Association of breast cancer risk in BRCA1 and BRCA2 mutation carriers with genetic variants showing differential allelic expression: identification of a modifier of breast cancer risk at locus 11q22.3.

Purpose: Cis-acting regulatory SNPs resulting in differential allelic expression (DAE) may, in part, explain the underlying phenotypic variation associated with many complex diseases. To investigate whether common variants associated with DAE were involved in breast cancer susceptibility among BRCA1 and BRCA2 mutation carriers, a list of 175 genes was developed based of their involvement in cancer-related pathways.

Methods: Using data from a genome-wide map of SNPs associated with allelic expression, we assessed the association of ~320 SNPs located in the vicinity of these genes with breast and ovarian cancer risks in 15,252 BRCA1 and 8211 BRCA2 mutation carriers ascertained from 54 studies participating in the Consortium of Investigators of Modifiers of BRCA1/2.

Effects of dietary nitrate supplementation on symptoms of acute mountain sickness and basic physiological responses in a group of male adolescents during ascent to Mount Everest Base Camp.

Unlabelled: The purpose of this study was to investigate the effects of dietary nitrate supplementation, in the form of beetroot juice, on acute mountain sickness (AMS) symptoms and physiological responses, in a group of young males trekking to Mount Everest Base Camp (EBC). Forty healthy male students (mean age (SD): 16 (1) yrs) trekked to EBC over 11 days. Following an overnight fast, each morning participants completed the Lake Louise AMS questionnaire and underwent a series of physiological tests: resting blood pressure as well as resting and exercising heart rate, respiratory rate, and peripheral oxygen saturation.

No Evidence That Genetic Variation in the Myeloid-Derived Suppressor Cell Pathway Influences Ovarian Cancer Survival.

The precise mechanism by which the immune system is adversely affected in cancer patients remains poorly understood, but the accumulation of immunosuppressive/protumorigenic myeloid-derived suppressor cells (MDSCs) is thought to be a prominent mechanism contributing to immunologic tolerance of malignant cells in epithelial ovarian cancer (EOC). To this end, we hypothesized genetic variation in MDSC pathway genes would be associated with survival after EOC diagnoses. We measured the hazard of death due to EOC within 10 years of diagnosis, overall and by invasive subtype, attributable to SNPs in 24 genes relevant in the MDSC pathway in 10,751 women diagnosed with invasive EOC.

Do external support devices reduce sternal wound complications after cardiac surgery?

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether external support devices reduce sternal wound complications after cardiac surgery with sternotomy. Altogether 116 papers were found using the reported search, of which six presented the best evidence to answer the clinical question.

Alcohol consumption, smoking, and drug use in pregnancy: Prevalence and risk factors in Southern Thailand.

Introduction: Substance use during pregnancy contributes to the risk of adverse health outcomes in mothers and children-in utero and during later development. In this study, we investigated the prevalence of substance use and associated factors in pregnant women receiving antenatal care in public hospitals in Thailand.

Methods: Women (3578) attending 7 antenatal care clinics in Songkhla for the first time during their current pregnancy were interviewed with a structured questionnaire focusing on demographic data, obstetric history, use of alcohol, tobacco, and other substances, and the General Health Questionnaire was administered.

Evaluating the risk of ovarian cancer before surgery using the ADNEX model: a multicentre external validation study.

Background: The International Ovarian Tumour Analysis (IOTA) group have developed the ADNEX (The Assessment of Different NEoplasias in the adneXa) model to predict the risk that an ovarian mass is benign, borderline, stage I, stages II-IV or metastatic. We aimed to externally validate the ADNEX model in the hands of examiners with varied training and experience.

Methods: This was a multicentre cross-sectional cohort study for diagnostic accuracy.

Recent advances in the pathogenesis and treatment of osteoporosis.

Over recent decades, the perception of osteoporosis has changed from that of an inevitable consequence of ageing, to that of a well characterised and treatable chronic non-communicable disease, with major impacts on individuals, healthcare systems and societies. Characterisation of its pathophysiology from the hierarchical structure of bone and the role of its cell population, development of effective strategies for the identification of those most appropriate for treatment, and an increasing armamentarium of efficacious pharmacological therapies, have underpinned this evolution. Despite this marked progress, individuals who experience a fragility fracture remain under-treated in many areas of the world, and there is substantial need for investment both in secondary and primary prevention globally.

Fine-Scale Mapping at 9p22.2 Identifies Candidate Causal Variants That Modify Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers.

Population-based genome wide association studies have identified a locus at 9p22.2 associated with ovarian cancer risk, which also modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. We conducted fine-scale mapping at 9p22.

Herpes simplex virus keratitis: an update of the pathogenesis and current treatment with oral and topical antiviral agents.

Ophthalmic herpes simplex viral keratitis is responsible for a range of ocular manifestations from superficial epithelial disease to stromal keratitis and endotheliitis. The Herpetic Eye Disease Study has guided the management of herpetic eye disease for almost twenty years, but newer medications such as valacyclovir are now available and are considered to have better bioavailability than acyclovir. In this review, we examine the existing evidence on the pathogenesis of different ophthalmic herpes simplex viral keratitis disease modalities and the role of oral and topically administered antiviral drugs in the treatment of herpes simplex viral keratitis.

A Cancer Research UK First Time in Human Phase I Trial of IMA950 (Novel Multipeptide Therapeutic Vaccine) in Patients with Newly Diagnosed Glioblastoma.

Purpose: To perform a two-cohort, phase I safety and immunogenicity study of IMA950 in addition to standard chemoradiotherapy and adjuvant temozolomide in patients with newly diagnosed glioblastoma. IMA950 is a novel glioblastoma-specific therapeutic vaccine containing 11 tumor-associated peptides (TUMAP), identified on human leukocyte antigen (HLA) surface receptors in primary human glioblastoma tissue.

Experimental Design: Patients were HLA-A*02-positive and had undergone tumor resection.

Coronary bifurcation lesions treated with simple or complex stenting: 5-year survival from patient-level pooled analysis of the Nordic Bifurcation Study and the British Bifurcation Coronary Study.

Aims: Randomized trials of coronary bifurcation stenting have shown better outcomes from a simple (provisional) strategy rather than a complex (planned two-stent) strategy in terms of short-term efficacy and safety. Here, we report the 5-year all-cause mortality based on pooled patient-level data from two large bifurcation coronary stenting trials with similar methodology: the Nordic Bifurcation Study (NORDIC I) and the British Bifurcation Coronary Study: old, new, and evolving strategies (BBC ONE).

Methods And Results: Both multicentre randomized trials compared simple (provisional T-stenting) vs.

Quality of life, long-term survivors and long-term outcome from the ABC-02 study.

Background: The ABC-02 (Advanced Biliary Tract Cancer) study established cisplatin and gemcitabine (CisGem) as the standard first-line chemotherapy for patients with locally advanced or metastatic biliary tract cancer (BTC). We examine quality of life (QoL), describe the long-term survivors and provide a long-term outcome.

Methods: A total of 410 BTC patients were randomised to receive either CisGem or gemcitabine alone (Gem); 324 patients consented to complete EORTC QLQ-C30 and EORTC QLQ-PAN26 QoL questionnaires; 268 (83%) patients returned at least one QoL questionnaire (134 in each arm).

Genome-wide DNA methylation analysis of transient neonatal diabetes type 1 patients with mutations in ZFP57.

Background: Transient neonatal diabetes mellitus 1 (TNDM1) is a rare imprinting disorder characterized by intrautering growth retardation and diabetes mellitus usually presenting within the first six weeks of life and resolves by the age of 18 months. However, patients have an increased risk of developing diabetes mellitus type 2 later in life. Transient neonatal diabetes mellitus 1 is caused by overexpression of the maternally imprinted genes PLAGL1 and HYMAI on chromosome 6q24.

Skin surgery, an evidence-based update: meeting report.

The Evidence Based Update on Skin Surgery was held in Nottingham in May 2015. The meeting featured presentations on new diagnostic techniques, trials in development, discussions of recently published trials, and a question and answer session with an expert panel. This report aims to summarize the presentations and discussions from the day.

Epidemiology of fractures in the United Kingdom 1988-2012: Variation with age, sex, geography, ethnicity and socioeconomic status.

Unlabelled: Rates of fracture worldwide are changing. Using the Clinical Practice Research Datalink (CPRD), age, and gender, geographical, ethnic and socioeconomic trends in fracture rates across the United Kingdom were studied over a 24-year period 1988-2012. Previously observed patterns in fracture incidence by age and fracture site were evident.

Outcome and recurrence 1 year after pediatric arterial ischemic stroke in a population-based cohort.

Objective: Arterial ischemic stroke (AIS) is an important cause of acquired brain injury in children. Few prospective population-based studies of childhood AIS have been completed. We aimed to investigate the outcome of childhood AIS 12 months after the event in a population-based cohort.

TG4010 immunotherapy and first-line chemotherapy for advanced non-small-cell lung cancer (TIME): results from the phase 2b part of a randomised, double-blind, placebo-controlled, phase 2b/3 trial.

Background: MUC1 is a tumour-associated antigen expressed by many solid tumours, including non-small-cell lung cancer. TG4010 is a modified vaccinia Ankara expressing MUC1 and interleukin 2. In a previous study, TG4010 combined with chemotherapy showed activity in non-small-cell lung cancer and the baseline value of CD16, CD56, CD69 triple-positive activated lymphocytes (TrPAL) was shown to be potentially predictive of TG4010 efficacy.

Local Variation in Femoral Neck Cortical Bone: In Vitro Measured Bone Mineral Density, Geometry and Mechanical Properties.

Age- and disease (osteoporotic fractured and osteoarthritic tissue)-related changes in the distribution of cortical bone were examined, using a multimodality approach, including measurement of local density, geometry and mechanical properties, where changes in these properties can give rise to instability and increasing probability of fracture. In contrast to the majority of previously reported research, this study also focuses on the characteristic non-circular femoral neck cross-sectional geometry and variation in bone mineral density (BMD) around the femoral neck. Twenty-two osteoarthritic and 7 osteoporotic femoral neck slices, collected from elective and trauma-related arthroplasty, and 16 cadaveric donor tissue controls were tested mechanically using Reference Point Indentation (BioDent™, Active Life Technologies®, Santa Barbara, CA) and then scanned with in vitro-based radiography intended to replicate the dual-energy X-ray absorptiometry technique.

Recent advances in the pathogenesis and treatment of osteoporosis.

Over recent decades, the perception of osteoporosis has changed from that of an inevitable consequence of ageing, to that of a well characterised and treatable chronic non-communicable disease, with major impacts on individuals, healthcare systems and societies. Characterisation of its pathophysiology from the hierarchical structure of bone and the role of its cell population, development of effective strategies for the identification of those most appropriate for treatment, and an increasing armamentarium of efficacious pharmacological therapies, have underpinned this evolution. Despite this marked progress, individuals who experience a fragility fracture remain under-treated in many areas of the world, and there is substantial need for investment both in secondary and primary prevention globally.

The evolution of corneal and refractive surgery with the femtosecond laser.

The use of femtosecond lasers has created an evolution in modern corneal and refractive surgery. With accuracy, safety, and repeatability, eye surgeons can utilize the femtosecond laser in almost all anterior refractive procedures; laser in situ keratomileusis (LASIK), small incision lenticule extraction (SMILE), penetrating keratoplasty (PKP), insertion of intracorneal ring segments, anterior and posterior lamellar keratoplasty (Deep anterior lamellar keratoplasty (DALK) and Descemet's stripping endothelial keratoplasty (DSEK)), insertion of corneal inlays and cataract surgery. As the technology matures, it will push surgical limits and open new avenues for ophthalmic intervention in areas not yet explored.