Application of whole genome and RNA sequencing to investigate the genomic landscape of common variable immunodeficiency disorders.

Common Variable Immunodeficiency Disorders (CVIDs) are the most prevalent cause of primary antibody failure. CVIDs are highly variable and a genetic causes have been identified in <5% of patients. Here, we performed whole genome sequencing (WGS) of 34 CVID patients (94% sporadic) and combined them with transcriptomic profiling (RNA-sequencing of B cells) from three patients and three healthy controls. We identified variants in CVID disease genes TNFRSF13B, TNFRSF13C, LRBA and NLRP12 and enrichment of variants in known and novel disease pathways. The pathways identified include B-cell receptor signalling, non-homologous end-joining, regulation of apoptosis, T cell regulation and ICOS signalling. Our data confirm the polygenic nature of CVID and suggest individual-specific aetiologies in many cases. Together our data show that WGS in combination with RNA-sequencing allows for a better understanding of CVIDs and the identification of novel disease associated pathways

Effects of a brief mindfulness-based intervention on emotional regulation and levels of mindfulness in senior students

Mindfulness-based interventions have been applied in diverse populations and achieved mental health benefits. This study examined the effects of a brief mindfulness program for emotional regulation and levels of mindfulness on senior students in Brazil. The intervention consisted of six weekly meetings attended by 30 participants. It is a pre-experimental research, with pre- and post-test comparative and correlation measurements. The preliminary results, which relied on parametrical and non-parametrical tests, revealed a reduction in total emotional regulation difficulties (p = 0.0001; r = − 0.55). Also, there was an increase in the levels of mindfulness in the subtests for both dimensions under evaluation: “Awareness” (p = 0.0001; d = 0.77) and “Acceptance” (p = 0.048; d = 0.37). By associating the amount of meditative practices performed by students with the variables, a significant positive correlation was found with the mindfulness dimension “Awareness” (rP = 0.422; p = 0.020), and there was a significant negative correlation with Difficulties in emotion regulation (rS = − 0.478; p = 0.008) and with its respective subscales “Non-acceptance” (rS = − 0.654; p = 0.0001) and “Clarity” (rS = − 0.463; p = 0.010). In conclusion, the application of a brief mindfulness-based intervention is promising in Brazilian university contexts; moreover, it can bring benefits to students, e.g., an increase in emotion regulation as well as in levels of mindfulness. We suggest that further research should use an experimental design and follow-up.info:eu-repo/semantics/publishedVersio

Factors influencing success of clinical genome sequencing across a broad spectrum of disorders

To assess factors influencing the success of whole-genome sequencing for mainstream clinical diagnosis, we sequenced 217 individuals from 156 independent cases or families across a broad spectrum of disorders in whom previous screening had identified no pathogenic variants. We quantified the number of candidate variants identified using different strategies for variant calling, filtering, annotation and prioritization. We found that jointly calling variants across samples, filtering against both local and external databases, deploying multiple annotation tools and using familial transmission above biological plausibility contributed to accuracy. Overall, we identified disease-causing variants in 21% of cases, with the proportion increasing to 34% (23/68) for mendelian disorders and 57% (8/14) in family trios. We also discovered 32 potentially clinically actionable variants in 18 genes unrelated to the referral disorder, although only 4 were ultimately considered reportable. Our results demonstrate the value of genome sequencing for routine clinical diagnosis but also highlight many outstanding challenges

Factors influencing success of clinical genome sequencing across a broad spectrum of disorders

To assess factors influencing the success of whole-genome sequencing for mainstream clinical diagnosis, we sequenced 217 individuals from 156 independent cases or families across a broad spectrum of disorders in whom previous screening had identified no pathogenic variants. We quantified the number of candidate variants identified using different strategies for variant calling, filtering, annotation and prioritization. We found that jointly calling variants across samples, filtering against both local and external databases, deploying multiple annotation tools and using familial transmission above biological plausibility contributed to accuracy. Overall, we identified disease-causing variants in 21% of cases, with the proportion increasing to 34% (23/68) for mendelian disorders and 57% (8/14) in family trios. We also discovered 32 potentially clinically actionable variants in 18 genes unrelated to the referral disorder, although only 4 were ultimately considered reportable. Our results demonstrate the value of genome sequencing for routine clinical diagnosis but also highlight many outstanding challenges

Is procrastination a vulnerability factor for hypertension and cardiovascular disease? Testing an extension of the procrastination–health model

Personality is an important epidemiological factor for understanding health outcomes. This study investigated the associations of trait procrastination with hypertension and cardiovascular disease (HT/CVD) and maladaptive coping by testing an extension of the procrastination–health model among individuals with and without HT/CVD. Individuals with self-reported HT/CVD (N = 182) and healthy controls (N = 564), from a community sample, completed an online survey including measures of personality, coping, and health outcomes. Logistic regression analysis controlling for demographic and higher order personality factors found that older age, lower education level and higher procrastination scores were associated with HT/CVD. Moderated mediation analyses with bootstrapping revealed that procrastination was more strongly associated with maladaptive coping behaviours in participants with HT/CVD than the healthy controls, and the indirect effects on stress through maladaptive coping were larger for the HT/CVD sample. Results suggest procrastination is a vulnerability factor for poor adjustment to and management of HT/CVD

Study motivation under social temptation; effects of trait procrastination

The present study sought to examine the view that procrastination can be explained as a result of the joint effect of a general discounting mechanism and a personality trait. To demonstrate the discounting mechanism, the process of study motivation prior to an examination was mentally simulated by 302 university students. Study motivation was operationalised in three ways: (1) As an estimate of general motivation towards studying, (2) as a measure of resistance to temptation averaged over five social situations, and (3) as a weekly average of hours spent studying each day. Results indicate that discounting of study motivation as a function of time left until the examination closely follows the formula suggested by the self-control literature. Differences in rate of discounting between high, moderate, and low procrastinators were significant for actual study behaviour, but not for general motivation or resistance to temptation. This may be similar to the general finding that procrastinators tend to differ from non-procrastinators in behaviour rather than in intentions. The results are taken as support for the theoretical view on procrastination adopted in this study. (C) 2000 Elsevier Science Ltd. All rights reserved

TRAIT PROCRASTINATION, TIME MANAGEMENT, AND ACADEMIC BEHAVIOR

Fifty-five female and 10 male university students enrolled in a three-week Summer course completed a personality questionnaire. They also indicated their study and work intentions, completed a dilatory behavior scale concerning their non-task-related behavior on each of four course tasks, indicated their overall actual study behavior, and rated their agitation and dejection. Trait procrastinators obtained lower scores on three Time Management subscales compared to non-procrastinators, and reported higher levels of dilatory behavior. The Time Management subscales were negatively related to dilatory behavior on two of the course assignments, but in neither case were these variables found to mediate the trait procrastination-dilatory behavior link. Trait procrastination was positively related to dejection at the outset of the course prior to making study and work plans and positively related to agitation experienced during the last week of class. The Time Management subscale, Perceived Control of Time, was negatively related to agitation on each assessment. More importantly, the low perceived control of time associated with trait procrastinators appeared to mediate their higher agitation levels during the last week of class

The struggle between the present and the future procrastinators and the punctual

Abstract: Two studies investigated the role of impulsivity in procrastinators' problems. In the first study, 147 freshmen completed questionnaires measuring the big five personality factors, a broad impulsivity scale, and Lay's general procrastination scale, and their perceptions concerning a compulsory course. The data revealed that procrastination was closely related to a lack of perseverance, that is, the inability to complete projects. This relation explained a large part of the well-documented relation between conscientiousness and procrastination. In the second study, a subsample of these students was followed-up during 11 weeks before their exams. They had to provide their study intentions and behavior, the reasons why they failed to enact upon their intentions, and the perceived impact of studying on their final grade. The data revealed that all students tend to postpone the bulk of their study activities to the last week before an exam, and that this trend could nicely be described by a hyperbolic curve. The results also revealed that procrastinators postponed more of their intentions, mainly because of fun alternatives, but did not intend to study less or later. At the contrary, they even seemed to compensate for their vulnerability by formulating more intentions earlier. Procrastinators emerged as highly motivated students that lack the ability to ward off temptations and distractions during their studying activities.Departement Toegepaste economische wetenschappen.status: publishe