Genomics and successful aging: grounds for renewed optimism?

This is a pre-copyedited, author-produced PDF of an article accepted for publication in the Journals of Gerentology following peer review. The version of record is available online at: doi: 10.1093/gerona/gls091.Successful aging depends in part on delaying age-related disease onsets until later in life. Conditions including coronary artery disease, Alzheimer's disease, prostate cancer, and type 2 diabetes are moderately heritable. Genome-wide association studies have identified many risk associated single-nucleotide polymorphisms for these conditions, but much heritability remains unaccounted for. Nevertheless, a great deal is being learned.Dunhill Medical TrustU.S. National Institutes of Healt

Resolving the Gap and AU-scale Asymmetries in the Pre-transitional Disk of V1247 Orionis

archiveprefix: arXiv primaryclass: astro-ph.SR keywords: accretion, accretion disks, protoplanetary disks, stars: pre-main sequence, techniques: interferometric eid: 80 adsurl: http://adsabs.harvard.edu/abs/2013ApJ...768...80K adsnote: Provided by the SAO/NASA Astrophysics Data SystemarticlePre-transitional disks are protoplanetary disks with a gapped disk structure, potentially indicating the presence of young planets in these systems. In order to explore the structure of these objects and their gap-opening mechanism, we observed the pre-transitional disk V1247 Orionis using the Very Large Telescope Interferometer, the Keck Interferometer, Keck-II, Gemini South, and IRTF. This allows us to spatially resolve the AU-scale disk structure from near- to mid-infrared wavelengths (1.5-13 μm), tracing material at different temperatures and over a wide range of stellocentric radii. Our observations reveal a narrow, optically thick inner-disk component (located at 0.18 AU from the star) that is separated from the optically thick outer disk (radii gsim 46 AU), providing unambiguous evidence for the existence of a gap in this pre-transitional disk. Surprisingly, we find that the gap region is filled with significant amounts of optically thin material with a carbon-dominated dust mineralogy. The presence of this optically thin gap material cannot be deduced solely from the spectral energy distribution, yet it is the dominant contributor at mid-infrared wavelengths. Furthermore, using Keck/NIRC2 aperture masking observations in the H, K', and L' bands, we detect asymmetries in the brightness distribution on scales of ~15-40 AU, i.e., within the gap region. The detected asymmetries are highly significant, yet their amplitude and direction changes with wavelength, which is not consistent with a companion interpretation but indicates an inhomogeneous distribution of the gap material. We interpret this as strong evidence for the presence of complex density structures, possibly reflecting the dynamical interaction of the disk material with sub-stellar mass bodies that are responsible for the gap clearing.This work was done in part under contract with the California Institute of Technology (Caltech), funded by NASA through the Sagan Fellowship Program (S.K. and C.E. are Sagan Fellows). Data presented herein were obtained at the W. M. Keck Observatory from telescope time allocated to the National Aeronautics and Space Administration through the agency's scientific partnership with the California Institute of Technology and the University of California. The Observatory was made possible by the generous financial support of the W. M. Keck Foundation. The authors wish to recognize and acknowledge the very significant cultural role and reverence that the summit of Mauna Kea has always had within the indigenous Hawaiian community. We are most fortunate to have the opportunity to conduct observations from this mountain. This work was supported in part by the Aerospace Corporation's Independent Research and Development (IR&D) program. This work was supported by NASA ADP grant NNX09AC73G

Cortical thickness abnormalities in trichotillomania: international multi-site analysis

Trichotillomania is a prevalent but often hidden psychiatric condition, characterized by repetitive hair pulling. The aim of this study was to confirm or refute structural brain abnormalities in trichotillomania by pooling all available global data. De-identified MRI scans were pooled by contacting authors of previous studies. Cortical thickness and sub-cortical volumes were compared between patients and controls. Patients (n = 76) and controls (n = 41) were well-matched in terms of demographic characteristics. Trichotillomania patients showed excess cortical thickness in a cluster maximal at right inferior frontal gyrus, unrelated to symptom severity. No significant sub-cortical volume differences were detected in the regions of interest. Morphometric changes in the right inferior frontal gyrus appear to play a central role in the pathophysiology of trichotillomania, and to be trait in nature. The findings are distinct from other impulsive-compulsive disorders (OCD, ADHD, gambling disorder), which have typically been associated with reduced, rather than increased, cortical thickness. Future work should examine sub-cortical and cerebellar morphology using analytic approaches designed for this purpose, and should also characterize grey matter densities/volumes.This work was funded by a Wellcome Trust Clinical Fellowship to Dr. Chamberlain (UK; Reference 110,049/Z/15/Z) and by a grant from the Trichotillomania Learning Center to Dr. Grant. Drs. Lochner and Stein were funded by the South African Medical Research Council. Dr. Keuthen was funded by an anonymous benefactor for the collection of her imaging data

Stellar winds from Massive Stars

We review the various techniques through which wind properties of massive stars - O stars, AB supergiants, Luminous Blue Variables (LBVs), Wolf-Rayet (WR) stars and cool supergiants - are derived. The wind momentum-luminosity relation (e.g. Kudritzki et al. 1999) provides a method of predicting mass-loss rates of O stars and blue supergiants which is superior to previous parameterizations. Assuming the theoretical sqrt(Z) metallicity dependence, Magellanic Cloud O star mass-loss rates are typically matched to within a factor of two for various calibrations. Stellar winds from LBVs are typically denser and slower than equivalent B supergiants, with exceptional mass-loss rates during giant eruptions Mdot=10^-3 .. 10^-1 Mo/yr (Drissen et al. 2001). Recent mass-loss rates for Galactic WR stars indicate a downward revision of 2-4 relative to previous calibrations due to clumping (e.g. Schmutz 1997), although evidence for a metallicity dependence remains inconclusive (Crowther 2000). Mass-loss properties of luminous (> 10^5 Lo) yellow and red supergiants from alternative techniques remain highly contradictory. Recent Galactic and LMC results for RSG reveal a large scatter such that typical mass-loss rates lie in the range 10^-6 .. 10^-4 Mo/yr, with a few cases exhibiting 10^-3 Mo/yr.Comment: 16 pages, 2 figures, Review paper to appear in Proc `The influence of binaries on stellar population studies', Brussels, Aug 2000 (D. Vanbeveren ed.), Kluwe

Eta Carinae and the Luminous Blue Variables

We evaluate the place of Eta Carinae amongst the class of luminous blue variables (LBVs) and show that the LBV phenomenon is not restricted to extremely luminous objects like Eta Car, but extends luminosities as low as log(L/Lsun) = 5.4 - corresponding to initial masses ~25 Msun, and final masses as low as ~10-15 Msun. We present a census of S Doradus variability, and discuss basic LBV properties, their mass-loss behaviour, and whether at maximum light they form pseudo-photospheres. We argue that those objects that exhibit giant Eta Car-type eruptions are most likely related to the more common type of S Doradus variability. Alternative atmospheric models as well as sub-photospheric models for the instability are presented, but the true nature of the LBV phenomenon remains as yet elusive. We end with a discussion on the evolutionary status of LBVs - highlighting recent indications that some LBVs may be in a direct pre-supernova state, in contradiction to the standard paradigm for massive star evolution.Comment: 27 pages, 6 figures, Review Chapter in "Eta Carinae and the supernova imposters" (eds R. Humphreys and K. Davidson) new version submitted to Springe

A Dust Trap in the Young Multiple System HD 34700

This is the author accepted manuscript. The final version is available from the American Astronomical Society via the DOI in this recordMillimeter observations of disks around young stars reveal substructures indicative of gas pressure traps that may aid grain growth and planet formation. We present Submillimeter Array observations of HD 34700- two Herbig Ae stars in a close binary system (Aa/Ab, ∼0.25 AU), surrounded by a disk presenting a large cavity and spiral arms seen in scattered light, and two distant, lower mass companions. These observations include 1.3 mm continuum emission and the 12CO 2-1 line at ∼ 0. 005 (178 AU) resolution. They resolve a prominent azimuthal asymmetry in the continuum, and Keplerian rotation of a circumbinary disk in the 12CO line. The asymmetry is located at a radius of 155+11 −7 AU, consistent with the edge of the scattered light cavity, being resolved in both radius (72+14 −15 AU) and azimuth (FWHM = 64◦+8 −7 ). The strong asymmetry in millimeter continuum emission could be evidence for a dust trap, together with the more symmetric morphology of 12CO emission and small grains. We hypothesize an unseen circumbinary companion, responsible for the cavity in scattered light and creating a vortex at the cavity edge that manifests in dust trapping. The disk mass has limitations imposed by the detection of 12CO and non-detection of 13CO. We discuss its consequences for the potential past gravitational instability of this system, likely accounting for the rapid formation of a circumbinary companion. We also report the discovery of resolved continuum emission associated with HD 34700B (projected separation ∼ 1850AU), which we explain through a circumstellar disk.National Science Foundation (NSF

Planning ahead in public health? A qualitative study of the time horizons used in public health decision-making

<p>Abstract</p> <p>Background</p> <p>In order to better understand factors that influence decisions for public health, we undertook a qualitative study to explore issues relating to the time horizons used in decision-making.</p> <p>Methods</p> <p>Qualitative study using semi-structured interviews. 33 individuals involved in the decision making process around coronary heart disease were purposively sampled from the UK National Health Service (national, regional and local levels), academia and voluntary organizations. Analysis was based on the framework method using N-VIVO software. Interviews were transcribed, coded and emergent themes identified.</p> <p>Results</p> <p>Many participants suggested that the timescales for public health decision-making are too short. Commissioners and some practitioners working at the national level particularly felt constrained in terms of planning for the long-term. Furthermore respondents felt that longer term planning was needed to address the wider determinants of health and to achieve societal level changes. Three prominent 'systems' issues were identified as important drivers of short term thinking: the need to demonstrate impact within the 4 year political cycle; the requirement to 'balance the books' within the annual commissioning cycle and the disruption caused by frequent re-organisations within the health service. In addition respondents suggested that the tools and evidence base for longer term planning were not well established.</p> <p>Conclusion</p> <p>Many public health decision and policy makers feel that the timescales for decision-making are too short. Substantial systemic barriers to longer-term planning exist. Policy makers need to look beyond short-term targets and budget cycles to secure investment for long-term improvement in public health.</p

Foraging time and temperature affected birth timing of Rhinolophus ferrumequinum and predicted year-to-year changes in a population in West Wales. U.K.

Movements of Rhinolophus ferrumequinum in and out of the nursery roost at Stackpole were monitored automatically from 1994 to 2018 with simultaneous measurements of roost and external air temperatures. Pups were counted manually in June–July and mean birth dates calculated. Maximum foraging times of the population between 16.00 h and 08.00 h and temperatures at midnight showed three types of activity. These types of activity explained why warmer springs were followed by earlier birth dates. When April was warmer the number of degree days, linked to the activity of night-flying insects, was higher so the maximum foraging times were longer. Hence, mean birth dates were earlier due to faster gestation. The indirect effect of degree days on the birth date, measured by the partial regression coefficient (ß = -0.321), was weaker than the direct effect (ß = - 0.628) and the mediating effect of maximum foraging time was significant (p < .001). During May-June and June-July bats foraged mainly from dusk to dawn so there was little variation in the maximum foraging times of the population, and it did not significantly mediate the effect of temperature on birth date. Birth dates were later when the external temperatures in June-July were higher (ß = 0.309), but the effect was small (R2 = 9.5%). Path analysis further revealed that longer maximum foraging times of the population in April predicted the year-to-year changes in the number of births and subsequently the number of adult females. Maximal foraging times of the population in April were a major influence on birth timing and ultimately determined whether the population grew or declined

Imaging the disc rim and a moving close-in companion candidate in the pre-transitional disc of V1247 Orionis

This is the author accepted manuscript. The final version is available from EDP Sciences via the DOI in this record.Context. V1247 Orionis harbours a pre-transitional disc with a partially cleared gap. Earlier interferometric and polarimetric observations revealed strong asymmetries both in the gap region and in the outer disc. The presence of a companion was inferred to explain these asymmetric structures and the ongoing disc clearing. Aims. Using an extensive set of multi-wavelength and multi-epoch observations we aimed to identify the origin of the previously detected asymmetries. Methods. We observed V1247 Ori at three epochs spanning ∼ 678 days using sparse aperture masking interferometry with Keck/NIRC2 and VLT/NACO. In addition, we search for signs of accretion through VLT/SPHERE-ZIMPOL spectral differential imaging in Hα and R-band continuum. Our SMA sub-millimetre interferometry in 880 µm continuum and in the CO(3-2) line allows us to constrain the orientation and direction of rotation of the outer disc. Results. We find the L’-band emission to be dominated by static features which trace forward-scattered dust emission from the inner edge of the outer disc located to the north-east. In H- and K-band, we see evidence for a companion candidate that moved systematically by 45◦ within the first ∼345 days. The separation of the companion candidate is not well constrained, but the observed position angle change is consistent with Keplerian motion of a body located on a 6 au orbit. From the SMA CO moment map, the location of the disc rim, and the detected orbital motion, we deduced the 3-dimensional orientation of the disc. We see no indication of accretion in Hα and set upper limits for an accreting companion. Conclusions. The measured contrast of the companion candidate in H and K is consistent with an actively accreting protoplanet. Hence, we identify V1247 Ori as a unique laboratory for studying companion-disc interactions and disc clearing.We acknowledge support from an ERC Starting Grant (Grant Agreement No. 639889), STFC Rutherford Fellowship Article number, page 14 of 17 M. Willson et al.: Imaging the disc rim and companion candidate in V1247 Ori (ST/J004030/1), STFC Rutherford Grant (ST/K003445/1), Marie SklodowskaCurie CIG grant (Ref. 618910), and Philip Leverhulme Prize (PLP-2013-110). We additionally acknowledge support from NASA KPDA grants (JPL-1452321, 1474717, 1485953, 1496788). The Submillimeter Array is a joint project between the Smithsonian Astrophysical Observatory and the Academia Sinica Institute of Astronomy and Astrophysics and is funded by the Smithsonian Institution and the Academia Sinica. The authors wish to recognize and acknowledge the very significant cultural role and reverence that the summit of Mauna Kea has always had within the indigenous Hawaiian community. We are most fortunate to have the opportunity to conduct observations from this mountain.Some of the data presented herein were obtained at the W.M. Keck Observatory, which is operated as a scientific partnership among the California Institute of Technology, the University of California and the National Aeronautics and Space Administration. The Observatory was made possible by the generous financial support of the W.M. Keck Foundation. J. Kluska acknowledges support from the research council of the KU Leuven under grant number C14/17/082. M. Curé and S. Kanaan acknowledge financial support from Centro de Astrofísica de Valparaiso. S. Kanaan thank the support of Fondecyt iniciacíon grant No. 11130702. T. Muto is partially supported by JSPS KAKENHI grant No. 26800106

Incidence and Risk Factors of Serious Adverse Events during Antituberculous Treatment in Rwanda: A Prospective Cohort Study

BACKGROUND: Tuberculosis (TB) and TB-human immunodeficiency virus infection (HIV) coinfection is a major public health concern in resource-limited settings. Although TB treatment is challenging in HIV-infected patients because of treatment interactions, immunopathological reactions, and concurrent infections, few prospective studies have addressed this in sub-Saharan Africa. In this study we aimed to determine incidence, causes of, and risk factors for serious adverse events among patients on first-line antituberculous treatment, as well as its impact on antituberculous treatment outcome. METHODS AND FINDINGS: Prospective observational cohort study of adults treated for TB at the Internal Medicine department of the Kigali University Hospital from May 2008 through August 2009. Of 263 patients enrolled, 253 were retained for analysis: median age 35 (Interquartile range, IQR 28-40), 55% male, 66% HIV-positive with a median CD4 count 104 cells/mm(3) (IQR 44-248 cells/mm(3)). Forty percent had pulmonary TB, 43% extrapulmonary TB and 17% a mixed form. Sixty-four (26%) developed a serious adverse event; 58/167 (35%) HIV-infected vs. 6/86 (7%) HIV-uninfected individuals. Commonest events were concurrent infection (n = 32), drug-induced hepatitis (n = 24) and paradoxical reactions/TB-IRIS (n = 23). HIV-infection (adjusted Hazard Ratio, aHR 3.4, 95% Confidence Interval, CI 1.4-8.7) and extrapulmonary TB (aHR 2, 95%CI 1.1-3.7) were associated with an increased risk of serious adverse events. For TB/HIV co-infected patients, extrapulmonary TB (aHR 2.0, 95%CI 1.1-3.9) and CD4 count <100 cells/mm3 at TB diagnosis (aHR 1.7, 95%CI 1.0-2.9) were independent predictors. Adverse events were associated with an almost two-fold higher risk of unsuccessful treatment outcome at 6 months (HR 1.89, 95%CI 1.3-3.0). CONCLUSION: Adverse events frequently complicate the course of antituberculous treatment and worsen treatment outcome, particularly in patients with extrapulmonary TB and advanced immunodeficiency. Concurrent infection accounts for most events. Our data suggest that deterioration in a patient already receiving antituberculous treatment should prompt an aggressive search for additional infections