Persistent hypertriglyceridemia in statin-treated patients with type 2 diabetes mellitus

Purpose: This paper reports the results of an audit that assessed the prevalence of residual hypertriglyceridemia and the potential need for intensified management among patients with statin-treated type 2 diabetes mellitus (T2DM) in primary care in the UK. Patients and methods: A cross-sectional, observational, systematic audit of patients with diagnosed diabetes from 40 primary care practices was undertaken. The audit collected basic demographic information and data on prescriptions issued during the preceding 4 months. T2DM patients were stratified according to the proportion that attained European Society of Cardiology treatment targets. Results: The audit collected data from 14,652 patients with diagnosed diabetes: 89.5% (n = 13,108) of the total cohort had T2DM. Of the people with T2DM, 22.2% (2916) were not currently receiving lipid-lowering therapy. Up to approximately 80% of these people showed evidence of dyslipidemia. Among the group that received lipid-lowering therapy, 94.7% (9647) were on statin monotherapy, which was usually simvastatin (69.5% of patients receiving statin monotherapy; 6707). The currently available statins were prescribed, with the most common dose being 40 mg simvastatin (44.2%; 4267). Irrespective of the statin used, around half of the patients receiving statin monotherapy did not attain the European Society of Cardiology treatment targets for triglycerides, low-density lipoprotein, high-density lipoprotein, and total cholesterol. Conclusion: T2DM patients managed in UK primary care commonly show persistent lipid abnormalities. Clinicians need to optimize compliance with lipid-lowering and other medications. Clinicians also need to consider intensifying statin regimens, prescribing additional lipid-modifying therapies, and specific treatments aimed at triglyceride lowering to improve dyslipidemia control in statin-treated patients with T2DM

Guidance on the use of MRI for treatment planning in radiotherapy clinical trials

The aim of this article is to propose meaningful guidance covering the technical and safety issues involved when designing or conducting radiotherapy clinical trials that use MRI for treatment planning. The complexity of imaging requirements will depend on the trial aims, design and MRI methods used.The use of MRI within the RT pathway is becoming more prevalent and clinically appropriate as access to MRI increases, treatment planning systems become more versatile and potential indications for MRI-planning in RT are documented. Novel MRI-planning opportunities are often initiated and validated within clinical trials.The guidance in this document is intended to assist researchers designing RT clinical trials involving MRI, so that they may provide sufficient information about the appropriate methods to be used for image acquisition, post-processing and quality assurance such that participating sites complete MRI to consistent standards. It has been produced in collaboration with the National Radiotherapy Trials Quality Assurance Group (RTTQA).As the use of MRI in RT is developed, it is highly recommended for researchers writing clinical trial protocols to include imaging guidance as part of their clinical trial documentation covering the trial-specific requirements for MRI procedures. Many of the considerations and recommendations in this guidance may well apply to MR-guided treatment machines, where clinical trials will be crucial. Similarly, many of these recommendations will apply to the general use of MRI in RT, outside of clinical trials.This document contains a large number of recommendations, not all of which will be relevant to any particular trial. Designers of RT clinical trials must therefore take this into account. They must also use their own judgement as to the appropriate compromise between accessibility of the trial and its technical rigour

An integrated analysis and comparison of serum, saliva and sebum for COVID-19 metabolomics.

The majority of metabolomics studies to date have utilised blood serum or plasma, biofluids that do not necessarily address the full range of patient pathologies. Here, correlations between serum metabolites, salivary metabolites and sebum lipids are studied for the first time. 83 COVID-19 positive and negative hospitalised participants provided blood serum alongside saliva and sebum samples for analysis by liquid chromatography mass spectrometry. Widespread alterations to serum-sebum lipid relationships were observed in COVID-19 positive participants versus negative controls. There was also a marked correlation between sebum lipids and the immunostimulatory hormone dehydroepiandrosterone sulphate in the COVID-19 positive cohort. The biofluids analysed herein were also compared in terms of their ability to differentiate COVID-19 positive participants from controls; serum performed best by multivariate analysis (sensitivity and specificity of 0.97), with the dominant changes in triglyceride and bile acid levels, concordant with other studies identifying dyslipidemia as a hallmark of COVID-19 infection. Sebum performed well (sensitivity 0.92; specificity 0.84), with saliva performing worst (sensitivity 0.78; specificity 0.83). These findings show that alterations to skin lipid profiles coincide with dyslipidaemia in serum. The work also signposts the potential for integrated biofluid analyses to provide insight into the whole-body atlas of pathophysiological conditions

Ultralow-light-level color image reconstruction using high-efficiency plasmonic metasurface mosaic filters

As single-photon imaging becomes progressively more commonplace in sensing applications such as low-light-level imaging, three-dimensional profiling, and fluorescence imaging, there exist a number of fields where multispectral information can also be exploited, e.g., in environmental monitoring and target identification. We have fabricated a high-transmittance mosaic filter array, where each optical filter was composed of a plasmonic metasurface fabricated in a single lithographic step. This plasmonic metasurface design utilized an array of elliptical and circular nanoholes, which produced enhanced optical coupling between multiple plasmonic interactions. The resulting metasurfaces produced narrow bandpass filters for blue, green, and red light with peak transmission efficiencies of 79%, 75%, and 68%, respectively. After the three metasurface filter designs were arranged in a 64×64 format random mosaic pattern, this mosaic filter was directly integrated onto a CMOS single-photon avalanche diode detector array. Color images were then reconstructed at light levels as low as approximately 5 photons per pixel, on average, via the simultaneous acquisition of low-photon multispectral data using both three-color active laser illumination and a broadband white-light illumination source

Services just for men? Insights from a national study of the well men services pilots.

Men continue to have a lower life expectancy in most countries compared to women. Explanations of this gendered health inequality tend to focus on male risk taking, unhealthy lifestyle choices and resistance to seeking help from health services. In the period 2005-2008 the Scottish Government funded a nationwide community health promotion programme aimed at improving men's health, called Well Men Service Pilots (henceforth WMS)

New insights into risk factors for transplant-associated thrombotic microangiopathy in pediatric HSCT

This study aimed to identify a risk profile for development of transplant-associated thrombotic microangiopathy (TA-TMA) in children undergoing hematopoietic stem cell transplantation (HSCT). Between 2013 and 2016, 439 children underwent 474 HSCTs at 2 supraregional United Kingdom centers. At a median of 153 days post-HSCT, TA-TMA occurred among 25 of 441 evaluable cases (5.6%) with no evidence of center variation. Sex, underlying disease, intensity of the conditioning, total body irradiation–based conditioning, the use of calcineurin inhibitors, venoocclusive disease, and viral reactivation did not influence the development of TA-TMA. Donor type: matched sibling donor/matched family donor vs matched unrelated donor vs mismatched unrelated donor/haplo-HSCT, showed a trend toward the development of TA-TMA in 1.8% vs 6.1% vs 8.3%, respectively. Presence of active comorbidity was associated with an increased risk for TA-TMA; 13% vs 3.7% in the absence of comorbidity. The risk of TA-TMA was threefold higher among patients who received >1 transplant. TA-TMA rates were significantly higher among patients with acute graft-versus-host disease (aGVHD) grades III to IV vs aGVHD grade 0 to II. On multivariate analysis, the presence of active comorbidity, >1 transplant, aGVHD grade III to IV were risk factors for TA-TMA (odds ratio [OR]: 5.1, 5.2, and 26.9; respectively), whereas the use of cyclosporine A/tacrolimus-based GVHD prophylaxis was not a risk factor for TA-TMA (OR: 0.3). Active comorbidity, subsequent transplant, and aGVHD grades III to IV were significant risk factors for TA-TMA. TA-TMA might represent a form of a vascular GVHD, and therefore, continuing control of aGVHD is important to prevent worsening of TA-TMA associated with GVHD

High-Frequency Elastic Coupling at the Interface of van der Waals Nanolayers Imaged by Picosecond Ultrasonics

Although the topography of van de Waals (vdW) layers and heterostructures can be imaged by scanning probe microscopy, high-frequency interface elastic properties are more difficult to assess. These can influence the stability, reliability and performance of electronic devices that require uniform layers and interfaces. Here, we use picosecond ultrasonics to image these properties in vdW layers and heterostructures based on well-known exfoliable materials, i.e. InSe, hBN and graphene. We reveal a strong, uniform elastic coupling between vdW layers over a wide range of frequencies of up to tens of gigahertz (GHz) and in-plane areas of 100 _m2. In contrast, the vdW layers can be weakly coupled to their supporting substrate, behaving effectively as free standing membranes. Our data and analysis demonstrate that picosecond ultrasonics offers opportunities can probe the high-frequency elastic coupling of vdW nanolayers and image both perfect and broken interfaces between different materials over a wide frequency range, as required for future scientific and technological developments

Dolutegravir Pharmacokinetics in the Genital Tract and Colorectum of HIV-Negative Men After Single and Multiple Dosing

To describe first dose and steady-state pharmacokinetics (PK) of dolutegravir (DTG) in blood plasma (BP), seminal fluid (SF), colorectal tissue (RT), and rectal mucosal fluid (RF) of healthy HIV negative men

Tales of Emergence - Synthetic Biology as a Scientific Community in the Making

International audienceThis article locates the beginnings of a synthetic biology network and thereby probes the formation of a potential disciplinary community. We consider the ways that ideas of community are mobilized, both by scientists and policy-makers in building an agenda for new forms of knowledge work, and by social scientists as an analytical device to understand new formations for knowledge production. As participants in, and analysts of, a network in synthetic biology, we describe our current understanding of synthetic biology by telling four tales of community making. The first tale tells of the mobilization of synthetic biology within a European context. The second tale describes the approach to synthetic biology community formation in the UK. The third narrates the creation of an institutionally based, funded 'network in synthetic biology'. The final tale de-localizes community-making efforts by focussing on 'devices' that make communities. In tying together these tales, our analysis suggests that the potential community can be understood in terms of 'movements'--the (re)orientation and enrolment of people, stories, disciplines and policies; and of 'stickiness'--the objects and glues that begin to bind together the various constitutive elements of community