Negotiating jurisdictional boundaries in response to new genetic possibilities in breast cancer care:The creation of an 'oncogenetic taskscape'

Changes in the nature and structure of healthcare pathways have implications for healthcare professionals' jurisdictional boundaries. The introduction of treatment focused BRCA1 and 2 genetic testing (TFGT) for newly diagnosed patients with breast cancer offers a contemporary example of pathway change brought about by technological advancements in gene testing and clinical evidence, and reflects the cultural shift towards genomics. Forming part of an ethnographically informed study of patient and practitioner experiences of TFGT at a UK teaching hospital, this paper focuses on the impact of a proposal to pilot a mainstreamed TFGT pathway on healthcare professionals' negotiations of professional jurisdiction. Based upon semi-structured interviews (n = 19) with breast surgeons, medical oncologists and members of the genetics team, alongside observations of breast multidisciplinary team meetings, during the time leading up to the implementation of the pilot, we describe how clinicians responded to the anticipated changes associated with mainstreaming. Interviews suggest that mainstreaming the breast cancer pathway, and the associated jurisdictional reconfigurations, had advocates as well as detractors. Medical oncologists championed the plans, viewing this adaptation in care provision and their professional role as a logical next step. Breast surgeons, however, regarded mainstreaming as an unfeasible expansion of their workload and questioned the relevance of TFGT to their clinical practice. The genetics team, who introduced the pilot, appeared cautiously optimistic about the potential changes. Drawing on sociological understandings of the negotiation of professional jurisdictions our work contributes a timely, micro-level examination of the responses among clinicians as they worked to renegotiate professional boundaries in response to the innovative application of treatment-focused BRCA testing in cancer care – a local and dynamic process which we refer to as an ‘oncogenetic taskscape in the making’

Identifying the larva of the fan mussel, Atrina fragilis (Pennant, 1777) (Pinnidae)

This work was funded by the Scottish Government project SP004 and a MSS PhD studentship to DS. Many thanks are due to the Crews of the MV Alba na Mara (MSS), RV Sir John Murray (SEPA) and the MV Lochnevis (Caledonian Macbrayne) for facilitating sample collection, John Dunn for assistance with the manufacture and installation of the ferry sampler, Marian Thomson and other staff at the University of Edinburgh for laboratory assistance, Anastasia Imsiridou, Sofia Galinou-Mitsoudi and Vassilis Katsares of the Greek Department of Fisheries and Aquaculture Technology for supplying reference adult A. fragilis DNA, Pablo Diaz and staff at the University of Aberdeen microscopy department for assistance with SEM analysis, the National Museum of Wales for allowing reproduction of the juvenile A. fragilis image, Keith Hiscock and Eve Southward of Plymouth Marine Laboratory for historical information on the identification of A. fragilis larvae, Colin McAlister and the staff of the Fishery offices in Mallaig and Fraserburgh for assistance in the transport of zooplankton samples and materials, and the British Oceanographic Data Centre for supplying data on the UK Tidal Gauge Network. Comments from Associate Editor Simon Cragg and two anonymous reviewers were greatly appreciated for improving the manuscriptPeer reviewedPostprintPostprintPostprintPostprintPostprintPostprintPostprintPostprintPostprin

The very flat radio - millimetre spectrum of Cygnus X-1

We present almost-simultaneous detections of Cygnus X-1 in the radio and mm regimes, obtained during the low/hard X-ray state. The source displays a flat spectrum between 2 and 220 GHz, with a spectral index flatter than 0.15 (3sigma). There is no evidence for either a low- or high-frequency cut-off, but in the mid-infrared (~30 microns) thermal emission from the OB-type companion star becomes dominant. The integrated luminosity of this flat-spectrum emission in quiescence is > 2 x 10^{31} erg/s (2 x 10^{24} W). Assuming the emission originates in a jet for which non-radiative (e.g. adiabatic expansion) losses dominate, this is a very conservative lower limit on the power required to maintain the jet. A comparison with Cyg X-3 and GRS 1915+105, the other X-ray binaries for which a flat spectrum at shorter than cm wavelengths has been observed, shows that the jet in Cyg X-1 is significantly less luminous and less variable, and is probably our best example to date of a continuous, steady, outflow from an X-ray binary. The emissive mechanism reponsible for such a flat spectral component remains uncertain. Specifically, we note that the radio-mm spectra observed from these X-ray binaries are much flatter than those of the `flat-spectrum' AGN, and that existing models of synchrotron emission from partially self-absorbed radio cores, which predict a high-frequency cut-off in the mm regime, are not directly applicable.Comment: Accepted for publication in MNRA

Moving into the mainstream: Healthcare professionals’ views of implementing treatment focussed genetic testing in breast cancer care

A proportion of breast cancers are attributable to BRCA1 or BRCA2 mutations. Technological advances has meant that mutation testing in newly diagnosed cancer patients can be used to inform treatment plans. Although oncologists increasingly deliver treatment-focused genetic testing (TFGT) as part of mainstream ovarian cancer care, we know little about non-genetics specialists' views about offering genetic testing to newly diagnosed breast cancer patients. This study sought to determine genetics and non-genetics specialists' views of a proposal to mainstream BRCA1 and 2 testing in newly diagnosed breast cancer patients. Qualitative interview study. Nineteen healthcare professionals currently responsible for offering TFGT in a standard (triage + referral) pathway (breast surgeons + clinical genetics team) and oncologists preparing to offer TFGT to breast cancer patients in a mainstreamed pathway participated in in-depth interviews. Genetics and non-genetics professionals' perceptions of mainstreaming are influenced by their views of: their clinical roles and responsibilities, the impact of TFGT on their workload and the patient pathway and the perceived relevance of genetic testing for patient care in the short-term. Perceived barriers to mainstreaming may be overcome by: more effective communication between specialities, clearer guidelines/patient pathways and the recruitment of mainstreaming champions

Ancient dental calculus reveals oral microbiome shifts associated with lifestyle and disease in Great Britain

We thank C. Stringer and R. Kruszynski of the Natural History Museum, London; S. Schiffels; D. Sayer; Oxford Archaeology East; M. Farrell of the Royal College of Surgeons of England; J. Pearson of the Inverness Museum; and all of the museums for access to samples. We also thank the Museum of London for allowing us to collect and destructively analyse archaeological dental calculus samples from their collections from London, particularly J. Bekvalac and R. Redfern. We would also like to acknowledge J. VanderBerg at EnDev Geographic for producing the map used in Fig. 1. A.C., C.A. and L.W. thank the Australian Research Council for research funding (DP110105038) and Laureate (FL140100260). The work was also supported by an Australian Research Council Future Fellowship Award to L.S.W. (FT180100407). This material is also based on work supported by the National Science Foundation Graduate Research Fellowship Program awarded to A.S.G. under Grant No. DGE1255832. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the National Science Foundation.Peer reviewedPostprintPostprintPostprin

Phase Correlations in Cosmic Microwave Background Temperature Maps

We study the statistical properties of spherical harmonic modes of temperature maps of the cosmic microwave background. Unlike other studies, which focus mainly on properties of the amplitudes of these modes, we look instead at their phases. In particular, we present a simple measure of phase correlation that can be diagnostic of departures from the standard assumption that primordial density fluctuations constitute a statistically homogeneous and isotropic Gaussian random field, which should possess phases that are uniformly random on the unit circle. The method we discuss checks for the uniformity of the distribution of phase angles using a non-parametric descriptor based on the use order statistics, which is known as Kuiper's statistic. The particular advantage of the method we present is that, when coupled to the judicious use of Monte Carlo simulations, it can deliver very interesting results from small data samples. In particular, it is useful for studying the properties of spherical harmonics at low l for which there are only small number of independent values of m and which therefore furnish only a small number of phases for analysis. We apply the method to the COBE-DMR and WMAP sky maps, and find departures from uniformity in both. In the case of WMAP, our results probably reflect Galactic contamination or the known variation of signal-to-noise across the sky rather than primordial non-Gaussianity.Comment: 18 pages, 4 figures, accepted for publication in MNRA

Effects of Acute Insulin-Induced Hypoglycemia on Indices of Inflammation Putative mechanism for aggravating vascular disease in diabetes

OBJECTIVE: To examine the effects of acute insulin-induced hypoglycemia on inflammation, endothelial dysfunction, and platelet activation in adults with and without type 1 diabetes. RESEARCH DESIGN AND METHODS: We studied 16 nondiabetic adults and 16 subjects with type 1 diabetes during euglycemia (blood glucose 4.5 mmol/l) and hypoglycemia (blood glucose 2.5 mmol/l). Markers of inflammation, thrombosis, and endothelial dysfunction (soluble P-selectin, interleukin-6, von Willebrand factor [vWF], tissue plasminogen activator [tPA], high-sensitivity C-reactive protein [hsCRP], and soluble CD40 ligand [sCD40L]) were measured; platelet-monocyte aggregation and CD40 expression on monocytes were determined using flow cytometry. RESULTS: In nondiabetic participants, platelet activation occurred after hypoglycemia, with increments in platelet-monocyte aggregation and P-selectin (P ≤ 0.02). Inflammation was triggered with CD40 expression increasing maximally at 24 h (3.13 ± 2.3% vs. 2.06 ± 1.0%) after hypoglycemia (P = 0.009). Both sCD40L and hsCRP (P = 0.02) increased with a nonsignificant rise in vWF and tPA, indicating a possible endothelial effect. A reduction in sCD40L, tPA, and P-selectin occurred during euglycemia (P = 0.03, P ≤ 0.006, and P = 0.006, respectively). In type 1 diabetes, both CD40 expression (5.54 ± 4.4% vs. 3.65 ± 1.8%; P = 0.006) and plasma sCD40L concentrations increased during hypoglycemia (peak 3.41 ± 3.2 vs. 2.85 ± 2.8 ng/ml; P = 0.03). Platelet-monocyte aggregation also increased significantly at 24 h after hypoglycemia (P = 0.03). A decline in vWF and P-selectin occurred during euglycemia (P ≤ 0.04). CONCLUSIONS: Acute hypoglycemia may provoke upregulation and release of vasoactive substances in adults with and without type 1 diabetes. This may be a putative mechanism for hypoglycemia-induced vascular injury

The radio spectrum of a quiescent stellar mass black hole

Observations of V404 Cyg performed with the Westerbork Synthesis Radio Telescope at four frequencies, over the interval 1.4-8.4 GHz, have provided us with the first broadband radio spectrum of a `quiescent' stellar mass black hole. The measured mean flux density is of 0.35 mJy, with a spectral index alpha=+ 0.09\pm0.19$ (such that S_nu \propto nu^{alpha}). Synchrotron emission from an inhomogeneous partially self-absorbed outflow of plasma accounts for the flat/inverted radio spectrum, in analogy with hard state black hole X-ray binaries, indicating that a steady jet is being produced between a few 10^{-6} and a few per cent of the Eddington X-ray luminosity.Comment: accepted for publication in MNRA

Initial response of young people with thyrotoxicosis to block and replace or dose titration thionamide

\ua9 2022 The authors Published by Bioscientifica Ltd.Objective: Patients with thyrotoxicosis are treated with anti-thyroid drug (ATD) using block and replace (BR) or a smaller, titrated dose of ATD (dose titration, DT). Design: A multi-centre, phase III, open-label trial of newly diagnosed paediatric thyrotoxicosis patients randomised to BR/DT. We compared the biochemical response to BR/DT in the first 6 months of therapy. Methods: Patients commenced 0.75 mg/kg carbimazole (CBZ) daily with randomisation to BR/DT. We examined baseline patient characteristics, CBZ dose, time to serum thyroid-stimulating hormone (TSH)/free thyroxine (FT4) normalisation and BMI Z-score change. Results: There were 80 patients (baseline) and 78 patients (61 female) at 6 months. Mean CBZ dose was 0.9 mg/kg/day (BR) and 0.5 mg/kg/day (DT). There was no difference in time to non-suppressed TSH concentration; 16 of 39 patients (BR) and 11 of 39 (DT) had suppressed TSH at 6 months. Patients with suppressed TSH had higher mean baseline FT4 levels (72.7 vs 51.7 pmol/L; 95% CI for difference 1.73, 31.7; P = 0.029). Time to normalise FT4 levels was reduced in DT (log-rank test, P = 0.049) with 50% attaining normal FT4 at 28 days (95% CI 25, 32) vs 35 days in BR (95% CI 28, 58). Mean BMI Z-score increased from 0.10 to 0.81 at 6 months (95% CI for difference 0.57, 0.86; P < 0.001) and was greatest in patients with higher baseline FT4 concentrations. Conclusions: DT-treated patients normalised FT4 concentrations more quickly than BR. Overall, 94% of patients have normal FT4 levels after 6 months, but 33% still have TSH suppression. Excessive weight gain occurs with both BR and DT therapy