Randomised controlled trial to establish the clinical and cost-effectiveness of expectant management versus preoperative imaging with magnetic resonance cholangiopancreatography in patients with symptomatic gallbladder disease undergoing laparoscopic cholecystectomy at low or moderate risk of common bile duct stones (The Sunflower Study): a study protocol.

Introduction: Surgery to remove the gallbladder (laparoscopic cholecystectomy (LC)) is the standard treatment for symptomatic gallbladder disease. One potential complication of gallbladder disease is that gallstones can pass into the common bile duct (CBD) where they may remain dormant, pass spontaneously into the bowel or cause problems such as obstructive jaundice or pancreatitis. Patients requiring LC are assessed preoperatively for their risk of CBD stones using liver function tests and imaging.

Developing a reporting guideline for artificial intelligence-centred diagnostic test accuracy studies: the STARD-AI protocol.

Introduction: Standards for Reporting of Diagnostic Accuracy Study (STARD) was developed to improve the completeness and transparency of reporting in studies investigating diagnostic test accuracy. However, its current form, STARD 2015 does not address the issues and challenges raised by artificial intelligence (AI)-centred interventions. As such, we propose an AI-specific version of the STARD checklist (STARD-AI), which focuses on the reporting of AI diagnostic test accuracy studies.

Lung function and peak oxygen uptake in chronic obstructive pulmonary disease phenotypes with and without emphysema.

Previous studies of associations of forced expiratory lung volume in one second (FEV1) with peak oxygen uptake (VO2peak) in chronic obstructive pulmonary disease (COPD) have not taken sex, age and height related variance of dynamic lung volumes into account. Nor have such demographic spread of spirometric measures been considered in studies comparing VO2peak between COPD phenotypes characterized by degree of emphysema. We aimed to assess the association of FEV1Z-score with VO2peak in COPD (n = 186) and investigate whether this association differs between emphysema (E-COPD) and non-emphysema (NE-COPD) phenotypes.

Potential impacts of general practitioners working in or alongside emergency departments in England: initial qualitative findings from a national mixed-methods evaluation.

Objectives: To explore the potential impacts of introducing General Practitioners into Emergency Departments (GPED) from the perspectives of service leaders, health professionals and patients. These 'expectations of impact' can be used to generate hypotheses that will inform future implementations and evaluations of GPED.

Design: Qualitative study consisting of 228 semistructured interviews.

Genome-Wide Association Study Identifies Two Novel Loci Associated with Female Stress and Urgency Urinary Incontinence.

Purpose: Genome-wide association studies have not identified replicable genetic risk loci for stress or urgency urinary incontinence.

Materials And Methods: We carried out a discovery stage, case control, genome-wide association study in 3 independent discovery cohorts of European women (8,979) for stress incontinence, urgency incontinence, and any incontinence phenotypes. We conducted replication in 6 additional studies of European ancestry (4,069).

Childhood obesity and multiple sclerosis: A Mendelian randomization study.

Background: Higher childhood body mass index (BMI) has been associated with an increased risk of multiple sclerosis (MS).

Objective: To evaluate whether childhood BMI has a causal influence on MS, and whether this putative effect is independent from early adult obesity and pubertal timing.

Methods: We performed Mendelian randomization (MR) using summary genetic data on 14,802 MS cases and 26,703 controls.

Bisphosphonates to reduce bone fractures in stage 3B+ chronic kidney disease: a propensity score-matched cohort study.

Background: Bisphosphonates are contraindicated in patients with stage 4+ chronic kidney disease. However, they are widely used to prevent fragility fractures in stage 3 chronic kidney disease, despite a lack of good-quality data on their effects.

Objectives: The aims of each work package were as follows.

Influence of agents and mechanisms of injury on anatomical burn locations in children <5 years old with a scald.

Objective: To demonstrate how the mechanism and agent of injury can influence the anatomical location of a scald.

Design: Prospective multicentre cross-sectional study.

Setting: 20 hospital sites across England and Wales including emergency departments, minor injury units and regional burns units.

Evaluation of the efficacy and impact of a clinical prediction tool to identify maltreatment associated with children's burns.

Background: An estimated 10%-24% of children attending emergency departments with a burn are maltreated.

Objective: To test whether a clinical prediction tool (Burns Risk assessment for Neglect or abuse Tool; BuRN-Tool) improved the recognition of maltreatment and increased the referral of high-risk children to safeguarding services for assessment.

Methods: A prospective study of children presenting with burns to four UK hospitals (2015-2018), each centre providing a minimum of 200 cases before and after the introduction of the BuRN-Tool.

The relative contributions of obesity, vitamin D, leptin, and adiponectin to multiple sclerosis risk: A Mendelian randomization mediation analysis.

Background: Obesity is associated with increased risk of multiple sclerosis (MS); however, the underlying mechanisms remain unclear.

Objective: To determine the extent to which decreased vitamin D bioavailability and altered levels of adiponectin and leptin mediate the association between obesity and MS.

Methods: We performed Mendelian randomization (MR) analyses to estimate the effects on MS of body mass index (BMI), 25-hydroxyvitamin D (25OHD), adiponectin, and leptin levels in a cohort of 14,802 MS cases and 26,703 controls.

Epigenetic profiling of social communication trajectories and co-occurring mental health problems: a prospective, methylome-wide association study.

While previous studies suggest that both genetic and environmental factors play an important role in the development of autism-related traits, little is known about potential biological mechanisms underlying these associations. Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC), we examined prospective associations between DNA methylation (DNAm: = 804, = 877) and trajectories of social communication deficits at age 8-17 years. Methylomic variation at three loci across the genome (false discovery rate = 0.

genetic variants and cognitive abilities: a large-scale Mendelian randomization study.

Introduction: PCSK9 inhibitors lower low-density lipoprotein (LDL) cholesterol and are efficacious at reducing vascular disease, however questions remain about potential effects on cognitive function.

Methods: We examined the association of genetic variants in with continuous measures of cognitive ability in UK Biobank. Six independent polymorphisms in were used in up to 337,348 individuals.

Why, when and how do secondary-care clinicians have emergency care and treatment planning conversations? Qualitative findings from the ReSPECT Evaluation study.

Background: The Recommended Summary Plan for Emergency Care and Treatment (ReSPECT) is an emergency care and treatment planning (ECTP) process, developed to offer a patient-centred approach to deciding about and recording treatment recommendations. Conversations between clinicians and patients or their representatives are central to the ReSPECT process. This study aims to understand why, when, and how ReSPECT conversations unfold in practice.

Exposure to multiple childhood social risk factors and adult body mass index trajectories from ages 20 to 64 years.

Background: While childhood social risk factors appear to be associated with adult obesity, it is unclear whether exposure to multiple childhood social risk factors is associated with accelerated weight gain during adulthood.

Methods: We used the Medical Research Council National Survey of Health and Development, a British population-based birth cohort study of participants born in 1946, height and weight were measured by nurses at ages 36, 43, 53 and 60-64 and self-reported at 20 and 26 years. The 9 childhood socioeconomic risk factors and 8 binary childhood psychosocial risk factors were measured, with 13 prospectively measured at age 4 years (or at 7 or 11 years if missing) and 3 were recalled when participants were age 43.

Additional SNPs improve risk stratification of a polygenic hazard score for prostate cancer.

Background: Polygenic hazard scores (PHS) can identify individuals with increased risk of prostate cancer. We estimated the benefit of additional SNPs on performance of a previously validated PHS (PHS46).

Materials And Method: 180 SNPs, shown to be previously associated with prostate cancer, were used to develop a PHS model in men with European ancestry.

Solution Structure and Conformational Dynamics of a Doublet Acyl Carrier Protein from Prodigiosin Biosynthesis.

The acyl carrier protein (ACP) is an indispensable component of both fatty acid and polyketide synthases and is primarily responsible for delivering acyl intermediates to enzymatic partners. At present, increasing numbers of multidomain ACPs have been discovered with roles in molecular recognition of trans-acting enzymatic partners as well as increasing metabolic flux. Further structural information is required to provide insight into their function, yet to date, the only high-resolution structure of this class to be determined is that of the doublet ACP (two continuous ACP domains) from mupirocin synthase.

Long-term effects of stress early in life on microRNA-30a and its network: Preventive effects of lurasidone and potential implications for depression vulnerability.

Exposure to early life stress can interfere with neurodevelopmental trajectories to increase the vulnerability for psychiatric disorders later in life. With this respect, epigenetic mechanisms play a key role for the long-lasting changes in brain functions that may elicit and sustain psychopathologic outcomes. Here, we investigated DNA methylation changes as possible epigenetic mechanism mediating the effect of prenatal stress (PNS), an experimental paradigm associated with behavioral and molecular alterations relevant for psychiatric disorders.

Sex Differences in the Risk of Coronary Heart Disease Associated With Type 2 Diabetes: A Mendelian Randomization Analysis.

Objective: Observational studies have demonstrated that type 2 diabetes is a stronger risk factor for coronary heart disease (CHD) in women compared with men. However, it is not clear whether this reflects a sex differential in the causal effect of diabetes on CHD risk or results from sex-specific residual confounding.

Research Design And Methods: Using 270 single nucleotide polymorphisms (SNPs) for type 2 diabetes identified in a type 2 diabetes genome-wide association study, we performed a sex-stratified Mendelian randomization (MR) study of type 2 diabetes and CHD using individual participant data in UK Biobank (251,420 women and 212,049 men).

Women's experiences and expectations after disclosure of intimate partner abuse to a healthcare provider: A qualitative meta-synthesis.

Objective: To identify and synthesise the experiences and expectations of women victim/survivors of intimate partner abuse (IPA) following disclosure to a healthcare provider (HCP).

Methods: The databases MEDLINE, Embase, CINAHL, PsychINFO, SocINDEX, ASSIA and the Cochrane Library were searched in February 2020. Included studies needed to focus on women's experiences with and expectations of HCPs after disclosure of IPA.

Adding web-based behavioural support to exercise referral schemes for inactive adults with chronic health conditions: the e-coachER RCT.

Background: There is modest evidence that exercise referral schemes increase physical activity in inactive individuals with chronic health conditions. There is a need to identify additional ways to improve the effects of exercise referral schemes on long-term physical activity.

Objectives: To determine if adding the e-coachER intervention to exercise referral schemes is more clinically effective and cost-effective in increasing physical activity after 1 year than usual exercise referral schemes.

Factors associated with the development of paediatric chronic otitis media by age nine: a prospective longitudinal cohort study of 6560 children.

Objective: This study aimed to analyse social, health and environmental factors associated with the development of chronic otitis media by age nine.

Method: This was a prospective, longitudinal, birth cohort study of 6560 children, reviewed at age nine. Chronic otitis media defined as previous surgical history or video-otoscopic changes of tympanic membrane retraction, perforation or cholesteatoma.