XMM-Newton Archival Study of the ULX Population in Nearby Galaxies

We present the results of an archival XMM-Newton study of the bright X-ray point sources (L_X > 10^38 erg/s) in 32 nearby galaxies. From our list of approximately 100 point sources, we attempt to determine if there is a low-state counterpart to the Ultraluminous X-ray (ULX) population, searching for a soft-hard state dichotomy similar to that known for Galactic X-ray binaries and testing the specific predictions of the IMBH hypothesis. To this end, we searched for "low-state" objects, which we defined as objects within our sample which had a spectrum well fit by a simple absorbed power law, and "high-state" objects, which we defined as objects better fit by a combined blackbody and a power law. Assuming that ``low-state'' objects accrete at approximately 10% of the Eddington luminosity (Done & Gierlinski 2003) and that "high-state" objects accrete near the Eddington luminosity we further divided our sample of sources into low and high state ULX sources. We classify 16 sources as low-state ULXs and 26 objects as high-state ULXs. As in Galactic black hole systems, the spectral indices, Gamma, of the low-state objects, as well as the luminosities, tend to be lower than those of the high-state objects. The observed range of blackbody temperatures for the high state is 0.1-1 keV, with the most luminous systems tending toward the lowest temperatures. We therefore divide our high-state ULXs into candidate IMBHs (with blackbody temperatures of approximately 0.1 keV) and candidate stellar mass BHs (with blackbody temperatures of approximately 1.0 keV). A subset of the candidate stellar mass BHs have spectra that are well-fit by a Comptonization model, a property similar of Galactic BHs radiating in the "very-high" state near the Eddington limit.Comment: 54 pages, submitted to ApJ (March 2005), accepted (May 2006); changes to organization of pape

Elemental Abundances of Nearby Galaxies through High Signal-to-Noise XMM-Newton Observations of ULXs

(abridged) In this paper, we examined XMM Newton EPIC spectra of 14 ultra-luminous X-ray sources (ULXs)in addition to the XMM RGS spectra of two sources (Holmberg II X-1 and Holmberg IX X-1). We determined oxygen and iron abundances of the host galaxy's interstellar medium (ISM) using K-shell (O) and L-shell (Fe) X-ray photo-ionization edges towards these ULXs. We found that the oxygen abundances closely matched recent solar abundances for all of our sources, implying that ULXs live in similar local environments despite the wide range of galaxy host properties. Also, we compare the X-ray hydrogen column densities (n_H) for 8 ULX sources with column densities obtained from radio H I observations. The X-ray model n_H values are in good agreement with the H I n_H values, implying that the hydrogen absorption towards the ULXs is not local to the source (with the exception of the source M81 XMM1). In order to obtain the column density and abundance values, we fit the X-ray spectra of the ULXs with a combined power law and one of several accretion disk models. We tested the abundances obtained from the XSPEC models bbody, diskbb, grad, and diskpn along with a power law, finding that the abundances were independent of the thermal model used. We comment on the physical implications of these different model fits. We also note that very deep observations allow a breaking of the degeneracy noted by Stobbart et al. (2006) favoring a high mass solution for the absorbed grad + power law model.Comment: 18 pages, accepted to Ap

Enteric helminths promote Salmonella co-infection by altering the intestinal metabolome

Intestinal helminth infections occur pre dominantly in regions where exposure to enteric bacterial pathogens is also common. Helminth infections inhibit host immunity against microbial pathogens, which has largely been attributed to the induction of regulatory or type 2 (Th2) immune responses. Here we demonstrate an additional three-way interaction in which helminth infection alters the metabolic environment of the host intestine to enhance bacterial pathogenicity. We show that an ongoing helminth infection increased colonization by Salmonella independently of T regulatory or Th2 cells. Instead, helminth infection altered the metabolic profile of the intestine, which directly enhanced bacterial expression of Salmonella pathogenicity island 1 (SPI-1) genes and increased intracellular invasion. These data reveal a novel mechanism by which a helminth-modified metabolome promotes susceptibility to bacterial co-infection

MyD88 signaling inhibits protective immunity to the gastrointestinal helminth parasite heligmosomoides polygyrus

Helminth parasites remain one of the most common causes of infections worldwide, yet little is still known about the immune signaling pathways that control their expulsion. C57BL/6 mice are chronically susceptible to infection with the gastrointestinal helminth parasite Heligmosomoides polygyrus. In this article, we report that C57BL/6 mice lacking the adapter protein MyD88, which mediates signaling by TLRs and IL-1 family members, showed enhanced immunity to H. polygyrus infection. Alongside increased parasite expulsion, MyD88-deficient mice showed heightened IL-4 and IL-17A production from mesenteric lymph node CD4+ cells. In addition, MyD88-/- mice developed substantial numbers of intestinal granulomas around the site of infection, which were not seen in MyD88-sufficient C57BL/6 mice, nor when signaling through the adapter protein TRIF (TIR domain-containing adapter-inducing IFN-β adapter protein) was also ablated. Mice deficient solely in TLR2, TLR4, TLR5, or TLR9 did not show enhanced parasite expulsion, suggesting that these TLRs signal redundantly to maintain H. polygyrus susceptibility in wild-type mice. To further investigate signaling pathways that are MyD88 dependent, we infected IL-1R1-/- mice with H. polygyrus. This genotype displayed heightened granuloma numbers compared with wild-type mice, but without increased parasite expulsion. Thus, the IL-1R-MyD88 pathway is implicated in inhibiting granuloma formation; however, protective immunity in MyD88-deficient mice appears to be granuloma independent. Like IL-1R1-/- and MyD88-/- mice, animals lacking signaling through the type 1 IFN receptor (i.e., IFNAR1-/-) also developed intestinal granulomas. Hence, IL-1R1, MyD88, and type 1 IFN receptor signaling may provide pathways to impede granuloma formation in vivo, but additional MyD88-mediated signals are associated with inhibition of protective immunity in susceptible C57BL/6 mice

Assessing Usual Care in Clinical Trials

Researchers designing clinical trials often specify usual care received by participants as the control condition expecting that all participants receive usual care regardless of group assignment. The assumption is that the groups in the study are affected similarly. We describe the assessment of usual care within the 16 studies in MACH 14, a multi-site collaboration on adherence to antiretroviral therapy. Only five of the studies in MACH 14 assessed usual care. Assessment protocols varied as did the timing and frequency of assessments. All usual care assessments addressed patient education focused on HIV, HIV medications, and medication adherence. Our findings support earlier work that calls for systematic assessments of usual care within the study design, inclusion of descriptions of usual care in reports of the study, and the influence of usual care on the experimental condition in clinical trials

Assessing Usual Care in Clinical Trials

Researchers designing clinical trials often specify usual care received by participants as the control condition expecting that all participants receive usual care regardless of group assignment. The assumption is that the groups in the study are affected similarly. We describe the assessment of usual care within the 16 studies in MACH 14, a multi-site collaboration on adherence to antiretroviral therapy. Only five of the studies in MACH 14 assessed usual care. Assessment protocols varied as did the timing and frequency of assessments. All usual care assessments addressed patient education focused on HIV, HIV medications, and medication adherence. Our findings support earlier work that calls for systematic assessments of usual care within the study design, inclusion of descriptions of usual care in reports of the study, and the influence of usual care on the experimental condition in clinical trials

Playing the game: service users' management of risk status in a UK medium secure forensic mental health service

In this article we examine how forensic mental health service users actively attempt to manage their risk status through playing the game of containing frustration and demonstrating compliance. The article draws on an observational study (2006 to 2009) which explored the practices of risk assessment and management within one inner city forensic mental health medium secure service in the UK. We used a grounded theory approach to explore service users and providers experiences of risk assessment and management. We interviewed forensic mental health service users and providers. We also collected data using participant and non-participant observation. Since access to forensic mental health services is tightly controlled, there are participant observation studies undertaken in these settings. We found that service users attempted to understand the system of assessment and sought to affect and reduce their risk status by engaging in overt, compliant behaviours. We argue that in doing so service users are active agents in the process of risk management. However, we indicate that there are adverse effects of this approach to risk management as the risk assessment process is subverted by the restriction of the flow of information, and service users are left with frustrations that they must contain and manage

Drug Adverse Event Detection in Health Plan Data Using the Gamma Poisson Shrinker and Comparison to the Tree-based Scan Statistic

Background: Drug adverse event (AE) signal detection using the Gamma Poisson Shrinker (GPS) is commonly applied in spontaneous reporting. AE signal detection using large observational health plan databases can expand medication safety surveillance. Methods: Using data from nine health plans, we conducted a pilot study to evaluate the implementation and findings of the GPS approach for two antifungal drugs, terbinafine and itraconazole, and two diabetes drugs, pioglitazone and rosiglitazone. We evaluated 1676 diagnosis codes grouped into 183 different clinical concepts and four levels of granularity. Several signaling thresholds were assessed. GPS results were compared to findings from a companion study using the identical analytic dataset but an alternative statistical method—the tree-based scan statistic (TreeScan). Results: We identified 71 statistical signals across two signaling thresholds and two methods, including closely-related signals of overlapping diagnosis definitions. Initial review found that most signals represented known adverse drug reactions or confounding. About 31% of signals met the highest signaling threshold. Conclusions: The GPS method was successfully applied to observational health plan data in a distributed data environment as a drug safety data mining method. There was substantial concordance between the GPS and TreeScan approaches. Key method implementation decisions relate to defining exposures and outcomes and informed choice of signaling thresholds

Autism Spectrum Disorder Symptoms Among Children Enrolled in the Study to Explore Early Development (SEED)

This study examined the phenotypic profiles of children aged 30–68 months in the Study to Explore Early Development (SEED). Children classified as autism spectrum disorder (ASD), developmental delay (DD) with ASD symptoms, DD without ASD symptoms, and population comparison (POP) differed significantly from each other on cognitive, adaptive, behavioral, and social functioning and the presence of parent-reported conditions. Children with ASD and DD with ASD symptoms had mild to severe ASD risk on several measures compared to children with other DD and POP who had little ASD risk across measures. We conclude that children in SEED have varying degrees of ASD impairment and associated deficits. SEED thus provides a valuable sample to explore ASD phenotypes and inform risk factor analyses