The impact of point mutations in the human androgen receptor : classification of mutations on the basis of transcriptional activity

Peer reviewedPublisher PD

Children’s Feedback Preferences in Response to an Experimentally Manipulated Peer Evaluation Outcome: The Role of Depressive Symptoms

The present study examined the linkage between pre-adolescent children’s depressive symptoms and their preferences for receiving positive vs. negative feedback subsequent to being faced with an experimentally manipulated peer evaluation outcome in real time. Participants (n = 142) ages 10 to 13, played a computer contest based on the television show Survivor and were randomized to either a peer rejection (i.e., receiving the lowest total ‘likeability’ score from a group of peer-judges), a peer success (i.e., receiving the highest score), or a control peer evaluation condition. Children’s self-reported feedback preferences were then assessed. Results revealed that participants assigned to the negative evaluation outcome, relative to either the success or the control outcome, showed a significantly higher subsequent preference for negatively tuned feedback. Contrary to previous work and predictions derived from self-verification theory, children higher in depressive symptoms were only more likely to prefer negative feedback in response to the negative peer evaluation outcome. These effects for depression were not accounted for by either state mood at baseline or mood change in response to the feedback manipulation

Correlates of sunscreen use among high school students: a cross-sectional survey

Abstract Background Adolescents put themselves at risk of later skin cancer development and accelerated photo-aging due to their high rates of ultraviolet radiation exposure and low rates of skin protection. The purpose of the current study was to determine which of the Integrative Model constructs are most closely associated with sunscreen use among high school students. Methods The current study of 242 high school students involved a survey based on the Integrative Model including demographic and individual difference factors, skin protection-related beliefs and outcome evaluations, normative beliefs, self-efficacy, sunscreen cues and availability, intentions, and sunscreen use. Our analyses included multiple linear regressions and bootstrapping to test for mediation effects. Results Sunscreen use was significantly associated with female gender, greater skin sensitivity, higher perceived sunscreen benefits, higher skin protection importance, more favorable sunscreen user prototype, stronger skin protection norms, greater perceived skin protection behavioral control, and higher sunscreen self-efficacy. Intentions to use sunscreen mediated the relationships between most skin protection-related beliefs and sunscreen use. Conclusions The current study identified specific variables that can be targeted in interventions designed to increase sunscreen use among adolescents.</p

AD51B in Familial Breast Cancer

Common variation on 14q24.1, close to RAD51B, has been associated with breast cancer: rs999737 and rs2588809 with the risk of female breast cancer and rs1314913 with the risk of male breast cancer. The aim of this study was to investigate the role of RAD51B variants in breast cancer predisposition, particularly in the context of familial breast cancer in Finland. We sequenced the coding region of RAD51B in 168 Finnish breast cancer patients from the Helsinki region for identification of possible recurrent founder mutations. In addition, we studied the known rs999737, rs2588809, and rs1314913 SNPs and RAD51B haplotypes in 44,791 breast cancer cases and 43,583 controls from 40 studies participating in the Breast Cancer Association Consortium (BCAC) that were genotyped on a custom chip (iCOGS). We identified one putatively pathogenic missense mutation c.541C&gt;T among the Finnish cancer patients and subsequently genotyped the mutation in additional breast cancer cases (n = 5259) and population controls (n = 3586) from Finland and Belarus. No significant association with breast cancer risk was seen in the meta-analysis of the Finnish datasets or in the large BCAC dataset. The association with previously identified risk variants rs999737, rs2588809, and rs1314913 was replicated among all breast cancer cases and also among familial cases in the BCAC dataset. The most significant association was observed for the haplotype carrying the risk-alleles of all the three SNPs both among all cases (odds ratio (OR): 1.15, 95% confidence interval (CI): 1.11–1.19, P = 8.88 x 10−16) and among familial cases (OR: 1.24, 95% CI: 1.16–1.32, P = 6.19 x 10−11), compared to the haplotype with the respective protective alleles. Our results suggest that loss-of-function mutations in RAD51B are rare, but common variation at the RAD51B region is significantly associated with familial breast cancer risk

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

MUSiC: a model-unspecific search for new physics in proton–proton collisions at √s=13TeV

Results of the Model Unspecific Search in CMS (MUSiC), using proton–proton collision data recorded at the LHC at a centre-of-mass energy of 13TeV, corresponding to an integrated luminosity of 35.9fb-1, are presented. The MUSiC analysis searches for anomalies that could be signatures of physics beyond the standard model. The analysis is based on the comparison of observed data with the standard model prediction, as determined from simulation, in several hundred final states and multiple kinematic distributions. Events containing at least one electron or muon are classified based on their final state topology, and an automated search algorithm surveys the observed data for deviations from the prediction. The sensitivity of the search is validated using multiple methods. No significant deviations from the predictions have been observed. For a wide range of final state topologies, agreement is found between the data and the standard model simulation. This analysis complements dedicated search analyses by significantly expanding the range of final states covered using a model independent approach with the largest data set to date to probe phase space regions beyond the reach of previous general searches

Combined searches for the production of supersymmetric top quark partners in proton–proton collisions at √s=13Te

A combination of searches for top squark pair production using proton–proton collision data at a center-of-mass energy of 13TeV at the CERN LHC, corresponding to an integrated luminosity of 137fb$^{-1}$ collected by the CMS experiment, is presented. Signatures with at least 2 jets and large missing transverse momentum are categorized into events with 0, 1, or 2 leptons. New results for regions of parameter space where the kinematical properties of top squark pair production and top quark pair production are very similar are presented. Depending on the model, the combined result excludes a top squark mass up to 1325GeV for a massless neutralino, and a neutralino mass up to 700GeV for a top squark mass of 1150GeV. Top squarks with masses from 145 to 295GeV, for neutralino masses from 0 to 100GeV, with a mass difference between the top squark and the neutralino in a window of 30GeV around the mass of the top quark, are excluded for the first time with CMS data. The results of theses searches are also interpreted in an alternative signal model of dark matter production via a spin-0 mediator in association with a top quark pair. Upper limits are set on the cross section for mediator particle masses of up to 420GeV

Search for a vector-like quark T′ → tH via the diphoton decay mode of the Higgs boson in proton-proton collisions at s \sqrt{s} = 13 TeV

A search for the electroweak production of a vector-like quark T′, decaying to a top quark and a Higgs boson is presented. The search is based on a sample of proton-proton collision events recorded at the LHC at = 13 TeV, corresponding to an integrated luminosity of 138 fb−1. This is the first T′ search that exploits the Higgs boson decay to a pair of photons. For narrow isospin singlet T′ states with masses up to 1.1 TeV, the excellent diphoton invariant mass resolution of 1–2% results in an increased sensitivity compared to previous searches based on the same production mechanism. The electroweak production of a T′ quark with mass up to 960 GeV is excluded at 95% confidence level, assuming a coupling strength κT = 0.25 and a relative decay width Γ/MT′ < 5%