A Long and Winding Road: Federally Qualified Health Centers, Community Variation and Prospects Under Reform

Outlines growth in the number of, demand, and federal funding for FQHCs between 1997 and 2009 in twelve communities and factors that shape FQHC development, including variations in Medicaid eligibility rules, employer-sponsored coverage, and demographics

Galaxy Clusters: Oblate or Prolate?

It is now well known that a combined analysis of the Sunyaev-Zel'dovich (SZ) effect and the X-ray emission observations can be used to determine the angular diameter distance to galaxy clusters, from which the Hubble constant is derived. Given that the SZ/X-ray Hubble constant is determined through a geometrical description of clusters, the accuracy to which such distance measurements can be made depends on how well one can describe intrinsic cluster shapes. Using the observed X-ray isophotal axial ratio distribution for a sample of galaxy clusters, we discuss intrinsic cluster shapes and, in particular, if clusters can be described by axisymmetric models, such as oblate and prolate ellipsoids. These models are currently favored when determining the SZ/X-ray Hubble constant. We show that the current observational data on the asphericity of galaxy clusters suggest that clusters are more consistent with a prolate rather than an oblate distribution. We address the possibility that clusters are intrinsically triaxial by viewing triaxial ellipsoids at random angles with the intrinsic axial ratios following an isotropic Gaussian distribution. We discuss implications of our results on current attempts at measuring the Hubble constant using galaxy clusters and suggest that an unbiased estimate of the Hubble constant, not fundamentally limited by projection effects, would eventually be possible with the SZ/X-ray method.Comment: 6 pages, 6 figures. MNRAS (in press

The imprint of photoevaporation on edge-on discs

We have performed hydrodynamic and radiative transfer calculations of a photoevaporating disc around a Herbig Ae/Be star to determine the evolution and observational impact of dust entrained in the wind. We find that the wind selectively entrains grains of different sizes at different radii resulting in a dust population that varies spatially and increases with height above the disc at radii > 10 AU. This variable grain population results in a 'wingnut' morphology to the dust density distribution. We calculate images of this dust distribution at NIR wavelengths that also show a wingnut morphology at all wavelengths considered. We have also considered the contribution that crystalline dust grains will have in the wind and show that a photoevaporative wind can result in a significant crystallinity fraction at all radii, when the disc is edge-on. However, when the disc's photosphere is unobscured, a photoevaporative wind makes no contribution to the observable crystallinity fraction in the disc. Finally, we conclude that the analysis of extended emission around edge-on discs could provide a new and independent method of testing photoevaporation models.Comment: 8 pages, 6 figures, accepted for publication in MNRA

Dual RNA-seq identifies genes and pathways modulated during Clostridioides difficile colonization

The gastrointestinal pathogen Clostridioides difficile is the most common cause of hospital-acquired diarrhea. Bacterial interactions with the gut mucosa are crucial for the establishment of C. difficile infection; however, key infection events like bacterial attachment and gut penetration are still poorly defined. To better understand the initial events that occur when this anaerobe interacts with the human gut epithelium, we employed a dual RNA-sequencing approach to study the bacterial and host transcriptomic profiles during C. difficile infection in a dual environment in vitro human gut model. Temporal changes in gene expression during infection were studied in bacterial and epithelial cells over 3–24 hours. While there were several common differentially expressed bacterial genes across different timepoints after infection, mammalian transcriptional profiles were quite distinct, with little overlap. Interestingly, an induction of colonic receptors for C. difficile toxins was observed, along with the downregulation of genes encoding immune response markers. Several cell wall-associated proteins were downregulated in C. difficile when associated with host cells, including slpA , which encodes the main S-layer protein. Gene function and pathway enrichment analyses revealed a potential modulation of the purine/pyrimidine synthesis pathways both in the mammalian and bacterial cells. We observed that proline-proline endopeptidase, a secreted metalloprotease responsible for cell surface protein cleavage, is downregulated during infection, and a mutant lacking this enzyme demonstrated enhanced adhesion to epithelial cells during infection. This study provides new insight into the host and bacterial pathways based on gene expression modulation during the initial contact of C. difficile with gut cells. IMPORTANCE The initial interactions between the colonic epithelium and the bacterium are likely critical in the establishment of Clostridioides difficile infection, one of the major causes of hospital-acquired diarrhea worldwide. Molecular interactions between C. difficile and human gut cells have not been well defined mainly due to the technical challenges of studying cellular host–pathogen interactions with this anaerobe. Here we have examined transcriptional changes occurring in the pathogen and host cells during the initial 24 hours of infection. Our data indicate several changes in metabolic pathways and virulence-associated factors during the initial bacterium-host cell contact and early stages of infection. We describe canonical pathways enriched based on the expression profiles of a dual RNA sequencing in the host and bacterium, and functions of bacterial factors that are modulated during infection. This study thus provides fresh insight into the early C. difficile infection process

A Massive Spiral Galaxy in the Zone of Avoidance

We report the discovery of a very HI-massive disk galaxy, HIZOA J0836-43, at a velocity of v_hel = 10689 km/s, corresponding to a distance of 148 Mpc (assuming H_0=75 km/s/Mpc). It was found during the course of a systematic HI survey of the southern Zone of Avoidance (|b| < 5 deg) with the multibeam system at the 64m Parkes radio telescope. Follow-up observations with the Australia Telescope Compact Array (ATCA) reveal an extended HI disk. We derive an HI mass of 7.5 x 10^10 Msun. Using the HI radius, we estimate a total dynamical mass of 1.4 x 10^12 Msun, similar to the most massive known disk galaxies such as Malin 1. HIZOA J0836-43 lies deep in the Zone of Avoidance (l, b = 262.48 deg, -1.64 deg) where the optical extinction is very high, A_B = 9.8. However, in the near-infrared wavebands, where the extinction is considerably lower, HIZOA J0836-43 is clearly detected by both DENIS and 2MASS. Deep AAT near-infrared (Ks and H-band) images show that HIZOA J0836-43 is an inclined disk galaxy with a prominent bulge (scale length 2.5 arcsec or 1.7 kpc), and an extended disk (scale length 7 arcsec or 4.7 kpc) which can be traced along the major axis out to a radius of 20 arcsec or 13.4 kpc (at 20 mag/arcsec^2 in Ks). The HI disk is much more extended, having a radius of 66 kpc at 1 Msun/pc^2. Detections in the radio continuum at 1.4 GHz and at 60 micron (IRAS) are consistent with HIZOA J0836-43 forming stars at a rate of ~35 Msun/yr. We compare the properties of HIZOA J0836-43 with those of the most HI-massive galaxies currently known, UGC 4288, UGC 1752 and Malin 1, all of which are classified as giant low surface brightness galaxies.Comment: Accepted for publication in MNRAS, 17 pages, 11 figures, 7 tables, version with high-resolution figures available at: http://frodo.as.arizona.edu/~jdonley/massive

Multicenter Consensus Approach to Evaluation of Neonatal Hypotonia in the Genomic Era: A Review

IMPORTANCE: Infants with hypotonia can present with a variety of potentially severe clinical signs and symptoms and often require invasive testing and multiple procedures. The wide range of clinical presentations and potential etiologies leaves diagnosis and prognosis uncertain, underscoring the need for rapid elucidation of the underlying genetic cause of disease. OBSERVATIONS: The clinical application of exome sequencing or genome sequencing has dramatically improved the timely yield of diagnostic testing for neonatal hypotonia, with diagnostic rates of greater than 50% in academic neonatal intensive care units (NICUs) across Australia, Canada, the UK, and the US, which compose the International Precision Child Health Partnership (IPCHiP). A total of 74% (17 of 23) of patients had a change in clinical care in response to genetic diagnosis, including 2 patients who received targeted therapy. This narrative review discusses the common causes of neonatal hypotonia, the relative benefits and limitations of available testing modalities used in NICUs, and hypotonia management recommendations. CONCLUSIONS AND RELEVANCE: This narrative review summarizes the causes of neonatal hypotonia and the benefits of prompt genetic diagnosis, including improved prognostication and identification of targeted treatments which can improve the short-term and long-term outcomes. Institutional resources can vary among different NICUs; as a result, consideration should be given to rule out a small number of relatively unique conditions for which rapid targeted genetic testing is available. Nevertheless, the consensus recommendation is to use rapid genome or exome sequencing as a first-line testing option for NICU patients with unexplained hypotonia. As part of the IPCHiP, this diagnostic experience will be collected in a central database with the goal of advancing knowledge of neonatal hypotonia and improving evidence-based practice

ART^2 : Coupling Lyman-alpha Line and Multi-wavelength Continuum Radiative Transfer

Narrow-band Lya line and broad-band continuum have played important roles in the discovery of high-redshift galaxies in recent years. Hence, it is crucial to study the radiative transfer of both Lya and continuum photons in the context of galaxy formation and evolution in order to understand the nature of distant galaxies. Here, we present a three-dimensional Monte Carlo radiative transfer code, All-wavelength Radiative Transfer with Adaptive Refinement Tree (ART^2), which couples Lya line and multi-wavelength continuum, for the study of panchromatic properties of galaxies and interstellar medium. This code is based on the original version of Li et al., and features three essential modules: continuum emission from X-ray to radio, Lya emission from both recombination and collisional excitation, and ionization of neutral hydrogen. The coupling of these three modules, together with an adaptive refinement grid, enables a self-consistent and accurate calculation of the Lya properties. As an example, we apply ART^2 to a cosmological simulation that includes both star formation and black hole growth, and study in detail a sample of massive galaxies at redshifts z=3.1 - 10.2. We find that these galaxies are Lya emitters (LAEs), whose Lya emission traces the dense gas region, and that their Lya lines show a shape characteristic of gas inflow. Furthermore, the Lya properties, including photon escape fraction, emergent luminosity, and equivalent width, change with time and environment. Our results suggest that LAEs evolve with redshift, and that early LAEs such as the most distant one detected at z ~ 8.6 may be dwarf galaxies with a high star formation rate fueled by infall of cold gas, and a low Lya escape fraction.Comment: 20 pages, 16 figures, accepted for publication in MNRA

The intrinsic shape of galaxy bulges

The knowledge of the intrinsic three-dimensional (3D) structure of galaxy components provides crucial information about the physical processes driving their formation and evolution. In this paper I discuss the main developments and results in the quest to better understand the 3D shape of galaxy bulges. I start by establishing the basic geometrical description of the problem. Our understanding of the intrinsic shape of elliptical galaxies and galaxy discs is then presented in a historical context, in order to place the role that the 3D structure of bulges play in the broader picture of galaxy evolution. Our current view on the 3D shape of the Milky Way bulge and future prospects in the field are also depicted.Comment: Invited Review to appear in "Galactic Bulges" Editors: Laurikainen E., Peletier R., Gadotti D. Springer Publishing. 24 pages, 7 figure

A multi-centre, open label, randomised, parallel-group, superiority Trial to compare the efficacy of URsodeoxycholic acid with RIFampicin in the management of women with severe early onset Intrahepatic Cholestasis of pregnancy : the TURRIFIC randomised trial

BackgroundSevere early onset (less than 34weeks gestation) intrahepatic cholestasis of pregnancy (ICP) affects 0.1% of pregnant women in Australia and is associated with a 3-fold increased risk of stillbirth, fetal hypoxia and compromise, spontaneous preterm birth, as well as increased frequencies of pre-eclampsia and gestational diabetes. ICP is often familial and overlaps with other cholestatic disorders.Treatment options for ICP are not well established, although there are limited data to support the use of ursodeoxycholic acid (UDCA) to relieve pruritus, the main symptom. Rifampicin, a widely used antibiotic including in pregnant women, is effective in reducing pruritus in non-pregnancy cholestasis and has been used as a supplement to UDCA in severe ICP. Many women with ICP are electively delivered preterm, although there are no randomised data to support this approach.MethodsWe have initiated an international multicentre randomised clinical trial to compare the clinical efficacy of rifampicin tablets (300mg bd) with that of UDCA tablets (up to 2000mg daily) in reducing pruritus in women with ICP, using visual pruritus scores as a measuring tool.DiscussionOur study will be the first to examine the outcomes of treatment specifically in the severe early onset form of ICP, comparing "standard" UDCA therapy with rifampicin, and so be able to provide for the first-time high-quality evidence for use of rifampicin in severe ICP. It will also allow an assessment of feasibility of a future trial to test whether elective early delivery in severe ICP is beneficial.Trial identifiersAustralian New Zealand Clinical Trials Registration Number (ANZCTR): 12618000332224p (29/08/2018). HREC No: HREC/18/WCHN/36.EudraCT number: 2018-004011-44.IRAS: 272398.NHMRC registration: APP1152418 and APP117853.Peer reviewe

SYT1-associated neurodevelopmental disorder: a case series.

Synaptotagmin 1 (SYT1) is a critical mediator of fast, synchronous, calcium-dependent neurotransmitter release and also modulates synaptic vesicle endocytosis. This paper describes 11 patients with de novo heterozygous missense mutations in SYT1. All mutations alter highly conserved residues, and cluster in two regions of the SYT1 C2B domain at positions Met303 (M303K), Asp304 (D304G), Asp366 (D366E), Ile368 (I368T) and Asn371 (N371K). Phenotypic features include infantile hypotonia, congenital ophthalmic abnormalities, childhood-onset hyperkinetic movement disorders, motor stereotypies, and developmental delay varying in severity from moderate to profound. Behavioural characteristics include sleep disturbance and episodic agitation. Absence of epileptic seizures and normal orbitofrontal head circumference are important negative features. Structural MRI is unremarkable but EEG disturbance is universal, characterized by intermittent low frequency high amplitude oscillations. The functional impact of these five de novo SYT1 mutations has been assessed by expressing rat SYT1 protein containing the equivalent human variants in wild-type mouse primary hippocampal cultures. All mutant forms of SYT1 were expressed at levels approximately equal to endogenous wild-type protein, and correctly localized to nerve terminals at rest, except for SYT1M303K, which was expressed at a lower level and failed to localize at nerve terminals. Following stimulation, SYT1I368T and SYT1N371K relocalized to nerve terminals at least as efficiently as wild-type SYT1. However, SYT1D304G and SYT1D366E failed to relocalize to nerve terminals following stimulation, indicative of impairments in endocytic retrieval and trafficking of SYT1. In addition, the presence of SYT1 variants at nerve terminals induced a slowing of exocytic rate following sustained action potential stimulation. The extent of disturbance to synaptic vesicle kinetics is mirrored by the severity of the affected individuals' phenotypes, suggesting that the efficiency of SYT1-mediated neurotransmitter release is critical to cognitive development. In summary, de novo dominant SYT1 missense mutations are associated with a recognizable neurodevelopmental syndrome, and further cases can now be diagnosed based on clinical features, electrophysiological signature and mutation characteristics. Variation in phenotype severity may reflect mutation-specific impact on the diverse physiological functions of SYT1