Investigations into the Sarcomeric Protein and Ca2+-Regulation Abnormalities Underlying Hypertrophic Cardiomyopathy in Cats (Felix catus).

Hypertrophic cardiomyopathy (HCM) is the most common single gene inherited cardiomyopathy. In cats (Felix catus) HCM is even more prevalent and affects 16% of the outbred population and up to 26% in pedigree breeds such as Maine Coon and Ragdoll. Homozygous MYBPC3 mutations have been identified in these breeds but the mutations in other cats are unknown. At the clinical and physiological level feline HCM is closely analogous to human HCM but little is known about the primary causative mechanism. Most identified HCM causing mutations are in the genes coding for proteins of the sarcomere. We therefore investigated contractile and regulatory proteins in left ventricular tissue from 25 cats, 18 diagnosed with HCM, including a Ragdoll cat with a homozygous MYBPC3 R820W, and 7 non-HCM cats in comparison with human HCM (from septal myectomy) and donor heart tissue. Myofibrillar protein expression was normal except that we observed 20–44% MyBP-C haploinsufficiency in 5 of the HCM cats. Troponin extracted from 8 HCM and 5 non-HCM cat hearts was incorporated into thin filaments and studied by in vitro motility assay. All HCM cat hearts had a higher (2.06 ± 0.13 fold) Ca2+-sensitivity than non-HCM cats and, in all the HCM cats, Ca2+-sensitivity was not modulated by troponin I phosphorylation. We were able to restore modulation of Ca2+-sensitivity by replacing troponin T with wild-type protein or by adding 100 μM Epigallocatechin 3-gallate (EGCG). These fundamental regulatory characteristics closely mimic those seen in human HCM indicating a common molecular mechanism that is independent of the causative mutation. Thus, the HCM cat is a potentially useful large animal model

What and how: doing good research with young people, digital intimacies, and relationships and sex education

© 2020, © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. As part of a project funded by the Wellcome Trust, we held a one-day symposium, bringing together researchers, practitioners, and policymakers, to discuss priorities for research on relationships and sex education (RSE) in a world where young people increasingly live, experience, and augment their relationships (whether sexual or not) within digital spaces. The introduction of statutory RSE in schools in England highlights the need to focus on improving understandings of young people and digital intimacies for its own sake, and to inform the development of learning resources. We call for more research that puts young people at its centre; foregrounds inclusivity; and allows a nuanced discussion of pleasures, harms, risks, and rewards, which can be used by those working with young people and those developing policy. Generating such research is likely to be facilitated by participation, collaboration, and communication with beneficiaries, between disciplines and across sectors. Taking such an approach, academic researchers, practitioners, and policymakers agree that we need a better understanding of RSE’s place in lifelong learning, which seeks to understand the needs of particular groups, is concerned with non-sexual relationships, and does not see digital intimacies as disconnected from offline everyday ‘reality’

Fly-by-light flight control system technology development plan

The results of a four-month, phased effort to develop a Fly-by-Light Technology Development Plan are documented. The technical shortfalls for each phase were identified and a development plan to bridge the technical gap was developed. The production configuration was defined for a 757-type airplane, but it is suggested that the demonstration flight be conducted on the NASA Transport Systems Research Vehicle. The modifications required and verification and validation issues are delineated in this report. A detailed schedule for the phased introduction of fly-by-light system components has been generated. It is concluded that a fiber-optics program would contribute significantly toward developing the required state of readiness that will make a fly-by-light control system not only cost effective but reliable without mitigating the weight and high-energy radio frequency related benefits

Is there an association between perceived social support and cardiovascular health behaviours in people with severe mental illnesses?

PURPOSE: People with severe mental illnesses (SMI) have an increased risk of cardiovascular disease (CVD). Research in the general population suggests that social support may protect against increased CVD morbidity and mortality; however, this may not apply to those with SMI. We aimed to explore the association between perceived social support and attendance at primary care nurse CVD risk reduction clinic appointments and CVD risk-reducing behaviours in an SMI population with elevated CVD risk factors. METHODS: We used longitudinal and cross-sectional data from a randomised controlled trial on 326 adults with SMI recruited via 76 general practices in England. Multilevel regression analysis estimated the effect of perceived social support on attendance at CVD risk reduction clinic appointments over 6 months, and adherence to CVD medication, physical activity, diet, smoking and alcohol use at baseline, adjusted by age, sex, ethnicity, deprivation, psychiatric diagnosis and employment. RESULTS: Perceived social support predicted greater appointment attendance in unadjusted (IRR = 1.005; 1.000-1.010; p = 0.05) but not adjusted analysis (IRR = 1.003; 0.998-1.009; p = 0.25). Perceived social support was associated with greater adherence to medication; for each 1% increase in social support, there was a 4.2% increase in medication adherence (OR = 1.042; 1.015-1.070; p = 0.002). No association was found between greater perceived social support and greater physical activity, lower sedentary behaviour, healthier diet, lower alcohol use or being a non-smoker. CONCLUSIONS: Social support may be an important facilitator for CVD medication adherence and is potentially important for primary care appointment attendance; however, alternative strategies might be needed to help people with SMI engage in physical activity, healthier diets and to reduce their smoking and alcohol use

The Phylogeography of Rabies in Grenada, West Indies, and Implications for Control

In Grenada, West Indies, rabies is endemic, and is thought to be maintained in a wildlife host, the small Indian mongoose (Herpestes auropunctatus) with occasional spillover into other hosts. Therefore, the present study was undertaken to improve understanding of rabies epidemiology in Grenada and to inform rabies control policy. Mongooses were trapped island-wide between April 2011 and March 2013 and examined for the presence of Rabies virus (RABV) antigen using the direct fluorescent antibody test (dFAT) and PCR, and for serum neutralizing antibodies (SNA) using the fluorescent antibody virus neutralization test (FAVN). An additional cohort of brain samples from clinical rabies suspects submitted between April 2011 and March 2014 were also investigated for the presence of virus. Two of the 171 (1.7%) live-trapped mongooses were RABV positive by FAT and PCR, and 20 (11.7%) had SNAs. Rabies was diagnosed in 31 of the submitted animals with suspicious clinical signs: 16 mongooses, 12 dogs, 2 cats and 1 goat. Our investigation has revealed that rabies infection spread from the northeast to the southwest of Grenada within the study period. Phylogenetic analysis revealed that the viruses from Grenada formed a monophyletic clade within the cosmopolitan lineage with a common ancestor predicted to have occurred recently (6–23 years ago), and are distinct from those found in Cuba and Puerto Rico, where mongoose rabies is also endemic. These data suggest that it is likely that this specific strain of RABV was imported from European regions rather than the Americas. These data contribute essential information for any potential rabies control program in Grenada and demonstrate the importance of a sound evidence base for planning interventions

New observations and models of circumstellar CO line emission of AGB stars in the Herschel SUCCESS programme

CONTEXT: Asymptotic giant branch (AGB) stars are in one of the latest evolutionary stages of low to intermediate-mass stars. Their vigorous mass loss has a significant effect on the stellar evolution, and is a significant source of heavy elements and dust grains for the interstellar medium. The mass-loss rate can be well traced by carbon monoxide (CO) line emission. AIMS: We present new Herschel HIFI and IRAM 30m telescope CO line data for a sample of 53 galactic AGB stars. The lines cover a fairly large range of excitation energy from the $J=1\to0$ line to the $J=9\to8$ line, and even the $J=14\to13$ line in a few cases. We perform radiative transfer modelling for 38 of these sources to estimate their mass-loss rates. METHODS: We used a radiative transfer code based on the Monte Carlo method to model the CO line emission. We assume spherically symmetric circumstellar envelopes that are formed by a constant mass-loss rate through a smoothly accelerating wind. RESULTS: We find models that are consistent across a broad range of CO lines for most of the stars in our sample, i.e., a large number of the circumstellar envelopes can be described with a constant mass-loss rate. We also find that an accelerating wind is required to fit, in particular, the higher-J lines and that a velocity law will have a significant effect on the model line intensities. The results cover a wide range of mass-loss rates ($\sim 10^{-8}$ to $2\times 10^{-5}~\mathrm{M}_\odot~\mathrm{ yr}^{-1}$) and gas expansion velocities (2 to $21.5$ km s$^{-1}$), and include M-, S-, and C-type AGB stars. Our results generally agree with those of earlier studies, although we tend to find slightly lower mass-loss rates by about 40%, on average. We also present "bonus" lines detected during our CO observations.Comment: 36 page

Polarisation Observations of H2_{2}O JK−1K1=532−441J_{K_{-1}K_{1}} = 5_{32} - 4_{41} 620.701 GHz Maser Emission with Herschel/HIFI in Orion KL

Context. The high intensities and narrow bandwidths exhibited by some astronomical masers make them ideal tools for studying star-forming giant molecular clouds. The water maser transition $J_{K_{-1}K_{1}}=5_{32}-4_{41}$ at 620.701 GHz can only be observed from above Earth's strongly absorbing atmosphere; its emission has recently been detected from space. Aims. We sought to further characterize the star-forming environment of Orion KL by investigating the linear polarisation of a source emitting a narrow 620.701 GHz maser feature with the heterodyne spectrometer HIFI on board the Herschel Space Observatory. Methods. High-resolution spectral datasets were collected over a thirteen month period beginning in 2011 March, to establish not only the linear polarisation but also the temporal variability of the source. Results. Within a $3\sigma$ uncertainty, no polarisation was detected to an upper limit of approximately 2%. These results are compared with coeval linear polarisation measurements of the 22.235 GHz $J_{K_{-1}K_{1}}=6_{16}-5_{23}$ maser line from the Effelsberg 100-m radio telescope, typically a much stronger maser transition. Although strongly polarised emission is observed for one component of the 22.235 GHz maser at 7.2 km s$^{-1}$, a weaker component at the same velocity as the 620.701 GHz maser at 11.7 km s$^{-1}$ is much less polarised.Comment: Accepted for publication in A&

Staggered orbital currents in the half-filled two-leg ladder

Using Abelian bosonization with a careful treatment of the Klein factors, we show that a certain phase of the half-filled two-leg ladder, previously identified as having spin-Peierls order, instead exhibits staggered orbital currents with no dimerization.Comment: 8 pages, 2 figures. Final versio

Survey of patient and public perceptions of electronic health records for healthcare, policy and research: Study protocol

BACKGROUND: Immediate access to patients’ complete health records via electronic databases could improve healthcare and facilitate health research. However, the possible benefits of a national electronic health records (EHR) system must be balanced against public concerns about data security and personal privacy. Successful development of EHR requires better understanding of the views of the public and those most affected by EHR: users of the National Health Service. This study aims to explore the correlation between personal healthcare experience (including number of healthcare contacts and number and type of longer term conditions) and views relating to development of EHR for healthcare, health services planning and policy and health research. METHODS/DESIGN: A multi-site cross-sectional self-complete questionnaire designed and piloted for use in waiting rooms was administered to patients from randomly selected outpatients’ clinics at a university teaching hospital (431 beds) and general practice surgeries from the four primary care trusts within the catchment area of the hospital. All patients entering the selected outpatients clinics and general practice surgeries were invited to take part in the survey during August-September 2011. Statistical analyses will be conducted using descriptive techniques to present respondents’ overall views about electronic health records and logistic regression to explore associations between these views and participants’ personal circumstances, experiences, sociodemographics and more specific views about electronic health records. DISCUSSION: The study design and implementation were successful, resulting in unusually high response rates and overall recruitment (85.5%, 5336 responses). Rates for face-to-face recruitment in previous work are variable, but typically lower (mean 76.7%, SD 20). We discuss details of how we collected the data to provide insight into how we obtained this unusually high response rate

Parametric study of prospective early commercial MHD power plants (PSPEC). General Electric Company, task 1: Parametric analysis

The performance and cost of moderate technology coal-fired open cycle MHD/steam power plant designs which can be expected to require a shorter development time and have a lower development cost than previously considered mature OCMHD/steam plants were determined. Three base cases were considered: an indirectly-fired high temperature air heater (HTAH) subsystem delivering air at 2700 F, fired by a state of the art atmospheric pressure gasifier, and the HTAH subsystem was deleted and oxygen enrichment was used to obtain requisite MHD combustion temperature. Coal pile to bus bar efficiencies in ease case 1 ranged from 41.4% to 42.9%, and cost of electricity (COE) was highest of the three base cases. For base case 2 the efficiency range was 42.0% to 45.6%, and COE was lowest. For base case 3 the efficiency range was 42.9% to 44.4%, and COE was intermediate. The best parametric cases in bases cases 2 and 3 are recommended for conceptual design. Eventual choice between these approaches is dependent on further evaluation of the tradeoffs among HTAH development risk, O2 plant integration, and further refinements of comparative costs