Multi-Centre Micro-Costing of Roux-En-Y Gastric Bypass, Sleeve Gastrectomy and Adjustable Gastric Banding Procedures for the Treatment of Severe, Complex Obesity.

Background: There is a growing interest in comparing the effectiveness and costs of alternative forms of bariatric surgery. We aimed to examine the per-patient, procedural costs of Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG) and adjustable gastric banding (AGB) in the United Kingdom.

Methods: Multi-centre (two National Health Service; NHS and one private hospital) micro-costing, using a time-and-motion study.

Airway Microbiome and Development of Bronchopulmonary Dysplasia in Preterm Infants: A Systematic Review.

Objectives: To summarize evidence regarding microbial dysbiosis of the airway associated with bronchopulmonary dysplasia (BPD) and to explore heterogeneity among studies.

Study Design: We included studies that evaluated the airway microbiome in preterm infants who developed BPD using culture-independent molecular techniques and reported alpha- and beta-diversity metrics and microbial profiles.

Results: The 6 included studies had substantial clinical and methodological heterogeneity.

Vasoactive intestinal peptide induces proliferation of human hepatocytes.

Objectives: Proliferation of hepatocytes in vitro can be stimulated by growth factors such as epidermal growth factor (EGF), but the role of vasoactive intestinal peptide (VIP) remains unclear. We have investigated the effect of VIP on maintenance and proliferation of human hepatocytes.

Materials And Methods: Human hepatocytes were isolated from liver specimens obtained from patients undergoing liver surgery.

Adjuvant bevacizumab for melanoma patients at high risk of recurrence: survival analysis of the AVAST-M trial.

Background: Bevacizumab is a recombinant humanised monoclonal antibody to vascular endothelial growth factor shown to improve survival in advanced solid cancers. We evaluated the role of adjuvant bevacizumab in melanoma patients at high risk of recurrence.

Patients And Methods: Patients with resected AJCC stage IIB, IIC and III cutaneous melanoma were randomised to receive either adjuvant bevacizumab (7.

Targeting gp100 and TRP-2 with a DNA vaccine: Incorporating T cell epitopes with a human IgG1 antibody induces potent T cell responses that are associated with favourable clinical outcome in a phase I/II trial.

A DNA vaccine, SCIB1, incorporating two CD8 and two CD4 epitopes from TRP-2/gp100 was evaluated in patients with metastatic melanoma. Each patient received SCIB1 via intramuscular injection with electroporation. The trial was designed to find the safest dose of SCIB1 which induced immune/clinical responses in patients with or without tumour.

What are the optimum components in a care bundle aimed at reducing post-operative pulmonary complications in high-risk patients?

Background: Post-operative pulmonary complications (POPC) are common, predictable and associated with increased morbidity and mortality, independent of pre-operative risk. Interventions to reduce the incidence of POPC have been studied individually, but the use of a care bundle has not been widely investigated. The purpose of our work was to use Delphi consensus methodology and an independently chosen expert panel to formulate a care bundle for patients identified as being at high of POPC, as preparation towards an evaluation of its effectiveness at reducing POPC.

Maternal vitamin D supplementation during pregnancy.

Introduction: Maternal vitamin D status in pregnancy has been linked to many health outcomes in mother and offspring. A wealth of observational studies have reported on both obstetric outcomes and complications, including pre-eclampsia, gestational diabetes, mode and timing of delivery. Many foetal and childhood outcomes are also linked to vitamin D status, including measures of foetal size, body composition and skeletal mineralization, in addition to later childhood outcomes, such as asthma.

Novel and mutation and distinct genetic profiles in MALT lymphomas of different sites.

Mucosa-associated lymphoid tissue (MALT) lymphoma originates from a background of diverse chronic inflammatory disorders at various anatomic sites. The genetics underlying its development, particularly in those associated with autoimmune disorders, is poorly characterized. By whole exome sequencing of 21 cases of MALT lymphomas of the salivary gland and thyroid, we have identified recurrent somatic mutations in 2 G-protein coupled receptors ( and ) not previously reported in human malignancies, 3 genes (, , ) not previously implicated in MALT lymphoma, and a further 2 genes (, ) recently described in MALT lymphoma.

Anti-inflammatory potency testing of topical corticosteroids and calcineurin inhibitors in human volunteers sensitized to diphenylcyclopropenone.

Aims: To quantify the anti-inflammatory potency of topical corticosteroids and topical calcineurin inhibitors by measuring the contact allergic response to a diphenylcyclopropenone (DPCP) challenge in de novo sensitized human volunteers.

Methods: Two randomized, double-blind, vehicle-controlled studies were performed encompassing 76 volunteers: 29 in the first and 47 in the second study. Topical drugs were applied pre- and/or post-treatment in block designs.

Risks of breast or ovarian cancer in BRCA1 or BRCA2 predictive test negatives: findings from the EMBRACE study.

Purpose: BRCA1/BRCA2 predictive test negatives are proven noncarriers of a BRCA1/BRCA2 mutation that is carried by their relatives. The risk of developing breast cancer (BC) or epithelial ovarian cancer (EOC) in these women is uncertain. The study aimed to estimate risks of invasive BC and EOC in a large cohort of BRCA1/BRCA2 predictive test negatives.

Adult height is associated with increased risk of ovarian cancer: a Mendelian randomisation study.

Background: Observational studies suggest greater height is associated with increased ovarian cancer risk, but cannot exclude bias and/or confounding as explanations for this. Mendelian randomisation (MR) can provide evidence which may be less prone to bias.

Methods: We pooled data from 39 Ovarian Cancer Association Consortium studies (16,395 cases; 23,003 controls).

Human physiological and metabolic responses to an attempted winter crossing of Antarctica: the effects of prolonged hypobaric hypoxia.

An insufficient supply of oxygen to the tissues (hypoxia), as is experienced upon high-altitude exposure, elicits physiological acclimatization mechanisms alongside metabolic remodeling. Details of the integrative adaptive processes in response to chronic hypobaric hypoxic exposure remain to be sufficiently investigated. In this small applied field study, subjects (n = 5, male, age 28-54 years) undertook a 40 week Antarctica expedition in the winter months, which included 24 weeks residing above 2500 m.

Mobility shift of beta-dystroglycan as a marker of gene-related muscular dystrophy.

Background: Defects in glycosylation of alpha-dystroglycan (α-DG) cause autosomal-recessive disorders with wide clinical and genetic heterogeneity, with phenotypes ranging from congenital muscular dystrophies to milder limb girdle muscular dystrophies. Patients show variable reduction of immunoreactivity to antibodies specific for glycoepitopes of α-DG on a muscle biopsy. Recessive mutations in 18 genes, including guanosine diphosphate mannose pyrophosphorylase B (), have been reported to date.

Monitoring of arrhythmia and sudden death in a hemodialysis population: The CRASH-ILR Study.

Introduction: It has been suggested that sudden cardiac death (SCD) contributes around 50% of cardiovascular and 27% of all-cause mortality in hemodialysis patients. The true burden of arrhythmias and arrhythmic deaths in this population, however, remains poorly characterised. Cardio Renal Arrhythmia Study in Hemodialysis (CRASH-ILR) is a prospective, implantable loop recorder single centre study of 30 established hemodialysis patients and one of the first to provide long-term ambulatory ECG monitoring.

Incomplete penetrance, variable expressivity, or dosage insensitivity in four families with directly transmitted unbalanced chromosome abnormalities.

The direct transmission of microscopically visible unbalanced chromosome abnormalities (UBCAs) is rare and usually has phenotypic consequences. Here we report four families in which a normal phenotype was initially found in one or more family members. Each UBCA was interpreted with regard to overlapping examples and factors previously associated with transmitted imbalances including incidental ascertainment, low gene density, benign copy number variation (CNV) content, and gene relatedness.

A study of splicing mutations in disorders of sex development.

The presence of splicing sequence variants in genes responsible for sex development in humans may compromise correct biosynthesis of proteins involved in the normal development of gonads and external genitalia. In a cohort of Brazilian patients, we identified mutations in HSD17B3 and SRD5A2 which are both required for human sexual differentiation. A number of these mutations occurred within regions potentially critical for splicing regulation.

Germline variation in ADAMTSL1 is associated with prognosis following breast cancer treatment in young women.

To identify genetic variants associated with breast cancer prognosis we conduct a meta-analysis of overall survival (OS) and disease-free survival (DFS) in 6042 patients from four cohorts. In young women, breast cancer is characterized by a higher incidence of adverse pathological features, unique gene expression profiles and worse survival, which may relate to germline variation. To explore this hypothesis, we also perform survival analysis in 2315 patients aged ≤ 40 years at diagnosis.

Cross-sectional study of the provision of interventional oncology services in the UK.

Objective: To map out the current provision of interventional oncology (IO) services in the UK.

Design: Cross-sectional multicentre study.

Setting: All National Health Service (NHS) trusts in England and Scottish, Welsh and Northern Ireland health boards.

Adult Lifetime Diet Quality and Physical Performance in Older Age: Findings From a British Birth Cohort.

Background: Current evidence that links "healthier" dietary patterns to better measured physical performance is mainly from older populations; little is known about the role of earlier diet. We examined adult diet quality in relation to physical performance at age 60-64 years.

Methods: Diet quality was defined using principal component analysis of dietary data collected at age 36, 43, 53, and 60-64.

Heterozygous mutations affecting the protein kinase domain of cause a syndromic form of developmental delay and intellectual disability.

Introduction: Recent evidence has emerged linking mutations in to syndromic congenital heart disease. We present here genetic and phenotypic data pertaining to 16 individuals with mutations.

Methods: Patients were investigated by exome sequencing, having presented with developmental delay and additional features suggestive of a syndromic cause.

Identifying research priorities for public health research to address health inequalities: use of Delphi-like survey methods.

Background: In the funding of health research and public health research it is vital that research questions posed are important and that funded research meets a research need or a gap in evidence. Many methods are used in the identification of research priorities, however, these can be resource intensive, costly and logistically challenging. Identifying such research priorities can be particularly challenging for complex public health problems as there is a need to consult a number of experts across disciplines and with a range of expertise.

Outcome Analysis of Congenital Diaphragmatic Hernia Cohort before and after Implementation of Standardized Protocol in a Tertiary Neonatal Unit.

Despite evolving evidence and increased understanding, there is a strong argument that best outcomes in managing congenital diaphragmatic hernia (CDH) patients are achieved in centers which have a high admission rate of such patients and follow standardized operating protocols of management. Pneumothorax and air leak syndromes are one of the main causes of pre- and postoperative morbidity in these patients and experts believe that delivery room sedation and gentle ventilation strategies can minimize this. We observed a significant drop in incidence of pneumothorax and reduction of mortality following implementation of standardized guidelines at the neonatal unit at Southampton which is a tertiary-level neonatal care in the southern United Kingdom and a regional referral center for CDH patients.

ESPEN guidelines on nutritional support for polymorbid internal medicine patients.

Background & Aims: Polymorbidity (also known as multimorbidity) - defined as the co-occurrence of at least two chronic health conditions - is highly prevalent, particularly in the hospitalized population. Nonetheless, clinical guidelines largely address individual diseases and rarely account for polymorbidity. The aim of this project was to develop guidelines on nutritional support for polymorbid patients hospitalized in medical wards.

Morbidity After Cardiac Surgery in Patients With Adult Congenital Heart Disease in Comparison With Acquired Disease.

Background: Due to the advancements in congenital cardiac surgery and interventional cardiology in the last 5 decades, more than 85% of congenital heart patients now survive to adulthood.

Methods: This retrospective study included 135 Adult Congenital Heart Disease (ACHD) patients, who had cardiac surgery at Southampton General Hospital over 3 consecutive years. We also included 42 patients with a structurally normal heart who had cardiac surgery for acquired cardiac conditions as a control group.

Significant association between TNFAIP3 inactivation and biased immunoglobulin heavy chain variable region 4-34 usage in mucosa-associated lymphoid tissue lymphoma.

Both antigenic drive and genetic change play critical roles in the development of mucosa-associated lymphoid tissue (MALT) lymphoma, but neither alone is sufficient for malignant transformation, and lymphoma development critically depends on their cooperation. However, which of these different events concur and how they cooperate in MALT lymphomagenesis is totally unknown. To explore this, we investigated somatic mutations of 17 genes and immunoglobulin heavy chain variable region (IGHV) usage in 179 MALT lymphomas from various sites.