Examining the role of common variants in rare neurodevelopmental conditions.

Although rare neurodevelopmental conditions have a large Mendelian component, common genetic variants also contribute to risk. However, little is known about how this polygenic risk is distributed among patients with these conditions and their parents nor its interplay with rare variants. It is also unclear whether polygenic background affects risk directly through alleles transmitted from parents to children, or whether indirect genetic effects mediated through the family environment also play a role.

Nurse and doctor turnover and patient outcomes in NHS acute trusts in England: retrospective longitudinal study.

Objective: To investigate the association between monthly turnover rates of hospital nurses and senior doctors and patient health outcomes (mortality and unplanned hospital readmissions).

Design: Retrospective longitudinal study.

Setting: All 148 NHS acute trusts in England (1 April 2010 to 30 March 2019), excluding specialist and community NHS hospital trusts.

The Context of the Emergency Department as a Location for a Smoking Cessation Intervention-Process Evaluation Findings From the Cessation of Smoking Trial in the Emergency Department Trial.

Introduction: Hospital emergency departments (ED) offer an opportunity to engage with large numbers of people who smoke to prompt cessation, although the acceptability of opportunistic intervention in this context has been questioned. This process evaluation study was embedded into the Cessation of Smoking Trial in the Emergency Department (COSTED) randomized controlled trial and sought to explore the context of intervention delivery within the ED.

Aims And Methods: Qualitative interviews were conducted with participants and staff across six EDs participating in the COSTED randomized controlled trial.

Cost-utility analysis of provision of e-cigarette starter kits for smoking cessation in emergency departments: An economic evaluation of a randomized controlled trial.

Aims: To assess the cost-effectiveness of the Cessation of Smoking Trial in Emergency Department (COSTED) intervention compared with signposting to local stop smoking service (SSS) from the National Health Service (NHS) and personal social services (PSS) perspective.

Design, Setting And Participants: This was a two-group, multi-centre, pragmatic, individually randomized controlled trial set in six Emergency Departments (EDs) in urban and rural areas in the United Kingdom. Adult (≥ 18 years) daily smokers (at least one cigarette or equivalent per day) but not daily e-cigarette users, with carbon monoxide reading ≥ 8 parts per million, attending the ED (n = 972) were included.

Federated analysis of autosomal recessive coding variants in 29,745 developmental disorder patients from diverse populations.

Autosomal recessive coding variants are well-known causes of rare disorders. We quantified the contribution of these variants to developmental disorders in a large, ancestrally diverse cohort comprising 29,745 trios, of whom 20.4% had genetically inferred non-European ancestries.

The meaning of apathy in Huntington's disease: A qualitative study of caregiver perspectives.

Although one of the most prevalent and impactful features of Huntington's disease (HD), little is known about the impact of apathy on HD caregivers, although there is evidence it affects perceptions of distress and burden. Given the importance of the caregivers, we aimed to explore the lived experience of people supporting someone with HD and associated apathy. Semi-structured interviews were conducted with 11 caregivers and analysed using reflective thematic analysis, informed by a phenomenological framework.

International Council for Standardization in Haematology (ICSH) recommendations for the performance and interpretation of activated partial thromboplastin time and prothrombin time mixing tests.

This guidance document has been prepared on behalf of the International Council for Standardization in Haematology (ICSH). The aim of the document is to provide guidance and recommendations for the performance and interpretation of activated partial thromboplastin time (APTT) and prothrombin time (PT) plasma mixing tests in clinical laboratories in all regions of the world. The following areas are included in this document: preanalytical, analytical, postanalytical, and quality assurance considerations as they relate to the proper performance and interpretation of plasma mixing tests.

Intravenous Versus Subcutaneous Infliximab in Inflammatory Bowel Disease: A Systematic Review and Meta-analysis.

Background: Subcutaneous [SC] infliximab may provide multiple benefits over intravenous [IV] formulations. However, studies for efficacy and safety in inflammatory bowel disease [IBD] have been constrained by small sizes that limit the interpretation of outcomes, particularly for subgroups potentially at high risk of disease relapse.

Methods: We conducted a systematic review and random-effects meta-analysis up to January 2023, to evaluate the change in clinical remission after transitioning from IV to SC infliximab in patients with IBD in clinical remission.

Fetal brain growth and infant autistic traits.

Background: Structural differences exist in the brains of autistic individuals. To date only a few studies have explored the relationship between fetal brain growth and later infant autistic traits, and some have used fetal head circumference (HC) as a proxy for brain development. These findings have been inconsistent.

Resuscitate, not palliate, emergency care.

Emergency care in the UK is in crisis, and stories of long waits, poor care and harm have become commonplace. This situation can no longer be ignored. This article looks at some of the ways in which emergency care can be resuscitated.

Genomic Diagnosis of Rare Pediatric Disease in the United Kingdom and Ireland.

Background: Pediatric disorders include a range of highly penetrant, genetically heterogeneous conditions amenable to genomewide diagnostic approaches. Finding a molecular diagnosis is challenging but can have profound lifelong benefits.

Methods: We conducted a large-scale sequencing study involving more than 13,500 families with probands with severe, probably monogenic, difficult-to-diagnose developmental disorders from 24 regional genetics services in the United Kingdom and Ireland.

Targeting Senescence as a Therapeutic Opportunity for Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is associated with an elevated risk of recurrence and poor prognosis. Historically, only chemotherapy was available as systemic treatment, but immunotherapy and targeted therapies currently offer prolonged benefits. TNBC is a group of diseases with heterogeneous treatment sensitivity, and resistance is inevitable and early for a large proportion of the intrinsic subtypes.

An optoacoustic imaging feature set to characterise blood vessels surrounding benign and malignant breast lesions.

Combining optoacoustic (OA) imaging with ultrasound (US) enables visualisation of functional blood vasculature in breast lesions by OA to be overlaid with the morphological information of US. Here, we develop a simple OA feature set to differentiate benign and malignant breast lesions. 94 female patients with benign, indeterminate or suspicious lesions were recruited and underwent OA-US.

Digit ratio (2D:4D) and maternal testosterone-to-estradiol ratio measured in early pregnancy.

The ratio of index to ring finger (2D:4D) has been hypothesised to indicate prenatal androgen exposure, yet evidence for its validity is lacking. We report the first pre-registered study to investigate mothers' early pregnancy sex hormone concentrations in relation to their children's digit ratios measured at 18-22-month follow-up. Although the testosterone (T) to estradiol (E) ratio correlated negatively with right hand digit ratio (R2D:4D) and directional asymmetry (right-minus-left) in digit ratio (D), neither effect remained statistically significant once demographic and obstetric covariates were controlled for.

Urinary extracellular vesicles as a source of protein-based biomarkers in feline chronic kidney disease and hypertension.

Objectives: To validate a methodology for isolating feline urinary extracellular vesicles and characterise the urinary extracellular vesicle population and proteome in cats with normal renal function and cats with normotensive or hypertensive chronic kidney disease.

Methods: Feline urinary extracellular vesicles were isolated using three different methods (precipitation alone, precipitation followed by size exclusion chromatography and ultrafiltration followed by size exclusion chromatography, which were compared via transmission electron microscopy and nanoparticle tracking analysis. Cats with normal renal function (n=9), normotensive chronic kidney disease (n=10) and hypertensive chronic kidney disease (n=9) were identified and urinary extracellular vesicles isolated from patient urine samples via ultrafiltration followed by size exclusion chromatography.

Vitamin D and COVID-19-Revisited.

Vitamin D, when activated to 1,25-dihydroxyvitamin D, is a steroid hormone that induces responses in several hundred genes, including many involved in immune responses to infection. Without supplementation, people living in temperate zones commonly become deficient in the precursor form of vitamin D, 25-hydroxyvitamin D, during winter, as do people who receive less sunlight exposure or those with darker skin pigmentation. Studies performed pre-COVID-19 have shown significant but modest reduction in upper respiratory infections in people receiving regular daily vitamin D supplementation.

Systematic Review of the Effectiveness of Advocacy Interventions for Adult Victims of Domestic Violence Within an Emergency Department Setting.

Advocacy interventions for survivors of domestic violence are well established and supported by evidence in some community and healthcare settings. Survivors of domestic violence identified in emergency departments have important differences, and it is not clear whether evidence can be applied to this population. We conducted an inclusive systematic review of controlled studies evaluating the effectiveness of advocacy workers for adult survivors identified in emergency departments.

Multiparametric High-Content Cell Painting Identifies Copper Ionophores as Selective Modulators of Esophageal Cancer Phenotypes.

Esophageal adenocarcinoma is of increasing global concern due to increasing incidence, a lack of effective treatments, and poor prognosis. Therapeutic target discovery and clinical trials have been hindered by the heterogeneity of the disease, the lack of "druggable" driver mutations, and the dominance of large-scale genomic rearrangements. We have previously undertaken a comprehensive small-molecule phenotypic screen using the high-content Cell Painting assay to quantify the morphological response to a total of 19,555 small molecules across a panel of genetically distinct human esophageal cell lines to identify new therapeutic targets and small molecules for the treatment of esophageal adenocarcinoma.

Personalised Risk Prediction in Hereditary Breast and Ovarian Cancer: A Protocol for a Multi-Centre Randomised Controlled Trial.

Women who test positive for an inherited pathogenic/likely pathogenic gene variant in , and are at an increased risk of developing certain types of cancer-specifically breast (all) and epithelial ovarian cancer (only ). Women receive broad cancer risk figures that are not personalised (e.g.

Multiparameter platelet function analysis of bleeding patients with a prolonged platelet function analyser closure time.

Patients referred for evaluation of bleeding symptoms occasionally have a prolonged platelet function analyser (PFA) closure time, without evidence for von Willebrand disease or impaired platelet aggregation. The aim of this study was to establish a shear-dependent platelet function defect in these patients. Patients were included based on high bleeding score and prior PFA prolongation.

Paediatric NHS 111 Clinical Assessment Services pilot: an observational study.

Objective: To determine the feasibility and impact of having paediatric clinicians working in the Clinical Assessment Services (CAS) within NHS 111, a national telephone advice service.

Design: Observational study.

Setting: Six NHS 111 providers across England with CAS where volunteer paediatric clinicians (doctors and advanced nurse practitioners (ANPs)) worked between May and December 2020.

Maternal steroid levels and the autistic traits of the mother and infant.

Background: Prenatal sex steroids have been associated with autism in several clinical and epidemiological studies. It is unclear how this relates to the autistic traits of the mother and how early this can be detected during pregnancy and postnatal development.

Methods: Maternal serum was collected from pregnant women (n = 122) before or during their first ultrasound appointment [mean = 12.