A high-resolution study of the OH-stretch fundamental of methanol

The OH-stretch fundamental of CH3OH has been observed with 0.025 cm-1 resolution between 3430 and 3940 cm-1 and the resulting spectrum deconvoluted using the procedure of P. A. Jansson. Approximately 600 lines have been assigned to a total of 67 P- or R-branch series and some 30 excited state levels have been determined. Of these, 14 belong to the lowest torsional state with n = 0, 13 to N = 1 and 3 to N = 2. A nonlinear least-squares fit to these levels varying the major parameters used by Y. Y. Kwan and D. M. Dennison in their analysis of the normal state produces an rms deviation between observed and calculated levels of 0.51 cm-1. Variation of all the parameters including those of the smaller Kirtman perturbation terms produces only a slight improvement in the fit. Both analyses yield a barrier height of 411 cm-1 in the excited vibrational state as compared to the normal state value of 373 cm-1. A number of unexplained anomalies appear in the spectra including large and irregular changes in the coefficient of J2 + J for different torsion-rotation states.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/22170/1/0000601.pd

Metal-rich multi-phase gas in M87: AGN-driven metal transport, magnetic-field supported multi-temperature gas, and constraints on non-thermal emission observed with XMM-Newton

We use deep (~120 ks) XMM-Newton data of the M87 halo to analyze its spatially resolved temperature structure and chemical composition. We focus particularly on the regions of enhanced X-ray brightness associated with the inner radio lobes, which are known not to be described very well by single-temperature spectral models. Compared to a simple two-temperature fit, we obtain a better and more physical description of the spectra using a model that involves a continuous range of temperatures in each spatial bin. The range of temperatures of the multiphase gas spans ~0.6-3.2 keV. Such a multiphase structure is only possible if thermal conduction is suppressed by magnetic fields. In the multi-temperature regions, we find a correlation between the amount of gas cooler than the surrounding X-ray plasma and the metallicity, and conclude that the cool gas is more metal-rich than the ambient halo. We estimate the average Fe abundance of the cool gas to ~2.2 solar. Our results thus point toward the key role of the active galactic nucleus (AGN) in transporting heavy elements into the intracluster medium. The abundance ratios of O/Si/S/Fe in and outside the X-ray arms are similar, indicating that the dominant fraction of metals in the gas halo was uplifted by AGN outbursts relatively recently compared to the age of M87. Our estimate for the mass of the cool gas is 5e8 M_sun, which probably stems from a mixture of ICM, stellar mass loss, and Type Ia supernova products. ~30-110 Myr are required to produce the observed metals in the cool gas. Finally, we put upper limits on possible non-thermal X-ray emission from M87 and, combining it with the 90 cm radio maps, we put lower limits of around ~0.5-1.0 muG on the magnetic field strength.Comment: 18 pages, accepted for publication in A&A. Some significant changes following the referee repor

Hard X-ray and radio observations of Abell 754

We present a long BeppoSAX observation of Abell 754 that reports a nonthermal excess with respect to the thermal emission at energies greater than ~45 keV. A VLA radio observation at 1.4 GHz definitely confirms the existence of diffuse radio emission in the central region of the cluster, previously suggested by images at 74 and 330 MHz (Kassim et al 2001), and reports additional features. Besides, our observation determines a steeper radio halo spectrum in the 330-1400 MHz frequency range with respect to the spectrum detected at lower frequencies, indicating the presence of a spectral cutoff. The presence of a radio halo in A754, considered the prototype of a merging cluster, reinforces the link between formation of Mpc-scale radio regions and very recent or current merger processes. The radio results combined with the hard X-ray excess detected by BeppoSAX give information on the origin of the electron population responsible for nonthermal phenomena in galaxy clusters. We discuss also the possibility that 26W20, a tailed radio galaxy with BL Lac characteristics located in the field of view of the PDS, could be responsible for the observed nonthermal hard X-ray emission.Comment: 7 pages, 3 figures; Astronomy & Astrophysics, in pres

Constraining relativistic protons and magnetic fields in galaxy clusters through radio and gamma-ray observations : the case of A2256

Giant radio halos are the most relevant examples of diffuse synchrotron emission from galaxy clusters. A number of these sources have very steep spectrum, with spectral index $\alpha \geq 1.5-1.6$ ($F(\nu) \propto \nu^{-\alpha}$), and are ideal targets to test current models for the origin of the relativistic particles. A2256 hosts the nearest radio halo with very steep spectrum, with $\alpha =1.61$, and a very large population of relativistic protons in the cluster would be necessary to explain the halo as due to synchrotron emission from secondary particles. In this case the 0.1-1 GeV $\gamma$--ray luminosity is expected 10-20 times larger than that of clusters hosting radio halos with similar radio power at GHz frequencies but with spectra more typical of the presently observed halo population, $\alpha \sim 1.2$. Under these assumptions incoming FERMI/GLAST observations are expected to detect A2256, provided that the magnetic field in the central cluster region is $\leq$10-15 $\mu$G. We show that this will allow for a prompt test of hadronic models for the origin of radio halos, and for complementary constraints on both the cluster magnetic field and the physics of particle acceleration mechanisms.Comment: 4 pages, 3 figures, to appear in Astronomy and Astrophysic

Bridging the gap from medical to psychological safety assessment: consensus study in a digital mental health context

Background: Digital Mental Health Interventions (DMHIs) that meet the definition of a medical device are regulated by the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK. The MHRA uses procedures that were originally developed for pharmaceuticals to assess the safety of DMHIs. There is recognition that this may not be ideal, as is evident by an ongoing consultation for reform led by the MHRA and the National Institute for Health and Care Excellence. Aims: The aim of this study was to generate an experts’ consensus on how the medical regulatory method used for assessing safety could best be adapted for DMHIs. Method: An online Delphi study containing three rounds was conducted with an international panel of 20 experts with experience/knowledge in the field of UK digital mental health. Results: Sixty-four items were generated, of which 41 achieved consensus (64%). Consensus emerged around ten recommendations, falling into five main themes: Enhancing the quality of adverse events data in DMHIs; Re-defining serious adverse events for DMHIs; Reassessing short-term symptom deterioration in psychological interventions as a therapeutic risk; Maximising the benefit of the Yellow Card Scheme; and Developing a harmonised approach for assessing the safety of psychological interventions in general. Conclusion: The implementation of the recommendations provided by this consensus could improve the assessment of safety of DMHIs, making them more effective in detecting and mitigating risk

Genome-Wide Association Study Using Extreme Truncate Selection Identifies Novel Genes Affecting Bone Mineral Density and Fracture Risk

Osteoporotic fracture is a major cause of morbidity and mortality worldwide. Low bone mineral density (BMD) is a major predisposing factor to fracture and is known to be highly heritable. Site-, gender-, and age-specific genetic effects on BMD are thought to be significant, but have largely not been considered in the design of genome-wide association studies (GWAS) of BMD to date. We report here a GWAS using a novel study design focusing on women of a specific age (postmenopausal women, age 55–85 years), with either extreme high or low hip BMD (age- and gender-adjusted BMD z-scores of +1.5 to +4.0, n = 1055, or −4.0 to −1.5, n = 900), with replication in cohorts of women drawn from the general population (n = 20,898). The study replicates 21 of 26 known BMD–associated genes. Additionally, we report suggestive association of a further six new genetic associations in or around the genes CLCN7, GALNT3, IBSP, LTBP3, RSPO3, and SOX4, with replication in two independent datasets. A novel mouse model with a loss-of-function mutation in GALNT3 is also reported, which has high bone mass, supporting the involvement of this gene in BMD determination. In addition to identifying further genes associated with BMD, this study confirms the efficiency of extreme-truncate selection designs for quantitative trait association studies

Genetic determinants of heel bone properties: genome-wide association meta-analysis and replication in the GEFOS/GENOMOS consortium

Quantitative ultrasound of the heel captures heel bone properties that independently predict fracture risk and, with bone mineral density (BMD) assessed by X-ray (DXA), may be convenient alternatives for evaluating osteoporosis and fracture risk. We performed a meta-analysis of genome-wide association (GWA) studies to assess the genetic determinants of heel broadband ultrasound attenuation (BUA; n = 14 260), velocity of sound (VOS; n = 15 514) and BMD (n = 4566) in 13 discovery cohorts. Independent replication involved seven cohorts with GWA data (in silico n = 11 452) and new genotyping in 15 cohorts (de novo n = 24 902). In combined random effects, meta-analysis of the discovery and replication cohorts, nine single nucleotide polymorphisms (SNPs) had genome-wide significant (P < 5 × 10(-8)) associations with heel bone properties. Alongside SNPs within or near previously identified osteoporosis susceptibility genes including ESR1 (6q25.1: rs4869739, rs3020331, rs2982552), SPTBN1 (2p16.2: rs11898505), RSPO3 (6q22.33: rs7741021), WNT16 (7q31.31: rs2908007), DKK1 (10q21.1: rs7902708) and GPATCH1 (19q13.11: rs10416265), we identified a new locus on chromosome 11q14.2 (rs597319 close to TMEM135, a gene recently linked to osteoblastogenesis and longevity) significantly associated with both BUA and VOS (P < 8.23 × 10(-14)). In meta-analyses involving 25 cohorts with up to 14 985 fracture cases, six of 10 SNPs associated with heel bone properties at P < 5 × 10(-6) also had the expected direction of association with any fracture (P < 0.05), including three SNPs with P < 0.005: 6q22.33 (rs7741021), 7q31.31 (rs2908007) and 10q21.1 (rs7902708). In conclusion, this GWA study reveals the effect of several genes common to central DXA-derived BMD and heel ultrasound/DXA measures and points to a new genetic locus with potential implications for better understanding of osteoporosis pathophysiology

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms