93 research outputs found

    Dark Matter In Disk Galaxies II: Density Profiles as Constraints on Feedback Scenarios

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    The disparity between the density profiles of galactic dark matter haloes predicted by dark matter only cosmological simulations and those inferred from rotation curve decomposition, the so-called cusp-core problem, suggests that baryonic physics has an impact on dark matter density in the central regions of galaxies. Feedback from black holes, supernovae and massive stars may each play a role by removing matter from the centre of the galaxy on shorter timescales than the dynamical time of the dark matter halo. Our goal in this paper is to determine constraints on such feedback scenarios based on the observed properties of a set of nearby galaxies. Using a Markov Chain Monte Carlo (MCMC) analysis of galactic rotation curves, via a method developed in a previous paper, we constrain density profiles and an estimated minimum radius for baryon influence, r1r_1, which we couple with a feedback model to give an estimate of the fraction of matter within that radius that must be expelled to produce the presently observed halo profile. We show that in the case of the gas rich dwarf irregular galaxy DDO 154, an outflow from a central source (e.g. a black hole or star forming region) could produce sufficient feedback on the halo without removing the disk gas. We examine the rotation curves of 8 galaxies taken from the THINGS data set and determine constraints on the radial density profiles of their dark matter haloes. For some of the galaxies, both cored haloes and cosmological ρ∝r−1\rho \propto r^{-1} cusps are excluded. These intermediate central slopes require baryonic feedback to be finely tuned. We also find for galaxies which exhibit extended cores in their haloes (e.g. NGC 925), the use of a split power-law halo profile yields models without the unphysical, sharp features seen in models based on the Einasto profile.Comment: 17 pages, 19 figures Submitted to MNRA

    Dark matter in disk galaxies I: a Markov Chain Monte Carlo method and application to DDO 154

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    We present a new method to constrain the dark matter halo density profiles of disk galaxies. Our algorithm employs a Markov Chain Monte Carlo (MCMC) approach to explore the parameter space of a general family of dark matter profiles. We improve upon previous analyses by considering a wider range of halo profiles and by explicitly identifying cases in which the data are insufficient to break the degeneracies between the model parameters. We demonstrate the robustness of our algorithm using artificial data sets and show that reliable estimates of the halo density profile can be obtained from data of comparable quality to those currently available for low surface brightness (LSB) galaxies. We present our results in terms of physical quantities which are constrained by the data, and find that the logarithmic slope of the halo density profile at the radius of the innermost data point of a measured rotation curve can be strongly constrained in LSB ([Vstar/Vobs]max ~ 0.16) galaxies. High surface brightness galaxies ([Vstar/Vobs]max ~ 0.79) require additional information on the mass-to-light ratio of the stellar population - our approach naturally identifies those galaxies for which this is necessary. We apply our method to observed data for the dwarf irregular galaxy DDO 154 and recover a logarithmic halo slope of -0.39 +- 0.11 at a radius of 0.14 kpc. Our analysis validates earlier estimates which were based on the fitting of a limited set of individual halo models, but constitutes a more robust constraint than was possible using other techniques since it marginalises over a wide range of halo profiles.Comment: Accepted by MNRAS 20/05/1

    High broad-band photoresponsivity of mechanically formed InSe-graphene van der Waals heterostructures

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    We exploit the broad-band transparency of graphene and the favorable band line up of graphene with van der Waals InSe crystals to create new functional heterostructures and high-performance photodetectors. The InSe-graphene heterostructure exhibits a high photoresponsivity, which exceeds that for other two-dimensional van der Waals crystals, and a spectral response that extends from the near-infrared to the visible spectrum. The highest photoresponsivity is achieved in device architectures where the InSe and graphene layers are vertically stacked, thus enabling effective extraction of photogenerated carriers from the InSe to the graphene electrodes

    Clinical spectrum and features of activated phosphoinositide 3-kinase δ syndrome: A large patient cohort study.

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    BACKGROUND: Activated phosphoinositide 3-kinase δ syndrome (APDS) is a recently described combined immunodeficiency resulting from gain-of-function mutations in PIK3CD, the gene encoding the catalytic subunit of phosphoinositide 3-kinase δ (PI3Kδ). OBJECTIVE: We sought to review the clinical, immunologic, histopathologic, and radiologic features of APDS in a large genetically defined international cohort. METHODS: We applied a clinical questionnaire and performed review of medical notes, radiology, histopathology, and laboratory investigations of 53 patients with APDS. RESULTS: Recurrent sinopulmonary infections (98%) and nonneoplastic lymphoproliferation (75%) were common, often from childhood. Other significant complications included herpesvirus infections (49%), autoinflammatory disease (34%), and lymphoma (13%). Unexpectedly, neurodevelopmental delay occurred in 19% of the cohort, suggesting a role for PI3Kδ in the central nervous system; consistent with this, PI3Kδ is broadly expressed in the developing murine central nervous system. Thoracic imaging revealed high rates of mosaic attenuation (90%) and bronchiectasis (60%). Increased IgM levels (78%), IgG deficiency (43%), and CD4 lymphopenia (84%) were significant immunologic features. No immunologic marker reliably predicted clinical severity, which ranged from asymptomatic to death in early childhood. The majority of patients received immunoglobulin replacement and antibiotic prophylaxis, and 5 patients underwent hematopoietic stem cell transplantation. Five patients died from complications of APDS. CONCLUSION: APDS is a combined immunodeficiency with multiple clinical manifestations, many with incomplete penetrance and others with variable expressivity. The severity of complications in some patients supports consideration of hematopoietic stem cell transplantation for severe childhood disease. Clinical trials of selective PI3Kδ inhibitors offer new prospects for APDS treatment.T.C. is supported by National Children’s Research Centre, Our Lady’s Children’s Hospital Crumlin, Dublin, Ireland. A.C. has a Wellcome Trust Postdoctoral Training Fellowship for Clinicians (103413/Z/13/Z). K.O. is supported by funding from BBSRC, MRC, Wellcome Trust and GSK. R.D. and D.S.K are funded by National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre, Cambridge, UK. C.S. and S.E. are supported by the German Federal Ministry of Education and Research (BMBF 01 EO 0803 grant to the Center of Chronic immunodeficiency and BMBF 01GM1111B grant to the PID-NET initiative). S.N.F is supported in part by the Southampton UK National Institute for Health Research (NIHR) Wellcome Trust Clinical Research Facility and NIHR Respiratory Biomedical Research Unit. M.A.A.I. is funded by NHS Innovation London and King’s College Hospital Charitable Trust. A.F., S.L., A.D., F.R-L and S.K. are supported by the European Union’s 7th RTD Framework Programme (ERC advanced grant PID-IMMUNE contract 249816) and a government grant managed by the French Agence Nationale de la Recherche as part of the "Investments for the Future" program (ANR-10-IAHU-01). S.L. is supported by the Agence Nationale de la Recherche (ANR) (ANR-14-CE14-0028-01), the Foundation ARC pour la Recherche sur le Cancer (France), the Rare Diseases Foundation (France) and François Aupetit Association (France). S.L. is a senior scientist and S.K is a researcher at the Centre National de la Recherche Scientifique-CNRS (France). A.D. and S.K. are supported by the “Institut National de la Santé et de la Recherche Médicale". S.K. also supported by the Fondation pour la Recherche Médicale (grant number: ING20130526624), la Ligue Contre le Cancer (Comité de Paris) and the Centre de Référence Déficits Immunitaires Héréditaires (CEREDIH). S.O.B is supported by the Higher Education Funding Council for England. B.V. is supported by the UK Biotechnology and Biological Sciences Research Council [BB/I007806/1], Cancer Research UK [C23338/A15965) and the National Institute for Health Research (NIHR) University College London Hospitals Biomedical Research Centre. B.V. is consultant to Karus Therapeutics (Oxford, UK). S.N. is a Wellcome Trust Senior Research Fellow in Basic Biomedical Science (095198/Z/10/Z). S.N. is also supported by the European Research Council Starting grant 260477, the EU FP7 collaborative grant 261441 (PEVNET project) and the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre, UK. A.M.C. is funded by the Medical Research Council, British Lung Foundation, University of Sheffield and Cambridge NIHR-BRC. Research in A.M.C. laboratory has received non-commercial grant support from GSK, Novartis, and MedImmune.This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.jaci.2016.06.02

    Financial Systems and Industrial Policy in Germany and Great Britain: The Limits of Convergence

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    ARIA 2016: Care pathways implementing emerging technologies for predictive medicine in rhinitis and asthma across the life cycle

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    The Allergic Rhinitis and its Impact on Asthma (ARIA) initiative commenced during a World Health Organization workshop in 1999. The initial goals were (1) to propose a new allergic rhinitis classification, (2) to promote the concept of multi-morbidity in asthma a

    Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

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    Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

    ARIA 2016 : Care pathways implementing emerging technologies for predictive medicine in rhinitis and asthma across the life cycle

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    The Allergic Rhinitis and its Impact on Asthma (ARIA) initiative commenced during a World Health Organization workshop in 1999. The initial goals were (1) to propose a new allergic rhinitis classification, (2) to promote the concept of multi-morbidity in asthma and rhinitis and (3) to develop guidelines with all stakeholders that could be used globally for all countries and populations. ARIA-disseminated and implemented in over 70 countries globally-is now focusing on the implementation of emerging technologies for individualized and predictive medicine. MASK [MACVIA (Contre les Maladies Chroniques pour un Vieillissement Actif)-ARIA Sentinel NetworK] uses mobile technology to develop care pathways for the management of rhinitis and asthma by a multi-disciplinary group and by patients themselves. An app (Android and iOS) is available in 20 countries and 15 languages. It uses a visual analogue scale to assess symptom control and work productivity as well as a clinical decision support system. It is associated with an inter-operable tablet for physicians and other health care professionals. The scaling up strategy uses the recommendations of the European Innovation Partnership on Active and Healthy Ageing. The aim of the novel ARIA approach is to provide an active and healthy life to rhinitis sufferers, whatever their age, sex or socio-economic status, in order to reduce health and social inequalities incurred by the disease.Peer reviewe

    Adherence to treatment in allergic rhinitis using mobile technology. The MASK Study

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    Background: Mobile technology may help to better understand the adherence to treatment. MASK-rhinitis (Mobile Airways Sentinel NetworK for allergic rhinitis) is a patient-centred ICT system. A mobile phone app (the Allergy Diary) central to MASK is available in 22 countries. Objectives: To assess the adherence to treatment in allergic rhinitis patients using the Allergy Diary App. Methods: An observational cross-sectional study was carried out on all users who filled in the Allergy Diary from 1 January 2016 to 1 August 2017. Secondary adherence was assessed by using the modified Medication Possession Ratio (MPR) and the Proportion of days covered (PDC) approach. Results: A total of 12143 users were registered. A total of 6949 users reported at least one VAS data recording. Among them, 1887 users reported >= 7 VAS data. About 1195 subjects were included in the analysis of adherence. One hundred and thirty-six (11.28%) users were adherent (MPR >= 70% and PDC = 70% and PDC = 1.50) and 176 (14.60%) were switchers. On the other hand, 832 (69.05%) users were non-adherent to medications (MPR Conclusion and clinical relevance: Adherence to treatment is low. The relative efficacy of continuous vs on-demand treatment for allergic rhinitis symptoms is still a matter of debate. This study shows an approach for measuring retrospective adherence based on a mobile app. This also represents a novel approach for analysing medication-taking behaviour in a real-world setting.Peer reviewe
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