The kiss of death : a demystification of the late-nineteenth century 'femme fatale' in the works of Bram Stoker, Rider Haggard, Joseph Conrad and Thomas Hardy.

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Functional differences in the microbial processing of recent assimilates under two contrasting perennial bioenergy plantations

Land use change driven alteration of microbial communities can have implications on belowground C cycling and storage, although our understanding of the interactions between plant C inputs and soil microbes is limited. Using phospholipid fatty acids (PLFA's) we profiled the microbial communities under two contrasting UK perennial bioenergy crops, Short Rotation Coppice (SRC) willow and Miscanthus Giganteus (miscanthus), and used 13C – pulse labelling to investigate how recent carbon (C) assimilates were transferred through plant tissues to soil microbes. Total PLFA's and fungal to bacterial (F:B) ratios were higher under SRC willow (Total PLFA = 47.70 ± 1.66 SE μg PLFA g−1 dry weight soil, F:B = 0.27 ± 0.01 SE) relative to miscanthus (Total PLFA = 30.89 ± 0.73 SE μg PLFA g−1 dry weight soil, F:B = 0.17 ± 0.00 SE). Functional differences in microbial communities were highlighted by contrasting processing of labelled C. SRC willow allocated 44% of total 13C detected into fungal PLFA relative to 9% under miscanthus and 380% more 13C was returned to the atmosphere in soil respiration from SRC willow soil compared to miscanthus. Our findings elucidate the roles that bacteria and fungi play in the turnover of recent plant derived C under these two perennial bioenergy crops, and provide important evidence on the impacts of land use change to bioenergy on microbial community composition

Loss of FBXO7 results in a Parkinson’s-like dopaminergic degeneration via an RPL23-MDM2-TP53 pathway

The field of Parkinson’s disease research has been impeded by the absence of animal models that clearly phenocopy the features of this neurodegenerative condition. Mutations in FBXO7/PARK15 are associated with both sporadic Parkinson’s disease and a severe form of autosomal recessive early-onset Parkinsonism. Here we report that conditional deletion of Fbxo7 in the midbrain dopamine neurons results in an early reduction in striatal dopamine levels, together with a slow, progressive loss of midbrain dopamine neurons and onset of locomotor defects. Unexpectedly, a later compensatory response led to a near-full restoration of dopaminergic fibre innervation in the striatum, but nigral cell loss was irreversible. Mechanistically, there was increased expression in the dopamine neurons of FBXO7-interacting protein, RPL23, which is a sensor of ribosomal stress that inhibits MDM2, the negative regulator of p53. A corresponding activated p53 transcriptional signature biased towards pro-apoptotic genes was also observed. These data suggest the neuroprotective role of FBXO7 involves its suppression of the RPL23-MDM2-p53 axis that promotes cell death in dopaminergic midbrain neurons.Biotechnology and Biological Sciences Research Council (BB/J007846/1), DDPDgenes, Parkinson's UK and the CurePD Trust, and Wellcome Trust-MRC funded Cambridge Stem Cell Institute and an NIHR award of a Biomedical Research Centre for Addenbrooke’s Hospital/University of Cambridge

The behaviour of dark matter associated with 4 bright cluster galaxies in the 10kpc core of Abell 3827

Galaxy cluster Abell 3827 hosts the stellar remnants of four almost equally bright elliptical galaxies within a core of radius 10kpc. Such corrugation of the stellar distribution is very rare, and suggests recent formation by several simultaneous mergers. We map the distribution of associated dark matter, using new Hubble Space Telescope imaging and VLT/MUSE integral field spectroscopy of a gravitationally lensed system threaded through the cluster core. We find that each of the central galaxies retains a dark matter halo, but that (at least) one of these is spatially offset from its stars. The best-constrained offset is 1.62+/-0.48kpc, where the 68% confidence limit includes both statistical error and systematic biases in mass modelling. Such offsets are not seen in field galaxies, but are predicted during the long infall to a cluster, if dark matter self-interactions generate an extra drag force. With such a small physical separation, it is difficult to definitively rule out astrophysical effects operating exclusively in dense cluster core environments - but if interpreted solely as evidence for self-interacting dark matter, this offset implies a cross-section sigma/m=(1.7+/-0.7)x10^{-4}cm^2/g x (t/10^9yrs)^{-2}, where t is the infall duration.Comment: 15 pages, 9 figure

Fluxes and fate of dissolved methane released at the seafloor at the landward limit of the gas hydrate stability zone offshore western Svalbard

Widespread seepage of methane from seafloor sediments offshore Svalbard close to the landward limit of the gas hydrate stability zone (GHSZ) may, in part, be driven by hydrate destabilization due to bottom water warming. To assess whether this methane reaches the atmosphere where it may contribute to further warming, we have undertaken comprehensive surveys of methane in seawater and air on the upper slope and shelf region. Near the GHSZ limit at ?400 m water depth, methane concentrations are highest close to the seabed, reaching 825 nM. A simple box model of dissolved methane removal from bottom waters by horizontal and vertical mixing and microbially mediated oxidation indicates that ?60% of methane released at the seafloor is oxidized at depth before it mixes with overlying surface waters. Deep waters are therefore not a significant source of methane to intermediate and surface waters; rather, relatively high methane concentrations in these waters (up to 50 nM) are attributed to isopycnal turbulent mixing with shelf waters. On the shelf, extensive seafloor seepage at <100 m water depth produces methane concentrations of up to 615 nM. The diffusive flux of methane from sea to air in the vicinity of the landward limit of the GHSZ is ?4–20 ?mol m?2 d?1, which is small relative to other Arctic sources. In support of this, analyses of mole fractions and the carbon isotope signature of atmospheric methane above the seeps do not indicate a significant local contribution from the seafloor source

Autism in England: assessing underdiagnosis in a population-based cohort study of prospectively collected primary care data

Background: Autism has long been viewed as a paediatric condition, meaning that many autistic adults missed out on a diagnosis as children when autism was little known. We estimated numbers of diagnosed and undiagnosed autistic people in England, and examined how diagnostic rates differed by socio-demographic factors. / Methods: This population-based cohort study of prospectively collected primary care data from IQVIA Medical Research Data (IMRD) compared the prevalence of diagnosed autism to community prevalence to estimate underdiagnosis. 602,433 individuals registered at an English primary care practice in 2018 and 5,586,100 individuals registered between 2000 and 2018 were included. / Findings: Rates of diagnosed autism in children/young people were much higher than in adults/older adults. As of 2018, 2.94% of 10- to 14-year-olds had a diagnosis (1 in 34), vs. 0.02% aged 70+ (1 in 6000). Exploratory projections based on these data suggest that, as of 2018, 463,500 people (0.82% of the English population) may have been diagnosed autistic, and between 435,700 and 1,197,300 may be autistic and undiagnosed (59–72% of autistic people, 0.77%–2.12% of the English population). Age-related inequalities were also evident in new diagnoses (incidence): c.1 in 250 5- to 9-year-olds had a newly-recorded autism diagnosis in 2018, vs. c.1 in 4000 20- to 49-year-olds, and c.1 in 18,000 people aged 50+. / Interpretation: Substantial age-related differences in the proportions of people diagnosed suggest an urgent need to improve access to adult autism diagnostic services

Estimating life expectancy and years of life lost for autistic people in the UK: a matched cohort study

Background: Previous research has shown that people who have been diagnosed autistic are more likely to die prematurely than the general population. However, statistics on premature mortality in autistic people have often been misinterpreted. In this study we aimed to estimate the life expectancy and years of life lost experienced by autistic people living in the UK.// Methods: We studied people in the IQVIA Medical Research Database with an autism diagnosis between January 1, 1989 and January 16, 2019. For each participant diagnosed autistic, we included ten comparison participants without an autism diagnosis, matched by age, sex, and primary care practice. We calculated age- and sex-standardised mortality ratios comparing people diagnosed autistic to the reference group. We used Poisson regression to estimate age-specific mortality rates, and life tables to estimate life expectancy at age 18 and years of life lost. We analysed the data separately by sex, and for people with and without a record of intellectual disability. We discuss the findings in the light of the prevalence of recorded diagnosis of autism in primary care compared to community estimates.// Findings: From a cohort of nearly 10 million people, we identified 17,130 participants diagnosed autistic without an intellectual disability (matched with 171,300 comparison participants), and 6450 participants diagnosed autistic with an intellectual disability (matched with 64,500 comparison participants). The apparent estimates indicated that people diagnosed with autism but not intellectual disability had 1.71 (95% CI: 1.39–2.11) times the mortality rate of people without these diagnoses. People diagnosed with autism and intellectual disability had 2.83 (95% CI: 2.33–3.43) times the mortality rate of people without these diagnoses. Likewise, the apparent reduction in life expectancy for people diagnosed with autism but not intellectual disability was 6.14 years (95% CI: 2.84–9.07) for men and 6.45 years (95% CI: 1.37–11.58 years) for women. The apparent reduction in life expectancy for people diagnosed with autism and intellectual disability was 7.28 years (95% CI: 3.78–10.27) for men and 14.59 years (95% CI: 9.45–19.02 years) for women. However, these findings are likely to be subject to exposure misclassification biases: very few autistic adults and older-adults have been diagnosed, meaning that we could only study a fraction of the total autistic population. Those who have been diagnosed may well be those with greater support needs and more co-occurring health conditions than autistic people on average

Estimating life expectancy and years of life lost for autistic people in the UK: a matched cohort study

Background Previous research has shown that people who have been diagnosed autistic are more likely to die prematurely than the general population. However, statistics on premature mortality in autistic people have often been misinterpreted. In this study we aimed to estimate the life expectancy and years of life lost experienced by autistic people living in the UK. Methods We studied people in the IQVIA Medical Research Database with an autism diagnosis between January 1, 1989 and January 16, 2019. For each participant diagnosed autistic, we included ten comparison participants without an autism diagnosis, matched by age, sex, and primary care practice. We calculated age- and sex-standardised mortality ratios comparing people diagnosed autistic to the reference group. We used Poisson regression to estimate age-specific mortality rates, and life tables to estimate life expectancy at age 18 and years of life lost. We analysed the data separately by sex, and for people with and without a record of intellectual disability. We discuss the findings in the light of the prevalence of recorded diagnosis of autism in primary care compared to community estimates. Findings From a cohort of nearly 10 million people, we identified 17,130 participants diagnosed autistic without an intellectual disability (matched with 171,300 comparison participants), and 6450 participants diagnosed autistic with an intellectual disability (matched with 64,500 comparison participants). The apparent estimates indicated that people diagnosed with autism but not intellectual disability had 1.71 (95% CI: 1.39–2.11) times the mortality rate of people without these diagnoses. People diagnosed with autism and intellectual disability had 2.83 (95% CI: 2.33–3.43) times the mortality rate of people without these diagnoses. Likewise, the apparent reduction in life expectancy for people diagnosed with autism but not intellectual disability was 6.14 years (95% CI: 2.84–9.07) for men and 6.45 years (95% CI: 1.37–11.58 years) for women. The apparent reduction in life expectancy for people diagnosed with autism and intellectual disability was 7.28 years (95% CI: 3.78–10.27) for men and 14.59 years (95% CI: 9.45–19.02 years) for women. However, these findings are likely to be subject to exposure misclassification biases: very few autistic adults and older-adults have been diagnosed, meaning that we could only study a fraction of the total autistic population. Those who have been diagnosed may well be those with greater support needs and more co-occurring health conditions than autistic people on average. Interpretation The findings indicate that there is a group of autistic people who experience premature mortality, which is of significant concern. There is an urgent need for investigation into the reasons behind this. However, our estimates suggest that the widely reported statistic that autistic people live 16-years less on average is likely incorrect. Nine out of 10 autistic people may have been undiagnosed across the time-period studied. Hence, the results of our study do not generalise to all autistic people. Diagnosed autistic adults, and particularly older adults, are likely those with greater-than-average support needs. Therefore, we may have over-estimated the reduction in life expectancy experienced by autistic people on average. The larger reduction in life expectancy for women diagnosed with autism and intellectual disability vs. men may in part reflect disproportionate underdiagnosis of autism and/or intellectual disability in women

The behaviour of dark matter associated with four bright cluster galaxies in the 10kpc core of Abell 3827

Galaxy cluster Abell 3827 hosts the stellar remnants of four almost equally bright elliptical galaxies within a core of radius 10kpc. Such corrugation of the stellar distribution is very rare, and suggests recent formation by several simultaneous mergers. We map the distribution of associated dark matter, using new Hubble Space Telescope imaging andVery Large Telescope/Multi-Unit Spectroscopic Explorer integral field spectroscopy of a gravitationally lensed system threaded through the cluster core. We find that each of the central galaxies retains a dark matter halo, but that (at least) one of these is spatially offset from its stars. The best-constrained offset is $1.62^{+0.47}_{-0.49}$kpc, where the 68 per cent confidence limit includes both statistical error and systematic biases in mass modelling. Such offsets are not seen in field galaxies, but are predicted during the long infall to a cluster, if dark matter self-interactions generate an extra drag force. With such a small physical separation, it is difficult to definitively rule out astrophysical effects operating exclusively in dense cluster core environments - but if interpreted solely as evidence for self-interacting dark matter, this offset implies a cross-section σDM/m∼(1.7±0.7)×10−4cm2g−1×(tinfall/109 yr)−2, where tinfall is the infall duratio

Protocol for the Rare Dementia Support Impact Study: RDS Impact

OBJECTIVES: The Rare Dementia Support (RDS) Impact study will be the first major study of the value of multicomponent support groups for people living with or supporting someone with a rare form of dementia. The multicentre study aims to evaluate the impact of multicomponent support offered and delivered to people living with a rare form of dementia, comprising the following five Work Packages (WPs): (1) Longitudinal cohort interviews; (2) Theoretical development; (3) Developing measures; (4) Novel interventions; and (5) Economic analysis. METHODS: This is a mixed-methods design, including a longitudinal cohort study (quantitative and qualitative) and a feasibility randomised control trial (RCT). A cohort of >1000 individuals will be invited to participate. The primary and secondary outcomes will be in-part determined through a co-design Nominal Groups Technique pre-study involving caregivers to people living with a diagnosis of a rare dementia. Quantitative analyses of differences and predictors will be based on pre-specified hypotheses. A variety of quantitative (e.g. ANOVA and multiple linear regression techniques), qualitative (e.g. thematic analysis) and innovative analytical methods will also be developed and applied by involving the arts as a research method. RESULTS: The UCL Research Ethics Committee have approved this study. Data collection will begin in Q4 2019. CONCLUSIONS: The study will capture information through a combination of longitudinal interviews, questionnaires and scales, and novel creative data collection methods. The notion of 'impact' in the context of support for rare dementias will involve theoretical development, novel measures and methods of support interventions, and health economic analyses