Cosmic ray electrons and positrons from discrete stochastic sources

The distances that galactic cosmic ray electrons and positrons can travel are severely limited by energy losses to at most a few kiloparsec, thereby rendering the local spectrum very sensitive to the exact distribution of sources in our galactic neighbourhood. However, due to our ignorance of the exact source distribution, we can only predict the spectrum stochastically. We argue that even in the case of a large number of sources the central limit theorem is not applicable, but that the standard deviation for the flux from a random source is divergent due to a long power law tail of the probability density. Instead, we compute the expectation value and characterise the scatter around it by quantiles of the probability density using a generalised central limit theorem in a fully analytical way. The uncertainty band is asymmetric about the expectation value and can become quite large for TeV energies. In particular, the predicted local spectrum is marginally consistent with the measurements by Fermi-LAT and HESS even without imposing spectral breaks or cut-offs at source. We conclude that this uncertainty has to be properly accounted for when predicting electron fluxes above a few hundred GeV from astrophysical sources.Comment: 16 pages, 8 figures; references and clarifying comment added; to appear in JCA

Sommerfeld Enhancement from Multiple Mediators

We study the Sommerfeld enhancement experienced by a scattering object that couples to a tower of mediators. This can occur in, e.g., models of secluded dark matter when the mediator scale is generated naturally by hidden-sector confinement. Specializing to the case of a confining CFT, we show that off-resonant values of the enhancement can be increased by ~ 20% for cases of interest when (i) the (strongly-coupled) CFT admits a weakly-coupled dual description and (ii) the conformal symmetry holds up to the Planck scale. Larger enhancements are possible for lower UV scales due to an increase in the coupling strength of the tower.Comment: 17p, 2 figures; v2 JHEP version (inconsequential typo fixed, references added

Absolute electron and positron fluxes from PAMELA/Fermi and Dark Matter

We extract the positron and electron fluxes in the energy range 10 - 100 GeV by combining the recent data from PAMELA and Fermi LAT. The {\it absolute positron and electron} fluxes thus obtained are found to obey the power laws: $E^{-2.65}$ and $E^{-3.06}$ respectively, which can be confirmed by the upcoming data from PAMELA. The positron flux appears to indicate an excess at energies E\gsim 50 GeV even if the uncertainty in the secondary positron flux is added to the Galactic positron background. This leaves enough motivation for considering new physics, such as annihilation or decay of dark matter, as the origin of positron excess in the cosmic rays.Comment: Accepted by JCA

Benralizumab Reduces Respiratory Exacerbations and Oral Glucocorticosteroid Dose in Patients with Severe Asthma and Eosinophilic Granulomatosis with Polyangiitis

Carlo Mümmler,1 Pontus Mertsch,1 Michaela Barnikel,1 Frank Haubner,2 Ulf Schönermarck,3 Ulrich Grabmaier,4 Hendrik Schulze-Koops,5 Jürgen Behr,1 Nikolaus Kneidinger,1,6 Katrin Milger1 1Department of Medicine V, LMU University Hospital, LMU Munich, Comprehensive Pneumology Center, Member of the German Center of Lung Research (DZL), Munich, Germany; 2Department of Otorhinolaryngology, LMU University Hospital, LMU Munich, Munich, Germany; 3Division of Nephrology, Department of Medicine IV, LMU University Hospital, LMU Munich, Munich, Germany; 4Department of Medicine I, LMU University Hospital, LMU Munich, Munich, Germany; 5Division of Rheumatology and Clinical Immunology, Department of Medicine IV, LMU University Hospital, LMU Munich, Munich, Germany; 6Division of Pulmonology, Department of Internal Medicine, Medical University of Graz, Graz, AustriaCorrespondence: Katrin Milger, Department of Medicine V, LMU University Hospital, Marchioninistr, 15, LMU Munich, Munich, 81377, Germany, Tel +49-89-4400-73071, Email [email protected]: Benralizumab reduces exacerbations and long-term oral glucocorticosteroid (OCS) exposure in patients with severe eosinophilic asthma. In patients with eosinophilic granulomatosis with polyangiitis (EGPA), uncontrolled symptoms and exacerbations of asthma and chronic rhinosinusitis (CRS) are important reasons for continued OCS therapies. We aimed to describe outcomes of patients with severe asthma and EGPA treated with benralizumab in real-life.Methods: We retrospectively analyzed adult patients from the Severe Asthma Unit at LMU Munich diagnosed with severe asthma and EGPA treated with benralizumab, differentiating two groups: Group A, patients with a stable daily OCS dose and diagnosis of EGPA > 6 months ago; and Group B, patients treated with high-dose daily OCS due to recent diagnosis of EGPA < 6 months ago. We compared outcome parameters at baseline and 12 months after initiation of benralizumab, including respiratory exacerbations, daily OCS dose, and lung function.Results: Group A included 17 patients, all receiving OCS therapy and additional immunosuppressants; 15 patients (88%) continued benralizumab for more than 12 months, demonstrating a significant reduction in daily OCS dose and exacerbations while FEV1 increased. Group B included 9 patients, all with high-dose daily OCS and some receiving cyclophosphamide pulse therapy for life-threatening disease. Benralizumab addition during induction was well tolerated. A total of 7/9 (78%) continued benralizumab for more than 12 months and preserved EGPA remission at the 12-month timepoint.Conclusion: In this real-life cohort of patients with severe asthma and EGPA, benralizumab initiation during remission maintenance reduced respiratory exacerbations and daily OCS dose. Benralizumab initiation during remission induction was associated with a high rate of clinical EGPA remission.Keywords: EGPA, asthma, CRS, vasculitis, glucocorticoid, OCS, anti-IL5R, biologics, benralizuma

Müller Cells Stabilize Microvasculature through Hypoxic Preconditioning

BACKGROUND/AIMS: Hypoxia of the retina is a common pathogenic drive leading to vision loss as a result of tissue ischemia, increased vascular permeability and ultimately retinal neovascularisation. Here we tested the hypothesis that Müller cells stabilize the neurovascular unit, microvasculature by suppression of HIF-1α activation as a result of hypoxic preconditioning. METHODS: Tube Formation Assay and In vitro Vascular Permeability Image Assay were used to analyze angiogenesis and vascular integrity. Seahorse XF Cell Mito Stress Test was used to measure mitochondrial respiration. Gene and protein expression were examined by qRTPCR, ELISA and western blot. RESULTS: Hypoxic insult induces a significant induction of proangiogenic factors including vascular endothelial growth factor (VEGF) and angiopoietinlike 4 (ANGPTL-4) resulting in angiogenesis and increased vascular permeability of vascular endothelial cells. Hypoxic preconditioning of a human retinal Müller glia cell line significantly attenuates HIF-1α activation through the inhibition of mTOR and concomitant induction of aerobic glycolysis, stabilizing endothelial cells. CONCLUSION: Hypoxic preconditioning of Müller cells confers a robust protection to endothelial cells, through the suppression of HIF1α activation and its downstream regulation of VEGF and ANGPTL-4

Secluded Dark Matter Coupled to a Hidden CFT

Models of secluded dark matter offer a variant on the standard WIMP picture and can modify our expectations for hidden sector phenomenology and detection. In this work we extend a minimal model of secluded dark matter, comprised of a U(1)'-charged dark matter candidate, to include a confining hidden-sector CFT. This provides a technically natural explanation for the hierarchically small mediator-scale, with hidden-sector confinement generating m_{gamma'}>0. Furthermore, the thermal history of the universe can differ markedly from the WIMP picture due to (i) new annihilation channels, (ii) a (potentially) large number of hidden-sector degrees of freedom, and (iii) a hidden-sector phase transition at temperatures T << M_{dm} after freeze out. The mediator allows both the dark matter and the Standard Model to communicate with the CFT, thus modifying the low-energy phenomenology and cosmic-ray signals from the secluded sector.Comment: ~50p, 8 figs; v2 JHEP versio

Neutrinos and cosmic rays

In this paper we review the status of the search for high-energy neutrinos from outside the solar system and discuss the implications for the origin and propagation of cosmic rays. Connections between neutrinos and gamma-rays are also discussed.Comment: 25 pages, 5 figures, for a topical issue of Astroparticle Physics on cosmic ray

Planck Intermediate Results. IX. Detection of the Galactic haze with Planck

Using precise full-sky observations from Planck, and applying several methods of component separation, we identify and characterize the emission from the Galactic "haze" at microwave wavelengths. The haze is a distinct component of diffuse Galactic emission, roughly centered on the Galactic centre, and extends to |b| ~35 deg in Galactic latitude and |l| ~15 deg in longitude. By combining the Planck data with observations from the WMAP we are able to determine the spectrum of this emission to high accuracy, unhindered by the large systematic biases present in previous analyses. The derived spectrum is consistent with power-law emission with a spectral index of -2.55 +/- 0.05, thus excluding free-free emission as the source and instead favouring hard-spectrum synchrotron radiation from an electron population with a spectrum (number density per energy) dN/dE ~ E^-2.1. At Galactic latitudes |b|<30 deg, the microwave haze morphology is consistent with that of the Fermi gamma-ray "haze" or "bubbles," indicating that we have a multi-wavelength view of a distinct component of our Galaxy. Given both the very hard spectrum and the extended nature of the emission, it is highly unlikely that the haze electrons result from supernova shocks in the Galactic disk. Instead, a new mechanism for cosmic-ray acceleration in the centre of our Galaxy is implied.Comment: 15 pages, 9 figures, submitted to Astronomy and Astrophysic

The Pierre Auger Observatory III: Other Astrophysical Observations

Astrophysical observations of ultra-high-energy cosmic rays with the Pierre Auger ObservatoryComment: Contributions to the 32nd International Cosmic Ray Conference, Beijing, China, August 201

Bronchiectasis and asthma: Data from the European Bronchiectasis Registry (EMBARC)

\ua9 2024 The AuthorsBackground: Asthma is commonly reported in patients with a diagnosis of bronchiectasis. Objective: The aim of this study was to evaluate whether patients with bronchiectasis and asthma (BE+A) had a different clinical phenotype and different outcomes compared with patients with bronchiectasis without concomitant asthma. Methods: A prospective observational pan-European registry (European Multicentre Bronchiectasis Audit and Research Collaboration) enrolled patients across 28 countries. Adult patients with computed tomography–confirmed bronchiectasis were reviewed at baseline and annual follow-up visits using an electronic case report form. Asthma was diagnosed by the local investigator. Follow-up data were used to explore differences in exacerbation frequency between groups using a negative binomial regression model. Survival analysis used Cox proportional hazards regression. Results: Of 16,963 patients with bronchiectasis included for analysis, 5,267 (31.0%) had investigator-reported asthma. Patients with BE+A were younger, were more likely to be female and never smokers, and had a higher body mass index than patients with bronchiectasis without asthma. BE+A was associated with a higher prevalence of rhinosinusitis and nasal polyps as well as eosinophilia and Aspergillus sensitization. BE+A had similar microbiology but significantly lower severity of disease using the bronchiectasis severity index. Patients with BE+A were at increased risk of exacerbation after adjustment for disease severity and multiple confounders. Inhaled corticosteroid (ICS) use was associated with reduced mortality in patients with BE+A (adjusted hazard ratio 0.78, 95% CI 0.63-0.95) and reduced risk of hospitalization (rate ratio 0.67, 95% CI 0.67-0.86) compared with control subjects without asthma and not receiving ICSs. Conclusions: BE+A was common and was associated with an increased risk of exacerbations and improved outcomes with ICS use. Unexpectedly we identified significantly lower mortality in patients with BE+A