University of Western Australia

About: University of Western Australia is a education organization based out in Perth, Western Australia, Australia. It is known for research contribution in the topics: Population & Poison control. The organization has 29613 authors who have published 87405 publications receiving 3064466 citations. The organization is also known as: UWA & University of WA.

Association analysis identifies 65 new breast cancer risk loci

Abstract: Breast cancer risk is influenced by rare coding variants in susceptibility genes, such as BRCA1, and many common, mostly non-coding variants. However, much of the genetic contribution to breast cancer risk remains unknown. Here we report the results of a genome-wide association study of breast cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of East Asian ancestry. We identified 65 new loci that are associated with overall breast cancer risk at P < 5 × 10-8. The majority of credible risk single-nucleotide polymorphisms in these loci fall in distal regulatory elements, and by integrating in silico data to predict target genes in breast cells at each locus, we demonstrate a strong overlap between candidate target genes and somatic driver genes in breast tumours. We also find that heritability of breast cancer due to all single-nucleotide polymorphisms in regulatory features was 2-5-fold enriched relative to the genome-wide average, with strong enrichment for particular transcription factor binding sites. These results provide further insight into genetic susceptibility to breast cancer and will improve the use of genetic risk scores for individualized screening and prevention.

Taking Stock: Integrating and Differentiating Multiple Proactive Behaviors

Abstract: The authors aimed to clarify the similarities, differences, and interrelationships among multiple types of proactive behavior. Factor analyses of managers’ self-ratings (N = 622) showed concepts were distinct from each other but related via a higher-order structure. Three higher-order proactive behavior categories were identified—proactive work behavior, proactive strategic behavior, and proactive person-environment fit behavior—each corresponding to behaviors aimed at bringing about change in the internal organization (e.g., voice), the fit between the organization and its environment (e.g., issue selling), and the fit between the individual and the organization (e.g., feedback seeking), respectively. Further analyses on a subsample (n = 319) showed similarities and differences in the antecedents of these behaviors.

Predictions for the rates of compact binary coalescences observable by ground-based gravitational-wave detectors

Abstract: We present an up-to-date, comprehensive summary of the rates for all types of compact binary coalescence sources detectable by the initial and advanced versions of the ground-based gravitational-wave detectors LIGO and Virgo. Astrophysical estimates for compact-binary coalescence rates depend on a number of assumptions and unknown model parameters and are still uncertain. The most confident among these estimates are the rate predictions for coalescing binary neutron stars which are based on extrapolations from observed binary pulsars in our galaxy. These yield a likely coalescence rate of 100 Myr−1 per Milky Way Equivalent Galaxy (MWEG), although the rate could plausibly range from 1 Myr−1 MWEG−1 to 1000 Myr−1 MWEG−1 (Kalogera et al 2004 Astrophys. J. 601 L179; Kalogera et al 2004 Astrophys. J. 614 L137 (erratum)). We convert coalescence rates into detection rates based on data from the LIGO S5 and Virgo VSR2 science runs and projected sensitivities for our advanced detectors. Using the detector sensitivities derived from these data, we find a likely detection rate of 0.02 per year for Initial LIGO–Virgo interferometers, with a plausible range between 2 × 10−4 and 0.2 per year. The likely binary neutron–star detection rate for the Advanced LIGO–Virgo network increases to 40 events per year, with a range between 0.4 and 400 per year.

Reducing Inappropriate Polypharmacy: The Process of Deprescribing

Abstract: Inappropriate polypharmacy, especially in older people, imposes a substantial burden of adverse drug events, ill health, disability, hospitalization, and even death. The single most important predictor of inappropriate prescribing and risk of adverse drug events in older patients is the number of prescribed drugs. Deprescribing is the process of tapering or stopping drugs, aimed at minimizing polypharmacy and improving patient outcomes. Evidence of efficacy for deprescribing is emerging from randomized trials and observational studies. A deprescribing protocol is proposed comprising 5 steps: (1) ascertain all drugs the patient is currently taking and the reasons for each one; (2) consider overall risk of drug-induced harm in individual patients in determining the required intensity of deprescribing intervention; (3) assess each drug in regard to its current or future benefit potential compared with current or future harm or burden potential; (4) prioritize drugs for discontinuation that have the lowest benefit-harm ratio and lowest likelihood of adverse withdrawal reactions or disease rebound syndromes; and (5) implement a discontinuation regimen and monitor patients closely for improvement in outcomes or onset of adverse effects. Whereas patient and prescriber barriers to deprescribing exist, resources and strategies are available that facilitate deliberate yet judicious deprescribing and deserve wider application.