Understanding neighborhood environment related to Hong Kong children\u27s physical activity: a qualitative study using nominal group technique

Relationships between the neighborhood environment and children\u27s physical activity have been well documented in Western countries but are less investigated in ultra-dense Asian cities. The aim of this study was to identify the environmental facilitators and barriers of physical activity behaviors among Hong Kong Chinese children using nominal group technique

A pilot study evaluating the use of ABCD2 score in pre-hospital assessment of patients with suspected transient ischaemic attack: experience and lessons learned

Background: Suspected transient ischaemic attack (TIA) is a common presentation to emergency medical services (EMS) in the United Kingdom (UK). Several EMS systems have adopted the ABCD2 score to aid pre-hospital risk stratification and decision-making on patient disposition, such as direct referral to an Emergency Department or specialist TIA clinic. However, the ABCD2 score, developed for hospital use, has not been validated for use in the pre-hospital context of EMS care. Methods: We conducted a pilot study to assess eligibility criteria, recruitment rates, protocol compliance, consent and follow-up procedures to inform the development of a definitive study to validate the ABCD2 tool in pre-hospital evaluation of patients with suspected TIA. Results: From 1st May–1st September 2013, nine patients with an EMS suspected diagnosis of TIA had the TIA diagnosis later confirmed by a specialist from five participating sites. This recruitment rate is comparable to stroke trials in the EMS setting. Bureaucratic obstacles and duplication of approval processes across participating sites took 13 months to resolve before recruitment commenced. Due to the initial difficulty in recruitment, a substantial amendment was approved to modify inclusion criteria, allowing patients with atrial fibrillation and/or taking anticoagulant therapy to participate in the study. Conclusions: It is possible to identify, recruit and follow up patients with suspected TIA in the EMS setting. Training large numbers of EMS staff is required as exposure to TIA patients is infrequent. Significant insight was gained into the complexity of NHS research governance mechanisms in the UK. This knowledge will facilitate the planning of a future adequately powered study to validate the ABCD2 tool in a pre-hospital setting

HDAC9 is implicated in atherosclerotic aortic calcification and affects vascular smooth muscle cell phenotype.

Aortic calcification is an important independent predictor of future cardiovascular events. We performed a genome-wide association meta-analysis to determine SNPs associated with the extent of abdominal aortic calcification (n = 9,417) or descending thoracic aortic calcification (n = 8,422). Two genetic loci, HDAC9 and RAP1GAP, were associated with abdominal aortic calcification at a genome-wide level (P < 5.0 × 10-8). No SNPs were associated with thoracic aortic calcification at the genome-wide threshold. Increased expression of HDAC9 in human aortic smooth muscle cells promoted calcification and reduced contractility, while inhibition of HDAC9 in human aortic smooth muscle cells inhibited calcification and enhanced cell contractility. In matrix Gla protein-deficient mice, a model of human vascular calcification, mice lacking HDAC9 had a 40% reduction in aortic calcification and improved survival. This translational genomic study identifies the first genetic risk locus associated with calcification of the abdominal aorta and describes a previously unknown role for HDAC9 in the development of vascular calcification

One Year of Yoga Training Alters Ghrelin Axis in Centrally Obese Adults With Metabolic Syndrome

Introduction: Metabolic syndrome (MetS) is a multiplex cardiometabolic manifestation associated with type 2 diabetes mellitus and cardiovascular diseases. Yoga training has been shown to alleviate MetS. Recently, circulatory ghrelin profile was demonstrated to be associated with MetS. This study examined the effects of 1 year of yoga training on β-cell function and insulin resistance, and the involvement of metabolic peptides, including unacylated ghrelin (UnAG), acylated ghrelin (AG), obestatin, growth hormone (GH), and insulin, in the beneficial effects of yoga training in centrally obese adults with MetS.Methods: This was a follow up study, in which data of risk factors of MetS, physical performance tests [resting heart rate (HR), chair stand test (CS), chair sit and reach test (CSR), back scratch test (BS), and single leg stand tests (SLS)] and serum samples of 79 centrally obese MetS subjects aged 58 ± 8 years (39 subjects received 1-year yoga training and 40 subjects received no training) were retrieved for analyses. β-cell function and insulin resistance were examined by Homeostasis Model Assessment (HOMA). Circulating levels of UnAG, AG, obestatin, GH, and insulin were determined by enzyme-linked immunosorbent assay using fasting serum samples. Generalized estimating equation analysis and Mann–Whitney U-test were used to detect statistically significant differences between groups.Results: Waist circumference (WC) was significantly decreased after yoga intervention (control: +2%; yoga: -4%). Significant improvements in HR (control: +2%; yoga: -5%), CS (control: -1%; yoga: +24%), CSR left (control: worsen by 0.90 cm; yoga: improved by 4.21 cm), CSR right (control: worsen by 0.75 cm; yoga: improved by 4.28 cm), right side of BS (control: improved by 0.19 cm; yoga: improved by 4.31 cm), SLS left (control: -10%; yoga: +86%), and SLS right (control: -6%; yoga: +47%) were observed after 1-year yoga training. No significant difference was found between the two groups in insulin, HOMA indices, and disposition index. Yoga training significantly increased circulating GH (control: -3%; yoga: +22%), total circulating ghrelin (control: -26%; yoga: +13%), and UnAG (control: -27%; yoga: +14%), whereas decreased AG (control: -7%; yoga: -33%) and obestatin (control: +24%; yoga: -29%).Conclusion: One-year of yoga training modulated total ghrelin, UnAG, AG, obestatin, and GH while exerting beneficial effects on physical functions and central obesity in adults with MetS. The beneficial effects of yoga may be associated with the alteration of ghrelin gene product and GH

Federated Learning on Heterogenous Data using Chest CT

Large data have accelerated advances in AI. While it is well known that population differences from genetics, sex, race, diet, and various environmental factors contribute significantly to disease, AI studies in medicine have largely focused on locoregional patient cohorts with less diverse data sources. Such limitation stems from barriers to large-scale data share in medicine and ethical concerns over data privacy. Federated learning (FL) is one potential pathway for AI development that enables learning across hospitals without data share. In this study, we show the results of various FL strategies on one of the largest and most diverse COVID-19 chest CT datasets: 21 participating hospitals across five continents that comprise >10,000 patients with >1 million images. We present three techniques: Fed Averaging (FedAvg), Incremental Institutional Learning (IIL), and Cyclical Incremental Institutional Learning (CIIL). We also propose an FL strategy that leverages synthetically generated data to overcome class imbalances and data size disparities across centers. We show that FL can achieve comparable performance to Centralized Data Sharing (CDS) while maintaining high performance across sites with small, underrepresented data. We investigate the strengths and weaknesses for all technical approaches on this heterogeneous dataset including the robustness to non-Independent and identically distributed (non-IID) diversity of data. We also describe the sources of data heterogeneity such as age, sex, and site locations in the context of FL and show how even among the correctly labeled populations, disparities can arise due to these biases

Maternal autoimmunity and inflammation are associated with childhood tics and obsessive-compulsive disorder: Transcriptomic data show common enriched innate immune pathways.

Although genetic variation is a major risk factor of neurodevelopmental disorders, environmental factors during pregnancy and early life are also important in disease expression. Animal models demonstrate that maternal inflammation causes fetal neuroinflammation and neurodevelopmental deficits, and brain transcriptomics of neurodevelopmental disorders in humans show upregulated differentially expressed genes are enriched in immune pathways. We prospectively recruited 200 sequentially referred children with tic disorders/obsessive-compulsive disorder (OCD), 100 autoimmune neurological controls, and 100 age-matched healthy controls. A structured interview captured the maternal and family history of autoimmune disease and other pro-inflammatory states. Maternal blood and published Tourette brain transcriptomes were analysed for overlapping enriched pathways. Mothers of children with tics/OCD had a higher rate of autoimmune disease compared with mothers of children with autoimmune neurological conditions (p = 0.054), and mothers of healthy controls (p = 0.0004). Autoimmunity was similarly elevated in first- and second-degree maternal relatives of children with tics/OCD (p 0.0001 and p = 0.014 respectively). Other pro-inflammatory states were also more common in mothers of children with tics/OCD than controls (p 0.0001). Upregulated differentially expressed genes in maternal autoimmune disease and Tourette brain transcriptomes were commonly enriched in innate immune processes. Pro-inflammatory states, including autoimmune disease, are more common in the mothers and families of children with tics/OCD. Exploratory transcriptome analysis indicates innate immune signalling may link maternal inflammation and childhood tics/OCD. Targeting inflammation may represent preventative strategies in pregnancy and treatment opportunities for children with neurodevelopmental disorders

Confidentiality, anonymity and amnesty for midwives in distress seeking online support – Ethical?

BACKGROUND: Midwife health is intrinsically linked to the quality of safe patient care. To ensure safe patient care, there is a need to deliver emotional support to midwives. One option that midwives may turn to may be a confidential online intervention, instead of localised, face-to-face support. RESEARCH DESIGN: Following the Realist And MEta-narrative Evidence Syntheses: Evolving Standards publication standards, this realist synthesis approach explores the ethical considerations in permitting confidentiality, anonymity and amnesty in online interventions to support midwives in work-related psychological distress. An iterative search methodology was used to select nine papers for review. To assimilate information, papers were examined for ideas relating to ethical dimensions of online interventions to support midwives in work-related psychological distress. This review takes a narrative approach. FINDINGS: Online interventions can support the development of insight, help seeking and open discussion. Additionally, Internet support groups can become morally persuasive in nature. Anonymity and confidentiality are both effective and therapeutic features of online interventions when used in collaboration with effective online moderation. Yet, ethical dilemmas remain where users cannot be identified. DISCUSSION: Confidentiality and anonymity remain key components of successful online interventions. However, sanctioning the corollary component of amnesty may provoke moral discomfort for those seeking immediate accountability. For others, amnesty is seen as essential for open disclosure and help seeking. Ultimately, the needs of midwives must be balanced with the requirement to protect the public and the professional reputation of midwifery. CONCLUSION: In supporting midwives online, the principles of anonymity, confidentiality and amnesty may evoke some resistance on ethical grounds. However, without offering identity protection, it may not be possible to create effective online support services for midwives. The authors of this article argue that the principles of confidentiality, anonymity and amnesty should be upheld in the pursuit of the greatest benefit for the greatest number of people

Applying neutral drift to the directed molecular evolution of a β-glucuronidase into a β-galactosidase: Two different evolutionary pathways lead to the same variant

<p>Abstract</p> <p>Background</p> <p>Directed protein evolution has been used to modify protein activity and research has been carried out to enhance the production of high quality mutant libraries. Many theoretical approaches suggest that allowing a population to undergo neutral selection may be valuable in directed evolution experiments.</p> <p>Findings</p> <p>Here we report on an investigation into the value of neutral selection in a classical model system for directed evolution, the conversion of the <it>E. coli </it>β-glucuronidase to a β-galactosidase activity. We find that neutral selection, i.e. selection for retaining glucuronidase activity, can efficiently identify the majority of sites of mutation that have been identified as beneficial for galactosidase activity in previous experiments. Each variant demonstrating increased galactosidase activity identified by our neutral drift experiments contained a mutation at one of four sites, T509, S557, N566 or W529. All of these sites have previously been identified using direct selection for beta galactosidase activity.</p> <p>Conclusions</p> <p>Our results are consistent with others that show that a neutral selection approach can be effective in selecting improved variants. However, we interpret our results to show that neutral selection is, in this case, not a more efficient approach than conventional directed evolution approaches. However, the neutral approach is likely to be beneficial when the resulting library can be screened for a range of related activities. More detailed statistical studies to resolve the apparent differences between this system and others are likely to be a fruitful avenue for future research.</p

The future of International Classification of Diseases coding in steatotic liver disease:An expert panel Delphi consensus statement

BACKGROUND: Following the adoption of new nomenclature for steatotic liver disease, we aimed to build consensus on the use of International Classification of Diseases codes and recommendations for future research and advocacy.METHODS: Through a two-stage Delphi process, a core group (n = 20) reviewed draft statements and recommendations (n = 6), indicating levels of agreement. Following revisions, this process was repeated with a large expert panel (n = 243) from 73 countries.RESULTS: Consensus ranged from 88.8% to 96.9% (mean = 92.3%).CONCLUSIONS: This global consensus statement provides guidance on harmonizing the International Classification of Diseases coding for steatotic liver disease and future directions to advance the field.</p