Interferon lambda protects the female reproductive tract against Zika virus infection

Zika virus infections can cause devastating congenital birth defects but the underlying interactions with the host immune system are not well understood. Here, the authors examine the immune basis of vaginal protection and susceptibility to Zika viral infection, and identify a hormonal dependent role for interferon-lambda-mediated protection against disease

A GREB1-steroid receptor feedforward mechanism governs differential GREB1 action in endometrial function and endometriosis

Cellular responses to the steroid hormones, estrogen (E2), and progesterone (P4) are governed by their cognate receptor\u27s transcriptional output. However, the feed-forward mechanisms that shape cell-type-specific transcriptional fulcrums for steroid receptors are unidentified. Herein, we found that a common feed-forward mechanism between GREB1 and steroid receptors regulates the differential effect of GREB1 on steroid hormones in a physiological or pathological context. In physiological (receptive) endometrium, GREB1 controls P4-responses in uterine stroma, affecting endometrial receptivity and decidualization, while not affecting E2-mediated epithelial proliferation. Of mechanism, progesterone-induced GREB1 physically interacts with the progesterone receptor, acting as a cofactor in a positive feedback mechanism to regulate P4-responsive genes. Conversely, in endometrial pathology (endometriosis), E2-induced GREB1 modulates E2-dependent gene expression to promote the growth of endometriotic lesions in mice. This differential action of GREB1 exerted by a common feed-forward mechanism with steroid receptors advances our understanding of mechanisms that underlie cell- and tissue-specific steroid hormone actions

Range Variability in CMR Feature Tracking Multilayer Strain across Different Stages of Heart Failure

Heart failure (HF) is associated with progressive ventricular remodeling and impaired contraction that affects distinctly various regions of the myocardium. Our study applied cardiac magnetic resonance (CMR) feature tracking (FT) to assess comparatively myocardial strain at 3 distinct levels: subendocardial (Endo-), mid (Myo-) and subepicardial (Epi-) myocardium across an extended spectrum of patients with HF. 59 patients with HF, divided into 3 subgroups as follows: preserved ejection fraction (HFpEF, N = 18), HF with mid-range ejection fraction (HFmrEF, N = 21), HF with reduced ejection fraction (HFrEF, N = 20) and a group of age- gender- matched volunteers (N = 17) were included. Using CMR FT we assessed systolic longitudinal and circumferential strain and strain-rate at Endo-, Myo- and Epi- levels. Strain values were the highest in the Endo- layer and progressively lower in the Myo- and Epi- layers respectively, this gradient was present in all the patients groups analyzed but decreased progressively in HFmrEF and further on in HFrEF groups. GLS decreased with the severity of the disease in all 3 layers: Normal > HFpEF > HFmrEF > HFrEF (Endo-: 1223.0 \ub1 3.5 > 1220.0 \ub1 3.3 > 1216.4 \ub1 2.2 > 1211.0 \ub1 3.2, p 1217.5.0 \ub1 2.6 > 1214.5 \ub1 2.1 > 129.6 \ub1 2.7, p 1212.2 \ub1 2.1 > 1210.6 \ub1 2.3 > 127.7 \ub1 2.3, p HFmrEF > HFrEF (Endo-: 1234.5 \ub1 6.2 > 1220.0 \ub1 4.2 > 12.3 \ub1 4.2, p 1213.0 \ub1 3.4 > 128.0 \ub1 2.7. p 127.9 \ub1 2.3 > 124.5 \ub1 1.9. p < 0.001). CMR feature tracking multilayer strain assessment identifies large range differences between distinct myocardial regions. Our data emphasizes the importance of sub-endocardial myocardium for cardiac contraction and thus, its predilect role in imaging detection of functional impairment. CMR feature tracking offers a convenient, readily available, platform to evaluate myocardial contraction with excellent spatial resolution, rendering further details about discrete areas of the myocardium. Using this technique across distinct groups of patients with heart failure (HF), we demonstrate that subendocardial regions of the myocardium exhibit much higher strain values than mid-myocardium or subepicardial and are more sensitive to detect contractile impairment. We also show comparatively higher values of circumferential strain compared with longitudinal and a higher sensitivity to detect contractile impairment. A newly characterized group of patients, HF with mid-range ejection fraction (EF), shows similar traits of decompensation but has relatively higher strain values as patients with HF with reduced EF

Genetics professionals’ experiences of facilitating parent/child communication through the genetic clinic

Acknowledgements We thank all the participants who took part, our project advisory team, patient representatives and Dr Heather Morgan. We are also grateful to the European Society of Human Genetics for inviting us to present an earlier version of this paper at their annual conference in 2015. In addition, we would like to thank the two reviewers who commented on the manuscript and provided helpful feedback. KFK was supported by a Postdoctoral Fellowship from the Chief Scientist Office of the Scottish Government (PDF/10/06). The views of this paper are the authors own.Peer reviewedPostprin

Capturing the essence of grounded theory: the importance of understanding commonalities and variants

This paper aims to capture the essence of grounded theory (GT) by setting out its commonalities and variants and, importantly, the implications of the latter for the implementation of the former, and for the truth claims and the contributions to knowledge that a GT study might make. Firstly, three ontological and epistemological variants of GT are outlined. Secondly, the commonalities of GT are set out as eight core elements of GT methodology that are individually necessary, but only sufficient collectively, to define a GT study. These elements are: an iterative process; theoretical sampling; theoretical sensitivity; codes, memos and concepts; constant comparison; theoretical saturation; fit, work, relevance and modifiability; and substantive theory. Thirdly, the implications of the ontological and epistemological variants of GT for, firstly, the implementation of the core common elements of the methodology and, secondly, the truth claims and contributions to knowledge that might be made, are discussed. Finally, the paper concludes by arguing that published GT studies in sport, exercise and health research have not always explicitly demonstrated a full understand of the commonalities and variants of GT, and that researchers publishing GT studies must take responsibility for doing this

Discovery of Two Very Low-Mass Binaries: Final Results of an Adaptive Optics Survey of Nearby M6.0-M7.5 Stars

We present updated results of a high-resolution, magnitude limited (Ks<12 mag) imaging survey of nearby low-mass M6.0-M7.5 field stars. The observations were carried out using adaptive optics at the Gemini North, VLT, Keck II, and Subaru telescopes. Our sample of 36 stars consists predominantly of nearby (<30 pc) field stars, 5 of which we have resolved as binaries. Two of the binary systems, 2MASSI J0429184-312356 and 2MASSI J1847034+552243, are presented here for the first time. All 5 discovered binary systems have separations between 0.08"-0.53" (2-9 AU) with similar mass ratios (q>0.8, delta Ks < 1 mag). This result supports the hypothesis that wide (a>20 AU) very low-mass (M_tot<0.19 M_sun) binary systems are rare. The projected semimajor axis distribution of these systems peak at ~ 5 AU and we report a sensitivity-corrected binary fraction of 9% (-3%, +4%) for stars with primaries of spectral type M6.0-M7.5 with separations >3 AU and mass ratios q>0.6. Within these instrumental sensitivities, these results support the overall trend that both the semimajor axis distribution and binary fraction are a function of the mass of the primary star and decrease with decreasing primary mass. These observations provide important constraints for low-mass binary star formation theories.Comment: 20 pages, 8 figures, accepted to Ap

Maximising transparency in a doctoral thesis: The complexities of writing about the use of QSR*NVIVO within a grounded theory study

This paper discusses the challenges of how to provide a transparent account of the use of the software programme QSR*NVIVO (QSR 2000) within a Grounded Theory framework (Glaser and Strauss 1967; Strauss and Corbin 1998). Psychology students are increasingly pursuing qualitative research projects such to the extent that the UK Economic and Social Research Council (ESRC) advise that students should have skill in the use of computer assisted qualitative data analysis software (CAQDAS) (Economic and Social Research Council 2001). Unlike quantitative studies, rigid formulae do not exist for writing-up qualitative projects for doctoral theses. Most authors, however, agree that transparency is essential when communicating the findings of qualitative research. Sparkes (2001) recommends that evaluative criteria for qualitative research should be commensurable with the aims, objectives, and epistemological assumptions of the research project. Likewise, the use of CAQDAS should vary according to the research methodology followed, and thus researchers should include a discussion of how CAQDAS was used. This paper describes how the evolving process of coding data, writing memos, categorising, and theorising were integrated into the written thesis. The structure of the written document is described including considerations about restructuring and the difficulties of writing about an iterative process within a linear document

Estimation of total collagen volume: a T1 mapping versus histological comparison study in healthy Landrace pigs

Right ventricular biopsy represents the gold standard for the assessment of myocardial fibrosis and collagen content. This invasive technique, however, is accompanied by perioperative complications and poor reproducibility. Extracellular volume (ECV) measured through cardiovascular magnetic resonance (CMR) has emerged as a valid surrogate method to assess fibrosis non-invasively. Nonetheless, ECV provides an overestimation of collagen concentration since it also considers interstitial space. Our study aims to investigate the feasibility of estimating total collagen volume (TCV) through CMR by comparing it with the TCV measured at histology. Seven healthy Landrace pigs were acutely instrumented closed-chest and transported to the MRI facility for measurements. For each protocol, CMR imaging at 3T was acquired. MEDIS software was used to analyze T1 mapping and ECV for both the left ventricular myocardium (LVmyo) and left ventricular septum (LVseptum). ECV was then used to estimate TCVCMR at LVmyo and LVseptum following previously published formulas. Tissues were prepared following an established protocol and stained with picrosirius red to analyze the TCVhisto in LVmyo and LVseptum. TCV measured at LVmyo and LVseptum with both histology (8 ± 5 ml and 7 ± 3 ml, respectively) and T1-Mapping (9 ± 5 ml and 8 ± 6 ml, respectively) did not show any regional differences. TCVhisto and TCVCMR showed a good level of data agreement by Bland–Altman analysis. Estimation of TCV through CMR may be a promising way to non-invasively assess myocardial collagen content and may be useful to track disease progression or treatment response

A search for binary systems among the nearest L dwarfs

We have used the NICMOS NIC1 camera on the Hubble Space Telescope to obtain high angular resolution images of 51 ultracool dwarfs in the immediate Solar Neighbourhood. Nine systems are resolved as binary, with component separations from 1.5 and 15 AU. All of the systems have components with similar luminosities, and, consequently, high mass ratios, q > 0.8. Limiting analysis to L dwarfs within 20 parsecs, the observed binary fraction is 12(+7/-3). Applying Bayesian analysis to our dataset, we derive a mass-ratio distribution that peaks strongly at unity. Modelling the semi-major axis distribution as a logarithmic Gaussian, the best fit is centered at log(a_0) = 0.8 AU (~6.3 AU), with a (logarithmic) width of 0.3. The current data are consistent with an overall binary frequency of ~24%.Comment: 29 pages, 4 tables, 8 figures; accepted for publication in A