosensory/motor cortical thickness distinguishes paresthesia-dominant from pain-dominant carpal tunnel syndrome.

PubMed

Maeda, Yumi; Kettner, Norman; Kim, Jieun; Kim, Hyungjun; Cina, Stephen; Malatesta, Cristina; Gerber, Jessica; McManus, Claire; Libby, Alexandra; Mezzacappa, Pia; Mawla, Ishtiaq; Morse, Leslie R; Audette, Joseph; Napadow, Vitaly

2016-05-01

Paresthesia-dominant and pain-dominant subgroups have been noted in carpal tunnel syndrome (CTS), a peripheral neuropathic disorder characterized by altered primary somatosensory/motor (S1/M1) physiology. We aimed to investigate whether brain morphometry dissociates these subgroups. Subjects with CTS were evaluated with nerve conduction studies, whereas symptom severity ratings were used to allocate subjects into paresthesia-dominant (CTS-paresthesia), pain-dominant (CTS-pain), and pain/paresthesia nondominant (not included in further analysis) subgroups. Structural brain magnetic resonance imaging data were acquired at 3T using a multiecho MPRAGE T1-weighted pulse sequence, and gray matter cortical thickness was calculated across the entire brain using validated, automated methods. CTS-paresthesia subjects demonstrated reduced median sensory nerve conduction velocity (P = 0.05) compared with CTS-pain subjects. In addition, cortical thickness in precentral and postcentral gyri (S1/M1 hand area) contralateral to the more affected hand was significantly reduced in CTS-paresthesia subgroup compared with CTS-pain subgroup. Moreover, in CTS-paresthesia subjects, precentral cortical thickness was negatively correlated with paresthesia severity (r(34) = -0.40, P = 0.016) and positively correlated with median nerve sensory velocity (r(36) = 0.51, P = 0.001), but not with pain severity. Conversely, in CTS-pain subjects, contralesional S1 (r(9) = 0.62, P = 0.042) and M1 (r(9) = 0.61, P = 0.046) cortical thickness were correlated with pain severity, but not median nerve velocity or paresthesia severity. This double dissociation in somatotopically specific S1/M1 areas suggests a neuroanatomical substrate for symptom-based CTS subgroups. Such fine-grained subgrouping of CTS may lead to improved personalized therapeutic approaches, based on superior characterization of the linkage between peripheral and central neuroplasticity.

[Diagnostic approach and therapeutic strategy in 133 infertile patients with astheno-necrozoospermia].

PubMed

Vicari, E

1999-02-01

One-hundred thirty-three patients (aged 22 to 48, median 27 years) found affected by repetitive severe astheno-necrozoospermia (ASNE) (forward sperm motility < 10%; viable forms < 25%) in their ejaculates detected by both conventional viability tests (eosin Y exclusion and HOS tests) associated with oligo (51.1%), poly (3.7%), terato- (82.7%), -zoospermia, hyperdesfoliation of seminal spermatids (36.8%), hypospermia (11.3%), a comprehensive (history analysis; physical examination; lab: hormonal, microbiological, hemato-chemical blood screening, ultrasound scans at didymo-epididymal and prostato-vesicular glands, genital venous doppler) work-up allowed to recognize the following possible causes of ASNE: infectious (24.1%), spermiotoxyc (16.5%), hormonal (15.0%), iatrogenic (12.8%), chronic extratesticular diseases (CETD) (10.9%), varicocele (6.8%), idiopathic (14.3%). Overall population, except CETD patients gave their written informed consent about trial options for a three month period: a. rational, evidence-based treatment, group-standardised for doses and lenght (treated patients = subgroups T: total number = 71); b. short-term treatment/no treatment, (matched-control = subgroups Co: total number = 47). Follow-up semen data performed after completion of the assigned trial, together detected a conventionally normal percentage (> 25%) of viable sperm (necrozoospermic-responders (NR) in 37 (52.1%) out of subgroup-T patients. All subgroups-T patient, excepted subgroup-T patient affected by idiophathic ASNE (NR = 0%), exhibited NR rate (range 50-69.2%) values always significantly higher than subgroups-Co (NR = 0%, in all subgroups). Moreover, in each subgroup-T patients the percentages of viable and forward motile sperms values were significantly higher than matched-controls. The results of this study indicate that in patients affected by ASNE an andrological comprehensive work-up is mandatory because ASNE has a heterogeneous pathogenesis and a favourable prognosis, in terms of viable forms sperm improvement is possible after evidence-based therapeutic strategy.

Empirical Bayes estimation of proportions with application to cowbird parasitism rates

USGS Publications Warehouse

Link, W.A.; Hahn, D.C.

1996-01-01

Bayesian models provide a structure for studying collections of parameters such as are considered in the investigation of communities, ecosystems, and landscapes. This structure allows for improved estimation of individual parameters, by considering them in the context of a group of related parameters. Individual estimates are differentially adjusted toward an overall mean, with the magnitude of their adjustment based on their precision. Consequently, Bayesian estimation allows for a more credible identification of extreme values in a collection of estimates. Bayesian models regard individual parameters as values sampled from a specified probability distribution, called a prior. The requirement that the prior be known is often regarded as an unattractive feature of Bayesian analysis and may be the reason why Bayesian analyses are not frequently applied in ecological studies. Empirical Bayes methods provide an alternative approach that incorporates the structural advantages of Bayesian models while requiring a less stringent specification of prior knowledge. Rather than requiring that the prior distribution be known, empirical Bayes methods require only that it be in a certain family of distributions, indexed by hyperparameters that can be estimated from the available data. This structure is of interest per se, in addition to its value in allowing for improved estimation of individual parameters; for example, hypotheses regarding the existence of distinct subgroups in a collection of parameters can be considered under the empirical Bayes framework by allowing the hyperparameters to vary among subgroups. Though empirical Bayes methods have been applied in a variety of contexts, they have received little attention in the ecological literature. We describe the empirical Bayes approach in application to estimation of proportions, using data obtained in a community-wide study of cowbird parasitism rates for illustration. Since observed proportions based on small sample sizes are heavily adjusted toward the mean, extreme values among empirical Bayes estimates identify those species for which there is the greatest evidence of extreme parasitism rates. Applying a subgroup analysis to our data on cowbird parasitism rates, we conclude that parasitism rates for Neotropical Migrants as a group are no greater than those of Resident/Short-distance Migrant species in this forest community. Our data and analyses demonstrate that the parasitism rates for certain Neotropical Migrant species are remarkably low (Wood Thrush and Rose-breasted Grosbeak) while those for others are remarkably high (Ovenbird and Red-eyed Vireo).

Molecular Classification of Grade 3 Endometrioid Endometrial Cancers Identifies Distinct Prognostic Subgroups.

PubMed

Bosse, Tjalling; Nout, Remi A; McAlpine, Jessica N; McConechy, Melissa K; Britton, Heidi; Hussein, Yaser R; Gonzalez, Carlene; Ganesan, Raji; Steele, Jane C; Harrison, Beth T; Oliva, Esther; Vidal, August; Matias-Guiu, Xavier; Abu-Rustum, Nadeem R; Levine, Douglas A; Gilks, C Blake; Soslow, Robert A

2018-05-01

Our aim was to investigate whether molecular classification can be used to refine prognosis in grade 3 endometrial endometrioid carcinomas (EECs). Grade 3 EECs were classified into 4 subgroups: p53 abnormal, based on mutant-like immunostaining (p53abn); MMR deficient, based on loss of mismatch repair protein expression (MMRd); presence of POLE exonuclease domain hotspot mutation (POLE); no specific molecular profile (NSMP), in which none of these aberrations were present. Overall survival (OS) and recurrence-free survival (RFS) rates were compared using the Kaplan-Meier method (Log-rank test) and univariable and multivariable Cox proportional hazard models. In total, 381 patients were included. The median age was 66 years (range, 33 to 96 y). Federation Internationale de Gynecologie et d'Obstetrique stages (2009) were as follows: IA, 171 (44.9%); IB, 120 (31.5%); II, 24 (6.3%); III, 50 (13.1%); IV, 11 (2.9%). There were 49 (12.9%) POLE, 79 (20.7%) p53abn, 115 (30.2%) NSMP, and 138 (36.2%) MMRd tumors. Median follow-up of patients was 6.1 years (range, 0.2 to 17.0 y). Compared to patients with NSMP, patients with POLE mutant grade 3 EEC (OS: hazard ratio [HR], 0.36 [95% confidence interval, 0.18-0.70]; P=0.003; RFS: HR, 0.17 [0.05-0.54]; P=0.003) had a significantly better prognosis; patients with p53abn tumors had a significantly worse RFS (HR, 1.73 [1.09-2.74]; P=0.021); patients with MMRd tumors showed a trend toward better RFS. Estimated 5-year OS rates were as follows: POLE 89%, MMRd 75%, NSMP 69%, p53abn 55% (Log rank P=0.001). Five-year RFS rates were as follows: POLE 96%, MMRd 77%, NSMP 64%, p53abn 47% (P=0.000001), respectively. In a multivariable Cox model that included age and Federation Internationale de Gynecologie et d'Obstetrique stage, POLE and MMRd status remained independent prognostic factors for better RFS; p53 status was an independent prognostic factor for worse RFS. Molecular classification of grade 3 EECs reveals that these tumors are a mixture of molecular subtypes of endometrial carcinoma, rather than a homogeneous group. The addition of molecular markers identifies prognostic subgroups, with potential therapeutic implications.

Molecularly defined diffuse leptomeningeal glioneuronal tumor (DLGNT) comprises two subgroups with distinct clinical and genetic features.

PubMed

Deng, Maximilian Y; Sill, Martin; Chiang, Jason; Schittenhelm, Jens; Ebinger, Martin; Schuhmann, Martin U; Monoranu, Camelia-Maria; Milde, Till; Wittmann, Andrea; Hartmann, Christian; Sommer, Clemens; Paulus, Werner; Gärtner, Jutta; Brück, Wolfgang; Rüdiger, Thomas; Leipold, Alfred; Jaunmuktane, Zane; Brandner, Sebastian; Giangaspero, Felice; Nozza, Paolo; Mora, Jaume; Morales la Madrid, Andres; Cruz Martinez, Ofelia; Hansford, Jordan R; Pietsch, Torsten; Tietze, Anna; Hernáiz-Driever, Pablo; Stoler, Iris; Capper, David; Korshunov, Andrey; Ellison, David W; von Deimling, Andreas; Pfister, Stefan M; Sahm, Felix; Jones, David T W

2018-05-15

Diffuse leptomeningeal glioneuronal tumors (DLGNT) represent rare CNS neoplasms which have been included in the 2016 update of the WHO classification. The wide spectrum of histopathological and radiological features can make this enigmatic tumor entity difficult to diagnose. In recent years, large-scale genomic and epigenomic analyses have afforded insight into key genetic alterations occurring in multiple types of brain tumors and provide unbiased, complementary tools to improve diagnostic accuracy. Through genome-wide DNA methylation screening of > 25,000 tumors, we discovered a molecularly distinct class comprising 30 tumors, mostly diagnosed histologically as DLGNTs. Copy-number profiles derived from the methylation arrays revealed unifying characteristics, including loss of chromosomal arm 1p in all cases. Furthermore, this molecular DLGNT class can be subdivided into two subgroups [DLGNT methylation class (MC)-1 and DLGNT methylation class (MC)-2], with all DLGNT-MC-2 additionally displaying a gain of chromosomal arm 1q. Co-deletion of 1p/19q, commonly seen in IDH-mutant oligodendroglioma, was frequently observed in DLGNT, especially in DLGNT-MC-1 cases. Both subgroups also had recurrent genetic alterations leading to an aberrant MAPK/ERK pathway, with KIAA1549:BRAF fusion being the most frequent event. Other alterations included fusions of NTRK1/2/3 and TRIM33:RAF1, adding up to an MAPK/ERK pathway activation identified in 80% of cases. In the DLGNT-MC-1 group, age at diagnosis was significantly lower (median 5 vs 14 years, p < 0.01) and clinical course less aggressive (5-year OS 100, vs 43% in DLGNT-MC-2). Our study proposes an additional molecular layer to the current histopathological classification of DLGNT, of particular use for cases without typical morphological or radiological characteristics, such as diffuse growth and radiologic leptomeningeal dissemination. Recurrent 1p deletion and MAPK/ERK pathway activation represent diagnostic biomarkers and therapeutic targets, respectively-laying the foundation for future clinical trials with, e.g., MEK inhibitors that may improve the clinical outcome of patients with DLGNT.

A genetic marker of the ACKR1 gene is present in patients with Type II congenital smell loss who have type I hyposmia and hypogeusia

PubMed Central

Stateman, William A.; Knöppel, Alexandra B.; Flegel, Willy A.; Henkin, Robert I.

2015-01-01

PURPOSE Our previous study of Type II congenital smell loss patients revealed a statistically significant lower prevalence of an FY (ACKR1, formerly DARC) haplotype compared to controls. The present study correlates this genetic feature with subgroups of patients defined by specific smell and taste functions. METHODS Smell and taste function measurements were performed by use of olfactometry and gustometry to define degree of abnormality of smell and taste function. Smell loss was classified as anosmia or hyposmia (types I, II or III). Taste loss was similarly classified as ageusia or hypogeusia (types I, II or III). Based upon these results patient erythrocyte antigen expression frequencies were categorized by smell and taste loss with results compared between patients within the Type II group and published controls. RESULTS Comparison of antigen expression frequencies revealed a statistically significant decrease in incidence of an Fyb haplotype only among patients with type I hyposmia and any form of taste loss (hypogeusia). In all other patient groups erythrocyte antigens were expressed at normal frequencies. CONCLUSIONS Data suggest that Type II congenital smell loss patients who exhibit both type I hyposmia and hypogeusia are genetically distinct from all other patients with Type II congenital smell loss. This distinction is based on decreased Fyb expression which correlated with abnormalities in two sensory modalities (hyposmia type I and hypogeusia). Only patients with these two specific sensory abnormalities expressed the Fyb antigen (encoded by the ACKR1 gene on the long arm of chromosome 1) at frequencies different from controls. PMID:27968956

Comprehensive Molecular Characterization of Papillary Renal Cell Carcinoma

PubMed Central

Linehan, W. Marston; Spellman, Paul T.; Ricketts, Christopher J.; Creighton, Chad J.; Fei, Suzanne S.; Davis, Caleb; Wheeler, David A.; Murray, Bradley A.; Schmidt, Laura; Vocke, Cathy D.; Peto, Myron; Al Mamun, Abu Amar M.; Shinbrot, Eve; Sethi, Anurag; Brooks, Samira; Rathmell, W. Kimryn; Brooks, Angela N.; Hoadley, Katherine A.; Robertson, A. Gordon; Brooks, Denise; Bowlby, Reanne; Sadeghi, Sara; Shen, Hui; Weisenberger, Daniel J.; Bootwalla, Moiz; Baylin, Stephen B.; Laird, Peter W.; Cherniack, Andrew D.; Saksena, Gordon; Haake, Scott; Li, Jun; Liang, Han; Lu, Yiling; Mills, Gordon B.; Akbani, Rehan; Leiserson, Mark D.M.; Raphael, Benjamin J.; Anur, Pavana; Bottaro, Donald; Albiges, Laurence; Barnabas, Nandita; Choueiri, Toni K.; Czerniak, Bogdan; Godwin, Andrew K.; Hakimi, A. Ari; Ho, Thai; Hsieh, James; Ittmann, Michael; Kim, William Y.; Krishnan, Bhavani; Merino, Maria J.; Mills Shaw, Kenna R.; Reuter, Victor E.; Reznik, Ed; Shelley, Carl Simon; Shuch, Brian; Signoretti, Sabina; Srinivasan, Ramaprasad; Tamboli, Pheroze; Thomas, George; Tickoo, Satish; Burnett, Kenneth; Crain, Daniel; Gardner, Johanna; Lau, Kevin; Mallery, David; Morris, Scott; Paulauskis, Joseph D.; Penny, Robert J.; Shelton, Candace; Shelton, W. Troy; Sherman, Mark; Thompson, Eric; Yena, Peggy; Avedon, Melissa T.; Bowen, Jay; Gastier-Foster, Julie M.; Gerken, Mark; Leraas, Kristen M.; Lichtenberg, Tara M.; Ramirez, Nilsa C.; Santos, Tracie; Wise, Lisa; Zmuda, Erik; Demchok, John A.; Felau, Ina; Hutter, Carolyn M.; Sheth, Margi; Sofia, Heidi J.; Tarnuzzer, Roy; Wang, Zhining; Yang, Liming; Zenklusen, Jean C.; Zhang, Jiashan (Julia); Ayala, Brenda; Baboud, Julien; Chudamani, Sudha; Liu, Jia; Lolla, Laxmi; Naresh, Rashi; Pihl, Todd; Sun, Qiang; Wan, Yunhu; Wu, Ye; Ally, Adrian; Balasundaram, Miruna; Balu, Saianand; Beroukhim, Rameen; Bodenheimer, Tom; Buhay, Christian; Butterfield, Yaron S.N.; Carlsen, Rebecca; Carter, Scott L.; Chao, Hsu; Chuah, Eric; Clarke, Amanda; Covington, Kyle R.; Dahdouli, Mahmoud; Dewal, Ninad; Dhalla, Noreen; Doddapaneni, HarshaVardhan; Drummond, Jennifer; Gabriel, Stacey B.; Gibbs, Richard A.; Guin, Ranabir; Hale, Walker; Hawes, Alicia; Hayes, D. Neil; Holt, Robert A.; Hoyle, Alan P.; Jefferys, Stuart R.; Jones, Steven J.M.; Jones, Corbin D.; Kalra, Divya; Kovar, Christie; Lewis, Lora; Li, Jie; Ma, Yussanne; Marra, Marco A.; Mayo, Michael; Meng, Shaowu; Meyerson, Matthew; Mieczkowski, Piotr A.; Moore, Richard A.; Morton, Donna; Mose, Lisle E.; Mungall, Andrew J.; Muzny, Donna; Parker, Joel S.; Perou, Charles M.; Roach, Jeffrey; Schein, Jacqueline E.; Schumacher, Steven E.; Shi, Yan; Simons, Janae V.; Sipahimalani, Payal; Skelly, Tara; Soloway, Matthew G.; Sougnez, Carrie; Tam, Angela; Tan, Donghui; Thiessen, Nina; Veluvolu, Umadevi; Wang, Min; Wilkerson, Matthew D.; Wong, Tina; Wu, Junyuan; Xi, Liu; Zhou, Jane; Bedford, Jason; Chen, Fengju; Fu, Yao; Gerstein, Mark; Haussler, David; Kasaian, Katayoon; Lai, Phillip; Ling, Shiyun; Radenbaugh, Amie; Van Den Berg, David; Weinstein, John N.; Zhu, Jingchun; Albert, Monique; Alexopoulou, Iakovina; Andersen, Jeremiah J; Auman, J. Todd; Bartlett, John; Bastacky, Sheldon; Bergsten, Julie; Blute, Michael L.; Boice, Lori; Bollag, Roni J.; Boyd, Jeff; Castle, Erik; Chen, Ying-Bei; Cheville, John C.; Curley, Erin; Davies, Benjamin; DeVolk, April; Dhir, Rajiv; Dike, Laura; Eckman, John; Engel, Jay; Harr, Jodi; Hrebinko, Ronald; Huang, Mei; Huelsenbeck-Dill, Lori; Iacocca, Mary; Jacobs, Bruce; Lobis, Michael; Maranchie, Jodi K.; McMeekin, Scott; Myers, Jerome; Nelson, Joel; Parfitt, Jeremy; Parwani, Anil; Petrelli, Nicholas; Rabeno, Brenda; Roy, Somak; Salner, Andrew L.; Slaton, Joel; Stanton, Melissa; Thompson, R. Houston; Thorne, Leigh; Tucker, Kelinda; Weinberger, Paul M.; Winemiller, Cythnia; Zach, Leigh Anne; Zuna, Rosemary

2016-01-01

Background Papillary renal cell carcinoma, accounting for 15% of renal cell carcinoma, is a heterogeneous disease consisting of different types of renal cancer, including tumors with indolent, multifocal presentation and solitary tumors with an aggressive, highly lethal phenotype. Little is known about the genetic basis of sporadic papillary renal cell carcinoma; no effective forms of therapy for advanced disease exist. Methods We performed comprehensive molecular characterization utilizing whole-exome sequencing, copy number, mRNA, microRNA, methylation and proteomic analyses of 161 primary papillary renal cell carcinomas. Results Type 1 and Type 2 papillary renal cell carcinomas were found to be different types of renal cancer characterized by specific genetic alterations, with Type 2 further classified into three individual subgroups based on molecular differences that influenced patient survival. MET alterations were associated with Type 1 tumors, whereas Type 2 tumors were characterized by CDKN2A silencing, SETD2 mutations, TFE3 fusions, and increased expression of the NRF2-ARE pathway. A CpG island methylator phenotype (CIMP) was found in a distinct subset of Type 2 papillary renal cell carcinoma characterized by poor survival and mutation of the fumarate hydratase (FH) gene. Conclusions Type 1 and Type 2 papillary renal cell carcinomas are clinically and biologically distinct. Alterations in the MET pathway are associated with Type 1 and activation of the NRF2-ARE pathway with Type 2; CDKN2A loss and CIMP in Type 2 convey a poor prognosis. Furthermore, Type 2 papillary renal cell carcinoma consists of at least 3 subtypes based upon molecular and phenotypic features. PMID:26536169

A quantum approach to homomorphic encryption

PubMed Central

Tan, Si-Hui; Kettlewell, Joshua A.; Ouyang, Yingkai; Chen, Lin; Fitzsimons, Joseph F.

2016-01-01

Encryption schemes often derive their power from the properties of the underlying algebra on the symbols used. Inspired by group theoretic tools, we use the centralizer of a subgroup of operations to present a private-key quantum homomorphic encryption scheme that enables a broad class of quantum computation on encrypted data. The quantum data is encoded on bosons of distinct species in distinct spatial modes, and the quantum computations are manipulations of these bosons in a manner independent of their species. A particular instance of our encoding hides up to a constant fraction of the information encrypted. This fraction can be made arbitrarily close to unity with overhead scaling only polynomially in the message length. This highlights the potential of our protocol to hide a non-trivial amount of information, and is suggestive of a large class of encodings that might yield better security. PMID:27658349

Lay Americans' views of why scientists disagree with each other.

PubMed

Johnson, Branden B; Dieckmann, Nathan F

2017-10-01

A survey experiment assessed response to five explanations of scientific disputes: problem complexity, self-interest, values, competence, and process choices (e.g. theories and methods). A US lay sample ( n = 453) did not distinguish interests from values, nor competence from process, as explanations of disputes. Process/competence was rated most likely and interests/values least; all, on average, were deemed likely to explain scientific disputes. Latent class analysis revealed distinct subgroups varying in their explanation preferences, with a more complex latent class structure for participants who had heard of scientific disputes in the past. Scientific positivism and judgments of science's credibility were the strongest predictors of latent class membership, controlling for scientific reasoning, political ideology, confidence in choice, scenario, education, gender, age, and ethnicity. The lack of distinction observed overall between different explanations, as well as within classes, raises challenges for further research on explanations of scientific disputes people find credible and why.

Physician social networks and variation in prostate cancer treatment in three cities.

PubMed

Pollack, Craig Evan; Weissman, Gary; Bekelman, Justin; Liao, Kaijun; Armstrong, Katrina

2012-02-01

To examine whether physician social networks are associated with variation in treatment for men with localized prostate cancer. 2004-2005 Surveillance, Epidemiology and End Results-Medicare data from three cities. We identified the physicians who care for patients with prostate cancer and created physician networks for each city based on shared patients. Subgroups of urologists were defined as physicians with dense connections with one another via shared patients. Subgroups varied widely in their unadjusted rates of prostatectomy and the racial/ethnic and socioeconomic composition of their patients. There was an association between urologist subgroup and receipt of prostatectomy. In city A, four subgroups had significantly lower odds of prostatectomy compared with the subgroup with the highest rates of prostatectomy after adjusting for patient clinical and sociodemographic characteristics. Similarly, in cities B and C, subgroups had significantly lower odds of prostatectomy compared with the baseline. Using claims data to identify physician networks may provide an insight into the observed variation in treatment patterns for men with prostate cancer. © Health Research and Educational Trust.

Metabolite profiling in retinoblastoma identifies novel clinicopathological subgroups

PubMed Central

Kohe, Sarah; Brundler, Marie-Anne; Jenkinson, Helen; Parulekar, Manoj; Wilson, Martin; Peet, Andrew C; McConville, Carmel M

2015-01-01

Background: Tumour classification, based on histopathology or molecular pathology, is of value to predict tumour behaviour and to select appropriate treatment. In retinoblastoma, pathology information is not available at diagnosis and only exists for enucleated tumours. Alternative methods of tumour classification, using noninvasive techniques such as magnetic resonance spectroscopy, are urgently required to guide treatment decisions at the time of diagnosis. Methods: High-resolution magic-angle spinning magnetic resonance spectroscopy (HR-MAS MRS) was undertaken on enucleated retinoblastomas. Principal component analysis and cluster analysis of the HR-MAS MRS data was used to identify tumour subgroups. Individual metabolite concentrations were determined and were correlated with histopathological risk factors for each group. Results: Multivariate analysis identified three metabolic subgroups of retinoblastoma, with the most discriminatory metabolites being taurine, hypotaurine, total-choline and creatine. Metabolite concentrations correlated with specific histopathological features: taurine was correlated with differentiation, total-choline and phosphocholine with retrolaminar optic nerve invasion, and total lipids with necrosis. Conclusions: We have demonstrated that a metabolite-based classification of retinoblastoma can be obtained using ex vivo magnetic resonance spectroscopy, and that the subgroups identified correlate with histopathological features. This result justifies future studies to validate the clinical relevance of these subgroups and highlights the potential of in vivo MRS as a noninvasive diagnostic tool for retinoblastoma patient stratification. PMID:26348444