Basin-scale reconstruction of euxinia and Late Devonian mass extinctions.

The Devonian-Carboniferous transition marks a fundamental shift in the surface environment primarily related to changes in ocean-atmosphere oxidation states1,2, resulting from the continued proliferation of vascular land plants that stimulated the hydrological cycle and continental weathering3,4, glacioeustasy5,6, eutrophication and anoxic expansion in epicontinental seas3,4, and mass extinction events2,7,8. Here we present a comprehensive spatial and temporal compilation of geochemical data from 90 cores across the entire Bakken Shale (Williston Basin, North America). Our dataset allows for the detailed documentation of stepwise transgressions of toxic euxinic waters into the shallow oceans that drove a series of Late Devonian extinction events. Other Phanerozoic extinctions have also been related to the expansion of shallow-water euxinia, indicating that hydrogen sulfide toxicity was a key driver of Phanerozoic biodiversity.

Athletes' Coping With the COVID-19 Pandemic: The Role of Self-Compassion and Cognitive Appraisal.

Coping with the COVID-19 pandemic had implications for athletes' mental well-being. This mixed-methods study examined the influence of self-compassion on athletes' coping during the pandemic through the mediator of cognitive appraisal. The prospective design involved 90 athletes completing two online surveys 1 week apart measuring self-compassion, cognitive appraisal, and coping strategies. The PROCESS macro was used for the mediation analysis. A qualitative thematic analysis was used to explore athletes' responses to the pandemic during the second survey. Self-compassion had an indirect negative effect on avoidance-focused coping by appraising the pandemic as less of a threat (95% confidence interval [-0.20, -0.001]) and had a total effect on emotion-focused coping (95% confidence interval [0.02, 0.40]). Based on the thematic analysis, athletes described many raw emotions and a variety of coping strategies during the pandemic. Self-compassion demonstrated promising benefits to athletes who dealt with the challenging situation of the pandemic.

Automated classification of cytogenetic abnormalities in hematolymphoid neoplasms.

MOTIVATION: Algorithms for classifying chromosomes, like convolutional deep neural networks (CNNs), show promise to augment cytogeneticists' workflows; however, a critical limitation is their inability to accurately classify various structural chromosomal abnormalities. In hematopathology, recurrent structural cytogenetic abnormalities herald diagnostic, prognostic and therapeutic implications, but are laborious for expert cytogeneticists to identify. Non-recurrent cytogenetic abnormalities also occur frequently cancerous cells. Here, we demonstrate the feasibility of using CNNs to accurately classify many recurrent cytogenetic abnormalities while being able to reliably detect non-recurrent, spurious abnormal chromosomes, as well as provide insights into dataset assembly, model selection and training methodology that improve overall generalizability and performance for chromosome classification. RESULTS: Our top-performing model achieved a mean weighted F1 score of 96.86% on the validation set and 94.03% on the test set. Gradient class activation maps indicated that our model learned biologically meaningful feature maps, reinforcing the clinical utility of our proposed approach. Altogether, this work: proposes a new dataset framework for training chromosome classifiers for use in a clinical environment, reveals that residual CNNs and cyclical learning rates confer superior performance, and demonstrates the feasibility of using this approach to automatically screen for many recurrent cytogenetic abnormalities while adeptly classifying non-recurrent abnormal chromosomes. AVAILABILITY AND IMPLEMENTATION: Software is freely available at https://github.com/DaehwanKimLab/Chromosome-ReAd. The data underlying this article cannot be shared publicly due to it being protected patient information. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Tai Chi versus health education as a frailty intervention for community-dwelling older adults with hypertension.

BACKGROUND: Frailty is associated with poor outcomes among older adults with hypertension and complicates its pharmacological management. Here, we assessed whether 12-weeks of instructor-guided, group Tai Chi (TC) practice improved frailty relative to Healthy Aging Practice-centered Education (HAP-E) classes in older adults with hypertension. METHODS: Secondary analysis of a randomized controlled trial in San Diego County, USA, of 167 community-dwelling individuals aged ≥ 60 yrs (70% female; 72.1 ± 7.5 yrs), defined as non-frail (66%) or frail (34%) based on 53-item deficit accumulation frailty index (FI). Linear mixed-effects models were used to assess pre-to-post intervention differences in FI and logistic regression to explore differential odds of clinically meaningful FI change. RESULTS: One hundred thirty-one participants completed post-intervention assessments. Frailty decreased pre-to-post intervention in the TC (ΔFI = - 0.016, d = - 0.39, - 0.75 to - 0.03), but not the HAP-E arm (ΔFI = - 0.009, d = - 0.13, - 0.52-0.27), despite no significant group differences between the TC and HAP-E arms (d = - 0.11, - 0.46-0.23). Furthermore, greater odds of improved FI were observed for frail participants in the TC (OR = 3.84, 1.14-14.9), but not the HAP-E (OR = 1.34, 0.39-4.56) arm. Subgroup analysis indicated treatment effects in TC were attributed to frail participants (frail: ΔFI = - 0.035, d = - 0.68, -1.26 to - 0.08; non-frail: ΔFI = - 0.005, d = - 0.19, - 0.59-0.22), which was not the case in the HAP-E arm (frail: ΔFI = - 0.017, d = - 0.23, - 0.81-0.35; non-frail: ΔFI = - 0.003, d = - 0.07, - 0.47-0.33). Frail participants were no more likely to drop-out of the study than non-frail (71% vs. 69% retained). CONCLUSIONS: Twelve weeks of twice-weekly guided TC practice was well-tolerated, associated with decreases in frailty, and increased odds of clinically meaningful FI improvement at post-intervention.

Tai chi or health education for older adults with hypertension: effects on mental health and psychological resilience to COVID-19.

OBJECTIVE: To compare the effectiveness of 12 weeks of community-based, in-person, group Tai Chi (TC) and Health Education (HAP-E) in improving health and wellbeing in older adults with hypertension and in promoting psychological resilience during COVID-19. METHODS: A 12-week randomized controlled trial (RCT) in San Diego County, USA. Self-reported depressive symptoms, anxiety, sleep disturbances, gratitude, resilience, mental and physical health were assessed in-person pre- and post-intervention, and by long-term follow-up surveys during COVID-19. Linear mixed-effects models were used to assess study arm differences over time and logistic regression to identify predictors of positive intervention response. RESULTS: Of 182 randomized participants (72.6 ± 7.9 yrs; 72% female), 131 completed the intervention. Modest improvements in health and wellbeing occurred post-intervention in both arms (Cohen's d: TC = 0.38, 95% CI: 0.25-0.51; HAP-E = 0.24, 0.11-0.37), though positive intervention responses were more than twice as likely in TC (OR = 2.29, 1.07-4.57). Younger age, higher anxiety, and poorer mental health at baseline predicted greater odds of response. Small declines in health and wellbeing were reported at the first COVID-19 follow-up, with smaller declines in the TC arm (Cohen's d: TC = -0.15, -0.31-0.00; HAP-E = -0.34, -0.49 to -0.19). Health and wellbeing stabilized at the second COVID-19 follow-up. Most participants (>70%) reported that the interventions benefitted their health and wellbeing during COVID-19. CONCLUSION: TC and HAP-E improved health and wellbeing, though TC conferred greater odds of an improved mental health response. Declines in health and wellbeing were observed at pandemic follow-up, with smaller declines in the TC arm, suggesting increased resilience.

Mental Fatigue Uniquely Influences Drop Landing Biomechanics for Individuals With a Concussion History.

CONTEXT: Induced mental fatigue negatively impacts sport performance and neurocognition. However, it is unclear how induced mental fatigue influences landing biomechanics. The purpose of this study was to examine the influence of mental fatigue on drop landing biomechanics in individuals with and without a concussion history. DESIGN: Crossover design. METHODS: Forty-eight (24 per group) recreationally active individuals were matched on age (±3 y), sex, and body mass index (±1 kg/m2). All participants completed an experimental (30-min Stroop task) and control (30-min reading magazines) intervention on separate days separated by a minimum of 24 hours. Drop landings were performed before and after both interventions. Outcomes included peak vertical ground reaction force (vGRF), vertical loading rate (VLR), knee flexion angle, knee abduction angle, external knee flexion moment, external knee abduction moment, and initial ground contact knee flexion and knee abduction angles. Separate 2 (group) × 2 (intervention) between-within analyses of covariance compared drop landing outcomes. Each group's average pre-Stroop and premagazine outcomes were covariates. RESULTS: There was a significant interaction for vGRF (P = .033, ηp2=.097) and VLR (P = .0497, ηp2=.083). The vGRF simple effects were not statistically significantly (P range = .052-.325). However, individuals with a concussion history displayed a medium effect size for greater vGRF post-Stroop compared with their own postmagazine vGRF (mean difference (95% confidence interval [95% CI] = 0.163 (-0.002 to 0.327) bodyweight (BW), p =.052, ηp2=.081. In contrast, the control group displayed a small effect size (mean difference [95% CI] = 0.095 [-0.069 to 0.259] BW, p =.251, ηp2=.029). Individuals with a concussion history displayed greater VLR post-Stroop compared with controls (mean difference [95% CI], 26.29 [6.19 to 46.40] BW/s, P = .012, ηp2=.134) and their own postmagazine values (mean difference [95% CI] = 32.61 [7.80 to 57.42] BW/s, p =.011, ηp2=.135). CONCLUSION: Mental fatigue leads to greater VLR for individuals with a concussion history. Athletic competition and activities of daily living can increase mental fatigue. Training programs may seek to teach mental fatigue reducing strategies to athletes with a concussion history.

Systemic Inflammation and Cognitive Decrements in Patients With Stage B Heart Failure.

OBJECTIVE: This study aimed to investigate the role of systemic inflammation in reduced cognitive functioning in patients with early-stage heart failure (HF) while determining associations with other cardiovascular risk factors. METHODS: Patients with stage B HF (n = 270; mean [standard deviation] age = 66.1 [10.1] years) were examined cross-sectionally for relationships among cardiovascular disease (CVD) and psychological risk factors, C-reactive protein (CRP), and Montreal Cognitive Assessment (MoCA) scores. A subsample (n = 83) at high risk for stage C HF (B-type natriuretic peptide levels ≥65 pg/ml) were followed up for 12 months for relationships between CRP levels and cognitive function. RESULTS: Baseline smoking (χ2 = 6.33), unmarried (χ2 = 12.0), hypertension (χ2 = 5.72), greater body mass index (d = 0.45), and physical fatigue (d = 0.25) were related to higher CRP levels (p values < .05). Cross-sectionally, CRP levels were negatively related to MoCA scores, beyond CVD (ΔR2 = 0.022, ß = -0.170, p < .010) and psychological risk factors (ΔR2 = 0.016, ß = 0.145, p < .027), and related to mild cognitive impairment criteria (odds ratio = 1.35, 95% confidence interval [CI] = 1.00-1.81, p = .046). Across 12 months, B-type natriuretic peptide high-risk patients with CRP levels ≥3 mg/L had lower MoCA scores (23.6; 95% CI = 22.4-24.8) than did patients with CRP levels <3 mg/L (25.4; 95% CI = 24.4-26.5; p = .024). CONCLUSIONS: Patients with stage B HF and heightened CRP levels had greater cognitive impairment at baseline and follow-up, independent of CVD and potentially psychological risk factors. Low-grade systemic inflammation may be one mechanism involved in cognitive dysfunction at early stages of HF.

Real-world disease-modifying therapy pathways from administrative claims data in patients with multiple sclerosis.

BACKGROUND: Over a dozen disease-modifying therapies (DMTs) have been approved for treatment of multiple sclerosis (MS). Treatment guidelines focus on when to initiate, change, and discontinue treatment but provide little guidance on how to select or sequence DMTs. This study assessed sequencing patterns of DMTs in patients with newly diagnosed MS. METHODS: Adults newly diagnosed with MS in the United States were identified from January 2007 to October 2017 using IBM MarketScan database. Patients had ≥12 months of continuous enrollment prior to diagnosis and ≥ 2 years of follow-up. Treatment pathways consisting of up to 3 DMT courses were reported, and each treatment course ended with discontinuation, switch, or end of follow-up. RESULTS: In total, 14,627 MS patients were treated with DMTs and had ≥2 years of follow-up. More than 400 DMT treatment pathways were observed. Glatiramer acetate was the most common DMT; 40% of patients initiated this treatment. Among these, 51.3% had 2 DMT courses during follow-up and 26.5% had 3 DMT courses. Approximately 70% of patients switched or discontinued their initial DMT, and rates of switch and discontinuation differed by initial DMT. Injectable DMTs were used most commonly over the study period (87.5% as first course to 66.6% as third course). Oral DMTs were more common as second or third treatment courses (29.9% and 31.8%, respectively). CONCLUSIONS: A wide variety in treatment patterns were observed among patients newly diagnosed with MS. Further examination of DMT prescribing practices is needed to understand the reasons behind treatment discontinuation and treatment cycling.

Adherence to fecal immunochemical test screening among adults at average risk for colorectal cancer.

PURPOSE: This study examined adherence to screening for fecal immunochemical test (FIT). METHODS: Adults (≥ 50-75) with a FIT between 1/1/2014 and 6/30/2019 in MarketScan administrative claims were selected (index = earliest FIT). Patients were followed for 10 years pre- and 3 years post-index. Patients at increased risk for CRC or with prior screening were excluded. Year over year adherence was measured post-index. RESULTS: Of 10,253 patients, the proportion adherent to repeat testing at year 2 was 23.4% and 10.6% at year 3. Of 76.6% not adherent in year 2, 5.4% were adherent in year 3. CONCLUSION: Results suggest adherence to FIT tests is poor, minimizing potential benefits. Future studies are needed to consider alternative test options and whether more choice will improve long-term adherence.

Resting-State Functional Connectivity and Psychopathology in Klinefelter Syndrome (47, XXY).

Klinefelter syndrome (47, XXY; henceforth: XXY syndrome) is a high-impact but poorly understood genetic risk factor for neuropsychiatric impairment. Here, we provide the first study to map alterations of functional brain connectivity in XXY syndrome and relate these changes to brain anatomy and psychopathology. We used resting-state functional magnetic resonance imaging data from 75 individuals with XXY and 84 healthy XY males to 1) implement a brain-wide screen for altered global resting-state functional connectivity (rsFC) in XXY versus XY males and 2) decompose these alterations through seed-based analysis. We then compared these rsFC findings with measures of regional brain anatomy, psychopathology, and cognition. XXY syndrome was characterized by increased global rsFC in the left dorsolateral prefrontal cortex (DLPFC)-reflecting DLPFC overconnectivity with diverse rsFC networks. Functional overconnectivity was partly coupled to co-occurring regional volumetric changes in XXY syndrome, and variation in DLPFC-precuneus rsFC was correlated with the severity of psychopathology. By providing the first view of altered rsFC in XXY syndrome and contextualizing observed changes relative to neuroanatomy and behavior, our study helps to advance biological understanding of XXY syndrome-both as a disorder in its own right and more broadly as a model of genetic risk for psychopathology.

Improved Motor Proficiency and Quality of Life in Youth With Prader-Willi Syndrome and Obesity 6 Months After Completing a Parent-Led, Game-Based Intervention.

PURPOSE: To determine changes and potential differences in physical activity (PA), gross motor proficiency (MP), and health parameters after a 6-month follow-up (FU) period following participation in a parent-led PA intervention in youth with or without Prader-Willi syndrome (PWS). METHODS: About 42 youth with PWS and 65 youth without PWS but with obesity (body fat percentage >95th percentile for age and sex), aged 8-16 years, participated. The intervention included preplanned PA sessions containing playground and console-based video games scheduled 4 days per week for 24 weeks. Families received training and curriculum materials. PA (accelerometry), MP (Bruininks-Oseretsky Test of MP), and health-related quality of life were obtained before (PRE), after completing the intervention (POST), and at FU. RESULTS: There were no significant changes in PA at any time point. At FU and POST, participants showed higher bilateral coordination (PRE = 9.3 [0.4], POST = 11.7 [0.5], and FU = 11.1 [0.6]); speed and agility (PRE = 9.2 [0.4], POST = 10.8 [0.4], and FU = 11.5 [0.5]); and strength (PRE = 8.0 [0.3], POST = 9.2 [0.3], and FU = 9.2 [0.3]) than at PRE. At FU (80.3 [2.1]) and POST (79.8 [1.7]), youth without PWS showed higher health-related quality of life than PRE (75.0 [1.8]). CONCLUSION: The improvements in MP and health-related quality of life at FU suggest long-term durability of intervention outcomes.

Drop Landing Biomechanics in Individuals With and Without a Concussion History.

Research has identified an increased risk of lower extremity injury postconcussion, which may be due to aberrant biomechanics during dynamic tasks. The purpose of this study was to compare the drop landing biomechanics between individuals with and without a concussion history. Twenty-five individuals with and 25 without a concussion history were matched on age (±3 y), sex, and body mass index (±1 kg/m2). Three-dimensional landing biomechanics were recorded to obtain dependent variables (peak vertical ground reaction force, loading rate, knee flexion angle and external moment, knee abduction angle and external moment, and knee flexion and abduction angle at ground contact). A 1-way multivariate analysis of variance compared outcomes between groups. There was no difference in drop landing biomechanics between individuals with and without a concussion history (F10,39 = 0.460, P = .877, Wilk Λ = .918). There was an effect of time since concussion on knee flexion characteristics. Time since most recent concussion explained a significant amount of variation in both peak (ΔR2 = .177, ß = -0.305, ΔP = .046) and initial ground contact (ΔR2 = .292, ß = -0.204, ΔP = .008) knee flexion angle after covarying for sex and body mass index. Therefore, time since concussion should be considered when evaluating biomechanical patterns.

Sex chromosome aneuploidy alters the relationship between neuroanatomy and cognition.

Sex chromosome aneuploidy (SCA) increases the risk for cognitive deficits, and confers changes in regional cortical thickness (CT) and surface area (SA). Neuroanatomical correlates of inter-individual variation in cognitive ability have been described in health, but are not well-characterized in SCA. Here, we modeled relationships between general cognitive ability (estimated using full-scale IQ [FSIQ] from Wechsler scales) and regional estimates of SA and CT (from structural MRI scans) in both aneuploid (28 XXX, 55 XXY, 22 XYY, 19 XXYY) and typically-developing euploid (79 XX, 85 XY) individuals. Results indicated widespread decoupling of normative anatomical-cognitive relationships in SCA: we found five regions where SCA significantly altered SA-FSIQ relationships, and five regions where SCA significantly altered CT-FSIQ relationships. The majority of areas were characterized by the presence of positive anatomy-IQ relationships in health, but no or slightly negative anatomy-IQ relationships in SCA. Disrupted anatomical-cognitive relationships generalized from the full cohort to karyotypically defined subcohorts (i.e., XX-XXX; XY-XYY; XY-XXY), demonstrating continuity across multiple supernumerary SCA conditions. As the first direct evidence of altered regional neuroanatomical-cognitive relationships in supernumerary SCA, our findings shed light on potential genetic and structural correlates of the cognitive phenotype in SCA, and may have implications for other neurogenetic disorders.

Self-reported sleep disturbances are associated with poorer cognitive performance in older adults with hypertension: a multi-parameter risk factor investigation.

OBJECTIVES: Given the evidence of multi-parameter risk factors in shaping cognitive outcomes in aging, including sleep, inflammation, cardiometabolism, and mood disorders, multidimensional investigations of their impact on cognition are warranted. We sought to determine the extent to which self-reported sleep disturbances, metabolic syndrome (MetS) factors, cellular inflammation, depressive symptomatology, and diminished physical mobility were associated with cognitive impairment and poorer cognitive performance. DESIGN: This is a cross-sectional study. SETTING: Participants with elevated, well-controlled blood pressure were recruited from the local community for a Tai Chi and healthy-aging intervention study. PARTICIPANTS: One hundred forty-five older adults (72.7 ± 7.9 years old; 66% female), 54 (37%) with evidence of cognitive impairment (CI) based on Montreal Cognitive Assessment (MoCA) score ≤24, underwent medical, psychological, and mood assessments. MEASUREMENTS: CI and cognitive domain performance were assessed using the MoCA. Univariate correlations were computed to determine relationships between risk factors and cognitive outcomes. Bootstrapped logistic regression was used to determine significant predictors of CI risk and linear regression to explore cognitive domains affected by risk factors. RESULTS: The CI group were slower on the mobility task, satisfied more MetS criteria, and reported poorer sleep than normocognitive individuals (all p < 0.05). Multivariate logistic regression indicated that sleep disturbances, but no other risk factors, predicted increased risk of evidence of CI (OR = 2.00, 95% CI: 1.26-4.87, 99% CI: 1.08-7.48). Further examination of MoCA cognitive subdomains revealed that sleep disturbances predicted poorer executive function (ß = -0.26, 95% CI: -0.51 to -0.06, 99% CI: -0.61 to -0.02), with lesser effects on visuospatial performance (ß = -0.20, 95% CI: -0.35 to -0.02, 99% CI: -0.39 to 0.03), and memory (ß = -0.29, 95% CI: -0.66 to -0.01, 99% CI: -0.76 to 0.08). CONCLUSIONS: Our results indicate that the deleterious impact of self-reported sleep disturbances on cognitive performance was prominent over other risk factors and illustrate the importance of clinician evaluation of sleep in patients with or at risk of diminished cognitive performance. Future, longitudinal studies implementing a comprehensive neuropsychological battery and objective sleep measurement are warranted to further explore these associations.

The Relationship Between Self-Regulatory Efficacy and Physical Activity in Adolescents With a Caveat: A Cross-Lag Design Examining Weather.

PURPOSE: The use of self-efficacy to predict physical activity has a long history. However, this relationship is complex, as self-efficacy is thought to influence and be influenced by physical activity. The directionality of the self-regulatory efficacy (SRE) and physical activity relationship was examined using a cross-lagged design. A secondary purpose was to examine these relationships across differing weather conditions. METHODS: Canadian adolescents (N = 337; aged between 13 and 18 years) completed the physical activity and SRE measures 4 times during a school year. Structural equation modeling was used to perform a cross-lag analysis. RESULTS: The relationships between physical activity and SRE appeared to be weather dependent. During a more challenging weather period (eg, cold weather), the relationship between physical activity and SRE was bidirectional. However, no relationship emerged when the 2 constructs were assessed during a more optimal weather period (eg, warm weather). CONCLUSIONS: Some support has been provided for the bidirectional nature of the relationship between physical activity and SRE. The relationship appeared to be qualified by climate considerations, suggesting that future research examine how weather may relate not just to physical activity but also to the correlates of physical activity.

Long-term treatment patterns of prophylactic and acute migraine medications and incidence of opioid-related adverse events in patients with migraine.

OBJECTIVES: To describe long-term treatment patterns in migraine patients initiating prophylactic therapy and to evaluate acute medication use and adverse events associated with opioids. METHODS: This study used the 2005-2014 IBM MarketScan® databases to evaluate migraine patients initiating prophylactic medication. Outcome measures included persistence with prophylactic migraine medications over 2-5 years. Acute medication use and gastrointestinal-related adverse events and opioid abuse following opioid use were evaluated. Cox proportional hazards models were used to evaluate predictors of non-persistence and predictors of gastrointestinal-related AEs and opioid abuse associated with long-term opioid use. RESULTS: In total, 147,832 patients were analyzed. Non-persistence was observed in 90% of patients; 39% switched, 30% restarted, and 31% discontinued treatment. Over the follow-up, 59.9% of patients received triptans, 66.6% non-steroidal anti-inflammatory drugs, 77.4% opioids, and 2.6% ergotamines. Among opioid users, 16.6% experienced nausea/vomiting, 12.2% had constipation, and 10.4% had diarrhea. Opioid abuse was reported in <1% of opioid users. Gastrointestinal-related adverse events increased with increasing number of days' supply of opioids. CONCLUSIONS: Non-persistence to prophylactic treatment was frequent among migraine patients. Opioid use was common in migraine patients and the risk of gastrointestinal-related adverse events and opioid abuse increased with long-term use of opioids. These results suggest a need for more effective prophylactic migraine treatments.

Copy number variations in a population with prune belly syndrome.

Prune Belly Syndrome (PBS) is a congenital multisystem myopathy with mild to lethal severity. While of uncertain etiology, 95% male predominance and familial occurrence suggest a genetic basis. As copy number variations (CNVs) can cause unexplained genetic disorders, we tested for novel CNVs in a large PBS population. We genotyped 21 unrelated PBS patients by high-resolution array comparative genomic hybridization (aCGH) and phenotyped using a novel PBS severity scoring system. Available parents were screened for detected CNV via quantitative PCR (qPCR). We additionally screened for recurrence of identified novel candidate CNVs on 106 PBS probands by qPCR. We identified 10 CNVs in 8 of 21 PBS patients tested (38%). Testing confirmed inheritance from an unaffected biological parent in six patients; parental samples were unavailable in two probands. One candidate CNV includes duplication of the X-chromosome AGTR2 gene, known to function in urinary tract development. Subsequent screening of the larger PBS cohort did not identify any recurrent CNVs. Presence of CNV did not correlate with PBS severity scoring. CNVs were uncommon in this large PBS population, but analysis of identified variants may inform disease pathogenesis and reveal targets for therapeutic intervention for this rare, severe disorder.

Differential Peripheral Inflammatory Factors Associated with Cognitive Function in Patients with Heart Failure.

OBJECTIVE: Cognitive deficits are common in patients with heart failure (HF), and can negatively affect self-care, predict rehospitalizations, and increase mortality rates 5-fold. Inflammation can produce vascular pathology, reducing cerebral blood flow to brain regions necessary for optimal cognitive function. The purpose of the investigation was to identify a pattern of peripheral blood inflammation-related biomarkers associated with cognitive impairment in patients with HF. METHODS: Forty-five outpatients (median age = 67 years, SD = 9.9) were recruited from University of California, San Diego (UCSD) and Veterans Affairs San Diego Healthcare Systems (VASDHS), diagnosed with New York Heart Association Stages I-III HF. Participants were administered the Montreal Cognitive Assessment (MoCA) as a measure of global cognitive impairment, and blood was analyzed for plasma biomarkers, interferon-γ, tumor necrosis factor-α (TNFα), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), brain-derived neurotrophic factor (BDNF), interleukin-8 (IL-8), matrix metallopeptidase-9 (MMP-9), IL-6, C-reactive protein (CRP), and serum amyloid-A (SAA). RESULTS: Almost half the patients scored below the threshold on the MoCA, indicating at least mild cognitive impairment. A factor analysis produced three biomarker factors: vascular inflammatory factor-1: TNFα, sICAM1, sVCAM1; neuroinflammatory factor-2: BDNF, MMP-9, IL-8; peripheral inflammatory factor-3: IL-6, CRP, SAA. Only vascular inflammatory factor-1 was significantly associated with cognitive function (MoCA) (ΔR2 = 0.214, beta = -0.468, p = 0.008). CONCLUSIONS: In this cohort with HF, vascular inflammation appears related to poorer cognitive function. This could indicate targets for treatment to reduce cognitive deficits in HF. However, this is a preliminary study, and further research is needed.

The influence of social identity on self-worth, commitment, and effort in school-based youth sport.

​​​The current study examined the influence of social identity for individual perceptions of self-worth, commitment, and effort in school-based youth athletes. Using a prospective research design, 303 athletes (Mage = 14.89, SD = 1.77; 133 female) from 27 sport teams completed questionnaires at 2 time points (T1 - demographics, social identity; T2 - self-worth, commitment, effort) during an athletic season. Multilevel analyses indicated that at the individual level, the social identity dimension of in-group ties (IGT) predicted commitment (b = 0.12, P = .006) and perceived effort (b = 0.14, P = .008), whereas in-group affect (IGA) predicted commitment (b = 0.25, P = .001) and self-worth (b = 2.62, P = .006). At the team level, means for IGT predicted commitment (b = 0.31, P < .001) and self-worth (b = 4.76, P = .024). Overall, social identity accounted for variance at both levels, ranging from 4% (self-worth) to 15% (commitment). Identifying with a group to a greater extent was found to predict athlete perceptions of self-worth, commitment, and effort. More specifically, at the individual level, IGT predicted commitment and effort, and IGA predicted commitment and self-worth. At the team level, IGT predicted commitment and self-worth.