Should we screen for coronary artery disease in asymptomatic chronic dialysis patients?

The hemodialysis population is characterized by a high prevalence of ‘asymptomatic’ coronary artery disease (CAD), which should be interpreted differently from asymptomatic disease in the general population. A hemodynamically significant stenosis may not become clinically apparent owing to impaired exercise tolerance and autonomic neuropathy. The continuous presence of silent ischemia may cause heart failure, arrhythmias, and sudden death. Whether revascularization of an asymptomatic dialysis patient improves outcome remains a moot point, although several observational studies and one small RCT suggest a benefit. It can therefore be defended to screen asymptomatic dialysis patients for CAD. A number of noninvasive screening tests are available, but none has proved equally practical and reliable in the dialysis population as in the general population. Myocardial perfusion scintigraphy (MPS) before and after a pharmacological stress such as dipyridamole can reveal both ischemia and myocardial scarring. When compared with coronary angiography, low sensitivities were reported and attributed to impaired vasodilation to dipyridamole in dialysis patients. A more likely explanation is that not every anatomical stenosis will lead to impaired coronary blood flow on MPS. Numerous studies have shown an incremental prognostic value of dipyridamole-MPS over clinical data for prediction of adverse cardiac events, in some studies even over coronary angiography. Pending the availability of high-quality evidence, in our opinion asymptomatic dialysis patients could undergo dipyridamole-MPS, followed by coronary angiography in case of an abnormal scan. This combined physiological and anatomical evaluation of the coronary circulation allows us to determine which coronary stenosis is clinically relevant and therefore should be revascularized

Sex‐biased disease dynamics increase extinction risk by impairing population recovery

The periodicity of life‐cycle events (phenology) modulates host availability to pathogens in a repeatable pattern. The effects of sexual differences in host phenology have been little explored in wildlife epidemiological studies. A recent series of ranavirosis outbreaks led to serious declines of Boscas’ newt populations at Serra da Estrela (Portugal). The peculiar phenology of this species, in which a large number of females remain in the aquatic habitat after the breeding season, turns it into a suitable model to test how sex‐biased mortality can affect host population persistence in the context of infectious diseases. We investigated how the phenology of Bosca's newt (i.e. biased number of females) mediated the impact of Ranavirus. We then evaluated the risk of extinction of the population under different scenarios of sex‐biased mortality using a population viability analysis. Two newt populations (one subject to yearly outbreaks and a comparative site where outbreaks have not been recorded) were tracked for trends over time following emergence of ranaviral disease, allowing us to assess the differential impact of the disease on both sexes. In addition to a significant decline in abundance of adult newts, our data suggest that phenology can affect disease dynamics indirectly, leading to reduction in females and a reversal of the sex ratio of the breeding population. Our models suggest that female‐biased mortality does not exacerbate Ranavirus‐driven population declines in the short‐term, but is likely to have a deleterious impact during the recovery process once the lethal effect of disease is removed from the system

Response to comment on 'Amphibian fungal panzootic causes catastrophic and ongoing loss of biodiversity'

Lambert et al. question our retrospective and holistic epidemiological assessment of the role of chytridiomycosis in amphibian declines. Their alternative assessment is narrow and provides an incomplete evaluation of evidence. Adopting this approach limits understanding of infectious disease impacts and hampers conservation efforts. We reaffirm that our study provides unambiguous evidence that chytridiomycosis has affected at least 501 amphibian species

The velocity dispersion and mass function of the outer halo globular cluster Palomar 4

We obtained precise line-of-sight radial velocities of 23 member stars of the remote halo globular cluster Palomar 4 (Pal 4) using the High Resolution Echelle Spectrograph (HIRES) at the Keck I telescope. We also measured the mass function of the cluster down to a limiting magnitude of V~28 mag using archival HST/WFPC2 imaging. We derived the cluster's surface brightness profile based on the WFPC2 data and on broad-band imaging with the Low-Resolution Imaging Spectrometer (LRIS) at the Keck II telescope. We find a mean cluster velocity of 72.55+/-0.22 km/s and a velocity dispersion of 0.87+/-0.18 km/s. The global mass function of the cluster, in the mass range 0.55<=M<=0.85 M_solar, is shallower than a Kroupa mass function and the cluster is significantly depleted in low-mass stars in its center compared to its outskirts. Since the relaxation time of Pal 4 is of the order of a Hubble time, this points to primordial mass segregation in this cluster. Extrapolating the measured mass function towards lower-mass stars and including the contribution of compact remnants, we derive a total cluster mass of 29800 M_solar. For this mass, the measured velocity dispersion is consistent with the expectations of Newtonian dynamics and below the prediction of Modified Newtonian Dynamics (MOND). Pal 4 adds to the growing body of evidence that the dynamics of star clusters in the outer Galactic halo can hardly be explained by MOND.Comment: 17 pages, accepted for publication in MNRAS; Fig. 8 surface brightness/density data at github.com/matthiasjfrank/pal4_surface_brightnes

The HLA class II allele DRB1*1501 is over-represented in patients with idiopathic pulmonary fibrosis

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive and medically refractory lung disease with a grim prognosis. Although the etiology of IPF remains perplexing, abnormal adaptive immune responses are evident in many afflicted patients. We hypothesized that perturbations of human leukocyte antigen (HLA) allele frequencies, which are often seen among patients with immunologic diseases, may also be present in IPF patients. Methods/Principal Findings: HLA alleles were determined in subpopulations of IPF and normal subjects using molecular typing methods. HLA-DRB1*15 was over-represented in a discovery cohort of 79 Caucasian IPF subjects who had lung transplantations at the University of Pittsburgh (36.7%) compared to normal reference populations. These findings were prospectively replicated in a validation cohort of 196 additional IPF subjects from four other U.S. medical centers that included both ambulatory patients and lung transplantation recipients. High-resolution typing was used to further define specific HLA-DRB1*15 alleles. DRB1*1501 prevalence in IPF subjects was similar among the 143 ambulatory patients and 132 transplant recipients (31.5% and 34.8%, respectively, p = 0.55). The aggregate prevalence of DRB1*1501 in IPF patients was significantly greater than among 285 healthy controls (33.1% vs. 20.0%, respectively, OR 2.0; 95%CI 1.3-2.9, p = 0.0004). IPF patients with DRB1*1501 (n = 91) tended to have decreased diffusing capacities for carbon monoxide (DLCO) compared to the 184 disease subjects who lacked this allele (37.8±1.7% vs. 42.8±1.4%, p = 0.036). Conclusions/Significance: DRB1*1501 is more prevalent among IPF patients than normal subjects, and may be associated with greater impairment of gas exchange. These data are novel evidence that immunogenetic processes can play a role in the susceptibility to and/or manifestations of IPF. Findings here of a disease association at the HLA-DR locus have broad pathogenic implications, illustrate a specific chromosomal area for incremental, targeted genomic study, and may identify a distinct clinical phenotype among patients with this enigmatic, morbid lung disease

Personality May Confound Common Measures of Mate-Choice

The measurement of female mating preferences is central to the study of the evolution of male ornaments. Although several different methods have been developed to assess sexual preference in some standardized way, the most commonly used procedure consists of recording female spatial association with different males presented simultaneously. Sexual preference is then inferred from time spent in front of each male. However, the extent to which the measurement of female mate-choice is related to exploration tendencies has not been addressed so far. In the present study we assessed the influence of variation in exploration tendencies, a trait closely associated to global personality, on the measurement of female mating preference in the zebra finch (Taeniopygia guttata) using the widely used four-chamber choice-apparatus. The number of movements performed within both exploration and mate-choice apparatus was consistent within and across the two contexts. In addition, personality explained variation in selectivity, preference strength and consistency. High-exploratory females showed lower selectivity, lower preference scores and displayed more consistent preference scores. Our results suggest that variation in personality may affect the measurement of female mating preference and may contribute to explain existing inconsistencies across studies

Exploring novel correlations in trilepton channels at the LHC for the minimal supersymmetric inverse seesaw model

We investigate signatures of the minimal supersymmetric inverse seesaw model at the large hadron collider (LHC) with three isolated leptons and large missing energy (3\ell + \mET or 2\ell + 1\tau + \mET, with \ell=e,\mu) in the final state. This signal has its origin in the decay of chargino-neutralino (\chpm1\ntrl2) pair, produced in pp collisions. The two body decays of the lighter chargino into a charged lepton and a singlet sneutrino has a characteristic decay pattern which is correlated with the observed large atmospheric neutrino mixing angle. This correlation is potentially observable at the LHC by looking at the ratios of cross sections of the trilepton + \mET channels in certain flavour specific modes. We show that even after considering possible leading standard model backgrounds these final states can lead to reasonable discovery significance at the LHC with both 7 TeV and 14 TeV center-of-mass energy.Comment: 28 pages, 9 .eps figures. 3 new figures and discussions on LHC observables added, minor modifications in text and in the abstract, 23 new references added, matches with the published version in JHE

Eight common genetic variants associated with serum dheas levels suggest a key role in ageing mechanisms

Dehydroepiandrosterone sulphate (DHEAS) is the most abundant circulating steroid secreted by adrenal glands-yet its function is unknown. Its serum concentration declines significantly with increasing age, which has led to speculation that a relative DHEAS deficiency may contribute to the development of common age-related diseases or diminished longevity. We conducted a meta-analysis of genome-wide association data with 14,846 individuals and identified eight independent common SNPs associated with serum DHEAS concentrations. Genes at or near the identified loci include ZKSCAN5 (rs11761528; p = 3.15×10-36), SULT2A1 (rs2637125; p = 2.61×10-19), ARPC1A (rs740160; p = 1.56×10-16), TRIM4 (rs17277546; p = 4.50×10-11), BMF (rs7181230; p = 5.44×10-11), HHEX (rs2497306; p = 4.64×10-9), BCL2L11 (rs6738028; p = 1.72×10-8), and CYP2C9 (rs2185570; p = 2.29×10-8). These genes are associated with type 2 diabetes, lymphoma, actin filament assembly, drug and xenobiotic metabolism, and zinc finger proteins. Several SNPs were associated with changes in gene expression levels, and the related genes are connected to biological pathways linking DHEAS with ageing. This study provides much needed insight into the function of DHEAS

MIGHTEE: Deep 1.4 GHz Source Counts and the Sky Temperature Contribution of Star Forming Galaxies and Active Galactic Nuclei

We present deep 1.4 GHz source counts from $\sim$5 deg$^2$ of the continuum Early Science data release of the MeerKAT International Gigahertz Tiered Extragalactic Exploration (MIGHTEE) survey down to $S_{1.4\textrm{GHz}}\sim$15 $\mu$Jy. Using observations over two extragalactic fields (COSMOS and XMM-LSS), we provide a comprehensive investigation into correcting the incompleteness of the raw source counts within the survey to understand the true underlying source count population. We use a variety of simulations that account for: errors in source detection and characterisation, clustering, and variations in the assumed source model used to simulate sources within the field and characterise source count incompleteness. We present these deep source count distributions and use them to investigate the contribution of extragalactic sources to the sky background temperature at 1.4 GHz using a relatively large sky area. We then use the wealth of ancillary data covering{a subset of the COSMOS field to investigate the specific contributions from both active galactic nuclei (AGN) and star forming galaxies (SFGs) to the source counts and sky background temperature. We find, similar to previous deep studies, that we are unable to reconcile the sky temperature observed by the ARCADE 2 experiment. We show that AGN provide the majority contribution to the sky temperature contribution from radio sources, but the relative contribution of SFGs rises sharply below 1 mJy, reaching an approximate 15-25% contribution to the total sky background temperature ($T_b\sim$100 mK) at $\sim$15 $\mu$Jy.Comment: 24 pages, 12 figures; Accepted for publication in MNRA