Rapid identification of mutations in GJC2 in primary lymphoedema using whole exome sequencing combined with linkage analysis with delineation of the phenotype.

Background: Primary lymphoedema describes a chronic, frequently progressive, failure of lymphatic drainage. This disorder is frequently genetic in origin, and a multigenerational family in which eight individuals developed postnatal lymphoedema of all four limbs was ascertained from the joint Lymphoedema/Genetic clinic at St George's Hospital. Methods: Linkage analysis was used to determine a locus, and exome sequencing was employed to look for causative variants. Results: Linkage analysis revealed cosegregation of a 16.1 Mb haplotype on chromosome 1q42 that contained 173 known or predicted genes. Whole exome sequencing in a single affected individual was undertaken, and the search for the causative variant was focused to within the linkage interval. This approach revealed two novel non-synonymous single nucleotide substitutions within the chromosome 1 locus, in NVL and GJC2. NVL and GJC2 were sequenced in an additional cohort of individuals with a similar phenotype and non-synonymous variants were found in GJC2 in four additional families. Conclusion: This report demonstrates the power of exome sequencing efficiently applied to a traditional positional cloning pipeline in disease gene discovery, and suggests that the phenotype produced by GJC2 mutations is predominantly one of 4 limb lymphoedema

Gravitational Lensing as Signal and Noise in Lyman-alpha Forest Measurements

In Lyman-alpha forest measurements it is generally assumed that quasars are mere background light sources which are uncorrelated with the forest. Gravitational lensing of the quasars violates this assumption. This effect leads to a measurement bias, but more interestingly it provides a valuable signal. The lensing signal can be extracted by correlating quasar magnitudes with the flux power spectrum and with the flux decrement. These correlations will be challenging to measure but their detection provides a direct measure of how features in the Lyman-alpha forest trace the underlying mass density field. Observing them will test the fundamental hypothesis that fluctuations in the forest are predominantly driven by fluctuations in mass, rather than in the ionizing background, helium reionization or winds. We discuss ways to disentangle the lensing signal from other sources of such correlations, including dust, continuum and background residuals. The lensing-induced measurement bias arises from sample selection: one preferentially collects spectra of magnified quasars which are behind overdense regions. This measurement bias is ~0.1-1% for the flux power spectrum, optical depth and the flux probability distribution. Since the effect is systematic, quantities such as the amplitude of the flux power spectrum averaged across scales should be interpreted with care.Comment: 22 pages, 8 figures; v2: references added, discussion expanded, matches PRD accepted versio

On the Connection Between Metal Absorbers and Quasar Nebulae

We establish a simple model for the distribution of cold gas around L* galaxies using a large set of observational constraints on the properties of strong MgII absorber systems. Our analysis suggests that the halos of L* galaxies are filled with cool gaseous clouds having sizes of order 1kpc and densities of ~10^{-2} cm^{-3}. We then investigate the physical effects of cloud irradiation by a quasar and study the resulting spectral signatures. We show that quasar activity gives rise to (i) extended narrow-line emission on ~100kpc scales and (ii) an anisotropy in the properties of the absorbing gas arising from the geometry of the quasar radiation field. Provided that quasars reside in halos several times more massive than those of L* galaxies, our model predictions appear to be in agreement with observations of narrow emission-line nebulae around quasars and the recent detections of ~100kpc cold gaseous envelopes around those objects, suggesting a common origin for these phenomena. We discuss the implications of our results for understanding absorption systems, probing quasar environments at high redshifts, and testing the quasar unification scheme.Comment: 15 pages, 13 figures (ApJ submitted

A functional non-central limit theorem for jump-diffusions with periodic coefficients driven by stable Levy-noise

We prove a functional non-central limit theorem for jump-diffusions with periodic coefficients driven by strictly stable Levy-processes with stability index bigger than one. The limit process turns out to be a strictly stable Levy process with an averaged jump-measure. Unlike in the situation where the diffusion is driven by Brownian motion, there is no drift related enhancement of diffusivity.Comment: Accepted to Journal of Theoretical Probabilit

Optical properties and spatial distribution of MgII absorbers from SDSS image stacking

We present a statistical analysis of the photometric properties and spatial distribution of more than 2,800 MgII absorbers with 0.37<z<1 and rest equivalent width W_0(\lambda2796)>0.8\AA detected in SDSS quasar spectra. Using an improved image stacking technique, we measure the cross-correlation between MgII gas and light (in the g, r, i and z-bands) from 10 to 200 kpc and infer the light-weighted impact parameter distribution of MgII absorbers. Such a quantity is well described by a power-law with an index that strongly depends on W_0, ranging from ~-1 for W_0~ 1.5\AA. At redshift 0.37<z<0.55, we find the average luminosity enclosed within 100 kpc around MgII absorbers to be M_g=-20.65+-0.11 mag, which is ~0.5 L_g*. The global luminosity-weighted colors are typical of present-day intermediate type galaxies. However, while the light of weaker absorbers originates mostly from red passive galaxies, stronger systems display the colors of blue star-forming galaxies. Based on these observations, we argue that the origin of strong MgII absorber systems might be better explained by models of metal-enriched gas outflows from star-forming/bursting galaxies. Our analysis does not show any redshift dependence for both impact parameter and rest-frame colors up to z=1. However, we do observe a brightening of the absorbers related light at high redshift (~50% from z~0.4 to 1). We argue that MgII absorbers are a phenomenon typical of a given evolutionary phase that more massive galaxies experience earlier than less massive ones, in a downsizing fashion. (abridged)Comment: ApJ in press, 28 pages, 16 figures, using emulateapj. Only typo corrections wrt the original submission (v1

Different Ways of Reading, or Just Making the Right Noises?

What does reading look like? Can learning to read be reduced to the acquisition of a set of isolable skills, or proficiency in reading be equated with the independence of the solitary, silent reader of prose fiction? These conceptions of reading and reading development, which figure strongly in educational policy, may appear to be simple common sense. But both ethnographic data and evidence from literary texts suggest that such paradigms offer, at most, a partial and ahistorical picture of reading. An important dimension, neglected in the dominant paradigms, is the irreducibly social quality of reading practices

Antibiotic Stewardship Implementation and Antibiotic Use at Hospitals With and Without On-site Infectious Disease Specialists.

BackgroundMany US hospitals lack infectious disease (ID) specialists, which may hinder antibiotic stewardship efforts. We sought to compare patient-level antibiotic exposure at Veterans Health Administration (VHA) hospitals with and without an on-site ID specialist, defined as an ID physician and/or ID pharmacist.MethodsThis retrospective VHA cohort included all acute-care patient admissions during 2016. A mandatory survey was used to identify hospitals' antibiotic stewardship processes and their access to an on-site ID specialist. Antibiotic use was quantified as days of therapy per days present and categorized based on National Healthcare Safety Network definitions. A negative binomial regression model with risk adjustment was used to determine the association between presence of an on-site ID specialist and antibiotic use at the level of patient admissions.ResultsEighteen of 122 (14.8%) hospitals lacked an on-site ID specialist; there were 525 451 (95.8%) admissions at ID hospitals and 23 007 (4.2%) at non-ID sites. In the adjusted analysis, presence of an ID specialist was associated with lower total inpatient antibacterial use (odds ratio, 0.92; 95% confidence interval, .85-.99). Presence of an ID specialist was also associated with lower use of broad-spectrum antibacterials (0.61; .54-.70) and higher narrow-spectrum β-lactam use (1.43; 1.22-1.67). Total antibacterial exposure (inpatient plus postdischarge) was lower among patients at ID versus non-ID sites (0.92; .86-.99).ConclusionsPatients at hospitals with an ID specialist received antibiotics in a way more consistent with stewardship principles. The presence of an ID specialist may be important to effective antibiotic stewardship

Antibiotic stewardship implementation and patient-level antibiotic use at hospitals with and without on-site Infectious Disease specialists.

Many US hospitals lack Infectious Disease (ID) specialists, which may hinder antibiotic stewardship efforts. We sought to compare patient-level antibiotic exposure at Veterans Health Administration (VHA) hospitals with and without an on-site ID specialist, defined as an ID physician and/or ID pharmacist. This retrospective VHA cohort included all acute-care patient-admissions during 2016. A mandatory survey was used to identify hospitals' antibiotic stewardship processes and their access to an on-site ID specialist. Antibiotic use was quantified as days of therapy (DOT) per days-present and categorized based on National Healthcare Safety Network definitions. A negative binomial regression model with risk adjustment was used to determine the association between presence of an on-site ID specialist and antibiotic use at the level of patient-admissions. Eighteen of 122 (14.8%) hospitals lacked an on-site ID specialist; there were 525,451 (95.8%) admissions at ID hospitals and 23,007 (4.2%) at non-ID sites. In the adjusted analysis, presence of an ID specialist was associated with lower total inpatient antibacterial use [OR 0.92, (95% CI, 0.85-0.99)]. Presence of an ID specialist was also associated with lower use of broad-spectrum antibacterials [OR 0.61 (95% CI, 0.54-0.70)] and higher narrow-spectrum beta-lactam use [OR 1.43 (95% CI, 1.22-1.67)]. Total antibacterial exposure (inpatient plus post-discharge) was lower among patients at ID versus non-ID sites [OR 0.92 (95% CI, 0.86-0.99)]. Patients at hospitals with an ID specialist received antibiotics in a way more consistent with stewardship principles. The presence of an ID specialist may be important to effective antibiotic stewardship