Gene-environment interactions involving functional variants: Results from the Breast Cancer Association Consortium.

Investigating the most likely causal variants identified by fine-mapping analyses may improve the power to detect gene-environment interactions. We assessed the interplay between 70 single nucleotide polymorphisms identified by genetic fine-scale mapping of susceptibility loci and 11 epidemiological breast cancer risk factors in relation to breast cancer. Analyses were conducted on up to 58,573 subjects (26,968 cases and 31,605 controls) from the Breast Cancer Association Consortium, in one of the largest studies of its kind.

Hypomorphic Missense Variants Confer Moderate Risks of Breast Cancer.

Breast cancer risks conferred by many germline missense variants in the and genes, often referred to as variants of uncertain significance (VUS), have not been established. In this study, associations between 19 BRCA1 and 33 BRCA2 missense substitution variants and breast cancer risk were investigated through a breast cancer case-control study using genotyping data from 38 studies of predominantly European ancestry (41,890 cases and 41,607 controls) and nine studies of Asian ancestry (6,269 cases and 6,624 controls). The BRCA2 c.

TP53-based interaction analysis identifies cis-eQTL variants for TP53BP2, FBXO28, and FAM53A that associate with survival and treatment outcome in breast cancer.

TP53 overexpression is indicative of somatic TP53 mutations and associates with aggressive tumors and poor prognosis in breast cancer. We utilized a two-stage SNP association study to detect variants associated with breast cancer survival in a TP53-dependent manner. Initially, a genome-wide study (n = 575 cases) was conducted to discover candidate SNPs for genotyping and validation in the Breast Cancer Association Consortium (BCAC).

Prioritizing problems in and solutions to homecare safety of people with dementia: supporting carers, streamlining care.

Background: Dementia care is predominantly provided by carers in home settings. We aimed to identify the priorities for homecare safety of people with dementia according to dementia health and social care professionals using a novel priority-setting method.

Methods: The project steering group determined the scope, the context and the criteria for prioritization.

ARIA 2016: Care pathways implementing emerging technologies for predictive medicine in rhinitis and asthma across the life cycle.

The Allergic Rhinitis and its Impact on Asthma (ARIA) initiative commenced during a World Health Organization workshop in 1999. The initial goals were (1) to propose a new allergic rhinitis classification, (2) to promote the concept of multi-morbidity in asthma and rhinitis and (3) to develop guidelines with all stakeholders that could be used globally for all countries and populations. ARIA-disseminated and implemented in over 70 countries globally-is now focusing on the implementation of emerging technologies for individualized and predictive medicine.

Identification of priorities for improvement of medication safety in primary care: a PRIORITIZE study.

Background: Medication error is a frequent, harmful and costly patient safety incident. Research to date has mostly focused on medication errors in hospitals. In this study, we aimed to identify the main causes of, and solutions to, medication error in primary care.

rs2735383, located at a microRNA binding site in the 3'UTR of NBS1, is not associated with breast cancer risk.

NBS1, also known as NBN, plays an important role in maintaining genomic stability. Interestingly, rs2735383 G > C, located in a microRNA binding site in the 3'-untranslated region (UTR) of NBS1, was shown to be associated with increased susceptibility to lung and colorectal cancer. However, the relation between rs2735383 and susceptibility to breast cancer is not yet clear.

Association of breast cancer risk with genetic variants showing differential allelic expression: Identification of a novel breast cancer susceptibility locus at 4q21.

There are significant inter-individual differences in the levels of gene expression. Through modulation of gene expression, cis-acting variants represent an important source of phenotypic variation. Consequently, cis-regulatory SNPs associated with differential allelic expression are functional candidates for further investigation as disease-causing variants.

Evidence that the 5p12 Variant rs10941679 Confers Susceptibility to Estrogen-Receptor-Positive Breast Cancer through FGF10 and MRPS30 Regulation.

Genome-wide association studies (GWASs) have revealed increased breast cancer risk associated with multiple genetic variants at 5p12. Here, we report the fine mapping of this locus using data from 104,660 subjects from 50 case-control studies in the Breast Cancer Association Consortium (BCAC). With data for 3,365 genotyped and imputed SNPs across a 1 Mb region (positions 44,394,495-45,364,167; NCBI build 37), we found evidence for at least three independent signals: the strongest signal, consisting of a single SNP rs10941679, was associated with risk of estrogen-receptor-positive (ER) breast cancer (per-g allele OR ER = 1.

Clinician-identified problems and solutions for delayed diagnosis in primary care: a PRIORITIZE study.

Background: Delayed diagnosis in primary care is a common, harmful and costly patient safety incident. Its measurement and monitoring are underdeveloped and underutilised. We created and implemented a novel approach to identify problems leading to and solutions for delayed diagnosis in primary care.

Fine scale mapping of the 17q22 breast cancer locus using dense SNPs, genotyped within the Collaborative Oncological Gene-Environment Study (COGs).

Genome-wide association studies have found SNPs at 17q22 to be associated with breast cancer risk. To identify potential causal variants related to breast cancer risk, we performed a high resolution fine-mapping analysis that involved genotyping 517 SNPs using a custom Illumina iSelect array (iCOGS) followed by imputation of genotypes for 3,134 SNPs in more than 89,000 participants of European ancestry from the Breast Cancer Association Consortium (BCAC). We identified 28 highly correlated common variants, in a 53 Kb region spanning two introns of the STXBP4 gene, that are strong candidates for driving breast cancer risk (lead SNP rs2787486 (OR = 0.

The interdigitating Y-plasty procedure for the correction of transverse vaginal septa.

Unlabelled: Transverse vaginal septa are rare congenital abnormalities of the female genital tract, the surgical management of which is hardly described in the literature. While thicker septa might require complex reconstructive surgery, this paper proposes a simple technique for the surgical management of thin septa, utilising two interdigitating Y-plasties, without the need for excision of any septal tissue. The authors also present their series of eight consecutive cases where this technique was used, with no major complications or any cases of vaginal re-stenosis.

An Exploratory Study into Objective and Reported Characteristics of Neuropathic Pain in Women with Chronic Pelvic Pain.

Chronic pelvic pain (CPP) affects 5.7-26.6% women worldwide.

No evidence that protein truncating variants in BRIP1 are associated with breast cancer risk: implications for gene panel testing.

Background: BRCA1 interacting protein C-terminal helicase 1 (BRIP1) is one of the Fanconi Anaemia Complementation (FANC) group family of DNA repair proteins. Biallelic mutations in BRIP1 are responsible for FANC group J, and previous studies have also suggested that rare protein truncating variants in BRIP1 are associated with an increased risk of breast cancer. These studies have led to inclusion of BRIP1 on targeted sequencing panels for breast cancer risk prediction.

Effectiveness of mHealth interventions for maternal, newborn and child health in low- and middle-income countries: Systematic review and meta-analysis.

Objective: To assess the effectiveness of mHealth interventions for maternal, newborn and child health (MNCH) in low- and middle-income countries (LMIC).

Methods: 16 online international databases were searched to identify studies evaluating the impact of mHealth interventions on MNCH outcomes in LMIC, between January 1990 and May 2014. Comparable studies were included in a random-effects meta-analysis.

Development of a Consensus Statement for the Definition, Diagnosis, and Treatment of Acute Exacerbations of Idiopathic Pulmonary Fibrosis Using the Delphi Technique.

Introduction: There is a lack of agreed and established guidelines for the treatment of acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF). This reflects, in part, the limited evidence-base underpinning the management of AE-IPF. In the absence of high-quality evidence, the aim of this research was to develop a clinician-led consensus statement for the definition, diagnosis and treatment of AE-IPF.

Inter-professional prescribing masterclass for medical students and non-medical prescribing students (nurses and pharmacists): a pilot study.

Background And Aims: Prescribing errors cause significant patient morbidity and mortality. Current legislation allows prescribing by different health professions. Inter-professional collaboration and learning may result in safer prescribing practice.

Modification of Occupational Exposures on Bladder Cancer Risk by Common Genetic Polymorphisms.

Few studies have demonstrated gene/environment interactions in cancer research. Using data on high-risk occupations for 2258 case patients and 2410 control patients from two bladder cancer studies, we observed that three of 16 known or candidate bladder cancer susceptibility variants displayed statistically significant and consistent evidence of additive interactions; specifically, the GSTM1 deletion polymorphism (P interaction ≤ .001), rs11892031 (UGT1A, P interaction = .

Functional Analysis of a Carotid Intima-Media Thickness Locus Implicates BCAR1 and Suggests a Causal Variant.

Background: Carotid intima-media thickness (IMT) is a marker of subclinical atherosclerosis that can predict cardiovascular disease events over traditional risk factors. This study examined the BCAR1-CFDP1-TMEM170A locus on chromosome 16, associated with carotid IMT and coronary artery disease in the IMT and IMT-Progression as Predictors of Vascular Events (IMPROVE) cohort, to identify the functional variant.

Methods And Results: In analysis of the locus lead single nucleotide polymorphism (SNP; rs4888378, intronic in CFDP1) in Progressione della Lesione Intimale Carotidea (PLIC), the protective AA genotype was associated with slower IMT progression in women (P=0.

Causes of accidental childhood deaths in China in 2010: A systematic review and analysis.

Background: Infectious causes of childhood deaths in the world have decreased substantially in the 21st century. This trend has exposed accidental deaths as an increasingly important future challenge. Presently, little is known about the cause structure of accidental childhood deaths in low- and middle-income country (LMIC) settings.

The ability of adults with an intellectual disability to recognise facial expressions of emotion in comparison with typically developing individuals: A systematic review.

This review systematically examined the literature on the ability of adults with an intellectual disability (ID) to recognise facial expressions of emotion. Studies were included that: recruited only adult participants with ID; that did not specifically recruit participants with co-morbid diagnoses of syndrome(s) related to ID; and that directly compared the performance of adults with ID with a group of people without ID. Nine papers met the eligibility criteria for review and were assessed against pre-defined quality rating criteria and the findings synthesised.

Use of brain MRI atlases to determine boundaries of age-related pathology: the importance of statistical method.

Introduction: Neurodegenerative disease diagnoses may be supported by the comparison of an individual patient's brain magnetic resonance image (MRI) with a voxel-based atlas of normal brain MRI. Most current brain MRI atlases are of young to middle-aged adults and parametric, e.g.

Prevalence of rheumatoid arthritis in low- and middle-income countries: A systematic review and analysis.

Background: Rheumatoid arthritis (RA) is an autoimmune disorder that affects the small joints of the body. It is one of the leading causes of chronic morbidity in high-income countries, but little is known about the burden of this disease in low- and middle-income countries (LMIC).

Methods: The aim of this study was to estimate the prevalence of RA in six of the World Health Organization's (WHO) regions that harbour LMIC by identifying all relevant studies in those regions.