Starburst-Driven Galactic Winds: Filament Formation and Emission Processes

We have performed a series of three-dimensional simulations of the interaction of a supersonic wind with a non-spherical radiative cloud. These simulations are motivated by our recent three-dimensional model of a starburst-driven galactic wind interacting with an inhomogeneous disk, which show that an optically emitting filament can be formed by the break-up and acceleration of a cloud into a supersonic wind. In this study we consider the evolution of a cloud with two different geometries (fractal and spherical) and investigate the importance of radiative cooling on the cloud's survival. We have also undertaken a comprehensive resolution study in order to ascertain the effect of the assumed numerical resolution on the results. We find that the ability of the cloud to radiate heat is crucial for its survival. While an adiabatic cloud is destroyed over a short period of time, a radiative cloud is broken up via the Kelvin-Helmholtz instability into numerous small, dense cloudlets, which are drawn into the flow to form a filamentary structure. The degree of fragmentation is highly dependent on the resolution of the simulation, with the number of cloudlets formed increasing as the Kelvin-Helmholtz instability is better resolved. Nevertheless, there is a clear qualitative trend, with the filamentary structure still persistent at high resolution. We confirm the mechanism behind the formation of the H-alpha emitting filaments found in our global simulations of a starburst-driven wind. Based on our resolution study, we conclude that bow shocks around accelerated gas clouds, and their interaction, are the main source of the soft X-ray emission observed in these galactic-scale winds. [ABRIDGED]Comment: Accepted to ApJ, 39 pages, 21 figures, movie file can obtained at http://www.mso.anu.edu.au/~jcooper/movie/halpha.mo

The multiple sclerosis risk sharing scheme monitoring study - early results and lessons for the future

Background: Risk sharing schemes represent an innovative and important approach to the problems of rationing and achieving cost-effectiveness in high cost or controversial health interventions. This study aimed to assess the feasibility of risk sharing schemes, looking at long term clinical outcomes, to determine the price at which high cost treatments would be acceptable to the NHS. Methods: This case study of the first NHS risk sharing scheme, a long term prospective cohort study of beta interferon and glatiramer acetate in multiple sclerosis ( MS) patients in 71 specialist MS centres in UK NHS hospitals, recruited adults with relapsing forms of MS, meeting Association of British Neurologists (ABN) criteria for disease modifying therapy. Outcome measures were: success of recruitment and follow up over the first three years, analysis of baseline and initial follow up data and the prospect of estimating the long term cost-effectiveness of these treatments. Results: Centres consented 5560 patients. Of the 4240 patients who had been in the study for a least one year, annual review data were available for 3730 (88.0%). Of the patients who had been in the study for at least two years and three years, subsequent annual review data were available for 2055 (78.5%) and 265 (71.8%) patients respectively. Baseline characteristics and a small but statistically significant progression of disease were similar to those reported in previous pivotal studies. Conclusion: Successful recruitment, follow up and early data analysis suggest that risk sharing schemes should be able to deliver their objectives. However, important issues of analysis, and political and commercial conflicts of interest still need to be addressed

FcγRIIIa Expression on Monocytes in Rheumatoid Arthritis: Role in Immune-Complex Stimulated TNF Production and Non-Response to Methotrexate Therapy

OBJECTIVE:The expression of FcγRIIIa/CD16 may render monocytes targets for activation by IgG-containing immune complexes (IC). We investigated whether FcγRIIIa/CD16 was upregulated in rheumatoid arthritis (RA), associated with TNF production in response to IC-stimulation, and if this predicted response to methotrexate therapy. METHODS:FcγRIIIa/CD16 expression on CD14(low) and CD14++ monocytes was measured by flow cytometry in healthy controls and RA patients (early and long-standing disease). Intracellular TNF-staining was carried out after in vitro LPS or heat-aggregated immunoglobulin (HAG) activation. FcγRIIIa/CD16 expression pre- and post-steroid/methotrexate treatment was examined. RESULTS:Increased FcγRIIIa/CD16 expression on CD14++ monocytes in long-standing RA patients compared to controls was demonstrated (p = 0.002) with intermediate levels in early-RA patients. HAG-induced TNF-production in RA patients was correlated with the percentage of CD14++ monocytes expressing FcγRIIIa/CD16 (p<0.001). The percentage of CD14++ monocytes expressing FcγRIIIa/CD16 at baseline in early DMARD-naïve RA patients was negatively correlated with DAS28-ESR improvement 14-weeks post-methotrexate therapy (p = 0.003) and was significantly increased in EULAR non-responders compared to moderate (p = 0.01) or good responders (p = 0.003). FcγRIIIa/CD16 expression was not correlated with age, presence of systemic inflammation or autoantibody titers. CONCLUSION:Increased FcγRIIIa/CD16 expression on CD14++ monocytes in RA may result in a cell that has increased responsiveness to IC-stimulation. This monocyte subset may contribute to non-response to methotrexate therapy

Three-Dimensional Simulations of a Starburst-Driven Galactic Wind

We have performed a series of three-dimensional simulations of a starburst-driven wind in an inhomogeneous interstellar medium. The introduction of an inhomogeneous disk leads to differences in the formation of a wind, most noticeably the absence of the ``blow-out'' effect seen in homogeneous models. A wind forms from a series of small bubbles that propagate into the tenuous gas between dense clouds in the disk. These bubbles merge and follow the path of least resistance out of the disk, before flowing freely into the halo. Filaments are formed from disk gas that is broken up and accelerated into the outflow. These filaments are distributed throughout a biconical structure within a more spherically distributed hot wind. The distribution of the inhomogeneous interstellar medium in the disk is important in determining the morphology of this wind, as well as the distribution of the filaments. While higher resolution simulations are required in order to ascertain the importance of mixing processes, we find that soft X-ray emission arises from gas that has been mass-loaded from clouds in the disk, as well as from bow shocks upstream of clouds, driven into the flow by the ram pressure of the wind, and the interaction between these shocks.Comment: 37 pages, 16 figures, mpg movie can be obtained at http://www.mso.anu.edu.au/~jcooper/movie/video16.mpg, accepted for publication in Ap

Promising insights into the health related quality of life for children with severe obesity

Background Childhood obesity is a growing health concern known to adversely affect quality of life in children and adolescents. The Patient Reported Outcomes Measurement Information System (PROMIS) pediatric measures were developed to capture child self-reports across a variety of health conditions experienced by children and adolescents. The purpose of this study is to begin the process of validation of the PROMIS pediatric measures in children and adolescents affected by obesity. Methods The pediatric PROMIS instruments were administered to 138 children and adolescents in a cross-sectional study of patient reported outcomes in children aged 8–17 years with age-adjusted body mass index (BMI) greater than the 85th percentile in a design to establish known-group validity. The children completed the depressive symptoms, anxiety, anger, peer relationships, pain interference, fatigue, upper extremity, and mobility PROMIS domains utilizing a computer interface. PROMIS domains and individual items were administered in random order and included a total of 95 items. Patient responses were compared between patients with BMI 85 to < 99th percentile versus ≥ 99th percentile. Results 136 participants were recruited and had all necessary clinical data for analysis. Of the 136 participants, 5% ended the survey early resulting in missing domain scores at the end of survey administration. In multivariate analysis, patients with BMI ≥ 99th percentile had worse scores for depressive symptoms, anger, fatigue, and mobility (p < 0.05). Parent-reported exercise was associated with better scores for depressive symptoms, anxiety, and fatigue (p < 0.05). Conclusions Children and adolescents ranging from overweight to severely obese can complete multiple PROMIS pediatric measures using a computer interface in the outpatient setting. In the 5% with missing domain scores, the missing scores were consistently found in the domains administered last, suggesting the length of the assessment is important. The differences in domain scores found in this study are consistent with previous reports investigating the quality of life in children and adolescents with obesity. We show that the PROMIS instrument represents a feasible and potentially valuable instrument for the future study of the effect of pediatric obesity on quality of life

Morphological and Physiological Characteristics of Ruptured Plaques in Native Arteries and Neoatherosclerotic Segments: An OCT-Based and Computational Fluid Dynamics Study.

Background Intravascular imaging has been used to assess the morphology of lesions causing an acute coronary syndrome (ACS) in native vessels (NV) and identify differences between plaques that ruptured (PR) and caused an event and those that ruptured without clinical manifestations. However, there is no data about the morphological and physiological characteristics of neoatherosclerotic plaques that ruptured (PR-NA) which constitute a common cause of stent failure. Methods We retrospectively analyzed data from patients admitted with an acute myocardial infarction that had optical coherence tomography (OCT) imaging of the culprit vessel before balloon pre-dilation. OCT pullbacks showing PR were segmented at every 0.4 mm. The extent of the formed cavity, lipid and calcific tissue, thrombus, and macrophages were measured, and the fibrous cap thickness (FCT) and the incidence of micro-channels and cholesterol crystals were reported. These data were used to reconstruct a representative model of the native and neoatherosclerotic lesion geometry that was processed with computational fluid dynamics (CFD) techniques to estimate the distribution of the endothelial shear stress and plaque structural stress. Result Eighty patients were included in the present analysis: 56 had PR in NV (PR-NV group) and 24 in NA segments (PR-NA group). The PR-NV group had a larger minimum lumen area (2.93 ± 2.03 vs. 2.00 ± 1.26 mm2, p = 0.015) but similar lesion length and area stenosis compared to PR-NA group. The mean FCT (186 ± 65 vs. 232 ± 80 μm, p = 0.009) and the lipid index was smaller (16.7 ± 13.8 vs. 25.9 ± 14.1, p = 0.008) while the of calcific index (8.3 ± 9.5 vs. 2.2 ± 1.6%, p = 0.002) and the incidence of micro-channels (41.4 vs. 12.5%, p = 0.013) was higher in the PR-NV group. Conversely, there was no difference in the incidence of cholesterol crystals, thrombus burden or the location of the rupture site between groups. CFD analysis revealed higher maximum endothelial shear stress (19.1 vs. 11.0 Pa) and lower maximum plaque structural stress (38.8 vs. 95.1 kPa) in the PR-NA compared to the PR-NV model. Conclusion We reported significant morphological and physiological differences between culprit ruptured plaques in native and stented segments. Further research is needed to better understand the causes of these differences and the mechanisms regulating neoatherosclerotic lesion destabilization

Health service needs and perspectives of remote forest communities in Papua New Guinea: study protocol for combined clinical and rapid anthropological assessments with parallel treatment of urgent cases

Introduction Our project follows community requests for health service incorporation into conservation collaborations in the rainforests of Papua New Guinea (PNG). This protocol is for health needs assessments, our first step in coplanning medical provision in communities with no existing health data. Methods and analysis The study includes clinical assessments and rapid anthropological assessment procedures (RAP) exploring the health needs and perspectives of partner communities in two areas, conducted over 6 weeks fieldwork. First, in Wanang village (population c.200), which is set in lowland rainforest. Second, in six communities (population c.3000) along an altitudinal transect up the highest mountain in PNG, Mount Wilhelm. Individual primary care assessments incorporate physical examinations and questioning (providing qualitative and quantitative data) while RAP includes focus groups, interviews and field observations (providing qualitative data). Given absence of in-community primary care, treatments are offered alongside research activity but will not form part of the study. Data are collected by a research fellow, primary care clinician and two PNG research technicians. After quantitative and qualitative analyses, we will report: ethnoclassifications of disease, causes, symptoms and perceived appropriate treatment; community rankings of disease importance and service needs; attitudes regarding health service provision; disease burdens and associations with altitudinal-related variables and cultural practices. To aid wider use study tools are in online supplemental file, and paper and ODK versions are available free from the corresponding author. Ethics and dissemination Challenges include supporting informed consent in communities with low literacy and diverse cultures, moral duties to provide treatment alongside research in medically underserved areas while minimising risks of therapeutic misconception and inappropriate inducement, and PNG research capacity building. Brighton and Sussex Medical School (UK), PNG Institute of Medical Research and PNG Medical Research Advisory Committee have approved the study. Dissemination will be via journals, village meetings and plain language summaries

Research priorities in the field of posttraumatic pain and disability: Results of a transdisciplinary consensus-generating workshop

© Copyright 2016 David M.Walton et al. Background. Chronic or persistent pain and disability following noncatastrophic \u27musculoskeletal\u27 (MSK) trauma is a pervasive public health problem. Recent intervention trials have provided little evidence of benefit from several specific treatments for preventing chronic problems. Such findings may appear to argue against formal targeted intervention for MSK traumas. However, these negative findings may reflect a lack of understanding of the causal mechanisms underlying the transition from acute to chronic pain, rendering informed and objective treatment decisions difficult. The Canadian Institutes of Health Research (CIHR) Institute ofMusculoskeletalHealth and Arthritis (IMHA) has recently identified better understanding of causalmechanisms as one of three priority foci of their most recent strategic plan. Objectives. A 2-day invitation-only active participation workshop was held inMarch 2015 that included 30 academics, clinicians, and consumers with the purpose of identifying consensus research priorities in the field of trauma-relatedMSK pain and disability, prediction, and prevention. Methods. Conversations were recorded, explored thematically, and member-checked for accuracy. Results. From the discussions, 13 themes were generated that ranged from a focus on identifying causal mechanisms and models to challenges with funding and patient engagement. Discussion. Novel priorities included the inclusion of consumer groups in research from the early conceptualization and design stages and interdisciplinary longitudinal studies that include evaluation of integrated phenotypes and mechanisms

Assessment of Virally Vectored Autoimmunity as a Biocontrol Strategy for Cane Toads

BACKGROUND: The cane toad, Bufo (Chaunus) marinus, is one of the most notorious vertebrate pests introduced into Australia over the last 200 years and, so far, efforts to identify a naturally occurring B. marinus-specific pathogen for use as a biological control agent have been unsuccessful. We explored an alternative approach that entailed genetically modifying a pathogen with broad host specificity so that it no longer caused disease, but carried a gene to disrupt the cane toad life cycle in a species specific manner. METHODOLOGY/PRINCIPAL FINDINGS: The adult beta globin gene was selected as the model gene for proof of concept of autoimmunity as a biocontrol method for cane toads. A previous report showed injection of bullfrog tadpoles with adult beta globin resulted in an alteration in the form of beta globin expressed in metamorphs as well as reduced survival. In B. marinus we established for the first time that the switch from tadpole to adult globin exists. The effect of injecting B. marinus tadpoles with purified recombinant adult globin protein was then assessed using behavioural (swim speed in tadpoles and jump length in metamorphs), developmental (time to metamorphosis, weight and length at various developmental stages, protein profile of adult globin) and genetic (adult globin mRNA levels) measures. However, we were unable to detect any differences between treated and control animals. Further, globin delivery using Bohle iridovirus, an Australian ranavirus isolate belonging to the Iridovirus family, did not reduce the survival of metamorphs or alter the form of beta globin expressed in metamorphs. CONCLUSIONS/SIGNIFICANCE: While we were able to show for the first time that the switch from tadpole to adult globin does occur in B. marinus, we were not able to induce autoimmunity and disrupt metamorphosis. The short development time of B. marinus tadpoles may preclude this approach