Testing the boundaries of closely related daisy taxa using metabolomic profiling

Advances in high-throughput, comprehensive small molecule analytical techniques have seen the development of the field of metabolomics. The coupling of mass spectrometry with high-resolution chromatography provides extensive chemical profiles from complex biological extracts. These profiles include thousands of compounds linked to gene expression, and can be used as taxonomic characters. Studies have shown metabolite profiles to be taxon specific in a range of organisms, but few have investigated taxonomically problematic plant taxa. This study used a phenetic analysis of metabolite profiles to test taxonomic boundaries in the Olearia phlogopappa (Asteraceae) complex as delimited by morphological data. Metabolite profiles were generated from both field- and shade house-grown material, using liquid chromatography-mass spectrometry (LC-MS). Aligned profiles of 51 samples from 12 taxa gave a final dataset of over 10,000 features. Multivariate analyses of field and shade house material gave congruent results, both confirming the distinctiveness of the morphologically defined species and subspecies in this complex. Metabolomics has great potential in alpha taxonomy, especially for testing the boundaries of closely related taxa where DNA sequence data has been uninformative

Arterial structure and function in vascular ageing: are you as old as your arteries?

Advancing age may be the most potent independent predictor of future cardiovascular events, a relationship that is not fully explained by time-related changes in traditional cardiovascular risk factors. Since some arteries exhibit differential susceptibility to atherosclerosis, generalisations regarding the impact of ageing in humans may be overly simplistic, whereas in vivo assessment of arterial function and health provide direct insight. Coronary and peripheral (conduit, resistance and skin) arteries demonstrate a gradual, age-related impairment in vascular function that is likely to be related to a reduction in endothelium-derived nitric oxide bioavailability and/or increased production of vasoconstrictors (e.g. endothelin-1). Increased exposure and impaired ability for defence mechanisms to resist oxidative stress and inflammation, but also cellular senescence processes, may contribute to age-related changes in vascular function and health. Arteries also undergo structural changes as they age. Gradual thickening of the arterial wall, changes in wall content (i.e. less elastin, advanced glycation end-products) and increase in conduit artery diameter are observed with older age and occur similarly in central and peripheral arteries. These changes in structure have important interactive effects on artery function, with increases in small and large arterial stiffness representing a characteristic change with older age. Importantly, direct measures of arterial function and structure predict future cardiovascular events, independent of age or other cardiovascular risk factors. Taken together, and given the differential susceptibility of arteries to atherosclerosis in humans, direct measurement of arterial function and health may help to distinguish between biological and chronological age-related change in arterial health in humans

Current management of children and young people with heterozygous familial hypercholesterolaemia - HEART UK statement of care

This consensus statement on the management of children and young people with heterozygous familial hypercholesterolaemia (FH) addresses management of paediatric FH in the UK, identified by cascade testing when a parent is diagnosed with FH and for those diagnosed following incidental lipid tests. Lifestyle and dietary advice appropriate for children with FH; suggested low density lipoprotein cholesterol (LDL-C) targets and the most appropriate lipid-lowering therapies to achieve these are discussed in this statement of care. Based on the population prevalence of FH as ~1/250 and the UK paediatric population, there are approximately 50,000 FH children under 18 years. Currently only about 550 of these children and young people have been identified and are under paediatric care

Observation of An Evolving Magnetic Flux Rope Prior To and During A Solar Eruption

Explosive energy release is a common phenomenon occurring in magnetized plasma systems ranging from laboratories, Earth's magnetosphere, the solar corona and astrophysical environments. Its physical explanation is usually attributed to magnetic reconnection in a thin current sheet. Here we report the important role of magnetic flux rope structure, a volumetric current channel, in producing explosive events. The flux rope is observed as a hot channel prior to and during a solar eruption from the Atmospheric Imaging Assembly (AIA) telescope on board the Solar Dynamic Observatory (SDO). It initially appears as a twisted and writhed sigmoidal structure with a temperature as high as 10 MK and then transforms toward a semi-circular shape during a slow rise phase, which is followed by fast acceleration and onset of a flare. The observations suggest that the instability of the magnetic flux rope trigger the eruption, thus making a major addition to the traditional magnetic-reconnection paradigm.Comment: 13 pages, 3 figure

A detailed radio study of the energetic, nearby, and puzzling GRB 171010A

We present the results of an intensive multi-epoch radio frequency campaign on the energetic and nearby GRB 171010A with the Karl G. Janksy Very Large Array and Arcminute Microkelvin Imager Large Array. We began observing GRB 171010A a day after its initial detection, and were able to monitor the temporal and spectral evolution of the source over the following weeks. The spectra and their evolution are compared to the canonical theories for broadband GRB afterglows, with which we find a general agreement. There are, however, a number of features that are challenging to explain with a simple forward shock model, and we discuss possible reasons for these discrepancies. This includes the consideration of the existence of a reverse shock component, potential microphysical parameter evolution and the effect of scintillation

Stigma of living as an autism carer: a brief psycho-social support intervention (SOLACE). Study protocol for a randomised controlled feasibility study.

Stigma is prominent in the lives of autistic individuals and their families and contributes significantly to the challenges faced by families raising an autistic child. Parents and carers can feel blamed for their child's behaviour, feel socially excluded and isolated and suffer from low self-esteem and poor psychological well-being. This increases the risk of experiencing self-stigma which further exacerbates these and other negative consequences. Therefore, there is a need for interventions that help parents/family carers cope with autism-related stigma as well as prevent the internalisation of stigma. The primary objective of this study is to assess the feasibility and acceptability of a stigma support intervention for parents and carers of autistic children titled 'Stigma of Living as an Autism Carer (SOLACE)'. The secondary objective is to explore the preliminary impact of the intervention on the mental health of the parents and carers. tests for differences within the group. Other outcomes of interest are stigma, self-stigma, self-esteem, self-blame, social isolation, self-compassion and perceived responsibility and control. Results from the feasibility randomised controlled trial will be used to refine the study protocol and inform the design of an intervention for future use in a larger, powered trial. SOLACE could potentially improve the psychological well-being of parents/family carers of autistic children through increased resistance to stigma. ISRCTN Registry number ISRCTN61093625 (October 13, 2017)

Genetic evidence that higher central adiposity causes gastro-oesophageal reflux disease: a Mendelian-randomization study

Background: Gastro-oesophageal reflux disease (GORD) is associated with multiple risk factors but determining causality is difficult. We used a genetic approach [Mendelian randomization (MR)] to identify potential causal modifiable risk factors for GORD. Methods: We used data from 451 097 European participants in the UK Biobank and defined GORD using hospital-defined ICD10 and OPCS4 codes and self-report data (N = 41 024 GORD cases). We tested observational and MR-based associations between GORD and four adiposity measures [body mass index (BMI), waist-hip ratio (WHR), a metabolically favourable higher body-fat percentage and waist circumference], smoking status, smoking frequency and caffeine consumption. Results: Observationally, all adiposity measures were associated with higher odds of GORD. Ever and current smoking were associated with higher odds of GORD. Coffee consumption was associated with lower odds of GORD but, among coffee drinkers, more caffeinated-coffee consumption was associated with higher odds of GORD. Using MR, we provide strong evidence that higher WHR and higher WHR adjusted for BMI lead to GORD. There was weak evidence that higher BMI, body-fat percentage, coffee drinking or smoking caused GORD, but only the observational effects for BMI and body-fat percentage could be excluded. This MR estimated effect for WHR equates to a 1.23-fold higher odds of GORD per 5-cm increase in waist circumference. Conclusions: These results provide strong evidence that a higher waist-hip ratio leads to GORD. Our study suggests that central fat distribution is crucial in causing GORD rather than overall weight.This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.S.E.J. is funded by the Medical Research Council (grant: MR/M005070/1). A.R.W., T.M.F and H.Y. are supported by the European Research Council grants: SZ-245 50371-GLUCOSEGENES-FP7-IDEAS-ERC and 323195. H.Y. is also funded by the Diabetes UK RD Lawrence fellowship (grant: 17/0005594). R.N.B. is funded by the Wellcome Trust and Royal Society, grant 104150/Z/14/Z. J.T. is supported by an Academy of Medical Sciences (AMS) Springboard award, which is supported by the AMS, the Wellcome Trust, GCRF, the Government Department of Business, Energy and Industrial strategy, the British Heart Foundation and Diabetes UK (SBF004\1079). N.A.K. declares personal fees from Falk, Takeda and Pharmacosmos; other fees from Janssen; and non-financial support from Janssen, AbbVie and Celltrion outside the submitted work. J.R.G. received honoraria from Falk, AbbVie and Shield therapeutics, outside the submitted work for unrelated topics. T.A. reports grants from AbbVie, MSD, Napp Pharmaceuticals, Celltrion, Pfizer, Janssen and Celgene during this study; personal fees and non-financial support from Immunodiagnostik; personal fees and non-financial support from Napp Pharmaceuticals, AbbVie and MSD; personal fees from Celltrion and Pfizer; grants and personal fees from Takeda; and grants and non-financial support from Tillotts, outside the submitted work.published version, accepted version (12 month embargo), submitted versio