NuSTAR Spectroscopy of Multi-Component X-ray Reflection from NGC 1068

We report on observations of NGC1068 with NuSTAR, which provide the best constraints to date on its $>10$~keV spectral shape. We find no strong variability over the past two decades, consistent with its Compton-thick AGN classification. The combined NuSTAR, Chandra, XMM-Newton, and Swift-BAT spectral dataset offers new insights into the complex reflected emission. The critical combination of the high signal-to-noise NuSTAR data and a spatial decomposition with Chandra allow us to break several model degeneracies and greatly aid physical interpretation. When modeled as a monolithic (i.e., a single N_H) reflector, none of the common Compton-reflection models are able to match the neutral fluorescence lines and broad spectral shape of the Compton reflection. A multi-component reflector with three distinct column densities (e.g., N_H~1.5e23, 5e24, and 1e25 cm^{-2}) provides a more reasonable fit to the spectral lines and Compton hump, with near-solar Fe abundances. In this model, the higher N_H components provide the bulk of the Compton hump flux while the lower N_H component produces much of the line emission, effectively decoupling two key features of Compton reflection. We note that ~30% of the neutral Fe Kalpha line flux arises from >2" (~140 pc), implying that a significant fraction of the <10 keV reflected component arises from regions well outside of a parsec-scale torus. These results likely have ramifications for the interpretation of poorer signal-to-noise observations and/or more distant objects [Abridged].Comment: Submitted to ApJ; 23 pages (ApJ format); 11 figures and 3 tables; Comments welcomed

Allele frequencies of hemojuvelin gene (HJV) I222N and G320V missense mutations in white and African American subjects from the general Alabama population

BACKGROUND: Homozygosity or compound heterozygosity for coding region mutations of the hemojuvelin gene (HJV) in whites is a cause of early age-of-onset iron overload (juvenile hemochromatosis), and of hemochromatosis phenotypes in some young or middle-aged adults. HJV coding region mutations have also been identified recently in African American primary iron overload and control subjects. Primary iron overload unexplained by typical hemochromatosis-associated HFE genotypes is common in white and black adults in Alabama, and HJV I222N and G320V were detected in a white Alabama juvenile hemochromatosis index patient. Thus, we estimated the frequency of the HJV missense mutations I222N and G320V in adult whites and African Americans from Alabama general population convenience samples. METHODS: We evaluated the genomic DNA of 241 Alabama white and 124 African American adults who reported no history of hemochromatosis or iron overload to detect HJV missense mutations I222N and G320V using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Analysis for HJV I222N was performed in 240 whites and 124 African Americans. Analysis for HJV G320V was performed in 241 whites and 118 African Americans. RESULTS: One of 240 white control subjects was heterozygous for HJV I222N; she was also heterozygous for HFE C282Y, but had normal serum iron measures and bone marrow iron stores. HJV I222N was not detected in 124 African American subjects. HJV G320V was not detected in 241 white or 118 African American subjects. CONCLUSIONS: HJV I222N and G320V are probably uncommon causes or modifiers of primary iron overload in adult whites and African Americans in Alabama. Double heterozygosity for HJV I222N and HFE C282Y may not promote increased iron absorption

NuSTAR discovery of a luminosity dependent cyclotron line energy in Vela X-1

We present NuSTAR observations of Vela X-1, a persistent, yet highly variable, neutron star high-mass X-ray binary (HMXB). Two observations were taken at similar orbital phases but separated by nearly a year. They show very different 3–79 keV flux levels as well as strong variability during each observation, covering almost one order of magnitude in flux. These observations allow, for the first time ever, investigations on kilo-second time-scales of how the centroid energies of cyclotron resonant scattering features (CRSFs) depend on flux for a persistent HMXB. We find that the line energy of the harmonic CRSF is correlated with flux, as expected in the sub-critical accretion regime. We argue that Vela X-1 has a very narrow accretion column with a radius of around 0.4 km that sustains a Coulomb interaction dominated shock at the observed luminosities of L_x ~ 3 × 10^36 erg s^−1. Besides the prominent harmonic line at 55 keV the fundamental line around 25 keV is clearly detected. We find that the strengths of the two CRSFs are anti-correlated, which we explain by photon spawning. This anti-correlation is a possible explanation for the debate about the existence of the fundamental line. The ratio of the line energies is variable with time and deviates significantly from 2.0, also a possible consequence of photon spawning, which changes the shape of the line. During the second observation, Vela X-1 showed a short off-state in which the power-law softened and a cut-off was no longer measurable. It is likely that the source switched to a different accretion regime at these low mass accretion rates, explaining the drastic change in spectral shape

"I'm the Momma": Using photo-elicitation to understand matrilineal influence on family food choice

<p>Abstract</p> <p>Background</p> <p>Many complex and subtle aspects relating to mothers and food choice are not well understood. Mothers play a primary role in their children's food choices, but research has not specifically examined how matrilineal family members who do not reside in the same household, such as a mother's mother, aunt, or grandmother, influence the current family's food choices.</p> <p>Methods</p> <p>Seven participants were recruited from the Household Food Inventory (HFI) Study in the Bryan/College Station, Texas. All participants completed an in-depth interview, photographed food-related activities, and discussed photographs in a follow-up in-depth interview. Interviews were transcribed verbatim from audio recordings. Transcripts were analyzed using several qualitative approaches including grounded theory to identify themes and subthemes.</p> <p>Results</p> <p>Participants discussed the following themes relating to the influence of their mother or other female relation (Mom) on their families' food choices: Relationship with Mom, Just like Mom, 'Kinda' like Mom, Different than Mom, and Mom's Influence on Children's Food Choices. Overall, participants used the photographs to illustrate how they were similar or different to their mothers, or other female family member, as well as how their mothers either supported or undermined control over their children's food choices. The "Mom effect" or matrilineal influence of mothers, aunts, and grandmothers on a mother's food choices was omnipresent, even though Mom was no longer living with the participants.</p> <p>Conclusions</p> <p>We found a matrilineal influence to have a residual and persistent influence on a family's food choices. This finding may be helpful for understanding the contextual elements of food choice and explaining why it is sometimes difficult to change mothers' food habits.</p

Age-Related Differences in Biomarkers of Acute Inflammation During Hospitalization for Sepsis

To evaluate age-related differences in inflammation biomarkers during the first 72 hours of hospitalization for sepsis

Study of Women, Infant feeding, and Type 2 diabetes mellitus after GDM pregnancy (SWIFT), a prospective cohort study: methodology and design

<p>Abstract</p> <p>Background</p> <p>Women with history of gestational diabetes mellitus (GDM) are at higher risk of developing type 2 diabetes within 5 years after delivery. Evidence that lactation duration influences incident type 2 diabetes after GDM pregnancy is based on one retrospective study reporting a null association. The Study of Women, Infant Feeding and Type 2 Diabetes after GDM pregnancy (SWIFT) is a prospective cohort study of postpartum women with recent GDM within the Kaiser Permanente Northern California (KPNC) integrated health care system. The primary goal of SWIFT is to assess whether prolonged, intensive lactation as compared to formula feeding reduces the 2-year incidence of type 2 diabetes mellitus among women with GDM. The study also examines whether lactation intensity and duration have persistent favorable effects on blood glucose, insulin resistance, and adiposity during the 2-year postpartum period. This report describes the design and methods implemented for this study to obtain the clinical, biochemical, anthropometric, and behavioral measurements during the recruitment and follow-up phases.</p> <p>Methods</p> <p>SWIFT is a prospective, observational cohort study enrolling and following over 1, 000 postpartum women diagnosed with GDM during pregnancy within KPNC. The study enrolled women at 6-9 weeks postpartum (baseline) who had been diagnosed by standard GDM criteria, aged 20-45 years, delivered a singleton, term (greater than or equal to 35 weeks gestation) live birth, were not using medications affecting glucose tolerance, and not planning another pregnancy or moving out of the area within the next 2 years. Participants who are free of type 2 diabetes and other serious medical conditions at baseline are screened for type 2 diabetes annually within the first 2 years after delivery. Recruitment began in September 2008 and ends in December 2011. Data are being collected through pregnancy and early postpartum telephone interviews, self-administered monthly mailed questionnaires (3-11 months postpartum), a telephone interview at 6 months, and annual in-person examinations at which a 75 g 2-hour OGTT is conducted, anthropometric measurements are obtained, and self- and interviewer-administered questionnaires are completed.</p> <p>Discussion</p> <p>This is the first, large prospective, community-based study involving a racially and ethnically diverse cohort of women with recent GDM that rigorously assesses lactation intensity and duration and examines their relationship to incident type 2 diabetes while accounting for numerous potential confounders not assessed previously.</p

Evaluation of a Peer Network-Based Sexual Risk Reduction Intervention for Men in Beer Halls in Zimbabwe: Results from a Randomized Controlled Trial

While much emphasis has been placed on involving men in AIDS prevention in sub-Saharan Africa, there remain few rigorously evaluated interventions in this area. A particularly appealing point of intervention is the sexual risk behavior associated with men’s alcohol consumption. This article reports the outcomes of The Sahwira HIV Prevention Program, a male-focused, peer-based intervention promoting the idea that men can assist their friends in avoiding high-risk sexual encounters associated with alcohol drinking. The intervention was evaluated in a randomized, controlled trial (RCT) implemented in 24 beer halls in Harare, Zimbabwe. A cadre of 413 male beer hall patrons (~20% of the patronage) was trained to assist their male peers within their friendship networks. Activities included one-on-one interactions, small group discussions, and educational events centering on the theme of men helping their male friends avoid risk. Venues were randomized into 12 control versus 12 intervention beer halls with little cross-contamination between study arms. The penetration and impact of the intervention were assessed by pre- and post-intervention cross-sectional surveys of the beer hall patronage. The intervention was implemented with a high degree of fidelity to the protocol, with exposure to the intervention activities significantly higher among intervention patrons compared to control. While we found generally declining levels of risk behavior in both study arms from baseline to post-intervention, we found no evidence of an impact of the intervention on our primary outcome measure: episodes of unprotected sex with non-wife partners in the preceding 6 months (median 5.4 episodes for men at intervention beer halls vs. 5.1 among controls, P = 0.98). There was also no evidence that the intervention reduced other risks for HIV. It remains an imperative to find ways to productively engage men in AIDS prevention, especially in those venues where male bonding, alcohol consumption, and sexual risk behavior are intertwined

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Renal systems biology of patients with systemic inflammatory response syndrome

A systems biology approach was used to comprehensively examine the impact of renal disease and hemodialysis (HD) on patient response during critical illness. To achieve this we examined the metabolome, proteome, and transcriptome of 150 patients with critical illness, stratified by renal function. Quantification of plasma metabolites indicated greater change as renal function declined, with the greatest derangements in patients receiving chronic HD. Specifically, 6 uremic retention molecules, 17 other protein catabolites, 7 modified nucleosides, and 7 pentose phosphate sugars increased as renal function declined, consistent with decreased excretion or increased catabolism of amino acids and ribonucleotides. Similarly, the proteome showed increased levels of low-molecular weight proteins and acute phase reactants. The transcriptome revealed a broad-based decrease in mRNA levels among patients on HD. Systems integration revealed an unrecognized association between plasma RNASE1 and several RNA catabolites and modified nucleosides. Further, allantoin, N1-methyl-4-pyridone-3-carboxamide, and n-acetylaspartate were inversely correlated with the majority of significantly down-regulated genes. Thus, renal function broadly affected the plasma metabolome, proteome, and peripheral blood transcriptome during critical illness; changes not effectively mitigated by hemodialysis. These studies allude to several novel mechanisms whereby renal dysfunction contributes to critical illness

An integrated transcriptome and expressed variant analysis of sepsis survival and death

BackgroundSepsis, a leading cause of morbidity and mortality, is not a homogeneous disease but rather a syndrome encompassing many heterogeneous pathophysiologies. Patient factors including genetics predispose to poor outcomes, though current clinical characterizations fail to identify those at greatest risk of progression and mortality.MethodsThe Community Acquired Pneumonia and Sepsis Outcome Diagnostic study enrolled 1,152 subjects with suspected sepsis. We sequenced peripheral blood RNA of 129 representative subjects with systemic inflammatory response syndrome (SIRS) or sepsis (SIRS due to infection), including 78 sepsis survivors and 28 sepsis non-survivors who had previously undergone plasma proteomic and metabolomic profiling. Gene expression differences were identified between sepsis survivors, sepsis non-survivors, and SIRS followed by gene enrichment pathway analysis. Expressed sequence variants were identified followed by testing for association with sepsis outcomes.ResultsThe expression of 338 genes differed between subjects with SIRS and those with sepsis, primarily reflecting immune activation in sepsis. Expression of 1,238 genes differed with sepsis outcome: non-survivors had lower expression of many immune function-related genes. Functional genetic variants associated with sepsis mortality were sought based on a common disease-rare variant hypothesis. VPS9D1, whose expression was increased in sepsis survivors, had a higher burden of missense variants in sepsis survivors. The presence of variants was associated with altered expression of 3,799 genes, primarily reflecting Golgi and endosome biology.ConclusionsThe activation of immune response-related genes seen in sepsis survivors was muted in sepsis non-survivors. The association of sepsis survival with a robust immune response and the presence of missense variants in VPS9D1 warrants replication and further functional studies.Trial registrationClinicalTrials.gov NCT00258869. Registered on 23 November 2005.Electronic supplementary materialThe online version of this article (doi:10.1186/s13073-014-0111-5) contains supplementary material, which is available to authorized users