von Willebrand disease: proposing definitions for future research

Thrombosis and Hemostasi

How identity and uncertainty affect online social influence

Computer simulations have been used to model psychological and sociological phenomena in order to provide insight into how they affect human behavior and population-wide systems. In this study, three agent-based simulations (ABSs) were developed to model opinion dynamics in an online social media context. The main focus was to test the effects of ‘social identity’ and ‘certainty’ on social influence. When humans interact, they influence each other’s opinions and behavior. It was hypothesized that the influence of other agents based on ingroup/outgroup perceptions can lead to extremism and polarization under conditions of uncertainty. The first two simulations isolated social identity and certainty respectively to see how social influence would shape the attitude formation of the agents, and the opinion distribution by extension. Problems with previous models were remedied to some extent, but not fully resolved. The third combined the two to see if the limitations of both designs would be ameliorated with added complexity. The combination proved to be moderating, and while stable opinion clusters form, extremism and polarization do not develop in the system without added forces.Computer Systems, Imagery and Medi

Development of measures to evaluate youth advocacy for obesity prevention

BACKGROUND: Youth advocacy has been successfully used in substance use prevention but is a novel strategy in obesity prevention. As a precondition for building an evidence base for youth advocacy for obesity prevention, the present study aimed to develop and evaluate measures of youth advocacy mediator, process, and outcome variables. METHODS: The Youth Engagement and Action for Health (YEAH!) program (San Diego County, CA) engaged youth and adult group leaders in advocacy for school and neighborhood improvements to nutrition and physical activity environments. Based on a model of youth advocacy, scales were developed to assess mediators, intervention processes, and proximal outcomes of youth advocacy for obesity prevention. Youth (baseline n = 136) and adult group leaders (baseline n = 47) completed surveys before and after advocacy projects. With baseline data, we created youth advocacy and adult leadership subscales using confirmatory factor analysis (CFA) and described their psychometric properties. RESULTS: Youth came from 21 groups, were ages 9–22, and most were female. Most youth were non-White, and the largest ethnic group was Hispanic/Latino (35.6 %). The proposed factor structure held for most (14/20 youth and 1/2 adult) subscales. Modifications were necessary for 6 of the originally proposed 20 youth and 1 of the 2 adult multi-item subscales, which involved splitting larger subscales into two components and dropping low-performing items. CONCLUSIONS: Internally consistent scales to assess mediators, intervention processes, and proximal outcomes of youth advocacy for obesity prevention were developed. The resulting scales can be used in future studies to evaluate youth advocacy programs

Surgical management of patients with von Willebrand disease: summary of 2 systematic reviews of the literature

von Willebrand disease (VWD) is the most common inherited bleeding disorder. The management of patients with VWD who are undergoing surgeries is crucial to prevent bleeding complications. We systematically summarized the evidence on the management of patients with VWD who are undergoing major and minor surgeries to support the development of practice guidelines. We searched Medline and EMBASE from inception through October 2019 for randomized clinical trials (RCTs), comparative observational studies, and case series that compared maintaining factor VIII (FVIII) levels or von Willebrand factor (VWF) levels at >0.50 IU/mL for at least 3 days in patients undergoing major surgery, and those with options for perioperative management of patients undergoing minor surgery. Two authors screened and abstracted data and assessed the risk of bias. We conducted meta-analyses when possible. We evaluated the certainty of the evidence using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. We included 7 case series for major surgeries and 2 RCTs and 12 case series for minor surgeries. Very-low-certainty evidence showed that maintaining FVIII levels or VWF levels of >0.50 IU/mL for at least 3 consecutive days showed excellent hemostatic efficacy (as labeled by the researchers) after 74% to 100% of major surgeries. Low- to very-low-certainty evidence showed that prescribing tranexamic acid and increasing VWF levels to 0.50 IU/mL resulted in fewer bleeding complications after minor procedures compared with increasing VWF levels to 0.50 IU/mL alone. Given the low-quality evidence for guiding management decisions, a shared-decision model leading to individualized therapy plans will be important in patients with VWD who are undergoing surgical and invasive procedures

Write, draw, show, and tell: a child-centred dual methodology to explore perceptions of out-of-school physical activity

Background Research to increase children’s physical activity and inform intervention design has, to date, largely underrepresented children’s voices. Further, research has been limited to singular qualitative methods that overlook children’s varied linguistic ability and interaction preference. The aim of this study was to use a novel combination of qualitative techniques to explore children’s current views, experiences and perceptions of out-of-school physical activity as well as offering formative opinion about future intervention design. Methods Write, draw, show and tell (WDST) groups were conducted with 35 children aged 10–11 years from 7 primary schools. Data were analysed through a deductive and inductive process, firstly using the Youth Physical Activity Promotion Model as a thematic framework, and then inductively to enable emergent themes to be further explored. Pen profiles were constructed representing key emergent themes. Results The WDST combination of qualitative techniques generated complimentary interconnected data which both confirmed and uncovered new insights into factors relevant to children’s out-of-school physical activity. Physical activity was most frequently associated with organised sports. Fun, enjoyment, competence, and physical activity provision were all important predictors of children’s out-of-school physical activity. Paradoxically, parents served as both significant enablers (i.e. encouragement) and barriers (i.e. restricting participation) to physical activity participation. Some of these key findings would have otherwise remained hidden when compared to more traditional singular methods based approaches. Conclusions Parents are in a unique position to promote health promoting behaviours serving as role models, physical activity gatekeepers and choice architects. Given the strong socialising effect parents have on children’s physical activity, family-based physical activity intervention may offer a promising alternative compared to traditional school-based approaches. Parents' qualitative input is important to supplement children’s voices and inform future family-based intervention design. The WDST method developed here is an inclusive, interactive and child-centred methodology which facilitates the exploration of a wide range of topics and enhances data credibility

Transcriptional profiling of HERV-K(HML-2) in amyotrophic lateral sclerosis and potential implications for expression of HML-2 proteins

Abstract Background Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder. About 90% of ALS cases are without a known genetic cause. The human endogenous retrovirus multi-copy HERV-K(HML-2) group was recently reported to potentially contribute to neurodegeneration and disease pathogenesis in ALS because of transcriptional upregulation and toxic effects of HML-2 Envelope (Env) protein. Env and other proteins are encoded by some transcriptionally active HML-2 loci. However, more detailed information is required regarding which HML-2 loci are transcribed in ALS, which of their proteins are expressed, and differences between the disease and non-disease states. Methods For brain and spinal cord tissue samples from ALS patients and controls, we identified transcribed HML-2 loci by generating and mapping HML-2-specific cDNA sequences. We predicted expression of HML-2 env gene-derived proteins based on the observed cDNA sequences. Furthermore, we determined overall HML-2 transcript levels by RT-qPCR and investigated presence of HML-2 Env protein in ALS and control tissue samples by Western blotting. Results We identified 24 different transcribed HML-2 loci. Some of those loci are transcribed at relatively high levels. However, significant differences in HML-2 loci transcriptional activities were not seen when comparing ALS and controls. Likewise, overall HML-2 transcript levels, as determined by RT-qPCR, were not significantly different between ALS and controls. Indeed, we were unable to detect full-length HML-2 Env protein in ALS and control tissue samples despite reasonable sensitivity. Rather our analyses suggest that a number of HML-2 protein variants other than full-length Env may potentially be expressed in ALS patients. Conclusions Our results expand and refine recent publications on HERV-K(HML-2) and ALS. Some of our results are in conflict with recent findings and call for further specific analyses. Our profiling of HML-2 transcription in ALS opens up the possibility that HML-2 proteins other than canonical full-length Env may have to be considered when studying the role of HML-2 in ALS disease

Chromatin and single-cell RNA-seq profiling reveal dynamic signaling and metabolic transitions during human spermatogonial stem cell development

Human adult spermatogonial stem cells (hSSCs) must balance self-renewal and differentiation. To understand how this is achieved, we profiled DNA methylation and open chromatin (ATAC-seq) in SSEA4+ hSSCs, analyzed bulk and single-cell RNA transcriptomes (RNA-seq) in SSEA4+ hSSCs and differentiating c-KIT+ spermatogonia, and performed validation studies via immunofluorescence. First, DNA hypomethylation at embryonic developmental genes supports their epigenetic "poising" in hSSCs for future/embryonic expression, while core pluripotency genes (OCT4 and NANOG) were transcriptionally and epigenetically repressed. Interestingly, open chromatin in hSSCs was strikingly enriched in binding sites for pioneer factors (NFYA/B, DMRT1, and hormone receptors). Remarkably, single-cell RNA-seq clustering analysis identified four cellular/developmental states during hSSC differentiation, involving major transitions in cell-cycle and transcriptional regulators, splicing and signaling factors, and glucose/mitochondria regulators. Overall, our results outline the dynamic chromatin/transcription landscape operating in hSSCs and identify crucial molecular pathways that accompany the transition from quiescence to proliferation and differentiation

Mobility, satisfaction with functional capacity and perceived quality of life (PQOL) in older persons with self-reported visual impairment: The pathway between ability to get around and PQOL

Research shows that ability to get around (AGA) is significantly associated with perceived quality of life (PQOL) among older persons with self-reported visual impairment. Much of this impact, however, is through satisfaction with one's functional capacity. Satisfaction with functional capacity is a construct composed of five items: satisfaction with (1) activities of daily living, (2) capacity to work, (3) self, (4) health and (5) sleep. At present, it is not known how AGA interacts individually with these items to influence PQOL. Purpose: The purpose of this study is to investigate the extent to which AGA interacts with each of these five items to affect PQOL. Methods: Structural equation modelling was employed in a secondary-analysis of data from 356 persons (aged 56-72) with self-reported visual impairment to identify the pathways by which AGA affects PQOL. Results: Satisfaction with self and health were the only items found to be both directly related to QOL and to provide a significant pathway between AGA and PQOL.Conclusion: AGA significantly affects PQOL both directly and indirectly through its impact on people's satisfaction with self and health. Lessons may be learnt from this to better focus mobility interventions to enhance PQOL in this population. Implications for Rehabilitation: The findings of this study indicate that ability to get around (AGA) has a significant impact on perceived quality of life (PQOL): the stated goal of many rehabilitation programs for older persons who are visually impaired. The study also found that the primary pathway by which AGA influenced PQOL was indirect through its association with both satisfaction with one's self and health rather than direct. Attempts to enhance PQOL by increasing AGA may be most effective if the focus of intervention was on restoring one's sense of self and health as opposed to focusing on meeting practical needs