The prevention of lower urinary tract symptoms (PLUS) research consortium: A transdisciplinary approach toward promoting bladder health and preventing lower urinary tract symptoms in women across the life course

Lower urinary tract symptoms (LUTS) are highly prevalent in women, and are expected to impose a growing burden to individuals and society as the population ages. The predominance of research related to LUTS has focused on underlying pathology, disease mechanisms, or the efficacy of treatments for women with LUTS. Although this research has been vital for helping to reduce or ameliorate LUTS conditions, it has done little to prevent the onset of LUTS. Health promotion and prevention require an expansion of scientific inquiry beyond the traditional paradigm of studying disease mechanisms and treatment to the creation of an evidence base to support recommendations for bladder health promotion and, in turn, prevention of LUTS. The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) introduced the concept of prevention as an important priority for women's urologic research as a prelude to supporting the formation of the Prevention of Lower Urinary Tract Symptoms (PLUS) research consortium. In this article, we introduce the PLUS research consortium to the scientific community; share the innovative paradigms by which the consortium operates; and describe its unique research mission: to identify factors that promote bladder health across the life course and prevent the onset of LUTS in girls and women

Functional and emotional outcomes after transient ischaemic attack: A 12-month prospective controlled cohort study

Background: Symptoms of transient ischemic attack are believed to fully resolve within 24 h of onset. Emerging evidence suggests that there may be prolonged functional and psychological impact, although studies have not been able to robustly identify whether these are the effect of transient ischemic attack or changes usually associated with ageing. We describe trajectories of disability and risk of anxiety and depression among patients seen at transient ischemic attack clinics over 12 months, compared to healthy controls. Methods: Thirty transient ischemic attack clinics across England participated. A total of 1320 participants were included: 373 diagnosed with transient ischemic attack, 186 with minor stroke, 310 with “possible transient ischemic attack,” 213 with another condition mimicking a transient ischemic attack and 238 controls recruited from primary care providers. Participants completed questionnaires after diagnosis then after 3, 6 and 12 months. Outcomes were the Nottingham Extended Activities of Daily Living Scale and the Hospital Anxiety and Depression Scale. Mixed effects regression was used to estimate group differences and trajectories. Results: At baseline, confirmed transient ischemic attack patients scored 1.31 HADS-Anxiety points (s.e. = 0.28; p < 0.001), 0.51 HADS-Depression points (s.e. = 0.26; p = 0.056), and 2.6 NEADL points (s.e. = 1.1; p = 0.020) worse than controls. At 12 months, the deficits were 0.78 (s.e. = 0.30; p = 0.008), 0.97 (s.e. = 0.23; p < 0.001), and 0.96 (s.e. = 0.92; p = 0.294) respectively. Differences among patients diagnosed with minor stroke were like or worse than transient ischemic attack patients. Conclusions: Transient ischemic attack clinic patients may have functional and emotional impairments compared to the general population irrespective of final diagnosis. The presence of emotional symptoms or risk of developing anxiety or depression did not always fully recover and may increase

1000 Norms Project: Protocol of a cross-sectional study cataloging human variation

Background Clinical decision-making regarding diagnosis and management largely depends on comparison with healthy or ‘normal’ values. Physiotherapists and researchers therefore need access to robust patient-centred outcome measures and appropriate reference values. However there is a lack of high-quality reference data for many clinical measures. The aim of the 1000 Norms Project is to generate a freely accessible database of musculoskeletal and neurological reference values representative of the healthy population across the lifespan. Methods/design In 2012 the 1000 Norms Project Consortium defined the concept of ‘normal’, established a sampling strategy and selected measures based on clinical significance, psychometric properties and the need for reference data. Musculoskeletal and neurological items tapping the constructs of dexterity, balance, ambulation, joint range of motion, strength and power, endurance and motor planning will be collected in this cross-sectional study. Standardised questionnaires will evaluate quality of life, physical activity, and musculoskeletal health. Saliva DNA will be analysed for the ACTN3 genotype (‘gene for speed’). A volunteer cohort of 1000 participants aged 3 to 100 years will be recruited according to a set of self-reported health criteria. Descriptive statistics will be generated, creating tables of mean values and standard deviations stratified for age and gender. Quantile regression equations will be used to generate age charts and age-specific centile values. Discussion This project will be a powerful resource to assist physiotherapists and clinicians across all areas of healthcare to diagnose pathology, track disease progression and evaluate treatment response. This reference dataset will also contribute to the development of robust patient-centred clinical trial outcome measures

Admixture Mapping of African–American Women in the AMBER Consortium Identifies New Loci for Breast Cancer and Estrogen-Receptor Subtypes

Recent genetic admixture coupled with striking differences in incidence of estrogen receptor (ER) breast cancer subtypes, as well as severity, between women of African and European ancestry, provides an excellent rationale for performing admixture mapping in African American women with breast cancer risk. We performed the largest breast cancer admixture mapping study with in African American women to identify novel genomic regions associated with the disease. We conducted a genome-wide admixture scan using 2,624 autosomal ancestry informative markers (AIMs) in 3,629 breast cancer cases (including 1,968 ER-positive, 1093 ER-negative, and 601 triple-negative) and 4,658 controls from the African American Breast Cancer Epidemiology and Risk (AMBER) Consortium, a collaborative study of four large geographically different epidemiological studies of breast cancer in African American women. We used an independent case-control study to test for SNP association in regions with genome-wide significant admixture signals. We found two novel genome-wide significant regions of excess African ancestry, 4p16.1 and 17q25.1, associated with ER-positive breast cancer. Two regions known to harbor breast cancer variants, 10q26 and 11q13, were also identified with excess of African ancestry. Fine-mapping of the identified genome-wide significant regions suggests the presence of significant genetic associations with ER-positive breast cancer in 4p16.1 and 11q13. In summary, we identified three novel genomic regions associated with breast cancer risk by ER status, suggesting that additional previously unidentified variants may contribute to the racial differences in breast cancer risk in the African American population

Kepler-20: A Sun-like Star with Three Sub-Neptune Exoplanets and Two Earth-size Candidates

We present the discovery of the Kepler-20 planetary system, which we initially identified through the detection of five distinct periodic transit signals in the Kepler light curve of the host star 2MASSJ19104752+4220194. We find a stellar effective temperature Teff=5455+-100K, a metallicity of [Fe/H]=0.01+-0.04, and a surface gravity of log(g)=4.4+-0.1. Combined with an estimate of the stellar density from the transit light curves we deduce a stellar mass of Mstar=0.912+-0.034 Msun and a stellar radius of Rstar=0.944^{+0.060}_{-0.095} Rsun. For three of the transit signals, our results strongly disfavor the possibility that these result from astrophysical false positives. We conclude that the planetary scenario is more likely than that of an astrophysical false positive by a factor of 2e5 (Kepler-20b), 1e5 (Kepler-20c), and 1.1e3 (Kepler-20d), sufficient to validate these objects as planetary companions. For Kepler-20c and Kepler-20d, the blend scenario is independently disfavored by the achromaticity of the transit: From Spitzer data gathered at 4.5um, we infer a ratio of the planetary to stellar radii of 0.075+-0.015 (Kepler-20c) and 0.065+-0.011 (Kepler-20d), consistent with each of the depths measured in the Kepler optical bandpass. We determine the orbital periods and physical radii of the three confirmed planets to be 3.70d and 1.91^{+0.12}_{-0.21} Rearth for Kepler-20b, 10.85 d and 3.07^{+0.20}_{-0.31} Rearth for Kepelr-20c, and 77.61 d and 2.75^{+0.17}_{-0.30} Rearth for Kepler-20d. From multi-epoch radial velocities, we determine the masses of Kepler-20b and Kepler-20c to be 8.7\+-2.2 Mearth and 16.1+-3.5 Mearth, respectively, and we place an upper limit on the mass of Kepler-20d of 20.1 Mearth (2 sigma).Comment: accepted by ApJ, 58 pages, 12 figures revised Jan 2012 to correct table 2 and clarify planet parameter extractio

People of the British Isles: preliminary analysis of genotypes and surnames in a UK control population

There is a great deal of interest in fine scale population structure in the UK, both as a signature of historical immigration events and because of the effect population structure may have on disease association studies. Although population structure appears to have a minor impact on the current generation of genome-wide association studies, it is likely to play a significant part in the next generation of studies designed to search for rare variants. A powerful way of detecting such structure is to control and document carefully the provenance of the samples involved. Here we describe the collection of a cohort of rural UK samples (The People of the British Isles), aimed at providing a well-characterised UK control population that can be used as a resource by the research community as well as providing fine scale genetic information on the British population. So far, some 4,000 samples have been collected, the majority of which fit the criteria of coming from a rural area and having all four grandparents from approximately the same area. Analysis of the first 3,865 samples that have been geocoded indicates that 75% have a mean distance between grandparental places of birth of 37.3km, and that about 70% of grandparental places of birth can be classed as rural. Preliminary genotyping of 1,057 samples demonstrates the value of these samples for investigating fine scale population structure within the UK, and shows how this can be enhanced by the use of surnames

Cross-ancestry GWAS meta-analysis identifies six breast cancer loci in African and European ancestry women

Our study describes breast cancer risk loci using a cross-ancestry GWAS approach. We first identify variants that are associated with breast cancer at P \u3c 0.05 from African ancestry GWAS meta-analysis (9241 cases and 10193 controls), then meta-analyze with European ancestry GWAS data (122977 cases and 105974 controls) from the Breast Cancer Association Consortium. The approach identifies four loci for overall breast cancer risk [1p13.3, 5q31.1, 15q24 (two independent signals), and 15q26.3] and two loci for estrogen receptor-negative disease (1q41 and 7q11.23) at genome-wide significance. Four of the index single nucleotide polymorphisms (SNPs) lie within introns of genes (KCNK2, C5orf56, SCAMP2, and SIN3A) and the other index SNPs are located close to GSTM4, AMPD2, CASTOR2, and RP11-168G16.2. Here we present risk loci with consistent direction of associations in African and European descendants. The study suggests that replication across multiple ancestry populations can help improve the understanding of breast cancer genetics and identify causal variants