Calibrated, cosmological hydrodynamical simulations with variable IMFs I: Method and effect on global galaxy scaling relations

The recently inferred variations in the stellar initial mass function (IMF) among local highmass early-type galaxies may require a reinterpretation of observations of galaxy populations and may have important consequences for the predictions of models of galaxy formation and evolution. We present a new pair of cosmological, hydrodynamical simulations based on the EAGLE model that self-consistently adopts an IMF that, respectively, becomes bottomor top-heavy in high-pressure environments for individual star-forming gas particles. In such models, the excess stellarmass-to-light (M/L) ratio with respect to a reference IMF is increased due to an overabundance of low-mass dwarf stars or stellar remnants, respectively. Crucially, both pressure-dependent IMFs have been calibrated to reproduce the observed trends of increasing excessM/L with central stellar velocity dispersion (σe) in early-type galaxies, while maintaining agreement with the observables used to calibrate the EAGLE model, namely the galaxy luminosity function, half-light radii of late-type galaxies, and black holemasses.We find that while theM/L excess is a good measure of the IMF for low-mass slope variations, it depends strongly on the age of the stellar population for high-mass slope variations. The normalization of the [Mg/Fe]-σerelation is decreased (increased) for bottom- (top-)heavy IMF variations, while the slope is not strongly affected. Bottom-heavy variations have little impact on galaxy metallicities, half-light radii of early-type galaxies, or star formation rates, while top-heavy variations significantly increase these quantities for high-mass galaxies, leading to tension with observations. © 2018 The Author(s). Published by Oxford University Press on behalf of The Royal Astronomical Society

Health benefits from nature experiences depend on dose

Nature within cities will have a central role in helping address key global public health 3 challenges associated with urbanization. However, there is almost no guidance on how much 4 or how frequently people need to engage with nature, and what types or characteristics of 5 nature need to be incorporated in cities for the best health outcomes. Here we use a nature 6 dose framework to examine the associations between the duration, frequency and intensity of 7 exposure to nature and health in an urban population. We show that people who made long 8 visits to green spaces had lower rates of depression and high blood pressure, and those who 9 visited more frequently had greater social cohesion. Higher levels of physical activity were 10 linked to both duration and frequency of green space visits. A dose-response analysis for 11 depression and high blood pressure suggest that visits to outdoor green spaces of 30 minutes 12 or more during the course of a week could reduce the population prevalence of these illnesses 13 by up to 7% and 9% respectively. Given that the societal costs of depression alone in 14 Australia are estimated at AUD$12.6 billion per annum, savings to public health budgets 15 across all health outcomes could be immense.D.F.S. is supported through ARC Discovery Grant DP120102857 and the Centre of Excellence for Environmental Decisions (CEED, Australia); R.A.F. holds an ARC Future Fellowship; B.B.L. is supported through the CSIRO Land and Water Flagship; and K.J.G. is supported by NERC grant NE/J015237/1. J. Rhodes, K. Johansen and S. Wu contributed to the development of the vegetation data. Authors would like to thank the Brisbane City Council for providing GIS data layers, the Department of Science, Information Technology and Innovation and the Department of Natural Resources and Mines, QLD for providing access to the airborne LiDAR

Calibrated, cosmological hydrodynamical simulations with variable IMFs - II. Correlations between the IMF and global galaxy properties

The manner in which the stellar initial mass function (IMF) scales with global galaxy properties is under debate. We use two hydrodynamical, cosmological simulations to predict possible trends for two self-consistent variable IMF prescriptions that, respectively, become locally bottom-heavy or top-heavy in high-pressure environments. Both simulations have been calibrated to reproduce the observed correlation between central stellar velocity dispersion and excess mass-to-light ratio (MLE) relative to a Salpeter IMF by increasing the mass fraction of, respectively, dwarf stars or stellar remnants. We find trends of MLE with galaxy age, metallicity, and [Mg/Fe] that agree qualitatively with observations. Predictions for correlations withexces luminosity, half-light radius, and black hole (BH) mass are presented. The significance of many of these correlations depends sensitively on galaxy selection criteria such as age, luminosity, and morphology. For an IMF with a varying high-mass end, some of these correlations are stronger than the correlation with the birth interstellar medium pressure (the property that governs the form of the IMF) because in this case the MLE has a strong age dependence. Galaxies with large MLE tend to have overmassive central BHs. This indicates that the abnormally high MLE observed in the centres of some high-mass galaxies does not imply that overmassive BHs are merely the result of incorrect IMF assumptions, nor that excess M/L ratios are solely the result of overmassive BHs. Satellite galaxies tend to scatter towards high MLE due to tidal stripping, which may have significant implications for the inferred stellar masses of ultracompact dwarf galaxies

Calibrated, cosmological hydrodynamical simulations with variable IMFs III: spatially resolved properties and evolution

Recent spatially resolved observations of massive early-type galaxies (ETGs) have uncovered evidence for radial gradients of the stellar initial mass function (IMF), ranging from super-Salpeter IMFs in the centre to Milky Way-like beyond the half-light radius, re. We compare these findings with our new cosmological, hydrodynamical simulations based on the Evolution and Assembly of GaLaxies and their Environments (EAGLE) model that self-consistently vary the IMF on a per-particle basis such that it becomes either bottom-heavy (LoM-50) or top-heavy (HiM-50) in high-pressure environments. These simulations were calibrated to reproduce inferred IMF variations such that the IMF becomes ‘heavier’ due to either excess dwarf stars or stellar remnants, respectively, in galaxies with increasing stellar velocity dispersion. In agreement with observations, both simulations produce negative radial IMF gradients, transitioning from high to low excess mass-to-light ratio (MLE) at around re. We find negative metallicity radial gradients for both simulations, but positive and flat [Mg/Fe] gradients in LoM-50 and HiM-50, respectively. Measured in radial bins, the MLE increases strongly with local metallicity for both simulations, in agreement with observations. However, the local MLE increases and decreases with local [Mg/Fe] in LoM-50 and HiM-50, respectively. These qualitative differences can be used to break degeneracies in the manner with which the IMF varies in these high-mass ETGs. At zz = 2, we find that the MLE has a higher and lower normalization for bottom- and top-heavy IMF variations, respectively. We speculate that a hybrid of our LoM and HiM models may be able to reconcile observed IMF diagnostics in star-forming galaxies and ETGs

Phylogenomics resolves major relationships and reveals significant diversification rate shifts in the evolution of silk moths and relatives

Background: Silkmoths and their relatives constitute the ecologically and taxonomically diverse superfamily Bombycoidea, which includes some of the most charismatic species of Lepidoptera. Despite displaying spectacular forms and diverse ecological traits, relatively little attention has been given to understanding their evolution and drivers of their diversity. To begin to address this problem, we created a new Bombycoidea-specific Anchored Hybrid Enrichment (AHE) probe set and sampled up to 571 loci for 117 taxa across all major lineages of the Bombycoidea, with a newly developed DNA extraction protocol that allows Lepidoptera specimens to be readily sequenced from pinned natural history collections. Results: The well-supported tree was overall consistent with prior morphological and molecular studies, although some taxa were misplaced. The bombycid Arotros Schaus was formally transferred to Apatelodidae. We identified important evolutionary patterns (e.g., morphology, biogeography, and differences in speciation and extinction), and our analysis of diversification rates highlights the stark increases that exist within the Sphingidae (hawkmoths) and Saturniidae (wild silkmoths). Conclusions: Our study establishes a backbone for future evolutionary, comparative, and taxonomic studies of Bombycoidea. We postulate that the rate shifts identified are due to the well-documented bat-moth “arms race”. Our research highlights the flexibility of AHE to generate genomic data from a wide range of museum specimens, both age and preservation method, and will allow researchers to tap into the wealth of biological data residing in natural history collections around the globe.Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.NHM Repositor

‘New Medicine Service’: supporting adherence in people starting a new medication for a long-term condition: 26-week follow-up of a pragmatic randomised controlled trial

OBJECTIVE: To examine the effectiveness and cost-effectiveness of the community pharmacy New Medicine Service (NMS) at 26 weeks. METHODS: Pragmatic patient-level parallel randomised controlled trial in 46 English community pharmacies. 504 participants aged ≥14, identified in the pharmacy when presenting a prescription for a new medicine for predefined long-term conditions, randomised to receive NMS (n=251) or normal practice (n=253) (NMS intervention: 2 consultations 1 and 2 weeks after prescription presentation). Adherence assessed through patient self-report at 26-week follow-up. Intention-to-treat analysis employed. National Health Service (NHS) costs calculated. Disease-specific Markov models estimating impact of non-adherence combined with clinical trial data to calculate costs per extra quality-adjusted life-year (QALY; NHS England perspective). RESULTS: Unadjusted analysis: of 327 patients still taking the initial medicine, 97/170 (57.1%) and 103/157 (65.6%) (p=0.113) patients were adherent in normal practice and NMS arms, respectively. Adjusted intention-to-treat analysis: adherence OR 1.50 (95% CI 0.93 to 2.44, p=0.095), in favour of NMS. There was a non-significant reduction in 26-week NHS costs for NMS: -£104 (95% CI -£37 to £257, p=0.168) per patient. NMS generated a mean of 0.04 (95% CI -0.01 to 0.13) more QALYs per patient, with mean reduction in lifetime cost of -£113.9 (-1159.4, 683.7). The incremental cost-effectiveness ratio was -£2758/QALY (2.5% and 97.5%: -38 739.5, 34 024.2. NMS has an 89% probability of cost-effectiveness at a willingness to pay of £20 000 per QALY. CONCLUSIONS: At 26-week follow-up, NMS was unable to demonstrate a statistically significant increase in adherence or reduction in NHS costs, which may be attributable to patient attrition from the study. Long-term economic evaluation suggested NMS may deliver better patient outcomes and reduced overall healthcare costs than normal practice, but uncertainty around this finding is high. TRIAL REGISTRATION NUMBER: NCT01635361, ISRCTN23560818, ISRCTN23560818, UKCRN12494

Replication of LDL SWAs hits in PROSPER/PHASE as validation for future (pharmaco)genetic analyses

<p><b>Background:</b> The PHArmacogenetic study of Statins in the Elderly at risk (PHASE) is a genome wide association study in the PROspective Study of Pravastatin in the Elderly at risk for vascular disease (PROSPER) that investigates the genetic variation responsible for the individual variation in drug response to pravastatin. Statins lower LDL-cholesterol in general by 30%, however not in all subjects. Moreover, clinical response is highly variable and adverse effects occur in a minority of patients. In this report we first describe the rationale of the PROSPER/PHASE project and second show that the PROSPER/PHASE study can be used to study pharmacogenetics in the elderly.</p> <p><b>Methods:</b> The genome wide association study (GWAS) was conducted using the Illumina 660K-Quad beadchips following manufacturer's instructions. After a stringent quality control 557,192 SNPs in 5,244 subjects were available for analysis. To maximize the availability of genetic data and coverage of the genome, imputation up to 2.5 million autosomal CEPH HapMap SNPs was performed with MACH imputation software. The GWAS for LDL-cholesterol is assessed with an additive linear regression model in PROBABEL software, adjusted for age, sex, and country of origin to account for population stratification.</p> <p><b>Results:</b> Forty-two SNPs reached the GWAS significant threshold of p = 5.0e-08 in 5 genomic loci (APOE/APOC1; LDLR; FADS2/FEN1; HMGCR; PSRC1/CELSR5). The top SNP (rs445925, chromosome 19) with a p-value of p = 2.8e-30 is located within the APOC1 gene and near the APOE gene. The second top SNP (rs6511720, chromosome 19) with a p-value of p = 5.22e-15 is located within the LDLR gene. All 5 genomic loci were previously associated with LDL-cholesterol levels, no novel loci were identified. Replication in WOSCOPS and CARE confirmed our results.</p> <p><b>Conclusion:</b> With the GWAS in the PROSPER/PHASE study we confirm the previously found genetic associations with LDL-cholesterol levels. With this proof-of-principle study we show that the PROSPER/PHASE study can be used to investigate genetic associations in a similar way to population based studies. The next step of the PROSPER/PHASE study is to identify the genetic variation responsible for the variation in LDL-cholesterol lowering in response to statin treatment in collaboration with other large trials.</p&gt

Survival of dental implants in patients with oral cancer treated by surgery and radiotherapy: a retrospective study

BACKGROUND: The aim of this retrospective study was to evaluate the survival of dental implants placed after ablative surgery, in patients affected by oral cancer treated with or without radiotherapy. METHODS: We collected data for 34 subjects (22 females, 12 males; mean age: 51 ± 19) with malignant oral tumors who had been treated with ablative surgery and received dental implant rehabilitation between 2007 and 2012. Postoperative radiation therapy (less than 50 Gy) was delivered before implant placement in 12 patients. A total of 144 titanium implants were placed, at a minimum interval of 12 months, in irradiated and non-irradiated residual bone. RESULTS: Implant loss was dependent on the position and location of the implants (P = 0.05-0.1). Moreover, implant survival was dependent on whether the patient had received radiotherapy. This result was highly statistically significant (P < 0.01). Whether the implant was loaded is another highly significant (P < 0.01) factor determinin

Impact of FTO genotypes on BMI and weight in polycystic ovary syndrome : a systematic review and meta-analysis

Aims/hypothesis FTO gene single nucleotide polymorphisms (SNPs) have been shown to be associated with obesity-related traits and type 2 diabetes. Several small studies have suggested a greater than expected effect of the FTO rs9939609 SNP on weight in polycystic ovary syndrome (PCOS). We therefore aimed to examine the impact of FTO genotype on BMI and weight in PCOS. Methods A systematic search of medical databases (PubMed, EMBASE and Cochrane CENTRAL) was conducted up to the end of April 2011. Seven studies describing eight distinct PCOS cohorts were retrieved; seven were genotyped for SNP rs9939609 and one for SNP rs1421085. The per allele effect on BMI and body weight increase was calculated and subjected to meta-analysis. Results A total of 2,548 women with PCOS were included in the study; 762 were TT homozygotes, 1,253 had an AT/CT genotype, and 533 were AA/CC homozygotes. Each additional copy of the effect allele (A/C) increased the BMI by a mean of 0.19 z score units (95% CI 0.13, 0.24; p = 2.26 × 10−11) and body weight by a mean of 0.20 z score units (95% CI 0.14, 0.26; p = 1.02 × 10−10). This translated into an approximately 3.3 kg/m2 increase in BMI and an approximately 9.6 kg gain in body weight between TT and AA/CC homozygotes. The association between FTO genotypes and BMI was stronger in the cohorts with PCOS than in the general female populations from large genome-wide association studies. Deviation from an additive genetic model was observed in heavier populations. Conclusions/interpretation The effect of FTO SNPs on obesity-related traits in PCOS seems to be more than two times greater than the effect found in large population-based studies. This suggests an interaction between FTO and the metabolic context or polygenic background of PCOS