Genome-Wide Significant Loci: How Important Are They? Systems Genetics to Understand Heritability of Coronary Artery Disease and Other Common Complex Disorders

AbstractGenome-wide association studies (GWAS) have been extensively used to study common complex diseases such as coronary artery disease (CAD), revealing 153 suggestive CAD loci, of which at least 46 have been validated as having genome-wide significance. However, these loci collectively explain <10% of the genetic variance in CAD. Thus, we must address the key question of what factors constitute the remaining 90% of CAD heritability. We review possible limitations of GWAS, and contextually consider some candidate CAD loci identified by this method. Looking ahead, we propose systems genetics as a complementary approach to unlocking the CAD heritability and etiology. Systems genetics builds network models of relevant molecular processes by combining genetic and genomic datasets to ultimately identify key “drivers” of disease. By leveraging systems-based genetic approaches, we can help reveal the full genetic basis of common complex disorders, enabling novel diagnostic and therapeutic opportunities

A relativistically covariant stochastic model for systems with a fluctuating number of particles

We construct a relativistically covariant stochastic model for systems of non-interacting spinless particles whose number undergoes random fluctuations. The model is compared with the canonical quantization of the free scalar field in the limit of infinite volume.Comment: 5 Pages; no figures; Plain REVTeX style. To be published in Phys. Lett.

ENGAGING CLINICIANS IN A PRE-IMPLEMENTATION ASSESSMENT OF THE WOMEN & PERSON-EMPOWERED COMMUNITY ACCESS FOR REPRODUCTIVE EQUITY (WE CARE) INTERVENTION

Objectives: To assess clinicians’ perspectives on WE CARE (an emergency department (ED) family planning counseling and referral intervention that uses an online health tool and community health workers) to inform intervention design for implementation. Methods: We conducted one-on-one, semi-structured interviews with Emergency Medicine, Family Medicine, and Obstetrics & Gynecology clinicians until thematic saturation. The Consolidated Framework for Implementation Research (CFIR) informed the interview guide and was used to code all transcripts. A CFIR expert conducted an external coding audit. Results: We interviewed 30 clinicians (female (77%), ED staff (47%), white (63%), and attending physicians (43%)). WE CARE was highly acceptable. Dominant CFIR domains include: (1) Clinicians suggested Design Quality and Packaging modifications, particularly the referral processes, to promote successful implementation; (2) transportation and insurance were essential Patient Needs and Resources; (3) WE CARE was Compatible with the Value of “no missed opportunity” to help patients; (4) Compatibility with Work Processes – WE CARE posed scheduling and reimbursement challenges to clinics; (5) Clinicians expressed concerns about an ED Culture of reproductive health frustrations, resistance to change, and competing priorities. Others identified the ED “safety net” culture and long wait times as assets to the intervention; (6) WE CARE had a significant Relative Advantage over the status quo. A few clinicians identified more advantageous alternatives (e.g., WE CARE in the clinic, home, or community settings); (7) Engaging Key Stakeholders throughout the hospital was a critical implementation element. Conclusions: Clinicians contextualized several implementation constructs relevant to designing and implementing an ED family planning intervention

Guidelines for the Selection of Physical Literacy Measures in Physical Education in Australia

Assessment of physical literacy poses a dilemma of what instrument to use. There is currently no guide regarding the suitability of common assessment approaches. The purpose of this brief communication is to provide a user's guide for selecting physical literacy assessment instruments appropriate for use in school physical education and sport settings. While recommendations regarding specific instruments are not provided, the guide offers information about key attributes and considerations for the use. A decision flow chart has been developed to assist teachers and affiliated school practitioners to select appropriate methods of assessing physical literacy. School PE and sport scenarios are presented to illustrate this process. It is important that practitioners are empowered to select the most appropriate instrument/s to suit their needs

Defining Physical Literacy for Application in Australia: A Modified Delphi Method

Purpose. The development of a physical literacy definition and standards framework suitable for implementation in Australia. Method. Modified Delphi methodology. Results . Consensus was established on four defining statements: Core – Physical literacy is lifelong holistic learning acquired and applied in movement and physical activity contexts; Composition – Physical literacy reflects ongoing changes integrating physical, psychological, cognitive and social capabilities; Importance – Physical literacy is vital in helping us lead healthy and fulfilling lives through movement and physical activity; Aspiration – A physically literate person is able to draw on their integrated physical, psychological, cognitive, and social capacities to support health promoting and fulfilling movement and physical activity, relative to their situation and context, throughout the lifespan. The standards framework addressed four learning domains (physical, psychological, cognitive, and social), spanning five learning configurations/levels. Conclusion. The development of a bespoke program for a new context has important implications for both existing and future program

Examining the transfer of soils to clothing materials: Implications for forensic investigations

Soil forensics has proven instrumental in assisting criminal investigation, and there is an increasing demand for experimental studies on such trace evidence. Here we present the first detailed study on the influence of clothing materials on soil transfer. We adopt an experimental approach to test the transfer of five common UK soils to five different clothing materials. Our experiment is designed to represent victim or perpetrator contact with soil at the scene of a crime. We highlight the complex relationship between soil transfer and clothing material type. Whilst over half of our soils tested displayed differential transfer to different clothing materials, soil moisture content and soil type were found to have a greater influence on the transfer of soils overall. Soil transfer is typically more effective across all material types when soils are wet and saturated. However, we find the relationship between soil transfer and material type to be more complex when soils are dry, with a significant bias in soil transfer to fleece material, which we attribute to static attraction. Encouragingly, for the analysis of forensic soils recovered from clothing artefacts, each of the transfer experiments we conducted led to soil transfer to every tested material. We suggest that future empirical studies now focus on the persistence of soils over time to clothing materials after transfer has occurred, and the transfer and persistence of soil palynomorphs present within soils

Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure

Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies