Search

Objective: Recurrent deletions involving 17q12 are associated with a variety of clinical phenotypes, including congenital abnormalities of the kidney and urinary tract (CAKUT), maturity onset diabetes of the young, type 5, and neurodevelopmental disorders. Structural and/or functional renal disease is the most common phenotypic feature, although the prenatal renal phenotypes and the postnatal correlates have not been well characterized. Method: We reviewed pre‐ and postnatal medical records of 26 cases with prenatally or postnatally identified 17q12/HNF1B microdeletions (by chromosomal microarray or targeted gene sequencing), obtained through a multicenter collaboration. We specifically evaluated 17 of these cases (65%) with reported prenatal renal ultrasound findings. Results: Heterogeneous prenatal renal phenotypes were noted, most commonly renal cysts (41%, n = 7/17) and echogenic kidneys (41%), although nonspecific dysplasia, enlarged kidneys, hydronephrosis, pelvic kidney with hydroureter, and lower urinary tract obstruction were also reported. Postnatally, most individuals developed renal cysts (73%, 11/15 live births), and there were no cases of end‐stage renal disease during childhood or the follow‐up period. Conclusion: Our findings demonstrate that copy number variant analysis to assess for 17q12 microdeletion should be considered for a variety of prenatally detected renal anomalies. It is important to distinguish 17q12 microdeletion from other etiologies of CAKUT as the prognosis for renal function and presence of associated findings are distinct and may influence pregnancy and postnatal management. Key points: What is already known about this topic? Recurrent deletions involving 17q12 are associated with a variety of clinical phenotypes, including renal abnormalities.Cystic renal changes, including cystic dysplasia, are the most commonly reported association postnatally. Hyperechogenic kidneys have been associated prenatally. What does this study add? This study broadens the spectrum of prenatal renal anomalies associated with 17q12 deletions.Despite prenatal onset of renal abnormalities, we demonstrate that individuals with 17q12 deletions displayed no progression to end‐stage renal disease during the postnatal follow‐up period. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Despite their increased application, the heritability of Alzheimer's disease (AD)–related blood‐based biomarkers remains unexplored. METHODS: Plasma amyloid beta 40 (Aβ40), Aβ42, the Aβ42/40 ratio, total tau (t‐tau), and neurofilament light (NfL) data came from 1035 men 60 to 73 years of age (μ = 67.0, SD = 2.6). Twin models were used to calculate heritability and the genetic and environmental correlations between them. RESULTS: Additive genetics explained 44% to 52% of Aβ42, Aβ40, t‐tau, and NfL. The Aβ42/40 ratio was not heritable. Aβ40 and Aβ42 were genetically near identical (rg = 0.94). Both Aβ40 and Aβ42 were genetically correlated with NfL (rg = 0.35 to 0.38), but genetically unrelated to t‐tau. DISCUSSION: Except for Aβ42/40, plasma biomarkers are heritable. Aβ40 and Aβ42 share mostly the same genetic influences, whereas genetic influences on plasma t‐tau and NfL are largely unique in early old‐age men. The absence of genetic associations between the Aβs and t‐tau is not consistent with the amyloid cascade hypothesis. [ABSTRACT FROM AUTHOR]

Background: Disparities in emergency department (ED) care based on race and ethnicity have been demonstrated. Patient perceptions of emergency care can have broad impacts, including poor health outcomes. Our objective was to measure and explore patient experiences of microaggressions and discrimination during ED care. Methods: This mixed‐methods study of adult patients from two urban academic EDs integrates quantitative discrimination measures and semistructured interviews of discrimination experiences during ED care. Participants completed demographic questionnaires and the Discrimination in Medical Settings (DMS) scale and were invited for a follow‐up interview. Transcripts of recorded interviews were analyzed leveraging conventional content analysis with line‐by‐line coding for thematic descriptions. Results: The cohort included 52 participants, with 30 completing the interview. Nearly half the participants were Black (n = 24, 46.1%) and half were male (n = 26, 50%). "No" or "rare" experiences of discrimination during the ED visit were reported by 22/48 (46%), some/moderate discrimination by 19/48 (39%), and significant discrimination in 7/48 (15%). Five main themes were found: (1) clinician behaviors—communication and empathy, (2) emotional response to health care team actions, (3) perceived reasons for discrimination, (4) environmental pressures in the ED, and (5) patients are hesitant to complain. We found an emergent concept where persons with moderate/high DMS scores, in discussing instances of discrimination, frequently reflected on previous health care experiences rather than on their current ED visit. Conclusions: Patients attributed microaggressions to many factors beyond race and gender, including age, socioeconomic status, and environmental pressures in the ED. Of those who endorsed moderate to significant discrimination via survey response during their recent ED visit, most described historical experiences of discrimination during their interview. Previous experiences of discrimination may have lasting effects on patient perceptions of current health care. System and clinician investment in patient rapport and satisfaction is important to prevent negative expectations for future encounters and counteract those already in place. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Long‐term blood pressure (BP) measures, such as visit‐to‐visit BP variability (BPV) and cumulative BP, are strong indicators of cardiovascular risks. This study modeled up to 20 years of BP patterns representative of midlife by using BPV and cumulative BP, then examined their associations with development of dementia in later life. METHODS: For 3201 individuals from the Framingham Heart Study, multivariate logistic regression analyses were performed to examine the association between long‐term BP patterns during midlife and the development of dementia (ages ≥ 65). RESULTS: After adjusting for covariates, every quartile increase in midlife cumulative BP was associated with a sequential increase in the risk of developing dementia (e.g., highest quartile of cumulative systolic blood pressure had approximately 2.5‐fold increased risk of all‐cause dementia). BPV was not significantly associated with dementia. DISCUSSION: Findings suggest that cumulative BP over the course of midlife predicts risk of dementia in later life. HIGHLIGHTS: Long‐term blood pressure (BP) patterns are strong indicators of vascular risks.Cumulative BP and BP variability (BPV) were used to reflect BP patterns across midlife.High cumulative BP in midlife is associated with increased dementia risk.Visit‐to‐visit BPV was not associated with the onset of dementia. [ABSTRACT FROM AUTHOR]

Youth mentoring may be able to support lonely and socially isolated youth. This study examined the association between participating in youth mentoring programs and mentee perception of social acceptance from peers. Regression models considered the association between mentoring and peer social acceptance in terms of demographics, program features, and baseline peer relationship quality for 693 youth from 27 mentoring programs. The construct validity of a social acceptance scale was explored. The scale suggested two factors of peer social acceptance. No significant changes in peer social acceptance were observed before and after participating in mentoring programs. Trends in social acceptance indicated that positive/negative feelings in the mentor−mentee relationship were associated with positive/negative indicators of peer social acceptance. Mentoring programs may be able to help prevent loneliness and social isolation through positive aspects of the mentor−mentee relationships, but additional intervention activities are likely necessary to support lonely and socially isolated youth. [ABSTRACT FROM AUTHOR]

Background: Frailty refers to a person's physical and functional capabilities and increases during aging. Abnormal white matter (AWM; e.g., hyperintensities on T2‐weighted MRI) is a neuroimaging marker of small‐vessel vascular disease associated with increased risk of Alzheimer's Disease and related dementias. While some studies have found associations between frailty indices (FIs) and global AWM, their association with accumulation of regional AWM and any related cognitive correlates is understudied. Method: 342 men from the Vietnam Era Twin Study of Aging with frailty measured at study baseline (mean age = 56.4) and structural MRI scans at follow‐up (mean 5.5 years later) were included (Table 1). The FI measure was based on a cumulative deficit model[1] using an index of 37 health‐ and function‐related items. Global AWM was defined using morphological operators on multi‐channel, three‐class tissue segmentation[2]. A novel watershed routine, applied to our AWM frequency atlas, generated 5 distinct AWM parcellations: frontal, posterior, anterior periventricular, deep, and temporal stem (Figure 1A). Cognitive factor scores (memory, processing speed, executive function, fluency) were derived from normative neuropsychological test performance. Result: Mixed‐effects linear regression models controlling for age, years of education and twin‐pair demonstrated that higher baseline FI was associated with greater future AWM volume in temporal stem (p = 0.03) and anterior periventricular (p = 0.02) regions, but not for global or other parcellations (Figure 1B). Baseline FI was not cross‐sectionally associated with any cognitive factor score but was associated longitudinally with decreased processing speed (p = 0.002) (Table 2). Conclusion: Higher cumulative frailty in late‐middle aged men was associated with greater future AWM burden and greater decline in processing speed. These findings suggest that cumulative frailty during the 6th decade is a relevant indicator and possible predictor of future pathological structural and functional processes in the brain. Longitudinal studies may elucidate whether frailty affects AWM progression and cognitive decline along a common causal pathway. References: [1] Rockwood K. A global clinical measure of fitness and frailty in elderly people. Canadian Medical Association Journal 2005;173:489‐95. [2] Fennema‐Notestine C, et al. White matter disease in midlife is heritable, related to hypertension, and shares some genetic influence with systolic blood pressure. NeuroImage: Clinical 2016;12:737‐45. [ABSTRACT FROM AUTHOR]

Genetics are presumed to contribute 30–40% to opioid use disorder (OUD), allowing for the possibility that genetic markers could be used to identify personal risk for developing OUD. We aimed to test the potential association among 180 candidate single nucleotide polymorphisms (SNPs), 120 of which were related to the dopamine reward pathway and 60 related to pharmacokinetics. Participants were randomly recruited in 2020–2021 in a cross‐sectional genetic association study. Self‐reported health history including Diagnostic and Statistical Manual of Mental Disorders (DSM‐5) OUD criteria and buccal swabs were collected. A total of 1,301 participants were included in the analyses for this study. Of included participants, 250 met the DSM‐5 criteria for ever having OUD. Logistic regression, adjusting for age and biologic sex, was used to characterize the association between each SNP and DSM‐5 criteria consistent with OUD. Six SNPs found in four genes were associated with OUD: increased odds with CYP3A5 (rs15524 and rs776746) and DRD3 (rs324029 and rs2654754), and decreased odds with CYP3A4 (rs2740574) and CYP1A2 (rs2069514). Homozygotic CYP3A5 (rs15524 and rs776746) had the highest adjusted odds ratio of 2.812 (95% confidence interval (CI) 1.737, 4.798) and 2.495 (95% CI 1.670, 3.835), respectively. Variants within the dopamine reward and opioid metabolism pathways have significant positive (DRD3 and CYP3A5) and negative (CYP3A4 and CYP1A2) associations with OUD. Identification of these variants provides promising possibilities for genetic prognostic and therapeutic targets for future investigation. [ABSTRACT FROM AUTHOR]

The current study aims to apply a staged approach to document heterogeneity in discussions in mentoring relationships, chiefly, discussion topics from weekly mentoring sessions with undergraduate women mentors (n = 40), then link each of the eight topics (relationships with friends, family, teachers, and romantic relationships, as well as goals, academic skills, academic problems, and hopes for the future) to developmental outcomes for middle school girls (n = 41) who participated in a school‐based mentoring program. In doing so, the authors hope to better understand the mechanisms that influence variability in mentoring treatment effects. Mentoring dyads engaged in unstructured one‐on‐one sessions and structured group meetings across the 2018−2019 academic year. The primary predictors for this study are weekly mentor‐reported discussion topics and activities addressed during unstructured one‐on‐one mentoring sessions, with 11 social‐emotional, academic, and behavioral outcomes measured via pre‐ and postsurveys administered by research assistants to mentees during the fall and spring. A series of 11 path analyses indicate small to moderate associations, both beneficial and negative, between key discussion topics, such as hopes for the future, family relationships, and goals, and several mentee‐reported outcomes of interest at the end of the intervention, including extrinsic motivation, life satisfaction, and self‐esteem. Study findings provide information about heterogeneity in mentoring practices to inform how various mechanisms of mentoring (e.g., discussions focused on relationships, goals and skills, and strengths) influence developmentally‐relevant effects for youth. [ABSTRACT FROM AUTHOR]

We examined data from a nationally implemented mentoring program over a 4‐year period, to identify demographic and relationship characteristics associated with premature termination. Data were drawn from a sample of 82,224 mentor and mentees. We found matches who reported shared racial or ethnic identities were associated with lower likelihood of premature termination as was mentee's positive feelings of the relationship. We also found that, if data were used as a screening tool, the data were suboptimal for accuracy classifying premature closure with sensitivity and specificity values equal to 0.43 and 0.75. As programs and policymakers consider ways to improve the impact of mentoring programs, these results suggest programs consider the types of data being collected to improve impact of care. Highlights: Mentors and mentees sharing racial identity had a lower risk of premature termination.The quality of the mentoring relationship was, on average, associated with premature termination.The quality of an individual mentoring relationship did not predict premature termination. [ABSTRACT FROM AUTHOR]

Loeys–Dietz syndrome (LDS) is a connective tissue disorder that commonly results in a dilated aorta, aneurysms, joint laxity, craniosynostosis, and soft skin that bruises easily. Neurodevelopmental abnormalities are uncommon in LDS. Two previous reports present a total of four patients with LDS due to pure 1q41 deletions involving TGFB2 (Gaspar et al., American Journal of Medical Genetics Part A, 2017, 173, 2289–2292; Lindsay et al., Nature Genetics, 2012, 44, 922–927). The current report describes an additional five patients with similar deletions. Seven of the nine patients present with some degree of hypotonia and gross motor delay, and three of the nine present with speech delay and/or intellectual disability (ID). The smallest deletion common to all patients is a 785 kb locus that contains two genes: RRP15 and TGFB2. Previous studies report that TGFB2 knockout mice exhibit severe perinatal anomalies (Sanford et al., Development, 1997, 124, 2659–2670) and TGFB2 is expressed in the embryonic mouse hindbrain floor (Chleilat et al., Frontiers in Cellular Neuroscience, 2019, 13). The deletion of TGFB2 may be associated with a neurodevelopmental phenotype with incomplete penetrance and variable expression. [ABSTRACT FROM AUTHOR]

Chromosomal aneuploidies, microduplications and microdeletions are the most common confirmed genetic causes of spina bifida. Microduplications of Xq27 containing the SOX3 gene have been reported in 11 cases, confirming the existence of an X‐chromosomal locus for spina bifida. A three generation kindred reported here with a SOX3 duplication has been identified in one of 17 kindreds with recurrences in the 29 years of the South Carolina Neural Tube Defect Prevention Program. Other recurrences during this time period included siblings with an APAF1 mutation, siblings with a CASP9 mutation, siblings with a microdeletion of 13q, and two sets of siblings with Meckel syndrome who did not have genetic/genomic studies performed. [ABSTRACT FROM AUTHOR]

Introduction: Practice effects (PEs) on cognitive tests obscure decline, thereby delaying detection of mild cognitive impairment (MCI). Importantly, PEs may be present even when there are performance declines, if scores would have been even lower without prior test exposure. We assessed how accounting for PEs using a replacementparticipants method impacts incidentMCI diagnosis. Methods: Of 889 baseline cognitively normal (CN) Alzheimer's Disease Neuroimaging Initiative (ADNI) participants, 722 returned 1 year later (mean age = 74.9 ± 6.8 at baseline). The scores of test-naïve demographically matched "replacement" participants who took tests for the first time were compared to returnee scores at follow-up. PEs--calculated as the difference between returnee follow-up scores and replacement participants scores--were subtracted from follow-up scores of returnees. PE-adjusted cognitive scoreswere then used to determine if individuals were below the impairment threshold for MCI. Cerebrospinal fluid amyloid beta, phosphorylated tau, and total tau were used for criterion validation. In addition, based on screening and recruitment numbers from a clinical trial of amyloid-positive individuals, we estimated the effect of earlier detection of MCI by accounting for cognitive PEs on a hypothetical clinical trial in which the key outcome was progression to MCI. Results: In the ADNI sample, PE-adjusted scores increased MCI incidence by 19% (P < .001), increased proportion of amyloid-positive MCI cases (+12%), and reduced proportion of amyloid-positive CNs (-5%; P's < .04). Additional calculations showed that the earlier detection and increasedMCI incidencewould also substantially reduce necessary sample size and study duration for a clinical trial of progression to MCI. Cost savings were estimated at ≈$5.41 million. Discussion: Detecting MCI as early as possible is of obvious importance. Accounting for cognitive PEs with the replacement-participants method leads to earlier detection of MCI, improved diagnostic accuracy, and can lead to multi-million-dollar cost reductions for clinical trials. [ABSTRACT FROM AUTHOR]

The proposed study integrates quantitative and qualitative approaches to examine mentors with different relationship trajectories reflect on their relationships. Using quantitative and qualitative methods, mentor reports of relationship quality are plotted over time and different growth patterns identified: (1) progressive, (2) stable‐high, (3) dip and recovery, (4) stable‐low, and (5) regressive. Qualitative coding was used to identify patterns in mentors' descriptions of their relationship experiences—including both what mentors wrote about and how they wrote about it. [ABSTRACT FROM AUTHOR]

Maternal relationship characteristics have been found to impact academic and behavioral outcomes for youth. However, less is known about how and through what mechanisms these characteristics impact outcomes for mentored youth. In this study, we examined if mentoring relationship quality mediated the relations between maternal relationship characteristics and academic and behavioral outcomes targeted by mentoring programs. Data were drawn from 205 participants who participated in a mentoring program that pairs adolescent girls with college women mentors for 1 year of mentoring. Mentoring relationship quality was the hypothesized mechanism of change and was included in the analysis as a mediator. Results revealed that maternal relationship characteristics (i.e., maternal quality communication/trust and maternal alienation) were directly related to academic and behavioral outcomes of mentoring. The relationship between maternal relationship characteristics and behavioral outcomes was mediated by mentoring relationship quality. Results suggested that girls with stronger maternal quality communication and trust as well as girls who felt more alienated from their mothers may benefit more from mentoring. Results can be used to inform mentor training to include a focus on relationship development with girls experiencing a variety of relational difficulties with their mothers to help improve targeted mentoring outcomes. [ABSTRACT FROM AUTHOR]

CSNK2B has recently been implicated as a disease gene for neurodevelopmental disability (NDD) and epilepsy. Information about developmental outcomes has been limited by the young age and short follow‐up for many of the previously reported cases, and further delineation of the spectrum of associated phenotypes is needed. We present 25 new patients with variants in CSNK2B and refine the associated NDD and epilepsy phenotypes. CSNK2B variants were identified by research or clinical exome sequencing, and investigators from different centers were connected via GeneMatcher. Most individuals had developmental delay and generalized epilepsy with onset in the first 2 years. However, we found a broad spectrum of phenotypic severity, ranging from early normal development with pharmacoresponsive seizures to profound intellectual disability with intractable epilepsy and recurrent refractory status epilepticus. These findings suggest that CSNK2B should be considered in the diagnostic evaluation of patients with a broad range of NDD with treatable or intractable seizures. [ABSTRACT FROM AUTHOR]

Background: Predicted brain age difference (PBAD) scores are novel metrics which compare chronological age to age predicted from neuroimaging data. PBADs are highly relevant to Alzheimer's disease (AD) and cognitive aging. Individuals with AD have predicted brain ages about 10 years older than their chronological age (Franke et al. 2010). Less is known about PBADs in midlife, but recent work on the sample studied here has demonstrated that PBADs are highly heritable (59‐75%), highly stable between middle‐ and early‐old age, and moderated by modifiable lifestyle behaviors earlier in midlife (age 40). The current study examined how midlife PBAD (mean age 56) predicted executive functions concurrently and longitudinally into early old age (mean age 68). Method: We examined 779 non‐demented men in the Vietnam Era Twin Study of Aging (VETSA) who completed cognitive and neuroimaging assessments at up to three assessments (M = 56, 62, and 68 years). PBADs were based on two methods (Liem et al., 2017, Cole et al. 2019) which include information about grey matter or both gray and white matter. Executive function was based on six tasks spanning inhibition, shifting and working memory. Analyses controlled for age, diabetes, hypertension, and APOE‐ε4 dosage. Result: Latent growth models revealed that greater PBAD at age 56 (i.e., greater brain age than chronological age) was associated with worse executive functioning at baseline and greater decline in executive functioning over the following 12 years. The latter association was observed only for PBADs that included white matter (Cole et al., 2019) and persisted even when excluding N = 61 individuals with amnestic mild cognitive impairment (MCI). Subsequent analyses indicated that associations were not moderated by APOE allele status or cognitive reserve (general cognitive ability at mean age 20). Conclusion: Our findings indicate that PBAD is associated with executive functioning in midlife and predicts executive function changes into early old age. They also suggest that PBADs capturing more information about brain health are better predictors of executive function decline across midlife into early‐old age. Finally, the persistence of these effects within cognitively normal subjects suggests PBADs are important predictors of cognitive decline before the onset of MCI/AD. [ABSTRACT FROM AUTHOR]

Mentoring, a common support practice for middle schoolers, can have varying effects on student academic and behavioral outcomes depending on the type of mentoring and quality of relationship formed. Although research has examined mentees' perception of relationship quality in mentoring relationships, fewer studies have looked at both mentor and mentee reports. The present study aims to explore how the interaction of mentor and mentee perceptions of the relationship quality is associated with student academic and behavioral outcomes. Major findings include the significant association between mentor‐reported relationship quality and academic outcomes for mentees, as well as some associations mentee‐ and mentor‐reported relationship quality and behavioral outcomes. Results illustrate the importance of training in mentoring programs, as well as how mentee‐ versus mentor‐report of the relationship may impact outcomes in distinct ways. This study can improve understanding of mentor–mentee relationships, which may improve student academic and behavioral outcomes. [ABSTRACT FROM AUTHOR]

Clinical development of combination chemotherapies for tuberculosis (TB) is complicated by partial or restricted phase II dose‐finding. Barriers include a propensity for drug resistance with monotherapy, practical limits on numbers of treatment arms for component dose combinations, and limited application of current dose selection methods to multidrug regimens. A multi‐objective optimization approach to dose selection was developed as a conceptual and computational framework for currently evolving approaches to clinical testing of novel TB regimens. Pharmacokinetic‐pharmacodynamic (PK‐PD) modeling was combined with an evolutionary algorithm to identify dosage regimens that yield optimal trade‐offs between multiple conflicting therapeutic objectives. The phase IIa studies for pretomanid, a newly approved nitroimidazole for specific cases of highly drug‐resistant pulmonary TB, were used to demonstrate the approach with Pareto optimized dosing that best minimized sputum bacillary load and the probability of drug‐related adverse events. Results include a population‐typical characterization of the recommended 200 mg once daily dosage, the optimality of time‐dependent dosing, examples of individualized therapy, and the determination of optimal loading doses. The approach generalizes conventional PK‐PD target attainment to a design problem that scales to drug combinations, and provides a benefit‐risk context for clinical testing of complex drug regimens. [ABSTRACT FROM AUTHOR]

Conservation of rare or threatened species requires a range of information, including a sound taxonomic foundation, to ensure appropriate management. However, rare species are often known from a limited number of specimens, and that can hinder taxonomic understanding. Seringia exastia and S. katatona are two conservation‐listed taxa that were poorly known in the remote Kimberley region of northern Western Australia. Recent surveys discovered additional populations of both species but also revealed extensive morphological variation that obscured the boundary between the two species and a third, more widespread species, S. nephrosperma. We applied genomic data (>5000 SNP loci) to investigate species boundaries and hybridisation within this group. We found unequivocal evidence that S. katatona is a hybrid between S. exastia and S. nephrosperma, which is consistent with its intermediate morphology in diagnostic characters between the two highly divergent parents. Unexpectedly, we also uncovered a lack of genome‐wide differentiation and polyphyly between S. exastia and an intended outgroup taxon, S. elliptica. These results have significant taxonomic implications, for which reason we present a revised taxonomic treatment that shows S. katatona to be a nothospecies, S. ×katatona, and synonymises S. elliptica under S. exastia, the oldest effectively published name. These taxonomic revisions present new information that will enable reconsideration of the current conservation status of these taxa and inform their management in northern Western Australia. [ABSTRACT FROM AUTHOR]

In the United States, the demand for child mental health services is increasing, while the supply is limited by workforce shortages. These shortages are unlikely to be corrected without significant structural changes in how mental health services are provided. One strategy for bridging this gap is task‐shifting, defined as a process by which services that are typically delivered by professionals are moved to individuals with less extensive qualifications or training. Although task‐shifting can increase the size of the workforce, there are challenges related to training new workers. In this paper, we propose Just‐In‐Time Training (JITT) as one strategy for improving task‐shifting efforts. We define JITT as on‐demand training experiences that only include what is necessary, when it is necessary, to promote competent service delivery. We offer a proof of concept from our own work shifting counseling and academic support tasks from school mental health professionals to pre‐baccalaureate mentors, citing lessons learned during our iterative process of JITT development. We conclude with a series of key considerations for scaling up the pairing of task‐shifting and JITT, including expanding the science of JITT and anticipating how task‐shifting and JITT would work within the context of dynamic mental health service systems. Highlights: Task‐shifting refers to redistributing tasks from professionals to workers who have less training.Task‐shifting may be a key strategy in expanding child services in low resource communities.Just‐in‐Time Training (JITT) refers to efficient, on‐demand training experiences.JITT may strengthen task‐shifting efforts.Task‐shifting and JITT involve unique ethical considerations. [ABSTRACT FROM AUTHOR]

We tested the hypothesis of school satisfaction being an antecedent to social coping behaviors in early adolescents (N = 892) using a two‐wave cross‐lagged panel design. We also explored the possible bidirectional relations between school satisfaction and social coping behaviors. Four types of social coping behaviors in peer conflict contexts included social support seeking, self‐reliance, internalizing behaviors, and externalizing behaviors. The findings showed that school satisfaction significantly predicted three of the four coping behaviors (social support seeking, self‐reliance, and externalizing behaviors) in the expected directions. Among all the social coping behaviors, only social support seeking significantly predicted school satisfaction over time. Taken together, the results suggest that school satisfaction may be an antecedent that predicts most social coping behaviors in early adolescents. Furthermore, the relations between social support seeking coping and school satisfaction appeared to be reciprocal. Implications, especially the importance of monitoring students' school satisfaction, are discussed. [ABSTRACT FROM AUTHOR]

The human hippocampus can be subdivided into subfields with unique functional properties and differential vulnerability to disease or neuropsychiatric conditions. Identifying genes that confer susceptibility to such processes is an important goal in developing treatments. Recent advances in automatic subfield segmentation from magnetic resonance images make it possible to use these measures as phenotypes in large‐scale genome‐wide association studies. Such analyses are likely to rely largely on standard resolution (~1 mm isotropic) T1‐weighted images acquired on 3.0T scanners. Determining whether the genetic architecture of subfields can be detected from such images is therefore an important step. We used Freesurfer v6.0 to segment hippocampal subfields in two large twin studies, the Vietnam Era Twin Study of Aging and the Human Connectome Project. We estimated heritability of subfields and the genetic overlap with total hippocampal volume. Heritability was similar across samples, but little genetic variance remained after accounting for genetic influences on total hippocampal volume. Importantly, we examined genetic relationships between subfields to determine whether subfields can be grouped based on a smaller number of underlying, genetically independent factors. We identified three genetic factors in both samples, but the high degree of cross loadings precluded formation of genetically distinct groupings of subfields. These results confirm the reliability of Freesurfer v6.0 generated subfields across samples for phenotypic analyses. However, the current results suggest that it will be difficult for large‐scale genetic analyses to identify subfield‐specific genes that are distinct from both total hippocampal volume and other subfields using segmentations generated from standard resolution T1‐weighted images. [ABSTRACT FROM AUTHOR]

School‐based mentoring programs are popular prevention programs thought to influence youth development; but rigorous evaluations indicate that these programs often have small effects on youth outcomes. Researchers suggest that these findings may be explained by (a) mentors and mentees failing to develop a close relationship and (b) mentors not setting goals or focusing on specific skills necessary improve outcomes. We assessed these explanations using data from approximately 1360 mentor and mentee pairs collected through a national study of school‐based mentoring (called, "The Student Mentoring Program"). Specifically, we tested the influence of mentee‐reported relationship quality and mentor‐reported use of goal‐setting and feedback‐oriented activities on academic, behavioral, and social‐emotional outcomes. Results suggested that youth reported relationship quality was associated with small to medium effects on outcomes. Moreover, goal‐setting and feedback‐oriented activities were associated with moderate to large effects on outcomes. We also found significant interactions between relationship quality and goal‐setting and feedback‐oriented activities on youth outcomes. We conclude that there appears to be a "sweet‐spot" wherein youth outcomes are maximized. The results of this study suggest a need for school‐based mentoring programs to monitor and support mentors in developing a close relationship while also providing opportunities to set goals and receive feedback. Highlights: When mentors set goals and give feedback to mentees, youth experience better outcomes.When youth report a good relationship with their mentor, youth experience better outcomes.However, mentors maximize impact when they have a good relationship, set goals, and give feedback. [ABSTRACT FROM AUTHOR]

Abstract: Background and aims: Disentangling the putative impact of cannabis on brain morphology from other comorbid substance use is critical. After controlling for the effects of nicotine, alcohol and multi‐substance use, this study aimed to determine whether frequent cannabis use is associated with significantly smaller subcortical grey matter volumes. Design: Exploratory analyses using mixed linear models, one per region of interest (ROI), were performed whereby individual differences in volume (outcome) at seven subcortical ROIs were regressed onto cannabis and comorbid substance use (predictors). Setting: Two large population‐based twin samples from the United States and Australia. Participants: A total of 622 young Australian adults [66% female; μage = 25.9, standard deviation SD) = 3.6] and 474 middle‐aged US males (μage = 56.1SD = 2.6) of predominately Anglo‐Saxon ancestry with complete substance use and imaging data. Subjects with a history of stroke or traumatic brain injury were excluded. Measurements: Magnetic resonance imaging (MRI) and volumetric segmentation methods were used to estimate volume in seven subcortical ROIs: thalamus, caudate nucleus, putamen, pallidum, hippocampus, amygdala and nucleus accumbens. Substance use measurements included maximum nicotine and alcohol use, total life‐time multi‐substance use, maximum cannabis use in the young adults and regular cannabis use in the middle‐aged males. Findings: After correcting for multiple testing (P = 0.007), cannabis use was unrelated to any subcortical ROI. However, maximum nicotine use was associated with significantly smaller thalamus volumes in middle‐aged males. Conclusions: In exploratory analyses based on young adult and middle‐aged samples, normal variation in cannabis use is unrelated statistically to individual differences in brain morphology as measured by subcortical volume. [ABSTRACT FROM AUTHOR]

Abstract: Identifying cheap, yet effective, oxygen evolution catalysts is critical to the advancement of water splitting. Using liquid exfoliated Co(OH)2 nanosheets as a model system, a simple procedure is developed to maximize the activity of any oxygen evolution reaction nanocatalyst. First the nanosheet edges are confirmed as the active areas by analyzing the catalytic activity as a function of nanosheet size. This allows the authors to select the smallest nanosheets (length ≈50 nm) as the best performing catalysts. While the number of active sites per unit electrode area can be increased via the electrode thickness, this is found to be impossible beyond ≈10 µm due to mechanical instabilities. However, adding carbon nanotubes increases both toughness and conductivity significantly. These enhancements mean that composite electrodes consisting of small Co(OH)2 nanosheets and 10 wt% nanotubes can be made into freestanding films with thickness of up to 120 µm with no apparent electrical limitations. The presence of diffusion limitations results in an optimum electrode thickness of 70 µm, yielding a current density of 50 mA cm−2 at an overpotential of 235 mV, close to the state of the art in the field. Applying this procedure to a high‐performance catalyst such as NiFeOx should significantly surpass the state of the art. [ABSTRACT FROM AUTHOR]

Abstract: Two basic neuroimaging‐based characterizations of white matter tracts are the magnitude of water diffusion along the principal tract orientation (axial diffusivity, AD) and water diffusion perpendicular to the principal orientation (radial diffusivity, RD). It is generally accepted that decreases in AD reflect disorganization, damage, or loss of axons, whereas increases in RD are indicative of disruptions to the myelin sheath. Previous reports have detailed the heritability of individual AD and RD measures, but have not examined the extent to which the same or different genetic or environmental factors influence these two phenotypes (except for corpus callosum). We implemented bivariate twin analyses to examine the shared and independent genetic influences on AD and RD. In the Vietnam Era Twin Study of Aging, 393 men (mean age = 61.8 years, SD = 2.6) underwent diffusion‐weighted magnetic resonance imaging. We derived fractional anisotropy (FA), mean diffusivity (MD), AD, and RD estimates for 11 major bilateral white matter tracts and the mid‐hemispheric corpus callosum, forceps major, and forceps minor. Separately, AD and RD were each highly heritable. In about three‐quarters of the tracts, genetic correlations between AD and RD were >.50 (median = .67) and showed both unique and common variance. Genetic variance of FA and MD were predominately explained by RD over AD. These findings are important for informing genetic association studies of axonal coherence/damage and myelination/demyelination. Thus, genetic studies would benefit from examining the shared and unique contributions of AD and RD. [ABSTRACT FROM AUTHOR]

Background: Composite scores of MRI‐based brain regions associated with Alzheimer's disease (AD) pathology, commonly termed 'AD signatures,' are tools developed to identify brain changes specific to mild AD. In recent work from our group, we found that a novel diffusion‐based cortical mean diffusivity (MD) signature among cognitively normal adults in their 50s aided prediction of 12‐year progression to MCI beyond age and polygenic risk for AD. Results held up after accounting for general brain age. In contrast, a cortical thickness/hippocampal volume‐based signature did not improve prediction. Given the importance of genetic influences on brain structure and AD, here we examined the phenotypic and genetic relationships among diffusion and structural AD signatures and brain age, and how those relationships change across midlife and early old age. Method: Our validated thickness/volume signature, novel MD signature, and a validated brain age measure were used in biometrical twin analyses to examine phenotypic, genetic, and environmental relationships both cross‐sectionally and longitudinally across 12 years. Participants were 736 men from three waves of the Vietnam Era Twin Study of Aging (VETSA; baseline age=56.1, SD=2.6, range=51.1‐60.2). Subsequent waves were at approximately 5.7‐year intervals. Result: Both AD signatures and brain age are heritable (56%‐72%), but each signature captured unique phenotypic and genetic variance that is also not explained by general brain aging. Genetic correlations across time within each signature were high (0.77‐0.98). Baseline MD signatures (age=56 years) predicted thickness/volume signatures over a decade later (r= ‐0.53, 95% CI: ‐0.62, ‐0.42), but baseline thickness/volume signatures showed a significantly weaker relationship with future MD signatures (r= ‐0.13, 95% CI: ‐0.24, ‐0.01). Interestingly, by wave 2 (average age=62 years), the thickness/volume signature appears to have caught up with the MD signature in terms of predictive ability. Conclusion: Findings lend further support to the idea that a signature based on brain microstructure captures very early AD‐related changes that are later reflected in the macrostructural signature. This MD signature explains substantial genetic variance that is consistent throughout midlife and into early old age, supporting the utility of the MD signature as a very early AD‐related neuroimaging biomarker and its potential role in clinical trials. [ABSTRACT FROM AUTHOR]

Background: Cortical surface area, cortical thickness, and hippocampal volume are well‐studied in relation to later life cognitive impairments and AD. Fewer studies have investigated how white mater microstructure relates to cognition in late life. Existing work has focused on fractional anisotropy (FA) and mean diffusivity (MD) measures that are thought to capture demyelination and axonal degradation and relate to cognitive decline in normal aging and AD. However, these measures are susceptible to partial volume effects. Here, we evaluated whether executive function and memory are associated with FA and MD after deploying a free‐water (FW) elimination post‐processing method that separates fluid (FW) from tissue (FW‐corrected FA and MD). Method: We examined 489 non‐demented men in the Vietnam Era Twin Study of Aging (VETSA) at mean age 68. Executive function was based on 6 tasks spanning inhibition, shifting, and working memory. Memory was based on 7 subtests from the Logical Memory, Visual Reproductions, and California Verbal Learning tests. Analyses focused on 11 cortical white matter tracts across three metrics: FW, FW‐corrected FA, and FW‐corrected MD. Analyses controlled for age, scanner, diabetes, hypertension, race, and ethnicity. We used false discovery rate to account for multiple testing. Result: Better executive functioning was associated with lower FW across all 11 tracts. Better memory was associated with lower FW in 3 tracts: the superior longitudinal fasciculus (SLF) and two sections of the inferior frontal gyrus (opercularis and triangularis). Despite widespread differences with FW, there was only one significant association with intracellular metrics (executive function and FW‐corrected FA in the SLF). Finally, indicators of cognitive reserve (education or general cognitive ability assessed in early adulthood) did not moderate these associations between cognition and white matter microstructure. Conclusion: Our findings leveraged a post‐processing method that separates extracellular fluid (FW) from intracellular tissue (FA, MD). We found that cognitive abilities in early old age are associated primarily with extracellular white matter microstructure (FW), which demonstrated global associations with executive function. Finally, there was no evidence that indicators of cognitive reserve influenced the strength of the association between cognition and white matter, at least in this sample of non‐demented men. [ABSTRACT FROM AUTHOR]

Abstract: Computer simulation is a highly advantageous method for understanding and improving health care operations with a wide variety of possible applications. Most computer simulation studies in emergency medicine have sought to improve allocation of resources to meet demand or to assess the impact of hospital and other system policies on emergency department (ED) throughput. These models have enabled essential discoveries that can be used to improve the general structure and functioning of EDs. Theoretically, computer simulation could also be used to examine the impact of adding or modifying specific provider tasks. Doing so involves a number of unique considerations, particularly in the complex environment of acute care settings. In this paper, we describe conceptual advances and lessons learned during the design, parameterization, and validation of a computer simulation model constructed to evaluate changes in ED provider activity. We illustrate these concepts using examples from a study focused on the operational effects of HIV screening implementation in the ED. Presentation of our experience should emphasize the potential for application of computer simulation to study changes in health care provider activity and facilitate the progress of future investigators in this field. [ABSTRACT FROM AUTHOR]

Abstract: In 2017, Academic Emergency Medicine convened a consensus conference entitled, “Catalyzing System Change through Health Care Simulation: Systems, Competency, and Outcomes.” This article, a product of the breakout session on “understanding complex interactions through systems modeling,” explores the role that computer simulation modeling can and should play in research and development of emergency care delivery systems. This article discusses areas central to the use of computer simulation modeling in emergency care research. The four central approaches to computer simulation modeling are described (Monte Carlo simulation, system dynamics modeling, discrete‐event simulation, and agent‐based simulation), along with problems amenable to their use and relevant examples to emergency care. Also discussed is an introduction to available software modeling platforms and how to explore their use for research, along with a research agenda for computer simulation modeling. Through this article, our goal is to enhance adoption of computer simulation, a set of methods that hold great promise in addressing emergency care organization and design challenges. [ABSTRACT FROM AUTHOR]

Increased mean diffusivity (MD) is hypothesized to reflect tissue degeneration and may provide subtle indicators of neuropathology as well as age-related brain changes in the absence of volumetric differences. Our aim was to determine the degree to which genetic and environmental variation in subcortical MD is distinct from variation in subcortical volume. Data were derived from a sample of 387 male twins (83 MZ twin pairs, 55 DZ twin pairs, and 111 incomplete twin pairs) who were MRI scanned as part of the Vietnam Era Twin Study of Aging. Quantitative estimates of MD and volume for 7 subcortical regions were obtained: thalamus, caudate nucleus, putamen, pallidum, hippocampus, amygdala, and nucleus accumbens. After adjusting for covariates, bivariate twin models were fitted to estimate the size and significance of phenotypic, genotypic, and environmental correlations between MD and volume at each subcortical region. With the exception of the amygdala, familial aggregation in MD was entirely explained by additive genetic factors across all subcortical regions with estimates ranging from 46 to 84%. Based on bivariate twin modeling, variation in subcortical MD appears to be both genetically and environmentally unrelated to individual differences in subcortical volume. Therefore, subcortical MD may be an alternative biomarker of brain morphology for complex traits worthy of future investigation. Hum Brain Mapp 38:2589-2598, 2017. © 2017 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Objective: This study examined patterns of change in adiposity across four decades starting in young adulthood as well as associations between change and midlife cardiometabolic outcomes.Methods: BMI was assessed at ages 20, 40, 56, and 62 years in 977 male veterans from the Vietnam Era Twin Study of Aging. Age 62 (range 56-66) cardiometabolic outcomes included hypertension, diabetes, dyslipidemia, inflammation, and ischemic heart disease. Analyses included latent growth modeling (LGM), latent class growth modeling (LCGM), and logistic regression models.Results: Linear BMI slope was associated with all outcomes. Accelerated (quadratic) BMI slope was significantly associated with greater risk for hypertension, diabetes, dyslipidemia, and inflammation; odds ratios ranged from 1.93 (diabetes) to 3.15 (dyslipidemia). Initial BMI did not predict later outcomes. Linear slope contributed significant unique variance for diabetes and dyslipidemia even controlling for age 62 BMI. LCGM revealed three trajectories. Men with the relatively stable, lower BMI trajectory had significantly better outcomes than those with trajectories with accelerated increases, especially those including obesity.Conclusions: How individuals reach late-midlife BMI is important. Steepness of BMI change across 40 years from young adulthood to late midlife, in addition to late-midlife BMI itself, was robustly associated with greater risk for poor cardiometabolic outcomes. [ABSTRACT FROM AUTHOR]

There is evidence that differences among individuals in white matter microstructure, as measured with diffusion tensor imaging (DTI), are under genetic control. However, little is known about the relative contribution of genetic and environmental effects on different diffusivity indices among late middle-aged adults. Here, we examined the magnitude of genetic influences for fractional anisotropy (FA), and mean (MD), axial (AD), and radial (RD) diffusivities in male twins aged 56-66 years old. Using an atlas-based registration approach to delineate individual white matter tracts, we investigated mean DTI-based indices within the corpus callosum, 12 bilateral tracts and all these regions of interest combined. All four diffusivity indices had high heritability at the global level (72%-80%). The magnitude of genetic effects in individual tracts varied from 0% to 82% for FA, 0% to 81% for MD, 8% to 77% for AD, and 0% to 80% for RD with most of the tracts showing significant heritability estimates. Despite the narrow age range of this community-based sample, age was correlated with all four diffusivity indices at the global level. In sum, all diffusion indices proved to have substantial heritability for most of the tracts and the heritability estimates were similar in magnitude for different diffusivity measures. Future studies could aim to discover the particular set of genes that underlie the significant heritability of white matter microstructure. Hum Brain Mapp 38:2026-2036, 2017. © 2017 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Theoretical and emerging empirical advances in the life satisfaction (LS) and social problem solving (SPS) literature suggest that LS and SPS may have bidirectional relations. The main purpose of this study was to test the hypothesis of bidirectionality between LS and two components of the SPS, orientation (SPS-O) and skills (SPS-S). Two waves of data were collected from a sample of 733 adolescents at a middle school over a 6-month period. Cross-lagged panel analysis results showed that statistically, LS significantly predicted SPS-O and SPS-S after six months; however, neither SPS-O nor SPS-S significantly predicted LS after six months. These findings suggest LS may function as an antecedent of SPS-O and SPS-S among early adolescents, which lead to a main implication that both SPS and LS could be the direct aims of educational and psychological programs to promote SPS development in early adolescents. Additional implication and future directions are discussed. [ABSTRACT FROM AUTHOR]

Recent studies have identified mutations in the ARID1B gene responsible for neurodevelopmentaldelays, intellectualdisability, growth delay, and dysmorphic features. ARID1B encodes a subunit of the BAF chromatin-remodeling complex, andmutations in multiple components of the BAF complex have been implicated as causes of Coffin-Siris syndrome, Nicolaides-Baraitser syndrome, and non-syndromic intellectual disability. The majority of documented pathogenic ARID1B mutations to date have arisen in a sporadic, de novo manner with no reports of inheritance of a pathogenic mutation from an affected parent. We describe here twopatients (a 21-year-old femaleandher 21-month-old son)with a novel frameshiftmutation in ARID1B inherited in an autosomal dominant fashion in the affected offspring. Both patients presented with neurodevelopmental delays, growth delay, and dysmorphic features including prominent nose with full nasal tip, long philtrum, and high-arched palate. Exome sequencing analysis in the female patient demonstrated a heterozygous deletion of nucleotide 1259 of the ARID1B gene (c.1259delA) resulting in a frameshift and creation of a premature stop codon. Further family testing by targeted Sanger sequencing confirmed that this arose as adenovomutationinthemotherandwaspassedontoher affected son. The clinical features of both patients are felt to be consistent with an ARID1B-related disorder. To our knowledge, this is the first report of a pathogenicmutationin ARID1B being passed from an affected parent to their offspring. [ABSTRACT FROM AUTHOR]

Herein, a thermal decomposition method was utilised to fabricate pure and mixed manganese and ruthenium oxides as catalysts for the oxygen evolution reaction (OER). X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD) reveal the manganese and ruthenium species produced at an annealing temperature of 600 °C to be Mn2O3 and RuO2/Ru, respectively. A number of the mixed Mn/Ru oxides exhibit overpotential values approximately 200 mV lower than previously reported for Mn2O3/RuO2 oxides (at a current density of 10 mA cm−2) for the OER, whereas the Mn 50 material exhibits similar overpotentials reported in the literature for RuO2. Turnover frequency ( TOF) numbers for the Mn/Ru oxides were also calculated, and the results show that the TOF values for some of the materials in this work are higher than RuO2. XPS analysis indicates a change in chemical environment of the Mn/Ru materials, which exhibit higher TOF values. Subsequently, the pure Ru 100 material used in this study has a lower overpotential at 10 mA cm−2, as compared to previously reported values in the literature for RuO2 in alkaline media. This may be attributed to the presence of metallic Ru found in the film or the decrease in crystallite size, as determined by XRD. XPS analysis was also carried out after the OER to help determine the order of activity of the materials in this work. [ABSTRACT FROM AUTHOR]

Key Clinical Message A focused genetic workup is useful in determining the cause of familial microcephaly, especially in the setting of mildly different phenotypes. As illustrated by this case from an impoverished international urban location, one must not assume the etiology for the apparent familial microcephaly is the same for all affected members. [ABSTRACT FROM AUTHOR]

Background: Aging‐related episodic memory (EM) decline and Alzheimer's disease (AD)‐related brain changes begin in late middle age around age 60. However, rate and severity of cognitive decline do not consistently correspond to the extent of neuropathological changes, suggesting a high degree of heterogeneity in EM trajectories. We tested if brain maintenance (BM; relative absence of changes in neural resources as a determinant of preserved cognition) and/or cognitive reserve (CR; a property of the brain that allows for sustained cognitive performance in the face of age‐related changes and brain insult or disease) explain individual differences and heterogeneity in EM in late middle age. Method: Participants were 1604 men from the Vietnam Era Twin Study of Aging. A practice effect‐adjusted composite EM score based on six measures was calculated at three time points with mean ages of 56, 62, and 68. Young adult general cognitive ability (GCA) and lifetime years of education were used as proxy measures of CR. BM was assessed as relative change (from age 56 to 68) in cortical thickness and surface area in a bilateral cortical signature of AD regions‐of‐interest (N = 321). We used linear mixed effect modeling. Result: On average, there was a significant decline in EM from age 56 to 68 (p<0.001). Education (p = 0.042) and young adult GCA (p<0.001) were positively related to EM, but there were no significant effects of education or GCA on the rate of EM change (all p's≥0.316). Relative brain changes were not related to EM (all p's≥0.067) and there were no significant interactions of CR proxies and brain changes on EM (all p's≥0.379). Conclusion: Higher education and higher young adult GCA were related to better EM performance across late middle age – with a stronger contribution of GCA compared to education – but EM change did not differ as a function of these proxy CR measures. Our results did not support effects of BM or CR on EM change in late middle age but rather reflected baseline differences in memory in those with low versus high education/cognitive ability. Whether differential change occurs at later ages or with increased AD pathology remains to be determined. [ABSTRACT FROM AUTHOR]

Background: The amyloid‐tau‐neurodegeneration (ATN) framework has led to an increased focus on Alzheimer's disease (AD) biomarkers. The costs and invasiveness of methods relying on cerebrospinal fluid or positron emission tomography imaging have led to efforts to develop sensitive blood‐based biomarkers. Although AD is highly heritable, the biometric genetic and environmental etiology of blood‐based biomarkers has never been explored. Method: We therefore analyzed plasma beta amyloid (Ab40, Ab42, Ab42/40), total Tau (t‐tau), and neurofilament light (NFL) biomarkers based on a sample of 1,050 men aged 60 to 73 years (m=67.1, SD=2.57) from the Vietnam Era Twin Study of Aging (VETSA). Unlike AB and tau, NFL does not define AD; however, as a biomarker of neurodegeneration it serves as the N component in the ATN framework. Result: Univariate analyses revealed that familial aggregation in Ab42, Ab42/40, t‐tau and NFL could be entirely explained by additive genetic influences accounting for 50% to 56% of the total variance. All remaining variances were unshared or unique environmental influences. For Ab40, additive genetic (31%) and shared environmental (44%) influences both contributed to total variance. In multivariate analyses, genetic influences accounted for 73% to 75% of the variance in the Ab biomarkers and 55% to 57% of the variance in t‐tau and NFL. The same analyses also revealed that Ab40 and Ab42 were statistically genetically identical and moderately correlated in terms of their environmental influences. All other bivariate associations ranged from small to moderate. Conclusion: Our findings suggest that plasma biomarkers are heritable and that Ab40 and Ab42 share the same genetic influences. In contrast, genetic influences on plasma t‐tau and NFL are mostly unique and uncorrelated with plasma Ab in early old‐age men. [ABSTRACT FROM AUTHOR]

Objective: Metabolic syndrome, a clustering of risk factors including insulin resistance, dyslipidemia, central obesity, and hypertension, increases risk for cardiovascular disease and cognitive decline. The etiology of the risk factors' cohesion remains unclear. How genetic and environmental influences explained co-occurrence of metabolic syndrome components was examined.Methods: Continuous measures of body mass index (BMI), waist circumference, blood pressure (BP), fasting insulin and glucose, high-density lipoprotein cholesterol (HDL), and triglycerides from 1,193 middle-aged twin men participating in the Vietnam Era Twin Study of Aging at average age 62 (range 56-67) were analyzed using multivariate biometrical modeling.Results: Four heritable factors were found: adiposity (BMI, waist circumference), insulin resistance (glucose, insulin), lipids (HDL, triglycerides), and BP (systolic, diastolic). Heritabilities were 0.42-0.68. In the best-fitting model, insulin resistance, lipids, and adiposity comprised a higher-order latent genetic factor. Adiposity and BP shared genetic influences independent of the latent genetic factor. All factors aggregated on a latent unique environmental factor.Conclusions: Metabolic syndrome components form the equivalent of two genetic factors. BP was genetically unrelated to insulin resistance and lipids. Adiposity was the only characteristic genetically and environmentally related to all other factors. These results inform strategies for gene discovery and prediction of health outcomes. [ABSTRACT FROM AUTHOR]

Intellectual disability (ID) is estimated to affect 1-3% of the general population and is a common reason for referrals to pediatric and adult geneticists, as well as neurologists. There are many genetic and non-genetic causes of ID; X-linked forms are identifiable through their characteristic inheritance pattern. Current testing methods have been able to identify over 100 genes on the X chromosome responsible for X-linked intellectual disability (XLID) syndromes. MED12 [MIM *300188] (mediator complex subunit 12) mutations have been linked to numerous XLID syndromes, including Lujan, FG, and Ohdo, and MED12 is included in many XLID panels. MED12 is located at Xq13.1 and its product has roles in transcriptional activation and repression. We describe two affected male siblings and their unaffected mother with a novel missense mutation in MED12, c.4147G>A (p.Ala1383Thr). The siblings share some features of Ohdo syndrome, including feeding difficulties, microcephaly, and speech delay. However, additional attributes such as hypertonia, eosinophilic esophagitis, penile chordee, and particular facial dysmorphisms depart sufficiently from individuals previously described such that they appear to represent a new and expanded phenotype. This case lends credence to the evolving theory that the subtypes of Ohdo, and perhaps other MED12 disorders, reflect a spectrum of characteristics, rather than distinct syndromes. As XLID panel testing and whole exome sequencing (WES) becomes a standard of care for affected males, further MED12 mutations will broaden the phenotype of these intriguing disorders and challenge clinicians to rethink the current diagnostic boundaries. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Traumatic Stress is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Theoretical models describing transport and kinetic processes involved in heterogeneous redox catalysis of solution phase reactants at RDE surfaces modified with catalytically active layers are presented. Model A regards the interaction between the surface immobilized redox active mediator and substrate being described in terms of bimolecular reaction kinetics. Model B assumes the interaction involves the formation of an adduct. Both consider the processes of heterogeneous electron transfer between immobilized mediator and support electrode, chemical reaction between redox mediator/reactant, and reactant diffusive mass transport, and expressions for the net reaction flux are derived. Kinetic case diagrams are constructed. [ABSTRACT FROM AUTHOR]