Extreme stretching of high G:D ratio carbon nanotube fibers using super-acid

Few-wall carbon nanotube (CNT) textiles with unparalleled graphitic perfection and a solitary, prominent radial breathing mode (RBM) associated with metallic chirality have been mechanically stretched in chlorosulfonic acid (CSA) to a degree so far unseen in CNT textiles (150–250% of original length) with notably little tension required. This dramatically enhanced their microstructural alignment and density and, after most of the residual CSA was removed by a vacuum bake, the de-doped fiber's electrical conductivity was found to be 45% greater than single-crystal graphite – a significant milestone for CNT conductor development towards graphitic intercalation compounds (GICs) and traditional metals. Correlation tables and validated, multivariate statistical models show that conductivity is overwhelmingly linked to stretching degree, although eventually saturates near single-crystal graphite levels, implying the existence of a maximum undoped conductivity. The degree of stretching within CSA is correlated with the original mechanical properties (tenacity, elongation-to-break, and linear density); the Raman G’:G ratio and the upper-end oxidation temperature in thermogravimetric analysis also predict the best results. Less graphenically pristine CNT materials stretch to a lower degree in CSA, similar to previous reports. This study highlights the importance of post-synthesis processing to achieve superior performance in carbon nanotube textile materials

Moving from information and collaboration to action: report from the 3rd International Dog Health Workshop, Paris in April 2017

Abstract Background Breed-related health problems in dogs have received increased focus over the last decade. Responsibility for causing and/or solving these problems has been variously directed towards dog breeders and kennel clubs, the veterinary profession, welfare scientists, owners, regulators, insurance companies and the media. In reality, all these stakeholders are likely to share some responsibility and optimal progress on resolving these challenges requires all key stakeholders to work together. The International Partnership for Dogs (IPFD), together with an alternating host organization, holds biennial meetings called the International Dog Health Workshops (IDHW). The Société Centrale Canine (French Kennel Club) hosted the 3rd IDHW, in Paris, in April, 2017. These meetings bring together a wide range of stakeholders in dog health, science and welfare to improve international sharing of information and resources, to provide a forum for ongoing collaboration, and to identify specific needs and actions to improve health, well-being and welfare in dogs. Results The workshop included 140 participants from 23 countries and was structured around six important issues facing those who work to improve dog health. These included individualized breed-specific strategies for health and breeding, extreme conformations, education and communication in relation to antimicrobial resistance, behavior and welfare, genetic testing and population-based evidence. A number of exciting actions were agreed during the meeting. These included setting up working groups to create tools to help breed clubs accelerate the implementation of breed-health strategies, review aspects of extreme conformation and share useful information on behavior. The meeting also heralded the development of an online resource of relevant information describing quality measures for DNA testing. A demand for more and better data and evidence was a recurring message stressed across all themes. Conclusions The meeting confirmed the benefits from inclusion of a diverse range of stakeholders who all play relevant and collaborative parts to improve future canine health. Firm actions were set for progress towards improving breed-related welfare. The next international workshop will be in the UK in 2019 and will be organized by the UK Kennel Club

Miniature Schnauzers under primary veterinary care in the UK in 2013: demography, mortality and disorders

Individual dog breeds are often reported as predisposed to specific breed-related disorders but reliable epidemiological data on disease prevalence are sparse. The Miniature Schnauzer in the UK is a popular small breed dog that is often considered as relatively healthy and long-lived, but is this really true? This study aimed to use data from the VetCompass™ Programme at the Royal Veterinary College to characterise the demography, mortality and common disorders of the general population of Miniature Schnauzers under veterinary care in the UK

Human well‐being and climate change mitigation

Climate change mitigation research is fundamentally motivated by the preservation of human lives and the environmental conditions which enable them. However, the field has to date rather superficial in its appreciation of theoretical claims in well‐being thought, with deep implications for the framing of mitigation priorities, policies, and research. Major strands of well‐being thought are hedonic well‐being—typically referred to as happiness or subjective well‐being—and eudaimonic well‐being, which includes theories of human needs, capabilities, and multidimensional poverty. Aspects of each can be found in political and procedural accounts such as the Sustainable Development Goals. Situating these concepts within the challenges of addressing climate change, the choice of approach is highly consequential for: (1) understanding inter‐ and intra‐generational equity; (2) defining appropriate mitigation strategies; and (3) conceptualizing the socio‐technical provisioning systems that convert biophysical resources into well‐being outcomes. Eudaimonic approaches emphasize the importance of consumption thresholds, beyond which dimensions of well‐being become satiated. Related strands of well‐being and mitigation research suggest constraining consumption to within minimum and maximum consumption levels, inviting normative discussions on the social benefits, climate impacts, and political challenges associated with a given form of provisioning. The question of how current socio‐technical provisioning systems can be shifted towards low‐carbon, well‐being enhancing forms constitutes a new frontier in mitigation research, involving not just technological change and economic incentives, but wide‐ranging social, institutional, and cultural shifts

A repurposing strategy for Hsp90 inhibitors demonstrates their potency against filarial nematodes

Novel drugs are required for the elimination of infections caused by filarial worms, as most commonly used drugs largely target the microfilariae or first stage larvae of these infections. Previous studies, conducted in vitro, have shown that inhibition of Hsp90 kills adult Brugia pahangi. As numerous small molecule inhibitors of Hsp90 have been developed for use in cancer chemotherapy, we tested the activity of several novel Hsp90 inhibitors in a fluorescence polarization assay and against microfilariae and adult worms of Brugia in vitro. The results from all three assays correlated reasonably well and one particular compound, NVP-AUY922, was shown to be particularly active, inhibiting Mf output from female worms at concentrations as low as 5.0 nanomolar after 6 days exposure to drug. NVP-AUY922 was also active on adult worms after a short 24 h exposure to drug. Based on these in vitro data, NVP-AUY922 was tested in vivo in a mouse model and was shown to significantly reduce the recovery of both adult worms and microfilariae. These studies provide proof of principle that the repurposing of currently available Hsp90 inhibitors may have potential for the development of novel agents with macrofilaricidal properties

Structure of HsdS Subunit from Thermoanaerobacter tengcongensis Sheds Lights on Mechanism of Dynamic Opening and Closing of Type I Methyltransferase

Type I DNA methyltransferases contain one specificity subunit (HsdS) and two modification subunits (HsdM). The electron microscopy model of M.EcoKI-M2S1 methyltransferase shows a reasonable closed state of this clamp-like enzyme, but the structure of the open state is still unclear. The 1.95 Å crystal structure of the specificity subunit from Thermoanaerobacter tengcongensis (TTE-HsdS) shows an unreported open form inter-domain orientation of this subunit. Based on the crystal structure of TTE-HsdS and the closed state model of M.EcoKI-M2S1, we constructed a potential open state model of type I methyltransferase. Mutational studies indicated that two α-helices (aa30-59 and aa466-495) of the TTE-HsdM subunit are important inter-subunit interaction sites in the TTE-M2S1 complex. DNA binding assays also highlighted the importance of the C-terminal region of TTE-HsdM for DNA binding by the TTE-M2S1 complex. On the basis of structural analysis, biochemical experiments and previous studies, we propose a dynamic opening and closing mechanism for type I methyltransferase

Computed tomographic pulmonary angiography and pulmonary embolism: predictive value of a d-dimer assay

<p>Abstract</p> <p>Background</p> <p>Computed tomographic pulmonary angiography (CTPA) is increasingly being used as first investigation for suspected pulmonary embolism (PE). The investigation has high predictive value, but is resource and time intensive and exposes patients to considerable radiation. Our aim was to assess the potential value of a negative d-dimer assay to exclude pulmonary emboli and reduce the number of performed CTPAs.</p> <p>Methods</p> <p>All CTPAs performed in a Scottish secondary care hospital for a fourteen month period were retrospectively reviewed. Collected data included the presence or absence of PE, d-dimer results and patient demographics. PE positive CTPAs were reviewed by a specialist panel.</p> <p>Results</p> <p>Pulmonary embolisms were reported for 66/405 (16.3%) CTPAs and d-dimer tests were performed for 216 (53%). 186/216 (86%) patients had a positive and 30 (14%) a negative d-dimer result. The panel agreed 5/66 (7.6%) false positive examinations. The d-dimer assay's negative predictive value was 93.3% (95% CI = 76.5%-98.8%) based on the original number of positive CTPAs and 100% (95% CI = 85.9%-100%) based on expert review. Significant non-PE intrapulmonary pathology was reported for 312/405 (77.0) CTPAs, including 13 new diagnoses of carcinoma.</p> <p>Conclusions</p> <p>We found that a low d-dimer score excluded all pulmonary embolisms, after a further specialist panel review identified initial false positive reports. However, current evidence-based guidelines still recommend that clinicians combine a d-dimer result with a validated clinical risk score when selecting suitable patients for CTPA. This may result in better use of limited resources, prevent patients being exposed to unnecessary irradiation and prevent potential complications as a result of iodinated contrast.</p

Assay strategies for the discovery and validation of therapeutics targeting <i>Brugia pahangi</i> Hsp90

The chemotherapy of lymphatic filariasis relies upon drugs such as diethylcarbamazine and ivermectin that largely target the microfilarial stages of the parasite, necessitating continued treatment over the long reproductive life span of the adult worm. The identification of compounds that target adult worms has been a long-term goal of WHO. Here we describe a fluorescence polarization assay for the identification of compounds that target Hsp90 in adult filarial worms. The assay was originally developed to identify inhibitors of Hsp90 in tumor cells, and relies upon the ability of small molecules to inhibit the binding of fluorescently labelled geldanamycin to Hsp90. We demonstrate that the assay works well with soluble extracts of Brugia, while extracts of the free-living nematode C. elegans fail to bind the probe, in agreement with data from other experiments. The assay was validated using known inhibitors of Hsp90 that compete with geldanamycin for binding to Hsp90, including members of the synthetic purine-scaffold series of compounds. The efficacy of some of these compounds against adult worms was confirmed in vitro. Moreover, the assay is sufficiently sensitive to differentiate between binding of purine-scaffold compounds to human and Brugia Hsp90. The assay is suitable for high-throughput screening and provides the first example of a format with the potential to identify novel inhibitors of Hsp90 in filarial worms and in other parasitic species where Hsp90 may be a target

Improving uptake of Fracture Prevention drug treatments: a protocol for Development of a consultation intervention (iFraP-D).

Funder: Wellcome TrustINTRODUCTION: Prevention of fragility fractures, a source of significant economic and personal burden, is hindered by poor uptake of fracture prevention medicines. Enhancing communication of scientific evidence and elicitation of patient medication-related beliefs has the potential to increase patient commitment to treatment. The Improving uptake of Fracture Prevention drug treatments (iFraP) programme aims to develop and evaluate a theoretically informed, complex intervention consisting of a computerised web-based decision support tool, training package and information resources, to facilitate informed decision-making about fracture prevention treatment, with a long-term aim of improving informed treatment adherence. This protocol focuses on the iFraP Development (iFraP-D) work. METHODS AND ANALYSIS: The approach to iFraP-D is informed by the Medical Research Council complex intervention development and evaluation framework and the three-step implementation of change model. The context for the study is UK fracture liaison services (FLS), which enact secondary fracture prevention. An evidence synthesis of clinical guidelines and Delphi exercise will be conducted to identify content for the intervention. Focus groups with patients, FLS clinicians and general practitioners and a usual care survey will facilitate understanding of current practice, and investigate barriers and facilitators to change. Design of the iFraP intervention will be informed by decision aid development standards and theories of implementation, behaviour change, acceptability and medicines adherence. The principles of co-design will underpin all elements of the study through a dedicated iFraP community of practice including key stakeholders and patient advisory groups. In-practice testing of the prototype intervention will inform revisions ready for further testing in a subsequent pilot and feasibility randomised trial. ETHICS AND DISSEMINATION: Ethical approval was obtained from North West-Greater Manchester West Research Ethics Committee (19/NW/0559). Dissemination and knowledge mobilisation will be facilitated through national bodies and networks, publications and presentations. TRIAL REGISTRATION NUMBER: researchregistry5041

The ESR1 (6q25) locus is associated with calcaneal ultrasound parameters and radial volumetric bone mineral density in European men

&lt;p&gt;&lt;b&gt;Purpose:&lt;/b&gt; Genome-wide association studies (GWAS) have identified 6q25, which incorporates the oestrogen receptor alpha gene (ESR1), as a quantitative trait locus for areal bone mineral density (BMD(a)) of the hip and lumbar spine. The aim of this study was to determine the influence of this locus on other bone health outcomes; calcaneal ultrasound (QUS) parameters, radial peripheral quantitative computed tomography (pQCT) parameters and markers of bone turnover in a population sample of European men.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methods:&lt;/b&gt; Eight single nucleotide polymorphisms (SNP) in the 6q25 locus were genotyped in men aged 40-79 years from 7 European countries, participating in the European Male Ageing Study (EMAS). The associations between SNPs and measured bone parameters were tested under an additive genetic model adjusting for centre using linear regression.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; 2468 men, mean (SD) aged 59.9 (11.1) years had QUS measurements performed and bone turnover marker levels measured. A subset of 628 men had DXA and pQCT measurements. Multiple independent SNPs showed significant associations with BMD using all three measurement techniques. Most notably, rs1999805 was associated with a 0.10 SD (95%CI 0.05, 0.16; p = 0.0001) lower estimated BMD at the calcaneus, a 0.14 SD (95%CI 0.05, 0.24; p = 0.004) lower total hip BMD(a), a 0.12 SD (95%CI 0.02, 0.23; p = 0.026) lower lumbar spine BMD(a) and a 0.18 SD (95%CI 0.06, 0.29; p = 0.003) lower trabecular BMD at the distal radius for each copy of the minor allele. There was no association with serum levels of bone turnover markers and a single SNP which was associated with cortical density was also associated with cortical BMC and thickness.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; Our data replicate previous associations found between SNPs in the 6q25 locus and BMD(a) at the hip and extend these data to include associations with calcaneal ultrasound parameters and radial volumetric BMD.&lt;/p&gt