The Origin of the Hot Gas in the Galactic Halo: Confronting Models with XMM-Newton Observations

We compare the predictions of three physical models for the origin of the hot halo gas with the observed halo X-ray emission, derived from 26 high-latitude XMM-Newton observations of the soft X-ray background between l=120\degr and l=240\degr. These observations were chosen from a much larger set of observations as they are expected to be the least contaminated by solar wind charge exchange emission. We characterize the halo emission in the XMM-Newton band with a single-temperature plasma model. We find that the observed halo temperature is fairly constant across the sky (~1.8e6-2.3e6 K), whereas the halo emission measure varies by an order of magnitude (~0.0005-0.006 cm^-6 pc). When we compare our observations with the model predictions, we find that most of the hot gas observed with XMM-Newton does not reside in isolated extraplanar supernova remnants -- this model predicts emission an order of magnitude too faint. A model of a supernova-driven interstellar medium, including the flow of hot gas from the disk into the halo in a galactic fountain, gives good agreement with the observed 0.4-2.0 keV surface brightness. This model overpredicts the halo X-ray temperature by a factor of ~2, but there are a several possible explanations for this discrepancy. We therefore conclude that a major (possibly dominant) contributor to the halo X-ray emission observed with XMM-Newton is a fountain of hot gas driven into the halo by disk supernovae. However, we cannot rule out the possibility that the extended hot halo of accreted material predicted by disk galaxy formation models also contributes to the emission.Comment: 20 pages, 14 figures. New version accepted for publication in ApJ. Changes include new section discussing systematic errors (Section 3.2), improved method for characterizing our model spectra (4.2.2), changes to discussion of other observations (5.1). Note that we can no longer rule out possibility that extended hot halo of accreted material contributes to observed halo emission (see 5.2.1

The origin of the hot gas in the galactic halo: Testing galactic fountain models' X-ray emission

We test the X-ray emission predictions of galactic fountain models against XMM-Newton measurements of the emission from the Milky Way's hot halo. These measurements are from 110 sight lines, spanning the full range of Galactic longitudes. We find that a magnetohydrodynamical simulation of a supernova-driven interstellar medium, which features a flow of hot gas from the disk to the halo, reproduces the temperature but significantly underpredicts the 0.5-2.0 keV surface brightness of the halo (by two orders of magnitude, if we compare the median predicted and observed values). This is true for versions of the model with and without an interstellar magnetic field. We consider different reasons for the discrepancy between the model predictions and the observations. We find that taking into account overionization in cooled halo plasma, which could in principle boost the predicted X-ray emission, is unlikely in practice to bring the predictions in line with the observations. We also find that including thermal conduction, which would tend to increase the surface brightnesses of interfaces between hot and cold gas, would not overcome the surface brightness shortfall. However, charge exchange emission from such interfaces, not included in the current model, may be significant. The faintness of the model may also be due to the lack of cosmic ray driving, meaning that the model may underestimate the amount of material transported from the disk to the halo. In addition, an extended hot halo of accreted material may be important, by supplying hot electrons that could boost the emission of the material driven out from the disk. Additional model predictions are needed to test the relative importance of these processes in explaining the observed halo emission.open2

Effect of physical activity, social support, and skills training on late-life emotional health: a systematic literature review and implications for public health research

Purpose: Given that emotional health is a critical component of healthy aging, we undertook a systematic literature review to assess whether current interventions can positively affect older adults’ emotional health. Methods: A national panel of health services and mental health researchers guided the review. Eligibility criteria included community-dwelling older adult (aged ≥ 50 years) samples, reproducible interventions, and emotional health outcomes, which included multiple domains and both positive (well-being) and illness-related (anxiety) dimensions. This review focused on three types of interventions – physical activity, social support, and skills training – given their public health significance and large number of studies identified. Panel members evaluated the strength of evidence (quality and effectiveness). Results: In all, 292 articles met inclusion criteria. These included 83 exercise/physical activity, 25 social support, and 40 skills training interventions. For evidence rating, these 148 interventions were categorized into 64 pairings by intervention type and emotional health outcome, e.g., strength training targeting loneliness or social support to address mood. 83% of these pairings were rated at least fair quality. Expert panelists found sufficient evidence of effectiveness only for skills training interventions with health outcomes of decreasing anxiety and improving quality of life and self-efficacy. Due to limitations in reviewed studies, many intervention–outcome pairings yielded insufficient evidence. Conclusion: Skills training interventions improved several aspects of emotional health in community-dwelling older adults, while the effects for other outcomes and interventions lacked clear evidence. We discuss the implications and challenges in moving forward in this important area

Capacity Building for a New Multicenter Network Within the ECHO IDeA States Pediatric Clinical Trials Network

Introduction: Research capacity building is a critical component of professional development for pediatrician scientists, yet this process has been elusive in the literature. The ECHO IDeA States Pediatric Clinical Trials Network (ISPCTN) seeks to implement pediatric trials across medically underserved and rural populations. A key component of achieving this objective is building pediatric research capacity, including enhancement of infrastructure and faculty development. This article presents findings from a site assessment inventory completed during the initial year of the ISPCTN. Methods: An assessment inventory was developed for surveying ISPCTN sites. The inventory captured site-level activities designed to increase clinical trial research capacity for pediatrician scientists and team members. The inventory findings were utilized by the ISPCTN Data Coordinating and Operations Center to construct training modules covering 3 broad domains: Faculty/coordinator development; Infrastructure; Trials/Research concept development. Results: Key lessons learned reveal substantial participation in the training modules, the importance of an inventory to guide the development of trainings, and recognizing local barriers to clinical trials research. Conclusions: Research networks that seek to implement successfully completed trials need to build capacity across and within the sites engaged. Our findings indicate that building research capacity is a multi-faceted endeavor, but likely necessary for sustainability of a unique network addressing high impact pediatric health problems. The ISPCTN emphasis on building and enhancing site capacity, including pediatrician scientists and team members, is critical to successful trial implementation/completion and the production of findings that enhance the lives of children and families

The role of ixazomib as an augmented conditioning therapy in salvage autologous stem cell transplant (ASCT) and as a post-ASCT consolidation and maintenance strategy in patients with relapsed multiple myeloma (ACCoRd [UK-MRA Myeloma XII] trial): study protocol for a Phase III randomised controlled trial

Background: Multiple myeloma (MM) is a plasma cell tumour with an approximate annual incidence of 4500 in the UK. Therapeutic options for patients with MM have changed in the last decade with the arrival of proteasome inhibitors and immunomodulatory drugs. Despite these options, almost all patients will relapse post first-line autologous stem cell transplantation (ASCT). First relapse management (second-line treatment) has evolved in recent years with an expanding portfolio of novel agents, driving response rates influencing the durability of response. A second ASCT, as part of relapsed disease management (salvage ASCT), has been shown to prolong the progression-free survival and overall survival following a proteasome inhibitor-containing re-induction regimen, in the Cancer Research UK-funded National Cancer Research Institute Myeloma X (Intensive) study. It is now recommended that salvage ASCT be considered for suitable patients by the International Myeloma Working Group and the National Institute for Health and Care Excellence NG35 guidance. Methods/design: ACCoRd (Myeloma XII) is a UK-nationwide, individually randomised, multi-centre, multiple randomisation, open-label phase III trial with an initial single intervention registration phase aimed at relapsing MM patients who have received ASCT in first-line treatment. We will register 406 participants into the trial to allow 284 and 248 participants to be randomised at the first and second randomisations, respectively. All participants will receive re-induction therapy until maximal response (four to six cycles of ixazomib, thalidomide and dexamethasone). Participants who achieve at least stable disease will be randomised (1:1) to receive either ASCTCon, using high-dose melphalan, or ASCTAug, using high-dose melphalan with ixazomib. All participants achieving or maintaining a minimal response or better, following salvage ASCT, will undergo a second randomisation (1:1) to consolidation and maintenance or observation. Participants randomised to consolidation and maintenance will receive consolidation with two cycles of ixazomib, thalidomide and dexamethasone, and maintenance with ixazomib until disease progression. Discussion: The question of how best to maximise the durability of response to salvage ASCT warrants clinical investigation. Given the expanding scope of oral therapeutic agents, patient engagement with long-term maintenance strategies is a real opportunity. This study will provide evidence to better define post-relapse treatment in MM

US Cosmic Visions: New Ideas in Dark Matter 2017: Community Report

This white paper summarizes the workshop "U.S. Cosmic Visions: New Ideas in Dark Matter" held at University of Maryland on March 23-25, 2017.Comment: 102 pages + reference

A study of the diagnostic accuracy of the PHQ-9 in primary care elderly

<p>Abstract</p> <p>Background</p> <p>The diagnostic accuracy of the Patient Health Questionnaire-9 (PHQ-9) for assessment of depression in elderly persons in primary care settings in the United States has not been previously addressed. Thus, the purpose of this study was to evaluate the test performance of the PHQ-9 for detecting major and minor depression in elderly patients in primary care.</p> <p>Methods</p> <p>A prospective study of diagnostic accuracy was conducted in two primary care, university-based clinics in the Pacific Northwest of the United States. Seventy-one patients aged 65 years or older participated; all completed the PHQ-9 and the 15-item Geriatric Depression Scale (GDS) and underwent the Structured Clinical Interview for Depression (SCID). Sensitivity, specificity, area under the receiver operating characteristic (ROC) curve, and likelihood ratios (LRs) were calculated for the PHQ-9, the PHQ-2, and the 15-item GDS for major depression alone and the combination of major plus minor depression.</p> <p>Results</p> <p>Two thirds of participants were female, with a mean age of 78 and two chronic health conditions. Twelve percent met SCID criteria for major depression and 13% minor depression. The PHQ-9 had an area under the curve (AUC) of 0.87 (95% confidence interval [CI], 0.74-1.00) for major depression, while the PHQ-2 and the 15-item GDS each had an AUC of 0.81 (95% CI for PHQ-2, 0.64-0.98, and for 15-item GDS, 0.70-0.91; <it>P </it>= 0.551). For major and minor depression combined, the AUC for the PHQ-9 was 0.85 (95% CI, 0.73-0.96), for the PHQ-2, 0.80 (95% CI, 0.68-0.93), and for the 15-item GDS, 0.71 (95% CI, 0.55-0.87; <it>P </it>= 0.187).</p> <p>Conclusions</p> <p>Based on AUC values, the PHQ-9 performs comparably to the PHQ-2 and the 15-item GDS in identifying depression among primary care elderly.</p

Interactions between Surround Suppression and Interocular Suppression in Human Vision

Several types of suppression phenomena have been observed in the visual system. For example, the ability to detect a target stimulus is often impaired when the target is embedded in a high-contrast surround. This contextual modulation, known as surround suppression, was formerly thought to occur only in the periphery. Another type of suppression phenomena is interocular suppression, in which the sensitivity to a monocular target is reduced by a superimposed mask in the opposite eye. Here, we explored how the two types of suppression operating across different spatial regions interact with one another when they simultaneously exert suppressive influences on a common target presented at the fovea. In our experiments, a circular target grating presented to the fovea of one eye was suppressed interocularly by a noise pattern of the same size in the other eye. The foveal stimuli were either shown alone or surrounded by a monocular annular grating. The orientation and eye-of-origin of the surround grating were varied. We found that the detection of the foveal target subjected to interocular suppression was severely impaired by the addition of the surround grating, indicating strong surround suppression in the fovea. In contrast, when the interocular suppression was released by superimposing a binocular fusion ring onto both the target and the dichoptic mask, the surround suppression effect was found to be dramatically decreased. In addition, the surround suppression was found to depend on the contrast of the dichoptic noise with the greatest surround suppression effect being obtained only when the noise contrast was at an intermediate level. These findings indicate that surround suppression and interocular suppression are not independent of each other, but there are strong interactions between them. Moreover, our results suggest that strong surround suppression may also occur at the fovea and not just the periphery

Locus-specific epigenetic remodeling controls addiction- and depression-related behaviors

Chronic exposure to drugs of abuse or stress regulates transcription factors, chromatin-modifying enzymes and histone post-translational modifications in discrete brain regions. Given the promiscuity of the enzymes involved, it has not yet been possible to obtain direct causal evidence to implicate the regulation of transcription and consequent behavioral plasticity by chromatin remodeling that occurs at a single gene. We investigated the mechanism linking chromatin dynamics to neurobiological phenomena by applying engineered transcription factors to selectively modify chromatin at a specific mouse gene in vivo. We found that histone methylation or acetylation at the Fosb locus in nucleus accumbens, a brain reward region, was sufficient to control drug- and stress-evoked transcriptional and behavioral responses via interactions with the endogenous transcriptional machinery. This approach allowed us to relate the epigenetic landscape at a given gene directly to regulation of its expression and to its subsequent effects on reward behavior