The Clinical Utility of a Precision Medicine Blood Test Incorporating Age, Sex, and Gene Expression for Evaluating Women with Stable Symptoms Suggestive of Obstructive Coronary Artery Disease: Analysis from the PRESET Registry.

Background: Evaluating women with symptoms suggestive of coronary artery disease (CAD) remains challenging. A blood-based precision medicine test yielding an age/sex/gene expression score (ASGES) has shown clinical validity in the diagnosis of obstructive CAD. We assessed the effect of the ASGES on the management of women with suspected obstructive CAD in a community-based registry. Materials and Methods: The prospective PRESET (A Registry to Evaluate Patterns of Care Associated with the Use of Corus® CAD in Real World Clinical Care Settings) Registry (NCT01677156) enrolled 566 patients presenting with symptoms suggestive of stable obstructive CAD from 21 United States primary care practices from 2012 to 2014. Demographics, clinical characteristics, and referrals to cardiology or further functional and/or anatomical cardiac studies after ASGES testing were collected for this subgroup analysis of women from the PRESET Registry. Patients were followed for 1-year post-ASGES testing. Results: This study cohort included 288 women with a median age 57 years. The median body mass index was 29.2, with hyperlipidemia and hypertension present in 48% and 43% of patients, respectively. Median ASGES was 8.5 (range 1-40), with 218 (76%) patients having low (≤15) ASGES. Clinicians referred 9% (20/218) low ASGES versus 44% (31/70) elevated ASGES women for further cardiac evaluation (odds ratio 0.14, p < 0.0001, adjusted for patient demographics and clinical covariates). Across the score range, higher ASGES were associated with a higher likelihood of posttest cardiac referral. At 1-year follow-up, low ASGES women experienced fewer major adverse cardiac events than elevated ASGES women (1.3% vs. 4.2% respectively, p = 0.16). Conclusions: Incorporation of ASGES into the diagnostic workup demonstrated clinical utility by helping clinicians identify women less likely to benefit from further cardiac evaluation

Feasibility of Using Subject-Collected Dust Samples in Epidemiologic and Clinical Studies of Indoor Allergens

Studies of indoor allergen exposures are often limited by the cost and logistics of sending technicians to homes to collect dust. In this study we evaluated the feasibility of having subjects collect their own dust samples. The objectives were to compare allergen concentrations between subject- and technician-collected samples and to examine the sample return rate. Using a dust collection device and written instructions provided to them by mail, 102 subjects collected a combined dust sample from a bed and bedroom floor. Later the same day, a technician collected a side-by-side sample. Dust samples were weighed and analyzed for the cat allergen Fel d 1 and the dust mite allergen Der p 1. Fifty additional subjects who were enrolled by telephone were mailed dust collection packages and asked to return a dust sample and questionnaire by mail. A technician did not visit their homes. Correlations between subject- and technician-collected samples were strong for concentrations of Fel d 1 (r = 0.88) and Der p 1 (r = 0.87). With allergen concentrations dichotomized at lower limits of detection and clinically relevant thresholds, agreements between methodologies ranged from 91 to 98%. Although dust weights were correlated (r = 0.48, p < 0.001), subjects collected lighter samples. Among the group of 50 subjects, 46 returned a dust sample and completed questionnaire. The median number of days to receive a sample was 15. With some limitations, subject-collected dust sampling appears to be a valid and practical option for epidemiologic and clinical studies that report allergen concentration as a measure of exposure

The Reproducibility of Lists of Differentially Expressed Genes in Microarray Studies

Reproducibility is a fundamental requirement in scientific experiments and clinical contexts. Recent publications raise concerns about the reliability of microarray technology because of the apparent lack of agreement between lists of differentially expressed genes (DEGs). In this study we demonstrate that (1) such discordance may stem from ranking and selecting DEGs solely by statistical significance (P) derived from widely used simple t-tests; (2) when fold change (FC) is used as the ranking criterion, the lists become much more reproducible, especially when fewer genes are selected; and (3) the instability of short DEG lists based on P cutoffs is an expected mathematical consequence of the high variability of the t-values. We recommend the use of FC ranking plus a non-stringent P cutoff as a baseline practice in order to generate more reproducible DEG lists. The FC criterion enhances reproducibility while the P criterion balances sensitivity and specificity

Changing discourses in women and science policy: responding to austerity in gender and SET

The issue of ‘women in science’ has been a recurring theme in government policy both in the UK and the EU (and indeed globally) for several decades. While considerable research has been done about the problem (Barnard et al 2010), most initiatives during the 80s and 90s tended to be localised and there was little attention to this within broader science policy despite intermittent funding most often linked to labour market concerns. However, in the UK the UKRC was set up and funded in 2004 as part of the government’s science and skills strategy (Greenfield et al, 2002) which for the first time gave substantial centralised and high level funding to support entry, retention and progression of women in science, engineering and technology (SET). Yet this support has been short lived - with government funding for the UKRC now being phased out as part of public sector cuts there is an increasing emphasis on ‘mainstreaming’ and this presents questions about what the future gender equality landscape may present for women in SET in the UK and how to respond to this. Using examples from policy documents and reports, the paper will discuss changing policy discourses that have addressed women, science and technology and considers how public spending cuts might impact on the continuation of policy and practice in this field

Fractured Identity in the Context of Intimate Partner Violence:Barriers to and Opportunities for Seeking Help in Health Settings

Intimate partner violence has profound effects on women's identities. However, detailed examination of how abuse affects identity is lacking. We interviewed 14 diverse women (Australia), applying social identity theory to analyze their experiences of identity and help-seeking in health settings. The destabilizing effect of violence on social identities was strongly supported. Women concealed abuse to preserve a public identity. However, when the violence threatened the most integrated identities, women unveiled an abuse identity, receiving mixed responses from health providers. A healing context where a woman can display an abuse identity safely is crucial to enable her to rebuild an integrated self-concept

Cooperative folding of intrinsically disordered domains drives assembly of a strong elongated protein.

Bacteria exploit surface proteins to adhere to other bacteria, surfaces and host cells. Such proteins need to project away from the bacterial surface and resist significant mechanical forces. SasG is a protein that forms extended fibrils on the surface of Staphylococcus aureus and promotes host adherence and biofilm formation. Here we show that although monomeric and lacking covalent cross-links, SasG maintains a highly extended conformation in solution. This extension is mediated through obligate folding cooperativity of the intrinsically disordered E domains that couple non-adjacent G5 domains thermodynamically, forming interfaces that are more stable than the domains themselves. Thus, counterintuitively, the elongation of the protein appears to be dependent on the inherent instability of its domains. The remarkable mechanical strength of SasG arises from tandemly arrayed 'clamp' motifs within the folded domains. Our findings reveal an elegant minimal solution for the assembly of monomeric mechano-resistant tethers of variable length.This research was supported by Biotechnology and Biological Research Council Grants BB/J006459/1 (D.T.G. and J.C.), BB/J005029/1 (F.W. and J.R.P), BB/G019452/1 (O.E.F and D.J.B) and BB/G020671/1 (C.G.B. and J.R.P.). H.K.H.F. is supported by a studentship from a Wellcome Trust 4-year PhD programme (WT095024MA). C.M.J. is supported by the German Federal Ministry of Education and Research (BMBF), grant BIOSCAT (contract N° 05K12YE1). J.C. is a Wellcome Trust Senior Research Fellow (WT/095195). J.R.P holds a British Heart Foundation Senior Basic Science Fellowship (FS/12/36/29588). The authors acknowledge the use of EMBL SAXS beamline P12 at Petra-3 (DESY, Hamburg, Germany) and Maxim Petoukhov (EMBL) for providing a modified version of SASR EF. The research leading to these results has received funding from the European Community's Seventh Framework Programme (FP7/2007-2013) under BioStruct-X (grant agreement N°283570). The authors would like to thank Diamond Light Source for beamtime (proposal mx-7864) and Johan Turkenburg and Sam Hart for assistance with crystal testing and data collection.This is the final version of the article. It first appeared from NPG via http://dx.doi.org/10.1038/ncomms827

People Like Me Evaluation Report

People Like Me is an intervention to support the increase of women and girls into STEM education and careers. As such it sits in a long tradition of efforts - in the UK and globally - to tackle gender inequality in the study of STEM subjects, and leading to employment/careers in the scientific, engineering and technology sectors. People Like Me is both a resource and a strategy with a number of potential points of impact. At the core is the concept that raising awareness of the range of possible careers and jobs in STEM will encourage girls to continue with studying science subjects in school, and also aspire to careers in these sectors. This report is the outcome of an independent evaluation carried out by the Open University into the impact and effectiveness of the intervention

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