BRCA1 and BRCA2 mutations in a population-based study of male breast cancer

Background: The contribution of BRCA1 and BRCA2 to the incidence of male breast cancer (MBC) in the United Kingdom is not known, and the importance of these genes in the increased risk of female breast cancer associated with a family history of breast cancer in a male first-degree relative is unclear. Methods: We have carried out a population-based study of 94 MBC cases collected in the UK. We screened genomic DNA for mutations in BRCA1 and BRCA2 and used family history data from these cases to calculate the risk of breast cancer to female relatives of MBC cases. We also estimated the contribution of BRCA1 and BRCA2 to this risk. Results: Nineteen cases (20%) reported a first-degree relative with breast cancer, of whom seven also had an affected second-degree relative. The breast cancer risk in female first-degree relatives was 2.4 times (95% confidence interval [CI] = 1.4–4.0) the risk in the general population. No BRCA1 mutation carriers were identified and five cases were found to carry a mutation in BRCA2. Allowing for a mutation detection sensitivity frequency of 70%, the carrier frequency for BRCA2 mutations was 8% (95% CI = 3–19). All the mutation carriers had a family history of breast, ovarian, prostate or pancreatic cancer. However, BRCA2 accounted for only 15% of the excess familial risk of breast cancer in female first-degree relatives. Conclusion: These data suggest that other genes that confer an increased risk for both female and male breast cancer have yet to be found

Individual Assessment of Arteriosclerosis by Empiric Clinical Profiling

BACKGROUND: Arteriosclerosis is a common cause of chronic morbidity and mortality. Myocardial infarction, stroke or other cardiovascular events identify vulnerable patients who suffer from symptomatic arteriosclerosis. Biomarkers to identify vulnerable patients before cardiovascular events occur are warranted to improve care for affected individuals. We tested how accurately basic clinical data can describe and assess the activity of arteriosclerosis in the individual patient. METHODOLOGY/PRINCIPAL FINDINGS: 269 in-patients who were treated for various conditions at the department of general medicine of an academic tertiary care center were included in a cross-sectional study. Personal history and clinical examination were obtained. When paraclinical tests were performed, the results were added to the dataset. The numerical variables in the clinical examination were statistically compared between patients with proven symptomatic arteriosclerosis (n = 100) and patients who had never experienced cardiovascular events in the past (n = 110). 25 variables were different between these two patient groups and contributed to the disease activity score. The percentile distribution of these variables defined the empiric clinical profile. Anthropometric data, signs of arterial, cardiac and renal disease, systemic inflammation and health economics formed the major categories of the empiric clinical profile that described an individual patient's disease activity. The area under the curve of the receiver operating curve for symptomatic arteriosclerosis was 0.891 (95% CI 0.799-0.983) for the novel disease activity score compared to 0.684 (95% CI 0.600-0.769) for the 10-year risk calculated according to the Framingham score. In patients suffering from symptomatic arteriosclerosis, the disease activity score deteriorated more rapidly after two years of follow-up (from 1.25 to 1.48, P = 0.005) compared to age- and sex-matched individuals free of cardiovascular events (from 1.09 to 1.19, P = 0.125). CONCLUSIONS/SIGNIFICANCE: Empiric clinical profiling and the disease activity score that are based on accessible, available and affordable clinical data are valid markers for symptomatic arteriosclerosis

Generalized Dynamic Analysis of Structural Single Rocking Walls (SRWs)

The investigation of structural single rocking walls (SRWs) continues to gain interest as they produce self-centering lateral load responses with reduced structural damage. The Simple Rocking Model (SRM) with modifications has been shown to capture these responses accurately if the SRW and its underlying base are infinitely rigid. This paper advances previous rocking models by accounting for: 1) the inelastic actions at or near the base of the SRW; and 2) the flexural responses within the wall. Included in the proposed advancements are hysteretic and inherent viscous damping associated with these two deformation components so that the total dynamic responses of SRWs can be captured with good accuracy. A system of nonlinear equations of motion is developed, in which the rocking base is discretized into fibers using a zero-length element to locate the associated compressive deformations and damage. The flexural deformations of the rocking body are captured using an elastic term, while the impact events are modeled using impulse-momentum equations. Comparisons with experiments of structural precast concrete and masonry SRWs show that the proposed approach accurately estimates the dynamic responses of different SRWs with and without unbonded posttensioning, for various dynamic excitations and degrees of hysteretic action. Using the proposed approach, a numerical investigation employs different configurations of structural SRWs to quantify the various sources of energy loss, including hysteretic action and impact damping, during various horizontal ground motions

Diving into the vertical dimension of elasmobranch movement ecology

This is the final version. Available on open access from the American Association for the Advancement of Science via the DOI in this recordData and materials availability: Processed data and code used in the analysis are accessible from the Zenodo Repository: 10.5281/zenodo.6885455Knowledge of the three-dimensional movement patterns of elasmobranchs is vital to understand their ecological roles and exposure to anthropogenic pressures. To date, comparative studies among species at global scales have mostly focused on horizontal movements. Our study addresses the knowledge gap of vertical movements by compiling the first global synthesis of vertical habitat use by elasmobranchs from data obtained by deployment of 989 biotelemetry tags on 38 elasmobranch species. Elasmobranchs displayed high intra- and interspecific variability in vertical movement patterns. Substantial vertical overlap was observed for many epipelagic elasmobranchs, indicating an increased likelihood to display spatial overlap, biologically interact, and share similar risk to anthropogenic threats that vary on a vertical gradient. We highlight the critical next steps toward incorporating vertical movement into global management and monitoring strategies for elasmobranchs, emphasizing the need to address geographic and taxonomic biases in deployments and to concurrently consider both horizontal and vertical movements.Bertarelli FoundationResearch EnglandMoore FoundationPackard FoundationInstituto Politecnico NacionalDarwin InitiativeGeorgia AquariumRolex Awards for EnterpriseWhitley Fund for Natur

Habitat use and movement patterns of tiger sharks (Galeocerdo cuvier) in eastern Australian waters

Abstract Understanding the movement of marine predators is vital for effective conservation and management. Despite being targeted by shark control programs, the tiger shark, Galeocerdo cuvier, is poorly studied off eastern Australia. To investigate the horizontal movement and habitat use in this region, 16 sharks (157–384 cm total length) were tagged with MiniPAT pop-up satellite archival tags in 2018 and 2019. Eleven of these individuals were also fitted with satellite-linked radio transmitting tags. After release, most sharks moved off the continental shelf and headed north, associating with seamounts as they moved towards Queensland. During their time at liberty they transited through temperate, sub-tropical and tropical waters and spent the majority of time in the upper 50 m of the water column and at temperatures between 22 and 25˚C. Horizontal movement was focused in waters off the continental shelf. Increased movement over shelf waters occurred during the austral spring and summer when the East Australian Current is at its strongest and warm waters encroach the continental shelf. Broad latitudinal movement along the east coast of Australia was evident and highlights the connectivity between tropical and warm-temperate regions.</jats:p