Exoplanet atmospheres with EChO: spectral retrievals using EChOSim

We demonstrate the effectiveness of the Exoplanet Characterisation Observatory mission concept for constraining the atmospheric properties of hot and warm gas giants and super Earths. Synthetic primary and secondary transit spectra for a range of planets are passed through EChOSim (Waldmann & Pascale 2014) to obtain the expected level of noise for different observational scenarios; these are then used as inputs for the NEMESIS atmospheric retrieval code and the retrieved atmospheric properties (temperature structure, composition and cloud properties) compared with the known input values, following the method of Barstow et al. (2013a). To correctly retrieve the temperature structure and composition of the atmosphere to within 2 {\sigma}, we find that we require: a single transit or eclipse of a hot Jupiter orbiting a sun-like (G2) star at 35 pc to constrain the terminator and dayside atmospheres; 20 transits or eclipses of a warm Jupiter orbiting a similar star; 10 transits/eclipses of a hot Neptune orbiting an M dwarf at 6 pc; and 30 transits or eclipses of a GJ1214b-like planet.Comment: 13 pages, 15 figures, 1 table. Accepted by Experimental Astronomy. The final publication will shortly be available at Springer via http://dx.doi.org/10.1007/s10686-014-9397-

Adenovirus infection in the lung results in graft failure after lung transplantation

AbstractObjectives: Our goal was to examine the relationship between viral pneumonia and outcome in pediatric patients undergoing lung or heart-lung transplantation. Methods: Prospective surveillance for common respiratory viruses of childhood was performed in all patients undergoing lung or heart-lung transplantation. Specimens were examined for the presence of replicating virus (by culture), viral genome (by polymerase chain reaction), and viral antigen (by immunofluorescence and immunohistochemical staining). The relationship between viral infection and outcome was examined. Results: Sixteen patients underwent 19 transplants during the study period, with follow-up of 1 to 26 months. Virus was identified in the transplanted lung in 29 instances; adenovirus was identified most commonly (8/16 patients) and had the greatest impact on outcome. In 2 patients with early, fulminant infection, adenovirus was also identified in the donor. Adenovirus was significantly associated with respiratory failure leading to death or graft loss and with the histologic diagnosis of obliterative bronchiolitis (P ≤ .002 in each case). Conclusions: Adenovirus infection in the transplanted lung is significantly associated with graft failure, histologic obliterative bronchiolitis, and death. Health care personnel and families must be vigilant in preventing exposure of transplant recipients to this virus. Availability of a rapid and reliable test for adenovirus in donors and recipients would have an impact on management and could improve outcome for pediatric lung recipients. (J Thorac Cardiovasc Surg 1998;116:617-23

The Transit Spectra of Earth and Jupiter

In recent years, a number of observations have been made of the transits of 'Hot Jupiters', such as HD 189733b, which have been modelled to derive atmospheric structure and composition. As measurement techniques improve, the transit spectra of 'Super-Earths' such as GJ 1214b are becoming better constrained, allowing model atmospheres to be fitted for this class of planet also. While it is not yet possible to constrain the atmospheric states of small planets such as the Earth or cold planets like Jupiter, this may become practical in the coming decades and if so, it is of interest to determine what we might infer from such measurements. Here we have constructed atmospheric models of the Solar System planets from 0.4 - 15.5 microns that are consistent with ground-based and satellite observations and from these calculate the primary transit and secondary eclipse spectra (with respect to the Sun and typical M-dwarfs) that would be observed by a 'remote observer', many light years away. From these spectra we test what current retrieval models might infer about their atmospheres and compare these with the 'ground truths' in order to assess: a) the inherent uncertainties in transit spectra observations; b) the relative merits of primary transit and secondary eclipse spectra; and c) the advantages of directly imaged spectra. We find that secondary eclipses would not give sufficient information, but that primary transits give much better determination. We find that a single transit of Jupiter in front of the Sun could potentially be used to determine temperature and stratospheric composition, but for the Earth the mean atmospheric composition could only be determined if it were orbiting an M-dwarf. For both planets we note that direct imaging with sufficient nulling of the light from the parent star provides the best method of determining the atmospheric properties of such planets

Rationale for the Cytogenomics of Cardiovascular Malformations Consortium: A Phenotype Intensive Registry Based Approach

Cardiovascular malformations (CVMs) are the most common birth defect, occurring in 1%-5% of all live births. Although the genetic contribution to CVMs is well recognized, the genetic causes of human CVMs are identified infrequently. In addition, a failure of systematic deep phenotyping of CVMs, resulting from the complexity and heterogeneity of malformations, has obscured genotype-phenotype correlations and contributed to a lack of understanding of disease mechanisms. To address these knowledge gaps, we have developed the Cytogenomics of Cardiovascular Malformations (CCVM) Consortium, a multi-site alliance of geneticists and cardiologists, contributing to a database registry of submicroscopic genetic copy number variants (CNVs) based on clinical chromosome microarray testing in individuals with CVMs using detailed classification schemes. Cardiac classification is performed using a modification to the National Birth Defects Prevention Study approach, and non-cardiac diagnoses are captured through ICD-9 and ICD-10 codes. By combining a comprehensive approach to clinically relevant genetic analyses with precise phenotyping, the Consortium goal is to identify novel genomic regions that cause or increase susceptibility to CVMs and to correlate the findings with clinical phenotype. This registry will provide critical insights into genetic architecture, facilitate genotype-phenotype correlations, and provide a valuable resource for the medical community

Viral Endomyocardial Infection Is an Independent Predictor and Potentially Treatable Risk Factor for Graft Loss and Coronary Vasculopathy in Pediatric Cardiac Transplant Recipients

ObjectivesThis study sought to evaluate the outcome and prevalence of viral endomyocardial infection after cardiac transplantation.BackgroundViral myocardial infection causes heart failure, but its role after cardiac transplantation is unclear. We hypothesized that viral infection of the cardiac allograft reduces graft survival.MethodsBetween June 1999 and November 2004, 94 pediatric cardiac transplant patients were screened for the presence of viral genome in serial endomyocardial biopsies (EMBs) using polymerase chain reaction (PCR) assays. Graft loss, advanced transplant coronary artery disease (TCAD), and acute rejection (AR) were compared in the PCR-positive (n = 37) and PCR-negative (n = 57) groups, using time-dependent Kaplan-Meier and Cox regression analyses. From November 2002 to November 2004, intravenous immunoglobulin therapy (IVIG) was administered to patients with PCR-positive EMBs. The outcomes of the IVIG-treated, PCR-positive patients (n = 20) were compared with IVIG-untreated, PCR-positive patients (n = 17).ResultsViral genomes were detected in EMBs from 37 (39%) patients; parvovirus B19, adenovirus, and Epstein-Barr virus (EBV) were the most common. The PCR-positive group (n = 37, 25% graft loss at 2.4 years) had decreased graft survival (p < 0.001) compared with the PCR-negative group (n = 57, 25% graft loss at 8.7 years) and developed advanced TCAD prematurely (p = 0.001). The number of AR episodes was similar in both groups. On multivariate analysis, presence of viral genome was an independent risk factor for graft loss (relative risk: 4.2, p = 0.015). The time to advanced TCAD after becoming PCR-positive was longer in the IVIG-treated patients (p = 0.03) with a trend toward improved graft survival (p = 0.06).ConclusionsViral endomyocardial infection is an independent predictor of graft loss in pediatric cardiac transplant recipients. This effect appears to be mediated through premature development of advanced TCAD. IVIG therapy in this subgroup may improve survival and merits further investigation

ANKRD1, the gene encoding cardiac ankyrin repeat protein, is a novel dilated cardiomyopathy gene.

OBJECTIVES: We evaluated ankyrin repeat domain 1 (ANKRD1), the gene encoding cardiac ankyrin repeat protein (CARP), as a novel candidate gene for dilated cardiomyopathy (DCM) through mutation analysis of a cohort of familial or idiopathic DCM patients, based on the hypothesis that inherited dysfunction of mechanical stretch-based signaling is present in a subset of DCM patients. BACKGROUND: CARP, a transcription coinhibitor, is a member of the titin-N2A mechanosensory complex and translocates to the nucleus in response to stretch. It is up-regulated in cardiac failure and hypertrophy and represses expression of sarcomeric proteins. Its overexpression results in contractile dysfunction. METHODS: In all, 208 DCM patients were screened for mutations/variants in the coding region of ANKRD1 using polymerase chain reaction, denaturing high-performance liquid chromatography, and direct deoxyribonucleic acid sequencing. In vitro functional analyses of the mutation were performed using yeast 2-hybrid assays and investigating the effect on stretch-mediated gene expression in myoblastoid cell lines using quantitative real-time reverse transcription-polymerase chain reaction. RESULTS: Three missense heterozygous ANKRD1 mutations (P105S, V107L, and M184I) were identified in 4 DCM patients. The M184I mutation results in loss of CARP binding with Talin 1 and FHL2, and the P105S mutation in loss of Talin 1 binding. Intracellular localization of mutant CARP proteins is not altered. The mutations result in differential stretch-induced gene expression compared with wild-type CARP. CONCLUSIONS: ANKRD1 is a novel DCM gene, with mutations present in 1.9% of DCM patients. The ANKRD1 mutations may cause DCM as a result of disruption of the normal cardiac stretch-based signaling

The bulk mineralogy, elemental composition, and water content of the Winchcombe CM chondrite fall

On the micro-scale, the Winchcombe CM carbonaceous chondrite contains a number of lithological units with a variety of degrees of aqueous alteration. However, an understanding of the average hydration state is useful when comparing to other meteorites and remote observations of airless bodies. We report correlated bulk analyses on multiple subsamples of the Winchcombe meteorite, determining an average phyllosilicate fraction (PSF) petrologic type of 1.2 and an average water content of 11.9 wt%. We show the elemental composition and distribution of iron and iron oxidation state are consistent with measurements from other CM chondrites, however Winchcombe shows a low Hg concentration of 58.1 ±0.5 ng/g. We demonstrate that infrared reflectance spectra of Winchcombe are consistent with its bulk modal mineralogy, and comparable to other CM chondrites with similar average petrologic types. Finally, we also evaluate whether spectral parameters can estimate H/Si ratios and water abundances, finding generally spectral parameters underestimate water abundance compared to measured values.Output Status: Forthcoming/Available Onlin

Genetic Study in Left Ventricular Noncompaction

Background—Left ventricular noncompaction (LVNC) has since been classified as a primary genetic cardiomyopathy, but the genetic basis is not fully evaluated. The aim of the present study was to identify the genetic spectrum using next-generation sequencing and to evaluate genotype–phenotype correlations in LVNC patients. Methods and Results—Using next-generation sequencing, we targeted and sequenced 73 genes related to cardiomyopathy in 102 unrelated LVNC patients. We identified 43 pathogenic variants in 16 genes in 39 patients (38%); 28 were novel variants. Sarcomere gene variants accounted for 63%, and variants in genes associated with channelopathies accounted for 12%. MYH7 and TAZ pathogenic variants were the most common, and rare variant collapsing analysis showed variants in these genes contributed to the risk of LVNC, although patients carrying MYH7 and TAZ pathogenic variants displayed different phenotypes. Patients with pathogenic variants had early age of onset and more severely decreased left ventricular ejection fractions. Survival analysis showed poorer prognosis in patients with pathogenic variants, especially those with multiple variants: All died before their first birthdays. Adverse events were noted in 17 patients, including 13 deaths, 3 heart transplants, and 1 implantable cardioverter-defibrillator insertion. Congestive heart failure at diagnosis and pathogenic variants were independent risk factors for these adverse events. Conclusions—Next-generation sequencing revealed a wide spectrum of genetic variations and a high incidence of pathogenic variants in LVNC patients. These pathogenic variants were independent risk factors for adverse events. Patients harboring pathogenic variants showed poor prognosis and should be followed closely