Explore the vast range of titles available.

DNA methylation variations are prevalent in human obesity but evidence of a causative role in disease pathogenesis is limited. Here, we combine epigenome-wide association and integrative genomics to investigate the impact of adipocyte DNA methylation variations in human obesity. We discover extensive DNA methylation changes that are robustly associated with obesity (N = 190 samples, 691 loci in subcutaneous and 173 loci in visceral adipocytes, P < 1 × 10-7). We connect obesity-associated methylation variations to transcriptomic changes at >500 target genes, and identify putative methylation-transcription factor interactions. Through Mendelian Randomisation, we infer causal effects of methylation on obesity and obesity-induced metabolic disturbances at 59 independent loci. Targeted methylation sequencing, CRISPR-activation and gene silencing in adipocytes, further identifies regional methylation variations, underlying regulatory elements and novel cellular metabolic effects. Our results indicate DNA methylation is an important determinant of human obesity and its metabolic complications, and reveal mechanisms through which altered methylation may impact adipocyte functions. DNA methylation variation is associated with human obesity but a whether it plays a causal role in disease pathogenesis is unclear. Here, the authors perfom an integrative genomic study in human adipocytes to show that DNA methylation variations contribute to obesity and type 2 diabetes susceptibility, revealing underlying genomic and molecular mechanisms.

The organisation of the genome in nuclear space is an important frontier of biology. Chromosome conformation capture methods such as Hi-C and Micro-C produce genome-wide chromatin contact maps that provide rich data containing quantitative and qualitative information about genome architecture. Most conventional approaches to genome-wide chromosome conformation capture data are limited to the analysis of pre-defined features, and may therefore miss important biological information. One constraint is that biologically important features can be masked by high levels of technical noise in the data. Here we introduce a replicate-based method for deep learning from chromatin conformation contact maps. Using a Siamese network configuration our approach learns to distinguish technical noise from biological variation and outperforms image similarity metrics across a range of biological systems. The features extracted from Hi-C maps after perturbation of cohesin and CTCF reflect the distinct biological functions of cohesin and CTCF in the formation of domains and boundaries, respectively. The learnt distance metrics are biologically meaningful, as they mirror the density of cohesin and CTCF binding. These properties make our method a powerful tool for the exploration of chromosome conformation capture data, such as Hi-C capture Hi-C, and Micro-C.

Abstract Health care systems and providers have rapidly adapted to virtual care delivery during this unprecedented time. Clinical programs initiated a variety of virtual care delivery models to maintain access to care, preserve personal protective equipment, and minimize infectious disease spread. Herein, we first describe the context within paediatric health delivery during the COVID-19 pandemic in Canada that fueled the rise of virtual care delivery. We then summarize the development, implementation, and beneficial impact of the innovative virtual care delivery programs currently in use at Children’s Hospital of Eastern Ontario (CHEO) for both inpatient and outpatient care, specifically in our ambulatory clinics, emergency department, and mental health program. We highlight the transferable unique ways CHEO has integrated virtual care delivery through our governance structure, stakeholder engagement including patient, caregivers and health care providers and staff, development, and use of eHealth tools and novel approaches for patient care requiring physical assessment. We conclude with our vision for the future of virtual care, one component of paediatric care delivery in the post-COVID-19 era, which requires a common framework for virtual care evaluation. Importantly, rapid implementation of a primarily virtual care model at CHEO sustained high volume quality paediatric care. We believe many of these programs should and will remain in the post-pandemic era. A comprehensive, unified approach to evaluation is essential to yield meaningful results that inform sustainable care delivery models that integrate virtual care, and ultimately help ensure the best health outcomes for our patients.

Background Family-centered rounds (FCR) are fundamental to pediatric inpatient care. During the COVID-19 pandemic, we aimed to design and implement a virtual family-centered rounds (vFCR) process that allowed continuation of inpatient rounds while following physical distancing guidelines and preserving personal protective equipment (PPE). Methods A multidisciplinary team developed the vFCR process using a participatory design approach. From April through July 2020, quality improvement methods were used to iteratively evaluate and improve the process. Outcome measures included satisfaction, perceived effectiveness, and perceived usefulness of vFCR. Data were collected via questionnaire distributed to patients, families, staff and medical staff, and analyzed using descriptive statistics and content analysis. Virtual auditors monitored time per patient round and transition time between patients as balancing measures. Results Seventy-four percent (51/69) of health care providers surveyed and 79% (26/33) of patients and families were satisfied or very satisfied with vFCR. Eighty eight percent (61/69) of health care providers and 88% (29/33) of patients and families felt vFCR were useful. Audits revealed an average vFCR duration of 8.4 min (SD = 3.9) for a single patient round and transition time between patients averaged 2.9 min (SD = 2.6). Conclusion Virtual family-centered rounds are an acceptable alternative to in-person FCR in a pandemic scenario, yielding high levels of stakeholder satisfaction and support. We believe vFCR are a useful method to support inpatient rounds, physical distancing, and preservation of PPE that may also be valuable beyond the pandemic. A rigorous process evaluation of vFCR is underway.

Previous studies have found that up to 60% of children with neurologic conditions have tried complementary and alternative medicine (CAM). To assess the use of CAM among patients presenting to neurology clinics at two academic centers in Canada. A survey instrument was developed to inquire about use of CAM products and therapies, including reasons for use, perceived helpfulness, and concurrent use with conventional medicine, and administered to patients or their parents/guardians at the Stollery Children's Hospital in Edmonton and the Children's Hospital of Eastern Ontario (CHEO) in Ottawa. Overall CAM use at the Stollery was 78%, compared to 48% at CHEO. The most common CAM products used were multi-vitamins (84%), vitamin C (37%), homeopathic remedies (24%), and fish oil/omega 3 s (22%). The most common CAM practices used were massage (47%), chiropractic (37%), faith healing (18%), aromatherapy (16%), homeopathy (16%), and relaxation (16%). Many patients used CAM products at the same time as conventional medicine but just over half (57%) discussed this concurrent use with their physician. CAM use is common in pediatric neurology patients and most respondents felt that it was helpful, with few or no harms associated. However, this use is often undisclosed, increasing possibility of interactions with conventional drugs. We urge clinicians to inquire about CAM use during routine history taking at every patient visit. Parents would clearly like more information about CAM from their specialty clinics; such information would be easier to share if more primary data were available about the safety and effectiveness of commonly used therapies.

Background The use of virtual care has increased dramatically in response to the COVID-19 pandemic, yet evidence is lacking regarding the impact of virtual care on patient outcomes, particularly in pediatrics. A standardized evaluation approach is required to support the integration of virtual care into pediatric health care delivery programs. The objective of this work was to develop a comprehensive and structured framework for pediatric virtual care evaluation. This framework is intended to engage and guide care providers, health centres, and stakeholders towards the development of a standardized approach to the evaluation of pediatric virtual care. Methods We brought together a diverse multidisciplinary team, including pediatric clinicians, researchers, digital health leads and analysts, program leaders, a human factors engineer, a family advisor and our manager of health equity and diversity. The team reviewed the literature, including published evaluation frameworks, and used a consensus-based method to develop a virtual care evaluation framework applicable to a broad spectrum of pediatric virtual care programs. We used an iterative process to develop framework components, including domains and sub-domains, examples of evaluation questions, measures, and data sources. Team members met repeatedly over seven months to generate and provide feedback on all components of the framework, making revision as needed until consensus was reached. The framework was then applied to an existing virtual care program. Results The resulting framework includes four domains (health outcomes, health delivery, individual experience, and program implementation) and 19 sub-domains designed to support the development and evaluation of pediatric virtual care programs. We also developed guidance on how to use the framework and illustrate its utility by applying it to an existing pediatric virtual care program. Conclusions This virtual care evaluation framework expands on previously developed frameworks by providing additional detail and a structure that supports practical application. It can be used to evaluate a wide range of pediatric virtual care programs in a standardized manner. Use of this comprehensive yet easy to use evaluation framework will inform appropriate implementation and integration of virtual care into routine practice and support its sustainability and continuous improvement.

X chromosome inactivation (XCI) generates clonal heterogeneity within XX individuals. Combined with sequence variation between human X chromosomes, XCI gives rise to intra-individual clonal diversity, whereby two sets of clones express mutually exclusive sequence variants present on one or the other X chromosome. Here we ask whether such clones merely co-exist or potentially interact with each other to modulate the contribution of X-linked diversity to organismal development. Focusing on X-linked coding variation in the human STAG2 gene, we show that Stag2 variant clones contribute to most tissues at the expected frequencies but fail to form lymphocytes in Stag2 WT Stag2 variant mouse models. Unexpectedly, the absence of Stag2 variant clones from the lymphoid compartment is due not solely to cell-intrinsic defects but requires continuous competition by Stag2 WT clones. These findings show that interactions between epigenetically diverse clones can operate in an XX individual to shape the contribution of X-linked genetic diversity in a cell-type-specific manner. Clones expressing variants of the X-chromosome-linked STAG2 gene only form lymphocytes in the absence of Stag2 WT clones. Interactions between epigenetic clones can thus modulate the impact of X-chromosome-linked genetic diversity in a cell-type-specific manner.

A unique and fascinating collection of letters from a soldier, planter, and journalist The Union states of what is now the Midwest have received far less attention from historians than those of the East, and much of Michigan's Civil War story remains untold. The eloquent letters of James W. King shed light on a Civil War regiment that played important roles in the battles of Stones River, Chickamauga, and Missionary Ridge. King enlisted in the 11th Michigan in 1861 as a private and rose to the rank of quartermaster sergeant. His correspondence continues into the era of Reconstruction, when he tried his hand at raising cotton in Tennessee and Alabama and found himself caught up in the social and political upheavals of the postwar South. King went off to war as an obscure nineteen-year-old farm boy, but he was anything but average. His letters to Sarah Jane Babcock, his future wife, vividly illustrate the plight and perspective of the rank-and-file Union infantryman while revealing the innermost thoughts of an articulate, romantic, and educated young man. King's wartime correspondence explores a myriad of issues faced by the common Federal soldier: the angst, uncertainty, and hope associated with long-distance courtship; the scourge of widespread and often fatal diseases; the rapid evolution of views on race and slavery; the doldrums of camp life punctuated with the horrors of combat and its aftermath; the gnawing anxiety while waiting for mail from home; the incessant gambling, drunkenness, and profanity of his comrades; and the omnipresent risk of death or crippling disability as the cost of performing his duty: to preserve the Union. Through meticulous research and careful editing, Eric R. Faust presents a story that does not cease with King's muster out, or even with Lee's surrender at Appomattox. King's postwar correspondence illuminates the struggles of a soldier disabled by wounds, trying to find his place in a civilian world forever changed by war. Like thousands of other Northern soldiers, King traveled south to raise cotton. The letters he penned on the plantation defy the timeworn stereotype of carpetbaggers as ruthless opportunists who deprived the South of its capital and dignity after the war. A kind twist of fate boosted King to prominence in his home state as editor of Michigan's foremost Republican newspaper and set him on a path to national notoriety. Through King's remarkable rise to the national stage, the reader gains insight into the heated political climate of the Reconstruction era and the Gilded Age, and more generally into the deeply complex legacy of the American Civil War.

Key Clinical Message Thanatophoric dysplasia is typically a neonatal lethal condition. However, for those rare individuals who do survive, there is the development of seizures, progression of craniocervical stenosis, ventilator dependence, and limitations in motor and cognitive abilities. Families must be made aware of these issues during the discussion of management plans. Thanatophoric dysplasia is typically a neonatal lethal condition. However, for those rare individuals who do survive, there is the development of seizures, progression of craniocervical stenosis, ventilator dependence, and limitations in motor and cognitive abilities. Families must be made aware of these issues during the discussion of management plans.