Extreme Subgroups Research Articles

Genetic Variations Among Families of Selectively Bred <i>Macrobrachium rosenbergii</i> (De Man) By RAPD-PCR Analysis

Giant freshwater prawn, Macrobrachium rosenbergii is an important freshwater crustacean widely cultured in several countries including India. Of late, its production has come down due to slow growth rate and disease occurrences. The ICAR-Central Institute of Freshwater Aquaculture (ICAR-CIFA), Bhubaneswar in collaboration with the WorldFish, Malaysia has initiated a selective breeding programme for growth improvement of this species. In the present study, two groups of families (I. six numbers of families for growth and II. six numbers of families for disease resistance) were selected for experimentation from the families produced in the fourth generation of selection programme. Each group consisted of two extreme sub-groups of three families in each with higher and lower growth (based on weight) under group I and, susceptible and resistant families (based on larval survival following challenge with Vibrio harveyi) under group II. RAPD- PCR was used to evaluate the genetic variations between and within groups separately. Twelve selected decamer primers were used to amplify DNA fragments of three individuals of each family and data were analyzed by POPGENE version 1.31 software. In group I, a total of 102 bands were scored by the primers out of which 41 bands (40.19%) found to be polymorphic. Genetic diversity within the group varied from 0.0272  0.0965 to 0.0463  0.1316. UPGMA dendrogram of this group based on Nei’s genetic distance showed that families 5 (low growth family 2) and 6 (low growth family 3) are distantly related to high growth families. In the second group of disease resistance, 35 bands (36.46%) were found to be polymorphic out of 96 bands scored. Genetic diversity varied between 0.0301 ± 0.0957 to 0.0438 ± 0.1381 within this group. UPGMA dendrogram showed that families 1 (susceptible group 1) and 2 (susceptible group 2) are distantly related to three resistant families. Thus, the present results showed the existence of genetic variations in both growth and disease resistance traits that could be utilized in the selective breeding programme in M. rosenbergii.

Is aspiration an effective acute stroke treatment in older adults?

Clinical outcomes after interventional stroke treatment rely on several factors, with older age being associated with poorer results, which are mainly attributed to patient's comorbidities and medications. The delivery of an aspiration catheter could be hindered by carotid tortuosity, which is more prevalent in elderly patients with increasing age. In this study, we aimed to compare the clinical and angiographic outcomes of a direct aspiration first-pass technique in interventional stroke treatment for elderly patients compared with younger patients. A total of 162 patients (92 women and 70 men, aged between 35 and 94 years +/- 12.4 years) were included in this study. Patients who were treated in a comprehensive stroke center due to a large-vessel occlusion stroke using aspiration as the first-choice treatment were included in this study. To evaluate carotid arteries, the tortuosity index (TI) was calculated for each segment of each carotid pathway. Age correlated significantly with the presence of carotid tortuosity (R = 0.408, p = 0.000), extracranial length ratio (R = 0.487, p = 0.000), and overall length ratio (R = 0.467, p = 0.000). No significant associations were found with coiling, kinking, or intracranial length ratio. Successful aspiration-based recanalization rate decreased with increasing age, and the differences between the age subgroups were not statistically significant. A comparison of the extreme subgroups, i.e., <60 years old vs. ≥80 years old, did not yield a statistically significant change (p = 0.068). Successful aspiration-based recanalization rate decreased with increasing age; however, these differences were not significant. Clinical outcomes did not significantly differ with regard to carotid tortuosity, regardless of the time of assessment. Neither intracranial nor extracranial tortuosity was significantly associated with reperfusion-related complications in either of the age subgroups.

Moderate low birth weight and socioemotional competence among children: The role of parenting factors in early childhood

BackgroundAlthough the importance of birth weight for socioemotional trajectories among children has become a topic of growing interest for researchers, the majority of prior studies were limited to the more extreme subgroups of low birth weight children. PurposeThe purpose of this study was to examine the longitudinal associations among moderate low birth weight status, parenting factors, and socioemotional competence among at-risk children. This paper also examined the role of parenting factors as a moderator in the associations between birth weight and indicators of socioemotional competence at age 9. MethodsParticipants include a subsample (N = 1809) of families participating in the Fragile Families and Child Wellbeing Study, a national longitudinal birth cohort study. Birth weight and prenatal data were taken from medical records. Parenting factors were assessed during in-home assessments at ages 3 and 5. Teachers reported on externalizing behaviors and social skills at age 9. Structural equation modeling was used to examine the associations among study variables. ResultsOverall, results indicate that moderate low birth weight was significantly associated with lower levels of teacher-reported socioemotional competence at age 9 even after accounting for a large battery of control variables. Results also showed that maternal warmth, but not parenting stress, moderated the longitudinal association between birth weight and indicators of socioemotional competence. ConclusionFindings highlight the importance of birth weight and positive parenting processes in socioemotional outcomes among children. The implications of these findings are discussed for targeting positive parenting interventions and developmental outcomes for at-risk children.

Bridging across patient subgroups in phase I oncology trials that incorporate animal data.

In this paper, we develop a general Bayesian hierarchical model for bridging across patient subgroups in phase I oncology trials, for which preliminary information about the dose–toxicity relationship can be drawn from animal studies. Parameters that re-scale the doses to adjust for intrinsic differences in toxicity, either between animals and humans or between human subgroups, are introduced to each dose–toxicity model. Appropriate priors are specified for these scaling parameters, which capture the magnitude of uncertainty surrounding the animal-to-human translation and bridging assumption. After mapping data onto a common, ‘average’ human dosing scale, human dose–toxicity parameters are assumed to be exchangeable either with the standardised, animal study-specific parameters, or between themselves across human subgroups. Random-effects distributions are distinguished by different covariance matrices that reflect the between-study heterogeneity in animals and humans. Possibility of non-exchangeability is allowed to avoid inferences for extreme subgroups being overly influenced by their complementary data. We illustrate the proposed approach with hypothetical examples, and use simulation to compare the operating characteristics of trials analysed using our Bayesian model with several alternatives. Numerical results show that the proposed approach yields robust inferences, even when data from multiple sources are inconsistent and/or the bridging assumptions are incorrect.

The Extended Utility of CHA2DS2VASc and HAS-BLED Scores in the Selection for Transcutaneous Left Atrial Appendage Closure.

Background and purpose: Left atrial appendage closure (LAAC) is an option for stroke prevention in atrial fibrillation patients. Randomized studies have demonstrated the effectiveness and safety of LAAC but included patients with an average risk of stroke and bleeding complications. The current study aimed to assess the extended utility of CHA2DS2VASc (congestive heart failure; hypertension; age ≥75 years [doubled]; type 2 diabetes; previous stroke, transient ischemic attack, or thromboembolism [doubled]; vascular disease; age 65 to 75 years; and sex category) and HAS-BLED (hypertension; abnormal renal/liver function; stroke; bleeding history or predisposition; labile INR, elderly, drugs/alcohol concomitantly) scores for qualification and prognosis after LAAC. Methods: The study population comprised 270 patients aged 72.8 ± 8.78 years. The occluders used were the Amplatzer Amulet (N = 205), Amplatzer Cardiac Plug (N = 53), and Watchman device (N = 12). The prognosis after LAAC was analyzed for different cohorts of patients distinguished based on different CHA2DS2VASc and HAS-BLED scores. The mean duration of follow-up was 21.6 ± 10.3 months. Results: The observed rates of ischemic stroke and bleeding were much lower than that expected (2.2% vs. 5.6%, and 0.76% vs. 6.05%, respectively). The mortality rate did not differ concerning the CHA2DS2CVASc score. It was significantly lower (8.3%) for HAS-BLED < 3, and it raised to 17.9% for HAS-BLED = 3 and to 25.9% for HAS-BLED > 3. Significant differences (p = 0.003) occurred for Kaplan–Meier curves for extreme HAS-BLED subgroups. A composite endpoint was most often found in high/very high risk of bleeding patients. Conclusions: HAS-BLED, but not CHA2DS2CVASc score, may be a useful tool to predict the prognosis of patients after LAAC. Qualification for LAAC based on the risk of stroke should not differ from qualification for anticoagulation. Despite the worse prognosis of patients with the highest bleeding risk, this group is likely to experience the greatest benefit from reducing the bleeding risk from LAAC.

Staging more important than grading? Evaluation of malignancy grading, depth of invasion, and resection margins in oral squamous cell carcinoma

ObjectivesThe present study evaluated the predictive value of staging and grading parameters concerning the presence of lymph-node metastases, overall survival (OS), and relapse-free survival (RFS) of patients with oral squamous cell carcinoma (OSCC).Materials and methodsHE-stains of 135 surgically treated (R0) primary OSCCs were analyzed using a both microscopic and software-based approach. Depth of invasion (DOI) and resection margins (RM) were measured, and each case was graded according to the malignancy grading system as described by Anneroth et al. and Bryne et al. on two different sites of the tumor (surface and invasion front; TS and IF).ResultsParameters that could be identified as significant predictors of OS and RFS were UICC cancer stage (p = 0.009 and p = 0.012); pT-stage as defined in the 7th edition (p = 0.029 and 0.015) and, after restaging using DOI, 8th edition (p = 0.023 and p = 0.005) of the TNM classification of malignant tumors; the presence of lymphonodular metastases (LM) (p = 0.004 and p = 0.011); degree of keratinization (p = 0.029 and p = 0.042); and pattern of growth (p = 0.029 and p = 0.024) at the TS after applying a binary scale for both parameters. Also, when directly comparing the most extreme subgroups (scores 1 and 4) of lymphoplasmacytic infiltration at the IF, there was a significant difference in OS (p = 0.046) and RFS (p = 0.005). Invasion of blood vessels (p = 0.013) and perineural invasion (p = 0.023) were significantly associated with a lower OS. Age lower than 60 years (univariate p = 0.029, multivariate p = 0.031), infiltration of lymphatic vessels (p = 0.003), infiltration of nerves (p = 0.010), pT-stage (8th edition) (p = 0.014), degree of keratinization at the IF (p = 0.033), and nuclear polymorphism at the IF (p = 0.043) after conversion to a binary scale were found to be significant prognostic parameters regarding the presence of LM. DOI evolved as a significant predictor for OS (p = 0.006), RFS (p = 0.003), and LM (p = 0.032) in metric and grouped analysis.ConclusionsThe current evaluation revealed depth of invasion as strongest histologic predictor of metastatic tumor growth, overall survival, and relapse-free survival in OSCC, confirming the current adaption of the T-classification. Other distinct histologic grading parameters investigated during this study can give valuable indications of a tumor’s potential aggressiveness, but the exact site, mode, and procedure need further exploration.Clinical relevanceIntegrating measurement of DOI also into the pretherapeutic staging process could aid in treatment planning.

Abstract C018: Disparity subtyping: Bringing precision medicine closer to disparity science

Abstract The genomics revolution also spawned the dawn of precision medicine. As in the National Research Council definition, if its promise is fully realized, then more accurate decisions about individual patient treatment decisions and outcomes will be possible. Disparities researchers have also begun looking to the precision medicine paradigm with the hope that some incorporation of its principles will allow for a more focused and precise path forward to reduce population disparities. While the emphasis may switch to populations from individuals, central to the paradigm still is the ability to classify individuals into subpopulations who differ in meaningful ways with respect to underlying biology and outcomes. Identification of these subpopulations is an active area of precision medicine research. For instance, there are countless papers on molecular subtyping of various cancer phenotypes. How to do such a thing in disparity science has proven elusive since it requires identifying disparity subpopulations, which is a somewhat abstract concept. In this paper we present two different strategies—level set identification and peeling. The former is based on a recursive partitioning algorithm combined with clustering of similar partitions; the latter adopts a strategy of sequentially searching for and then extracting extreme difference subgroups in a population. Using series of simulation studies and then also studying various cancer outcomes from The Cancer Genome Atlas (TCGA) repository, we demonstrate that such disparity subtypes can indeed be found, characterized, and then validated on test data. Citation Format: J. Sunil Rao, Huilin Yu, Jean-Eudes Dazard. Disparity subtyping: Bringing precision medicine closer to disparity science [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr C018.

Genomewide Mapping of Selection Signatures and Genes for Extreme Feather Pecking in Two Divergently Selected Laying Hen Lines.

Simple SummaryFeather pecking is a behavior frequently occurring in commercial layer flocks. It often leads to skin injuries and cannibalism. Besides economic losses, severe animal welfare problems cannot be ignored. Previous research has shown that the trait is heritable. Thus breeding against feather pecking is possible, but phenotyping in a commercial environment is economically unfeasible at the moment because of the lack of proper techniques. Therefore, understanding the genetic background of the trait is mandatory to establish a genomic breeding program. This would require genotypic information of the hens, which is feasible under practical conditions. In the present study, we used different methods to identify regions in the genome that influence feather pecking and extreme feather pecking. We found one trait associated with the genomic region. The use of genotypic information from this region in terms of selection against the undesired behavior may help to improve animal welfare in layer flocks.Feather pecking (FP) is a longstanding serious problem in commercial flocks of laying hens. It is a highly polygenic trait and the genetic background is still not completely understood. In order to find genomic regions influencing FP, selection signatures between laying hen lines divergently selected for high and low feather pecking were mapped using the intra-population iHS and the inter-population FST approach. In addition, the existence of an extreme subgroup of FP hens (EFP) across both selected lines has been demonstrated by fitting a mixture of negative binomial distributions to the data and calculating the posterior probability of belonging to the extreme subgroup (pEFP) for each hen. A genomewide association study (GWAS) was performed for the traits pEFP and FP delivered (FPD) with a subsequent post GWAS analysis. Mapping of selection signatures revealed no clear regions under selection. GWAS revealed a region on Chromosome 1, where the existence of a QTL influencing FP is likely. The candidate genes found in this region are a part of the GABAergic system, which has already been linked to FP in previous studies. Despite the polygenic nature of FP, selection on these candidate genes may reduce FP.

Adormecer a Ver Televisão como Fator de Risco para Perturbação do Sono na Idade Escolar

INTRODUÇÃO: O objetivo deste estudo foi avaliar a relação do hábito de adormecer a ver televisão com as perturbações do sono na idade escolar.&#x0D; MATERIAL E MÉTODOS: Estudo transversal envolvendo turmas de primeiro ciclo de 17 agrupamentos escolares das áreas da Grande Lisboa, Península de Setúbal e Alentejo. Foi utilizada a versão portuguesa do Children’s Sleep Habits Questionnaire (CSHQ-PT).&#x0D; RESULTADOS: Foram considerados questionários de 996 crianças com idades entre os 6 e os 10 anos. Adormecer a ver televisão ocorria habitualmente em 167 crianças (16,8%), às vezes em 294 crianças (29,5%) e raramente em 535 crianças (53,7%). Comparando as crianças dos subgrupos extremos (habitualmente e raramente, n= 702), as crianças com o hábito de adormecer a ver televisão mostraram mais problemas do sono (p &lt; 0,001) com cotações superiores nas seguintes escalas: Índice de Perturbação do Sono, Resistência em Ir para a Cama, Duração do Sono, Ansiedade Associada o Sono, Despertares Noturnos, Parassónias e Sonolência Diurna. Verificou-se uma correlação positiva do hábito de adormecer a ver televisão com o Índice de Perturbação do Sono (0,27) e uma correlação negativa com a escolaridade dos pais (-0,22).&#x0D; CONCLUSÃO: O hábito de adormecer a ver televisão pode ser encarado como um fator de risco para perturbação do sono nas crianças, devendo este tema ser abordado nas consultas de vigilância de saúde da criança, numa perspetiva preventiva deste tipo de perturbação.

Finite groups with given sets of 𝔉-subnormal subgroups

In this paper, the classes of groups with given systems of [Formula: see text]-subnormal subgroups are studied. In particular, it is showed that if [Formula: see text] and [Formula: see text] are a saturated homomorph and a hereditary saturated formation, respectively, then the class of groups whose [Formula: see text]-subgroups are all [Formula: see text]-subnormal is a hereditary saturated formation. As corollaries, some known results about supersoluble groups, classes of groups with [Formula: see text]-subnormal cyclic primary and Sylow subgroups are obtained. Also the new characterization of the class of groups whose extreme subgroups all belong [Formula: see text], where [Formula: see text] is a hereditary saturated formation, is obtained.

The expression and significance of interleukin-1β and tumor necrosis factor-α in synovial fluid of patients with knee osteoarthritis

Objective To detect expression level of interleukin (IL)-1β and tumor necrosis factor (TNF)-α in synovial fluid of patients with knee osteoarthritis, and the significance. Methods From May 2012 to May 2016, 60 patients with knee osteoarthritis were admitted in our department as observation group, and on the basis of severity, three subgroups were set up: moderate severe subgroup (n=16), severe subgroup (n=18), very severe subgroup (n=17), and extreme subgroup (n=9). Twenty patients without osteoarthritis at the same period served as the control group. The enzyme-linked immunosorbent assay (ELISA) was used to detect the expression levels of IL-1β and TNF-α. Results IL-1β concentrations in the control group, moderate severe subgroup, severe subgroup, and very severe subgroup and extreme severe subgroup were (9.823±1.286), (11.885±1.206), (13.571±2.052), (18.783±4.372), and (27.109±4.901) pg/ml, and TNF-α concentrations were (10.281±2.118), (13.807±4.208), (17.815±4.689), (20.425±6.335) and (21.722±7.924) pg/ml. The concentration of TNF-α and IL-1β of serious group, very serious group and extremely severe group were greater than the control group and the difference is statistically significant (P= 0.000); And the concentration of IL-1β of serious group, very serious group and extremely severe group increase in turn and has significant difference (F= 61.296, P= 0.000); The concentration of very serious group, extremely severe group is greater than the severe group, and the difference is statistically significant (F= 18.291, P= 0.000); The concentration of TNF-α and IL-1β shows increasing trend, as patients severity increased and positively related to the degree of disease (r= 0.850, P= 0.000; r= 0.849, P= 0.000). Conclusion The expression levels of IL-1β and TNF-α in synovial fluid of patients with knee osteoarthritis increase significantly, playing an important role in the onset and progression of the process. Key words: Knee osteoarthritis; Interleukin-1β; Tumor necrosis factor-α; Joint synovial fluid

Abstract 1758: A more mature immunophenotypic makeup of multiple myeloma clone(s) at diagnosis correlates with a higher genomic instability

Abstract Intro The sequence of events underlying the process of Multiple Myeloma (MM) plasma cells (PC) differentiation have not yet fully elucidated, even if recent findings suggest that different cell subpopulations, with distinct phenotype, compose the MM clone(s), whose plasticity has emerged as a typical feature. Aim To evaluate the phenotypic plasticity and genomic background of MM clone(s) at diagnosis in order to stratify patients (pts) according to the PC differentiation stages and possibly correlate with disease outcome. P&amp;M Phenotypic characterization of both CD138+/CD38+ and CD19+ populations was carried out on 44 newly diagnosed MM. Fresh BM samples was analysed by 6color multiparametric flow citometry analysis, combining CD138PE, CD38-PE-Cy7, CD20-APC, CD19-APC-Cy7, CD27-FITC, CD45-FITC, CD28-APC, CD44-FITC, CD54-APC, CD81-PerCP-Cy5.5, CD56-APC and SHH-PE, as a functional marker of Hedgehog pathway activation (Miltenyi Biotech). Cytoscan HD array were carried out in order to detect genomic copy number alterations (CNAs). Results According to the CD19 and CD81 markers co-expression, pts were stratified in 3 subgroups, recapitulating a progressive PC maturation process: the most immature one, including pts with CD19+/CD81+ PC (11/44 = 25%); the intermediate CD19-/CD81+ phenotype one (19/44 = 43%), and the CD19-/CD81- PC one, whose clone was mainly composed by most mature PCs. The two extreme subgroups were characterized by a differential expression of maturation markers: the more mature PCs displayed a higher expression of CD28 and CD44, which usually characterized advanced disease stages, as well as a reduced expression of CD20, CD27 and CD45, commonly associated to preceding PC differentiation stages (p&amp;lt;.05). Any differential expression of SHH pathway’s ligand was observed. On the contrary, a higher Hedgehog pathway activation was detected in the immature CD19+ compartment of pts with immature plasma cells (median SHH expression CD19+/CD81+ vs. CD19-/CD81-: 98,1% vs. 11,3%; p&amp;lt;.05), which probably highlighted a less quiescent immature reservoir pool. The CNAs analysis showed that mature PCs were characterized by a higher genomic instability, as compared to the more immature ones (total CNA: 306.9 vs. 171.5, p 0.08; genome changed: 36.96 vs. 13.55, p 0.01), including several alterations commonly associated to worse prognosis (e.g. del17p). Finally, a higher frequency of baseline clinical characteristics associated to bad prognosis was observed in the more mature, as compared to the more immature subgroups of pts (e.g. n. PET lesions, k/l ratio; p&amp;lt;.05). Conclusion MM clone(s) is a mixture of different cell populations endowed with an inner phenotypic plasticity. Various PC differentiation stages were appreciable already at diagnosis and genomic features associated to bad prognosis characterize pts carrying more mature clones. Acknowledgements: AIRC, Berlucchi, Prog. Bolondi, FUV Citation Format: Marina Martello, Rosalinda Termini, Barbara Santacroce, Enrica Borsi, Vincenza Solli, Lucia Pantani, Elena Zamagni, Paola Tacchetti, Francesca Ulbar, Gabriella Chirumbolo, Mario Arpinati, Giovanni Martinelli, Michele Cavo, Carolina Terragna. A more mature immunophenotypic makeup of multiple myeloma clone(s) at diagnosis correlates with a higher genomic instability [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1758. doi:10.1158/1538-7445.AM2017-1758

APOE and KIBRA Interactions on Brain Functional Connectivity in Healthy Young Adults.

Genetic variations of APOE and KIBRA have been associated with human memory and Alzheimer's disease. APOE and KIBRA can jointly modulate glutamate receptor to influence long-term potentiation; however, their interactions on brain functional connectivity remain unknown. Here, we investigated additive and epistatic interactions between APOE and KIBRA (rs17070145) on brain functional connectivity density (FCD) in 267 healthy young adults. A voxel-based FCD analysis was performed to identify brain regions with significant APOE-KIBRA interaction. Additive effects showed decreased FCD in the left parahippocampal gyrus and the right middle temporal gyrus and increased FCD in the bilateral middle occipital gyri, with the increase of the number of the risk-alleles of APOE and KIBRA. Epistatic effects showed APOE×KIBRA interaction in the FCD of the dorsolateral prefrontal cortex (DLPFC). The FCD of the DLPFC showed APOE risk-allele-dependent reduction (ε2>ε3>ε4) in KIBRA TT homozygotes, but APOE risk-allele-dependent increase (ε2<ε3<ε4) in KIBRA C-carriers. FCD differences were only significant between the 2 extreme subgroups in both additive and epistatic analyses. These findings suggest that APOE and KIBRA have region-dependent additive and epistatic interactions on brain connectivity in healthy young adults.

Benefits of Selenium Supplementation on Leukocyte DNA Integrity Interact with Dietary Micronutrients: A Short Communication.

A male cohort from New Zealand has previously shown variability in Selenium (Se) supplementation effects on measured biomarkers. The current analysis is to understand the reasons for variability of the H2O2-induced DNA damage recorded after Se supplementation. We have looked at the variation of demographic, lifestyle, medication, genetic and dietary factors and biomarkers measured at baseline and post-supplementation in these two extreme subgroups A and B. Group A showed increased H2O2-induced DNA damage and group B showed decreased damage after Se supplementation. We have also considered correlations of biomarkers and dietary factors in the complete dataset. The glutathione peroxidase (GPx) activity and DNA damage were significantly lower at post-supplementation in Group B compared to Group A. Post-supplementation, Group B showed a significant reduction in the GPx activity, while Group A showed a significant increase in DNA damage compared to baseline levels. Dietary methionine intake was significantly higher and folate intake was significantly lower in Group B compared to Group A. Se supplementation significantly increased the caspase-cleaved keratin 18 levels in both groups, indicating increased apoptotic potential of this supplement. Parameter correlation with the complete dataset showed dietary methionine to have a significant negative correlation with H2O2-induced DNA damage post-supplementation. The data suggest that Se supplementation is beneficial for the leukocyte DNA integrity only in interaction with the dietary methionine and folate intake.

Uncertainty about effects is a key factor influencing institutional review boards' approval of clinical studies

PurposeTo investigate factors, which influence institutional review boards' (IRBs') decision to approve or not approve clinical studies, a nationwide vignette-based online survey of IRB members was conducted. MethodsA factorial design was used, whereby seven aspects of each hypothetical study were randomly varied in 15 phrases in each vignette to produce unique vignettes. Participants indicated the degree of study approval and described factors influencing approval decision. Qualitative responses were thematically content analyzed. ResultsSixteen themes were obtained from 208 participants from 42 institutions. Uncertainty, adherence, study design, and harms were frequently and intensely cited to influence study approval. Analysis of two extreme subgroups (approvers vs. nonapprovers) showed that uncertainty influenced approval decisions, odds ratios (OR) = 3.5 (95% confidence interval [CI], 1.3–9.8) and OR = 3.2 (95% CI, 1.1–8.9), respectively, based on theme frequency and theme intensity, ignoring multiple observations per person. Taking into consideration multiple observations per person, similar results were obtained for uncertainty: OR = 8.9 (95% CI, 0.93–85.4). ConclusionsPerceived uncertainty about benefits and harms of a proposed intervention is a key driver in IRB members' approval of clinical trials. This, in turn, calls for improved standardization in the communications of information on benefits and harms in the research protocols considered by the IRBs.

The Heritability of Self-esteem: Evidences from Twin Studies

As an important aspect of individual difference,self-esteem has attracted increasing attentions from behavioral genetic scientists.In this paper,we reviewed twin studies on self-esteem and found that: 1) self-esteem is moderately heritable,though non-shared environmental factors also make a difference;2) the stability of self-esteem is largely genetically determined;3) the associations between self-esteem and cognition as well as affect are mainly genetically caused.Together,genetic influences on self-esteem are essential.Future twin study may pay more attention to the heritability of self-esteem fluctuation and implicit self-esteem on one hand,and the specificity of people from extreme sub-groups and those from different cultures on the other hand.

Annotation and Analyses of Temporal Aspects of Spoken Fluency

This article presents the methodology adopted for transcribing and quantifying temporal fluency phenomena in a spoken L2 corpus (L2 English, French, and Italian by learners of different proficiency levels). The CHILDES suite is being used for transcription and analysis, and we have adapted the CHAT format in order to code disfluencies as precisely as possible. We briefly present findings for two extreme subgroups in the corpus--our most hesitant and least hesitant learners--and compare the major differences in the temporal structure of the speech of these two learner groups with a native-speaker control group. Implications of these findings for the automatic assessment of spoken fluency will be discussed.

The normal structure of the unipotent subgroup in Lie type groups and its extremal subgroups

We study the normal structure of the unipotent radical U of a Borel subgroup in a Lie type group over a field K. Thus, all maximal Abelian normal subgroups in U are described. This gives a new solution of C. Parker and P. Rowley’s problem about extremal subgroups in U and the description in finite groups U of the large normal (and, as proved, also normal large) Abelian subgroups.

Tracing the evolution of chiropractic students’ confidence in clinical and patient communication skills during a clinical internship: a multi-methods study

BackgroundAnecdotal evidence points to variations in individual students’ evolving confidence in clinical and patient communication skills during a clinical internship. A better understanding of the specific aspects of internships that contribute to increasing or decreasing confidence is needed to best support students during the clinical component of their study.MethodsA multi-method approach, combining two large-scale surveys with 269 students and three in-depth individual interviews with a sub-sample of 29 students, was used to investigate the evolution of change in student confidence during a 10-month long internship. Change in levels of confidence in patient communication and clinical skills was measured and relationship to demographic factors were explored. The interviews elicited students’ accounts and reflections on what affected the evolution of their confidence during the internship.ResultsAt the start of their internship, students were more confident in their patient communication skills than their clinical skills but prior experience was significantly related to confidence in both. Initial confidence in patient communication skills was also related to age and prior qualification but not gender whilst confidence in clinical skills was related to gender but not age or prior qualification. These influences were maintained over time. Overall, students’ levels of confidence in patient communication and clinical skills confidence increased significantly over the duration of the internship with evidence that change over time in these two aspects were inter-related. To explore how specific aspects of the internship contributed to changing levels of confidence, two extreme sub-groups of interviewees were identified, those with the least increase and those with the highest increase in professional confidence over time. A number of key factors affecting the development of confidence were identified, including among others, interactions with clinicians and patients, personal agency and maturing as a student clinician.ConclusionThis study provides insight into the factors perceived by students as affecting the development of professional confidence during internships. One particularly promising area for educational intervention may be the promotion of a pro-active approach to professional learning.

Prediction of Warfarin Dose Reductions in Puerto Rican Patients, Based on Combinatorial CYP2C9 and VKORC1 Genotypes

The influence of CYP2C9 and VKORC1 polymorphisms on warfarin dose has been investigated in white, Asian, and African American populations but not in Puerto Rican Hispanic patients. To test the associations between genotypes, international normalized ratio (INR) measurements, and warfarin dosing and gauge the impact of these polymorphisms on warfarin dose, using a published algorithm. A retrospective warfarin pharmacogenetic association study in 106 Puerto Rican patients was performed. DNA samples from patients were assayed for 12 variants in both CYP2C9 and VKORC1 loci by HILOmet PhyzioType assay. Demographic and clinical nongenetic data were retrospectively collected from medical records. Allele and genotype frequencies were determined and Hardy-Weinberg equilibrium (HWE) was tested. Sixty-nine percent of patients were carriers of at least one polymorphism in either the CYP2C9 or the VKORC1 gene. Double, triple, and quadruple carriers accounted for 22%, 5%, and 1%, respectively. No significant departure from HWE was found. Among patients with a given CYP2C9 genotype, warfarin dose requirements declined from GG to AA haplotypes; whereas, within each VKORC1 haplotype, the dose decreased as the number of CYP2C9 variants increased. The presence of these loss-of-function alleles was associated with more out-of-range INR measurements (OR = 1.38) but not with significant INR >4 during the initiation phase. Analyses based on a published pharmacogenetic algorithm predicted dose reductions of up to 4.9 mg/day in carriers and provided better dose prediction in an extreme subgroup of highly sensitive patients, but also suggested the need to improve predictability by developing a customized model for use in Puerto Rican patients. This study laid important groundwork for supporting a prospective pharmacogenetic trial in Puerto Ricans to detect the benefits of incorporating relevant genomic information into a customized DNA-guided warfarin dosing algorithm.