Reverse genetics with a full-length infectious cDNA of the Middle East respiratory syndrome coronavirus

The identification of a novel, emerging human coronavirus with ∼50% mortality, designated Middle East respiratory syndrome coronavirus (MERS-CoV), emphasizes the importance of the rapid development of reagents that can be used to (i) characterize the replication and pathogenesis of emerging pathogens and (ii) develop therapeutics for treatment. In this report, we describe the development of a cassette-based infectious cDNA clone of MERS-CoV and verify that it functions similarly to the wild-type isolate in terms of replication, protein and RNA expression, and spike attachment protein processing. We also show that the virus replicates preferentially in differentiated primary lung cells

ASIME 2018 White Paper. In-Space Utilisation of Asteroids: Asteroid Composition -- Answers to Questions from the Asteroid Miners

In keeping with the Luxembourg government's initiative to support the future use of space resources, ASIME 2018 was held in Belval, Luxembourg on April 16-17, 2018. The goal of ASIME 2018: Asteroid Intersections with Mine Engineering, was to focus on asteroid composition for advancing the asteroid in-space resource utilisation domain. What do we know about asteroid composition from remote-sensing observations? What are the potential caveats in the interpretation of Earth-based spectral observations? What are the next steps to improve our knowledge on asteroid composition by means of ground-based and space-based observations and asteroid rendez-vous and sample return missions? How can asteroid mining companies use this knowledge? ASIME 2018 was a two-day workshop of almost 70 scientists and engineers in the context of the engineering needs of space missions with in-space asteroid utilisation. The 21 Questions from the asteroid mining companies were sorted into the four asteroid science themes: 1) Potential Targets, 2) Asteroid-Meteorite Links, 3) In-Situ Measurements and 4) Laboratory Measurements. The Answers to those Questions were provided by the scientists with their conference presentations and collected by A. Graps or edited directly into an open-access collaborative Google document or inserted by A. Graps using additional reference materials. During the ASIME 2018, first day and second day Wrap-Ups, the answers to the questions were discussed further. New readers to the asteroid mining topic may find the Conversation boxes and the Mission Design discussions especially interesting.Comment: Outcome from the ASIME 2018: Asteroid Intersections with Mine Engineering, Luxembourg. April 16-17, 2018. 65 Pages. arXiv admin note: substantial text overlap with arXiv:1612.0070

Attitudes towards community gambling venues and support for regulatory reform: An online panel study of residents in New South Wales, Australia

Background: Harmful gambling has been identified as an important public health issue that affects individuals, families and the broader community. One gambling product, electronic gambling machines (EGMs), has been associated with significant gambling harm in Australia. There has been limited research that has explored community perceptions of EGMs and attitudes towards reform. This study, conducted in NSW, Australia, aimed to explore community use of EGM venues (clubs and hotels containing EGMs), attitudes towards EGMs and whether the use of these venues influenced attitudes towards EGM reform. Methods: An online survey was conducted with 500 adults aged 16 years and over, representative of the population for age and gender. Discrete choice and open-ended questions were used to gather data on gambling behaviours, use of and attitudes towards EGMs and EGM venues and support for gambling harm reduction measures. Results: Three quarters of participants had visited an EGM venue in the previous year. Participants who had attended such venues were significantly more likely to use EGMs at least once per month. Participants attended EGM venues for a range of reasons including use of non-gambling facilities such as restaurants, the social aspects of the venue and ease of access to the venue. Some participants also attended EGM venues specifically for the gambling facilities. Most participants identified some negative impacts of EGMs for local communities and were supportive of measures to reduce the number of EGMs and prevent children's exposure to EGMs in such venues. Conclusions: This study shows a high level of support for EGM reform amongst both individuals who attend EGM venues and also those who do not. There is potential for government to further regulate EGMs and the environments where they are located

Team Collaboration: The Use of Behavior Principles for Serving Students With ASD

PurposeSpeech-language pathologists (SLPs) and behavior analysts are key members of school-based teams that serve children with autism spectrum disorders (ASD). Behavior analysts approach assessment and intervention through the lens of applied behavior analysis (ABA). ABA-based interventions have been found effective for targeting skills across multiple domains for children with ASD. However, some SLPs may be unfamiliar with the breadth of ABA-based interventions. The intent of this tutorial is to briefly introduce key ABA principles, provide examples of ABA-based interventions used within schools, and identify strategies for successful collaboration between behavior analysts and SLPs.MethodThis tutorial draws from empirical studies of ABA-based interventions for children with ASD within school settings, as well as discussions in the extant literature about the use of behavior principles by SLPs and strategies for interdisciplinary collaboration.ConclusionGiven the prevalence of ASD at 1 in 68 children (Centers for Disease Control and Prevention, 2014) and the high cost of serving these children within schools (an average cost of 286% over regular education; Chambers, Shkolnik, & Perez, 2003), the need for effective, comprehensive service provision and efficiency within interdisciplinary teams is paramount. Communication, mutual understanding, and recognition of common ground between SLPs and behavior analysts can lead to successful collaboration

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Comparative RNAi screening identifies a conserved core metazoan actinome by phenotype

RNAi Screens in Drosophila and human cells for novel actin regulators revealed conserved roles for proteins involved in nuclear actin export, RNA splicing, and ubiquitination

Attitudes towards community gambling venues and support for regulatory reform: an online panel study of residents in New South Wales, Australia

BACKGROUND: Harmful gambling has been identified as an important public health issue that affects individuals, families and the broader community. One gambling product, electronic gambling machines (EGMs), has been associated with significant gambling harm in Australia. There has been limited research that has explored community perceptions of EGMs and attitudes towards reform. This study, conducted in NSW, Australia, aimed to explore community use of EGM venues (clubs and hotels containing EGMs), attitudes towards EGMs and whether the use of these venues influenced attitudes towards EGM reform. METHODS: An online survey was conducted with 500 adults aged 16 years and over, representative of the population for age and gender. Discrete choice and open-ended questions were used to gather data on gambling behaviours, use of and attitudes towards EGMs and EGM venues and support for gambling harm reduction measures. RESULTS: Three quarters of participants had visited an EGM venue in the previous year. Participants who had attended such venues were significantly more likely to use EGMs at least once per month. Participants attended EGM venues for a range of reasons including use of non-gambling facilities such as restaurants, the social aspects of the venue and ease of access to the venue. Some participants also attended EGM venues specifically for the gambling facilities. Most participants identified some negative impacts of EGMs for local communities and were supportive of measures to reduce the number of EGMs and prevent children\u27s exposure to EGMs in such venues. CONCLUSIONS: This study shows a high level of support for EGM reform amongst both individuals who attend EGM venues and also those who do not. There is potential for government to further regulate EGMs and the environments where they are located

Identification of a BRCA2-Specific modifier locus at 6p24 related to breast cancer risk

Common genetic variants contribute to the observed variation in breast cancer risk for BRCA2 mutation carriers; those known to date have all been found through population-based genome-wide association studies (GWAS). To comprehensively identify breast cancer risk modifying loci for BRCA2 mutation carriers, we conducted a deep replication of an ongoing GWAS discovery study. Using the ranked P-values of the breast cancer associations with the imputed genotype of 1.4 M SNPs, 19,029 SNPs were selected and designed for inclusion on a custom Illumina array that included a total of 211,155 SNPs as part of a multi-consortial project. DNA samples from 3,881 breast cancer affected and 4,330 unaffected BRCA2 mutation carriers from 47 studies belonging to the Consortium of Investigators of Modifiers of BRCA1/2 were genotyped and available for analysis. We replicated previously reported breast cancer susceptibility alleles in these BRCA2 mutation carriers and for several regions (including FGFR2, MAP3K1, CDKN2A/B, and PTHLH) identified SNPs that have stronger evidence of association than those previously published. We also identified a novel susceptibility allele at 6p24 that was inversely associated with risk in BRCA2 mutation carriers (rs9348512; per allele HR = 0.85, 95% CI 0.80-0.90, P = 3.9×10−8). This SNP was not associated with breast cancer risk either in the general population or in BRCA1 mutation carriers. The locus lies within a region containing TFAP2A, which encodes a transcriptional activation protein that interacts with several tumor suppressor genes. This report identifies the first breast cancer risk locus specific to a BRCA2 mutation background. This comprehensive update of novel and previously reported breast cancer susceptibility loci contributes to the establishment of a panel of SNPs that modify breast cancer risk in BRCA2 mutation carriers. This panel may have clinical utility for women with BRCA2 mutations weighing options for medical prevention of breast cancer

Cardiac Biomarkers and the Diagnosis of Myocardial Infarction in Women

PURPOSE OF REVIEW: Women with suspected acute coronary syndrome are less likely to undergo investigation or receive treatment than men, and women consistently have poorer outcomes. This review summarises how the latest development in cardiac biomarkers could improve both diagnosis and outcomes in women. RECENT FINDINGS: Novel high-sensitivity cardiac troponin assays have identified differences in the reference range and therefore diagnostic threshold for myocardial infarction in men and women. These differences are present across multiple populations with different ethnic backgrounds and for a range of assays. The use of a uniform threshold for cardiac troponin does not provide equivalent prediction in men and women, with lower thresholds needed for women to provide comparable risk stratification. SUMMARY: Sex differences in cardiac troponin concentrations are not widely recognised in clinical practice and may be contributing to the under-diagnosis of myocardial infarction in women and discrepancies in patient care and outcomes

Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10-8, HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10-8, HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4×10-8, HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific associat