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- Abdalla, H., et al.
(författare)
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LMC N132D : A mature supernova remnant with a power-law gamma-ray spectrum extending beyond 8 TeV
- 2021
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 655
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Tidskriftsartikel (refereegranskat)abstract
- Context. Supernova remnants (SNRs) are commonly thought to be the dominant sources of Galactic cosmic rays up to the knee of the cosmic-ray spectrum at a few PeV. Imaging Atmospheric Cherenkov Telescopes have revealed young SNRs as very-high-energy (VHE, >100 GeV) gamma-ray sources, but for only a few SNRs the hadronic cosmic-ray origin of their gamma-ray emission is indisputably established. In all these cases, the gamma-ray spectra exhibit a spectral cutoff at energies much below 100 TeV and thus do not reach the PeVatron regime. Aims. The aim of this work was to achieve a firm detection for the oxygen-rich SNR LMC N132D in the VHE gamma-ray domain with an extended set of data, and to clarify the spectral characteristics and the localization of the gamma-ray emission from this exceptionally powerful gamma-ray-emitting SNR. Methods. We analyzed 252 h of High Energy Stereoscopic System (H.E.S.S.) observations towards SNR N132D that were accumulated between December 2004 and March 2016 during a deep survey of the Large Magellanic Cloud, adding 104 h of observations to the previously published data set to ensure a > 5 sigma detection. To broaden the gamma-ray spectral coverage required for modeling the spectral energy distribution, an analysis of Fermi-LAT Pass 8 data was also included. Results. We unambiguously detect N132D at VHE with a significance of 5.7 sigma. We report the results of a detailed analysis of its spectrum and localization based on the extended H.E.S.S. data set. The joint analysis of the extended H.E.S.S and Fermi-LAT data results in a spectral energy distribution in the energy range from 1.7 GeV to 14.8 TeV, which suggests a high luminosity of N132D at GeV and TeV energies. We set a lower limit on a gamma-ray cutoff energy of 8 TeV with a confidence level of 95%. The new gamma-ray spectrum as well as multiwavelength observations of N132D when compared to physical models suggests a hadronic origin of the VHE gamma-ray emission. Conclusions. SNR N132D is a VHE gamma-ray source that shows a spectrum extending to the VHE domain without a spectral cutoff at a few TeV, unlike the younger oxygen-rich SNR Cassiopeia A. The gamma-ray emission is best explained by a dominant hadronic component formed by diffusive shock acceleration. The gamma-ray properties of N132D may be affected by an interaction with a nearby molecular cloud that partially lies inside the 95% confidence region of the source position.
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| 2. |
- Abdalla, H., et al.
(författare)
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Search for Dark Matter Annihilation Signals from Unidentified Fermi-LAT Objects with HESS
- 2021
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Ingår i: Astrophysical Journal. - : Institute of Physics Publishing (IOPP). - 0004-637X .- 1538-4357. ; 918:1
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Tidskriftsartikel (refereegranskat)abstract
- Cosmological N-body simulations show that Milky Way-sized galaxies harbor a population of unmerged dark matter (DM) subhalos. These subhalos could shine in gamma-rays and eventually be detected in gamma-ray surveys as unidentified sources. We performed a thorough selection among unidentified Fermi-Large Area Telescope Objects (UFOs) to identify them as possible tera-electron-volt-scale DM subhalo candidates. We search for very-high-energy (E greater than or similar to 100 GeV) gamma-ray emissions using H.E.S.S. observations toward four selected UFOs. Since no significant very-high-energy gamma-ray emission is detected in any data set of the four observed UFOs or in the combined UFO data set, strong constraints are derived on the product of the velocity-weighted annihilation cross section sigma v by the J factor for the DM models. The 95% confidence level observed upper limits derived from combined H.E.S.S. observations reach sigma vJ values of 3.7 x 10(-5) and 8.1 x 10(-6) GeV(2 )cm(-2 )s(-1) in the W (+) W (-) and tau (+) tau (-) channels, respectively, for a 1 TeV DM mass. Focusing on thermal weakly interacting massive particles, the H.E.S.S. constraints restrict the J factors to lie in the range 6.1 x 10(19)-2.0 x 10(21) GeV(2 )cm(-5) and the masses to lie between 0.2 and 6 TeV in the W (+) W (-) channel. For the tau (+) tau (-) channel, the J factors lie in the range 7.0 x 10(19)-7.1 x 10(20) GeV(2 )cm(-5) and the masses lie between 0.2 and 0.5 TeV. Assuming model-dependent predictions from cosmological N-body simulations on the J-factor distribution for Milky Way-sized galaxies, the DM models with masses >0.3 TeV for the UFO emissions can be ruled out at high confidence level.
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| 7. |
- Ricordi, Camillo, et al.
(författare)
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National Institutes of Health-Sponsored Clinical Islet Transplantation Consortium Phase 3 Trial : Manufacture of a Complex Cellular Product at Eight Processing Facilities
- 2016
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 65:11, s. 3418-3428
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Tidskriftsartikel (refereegranskat)abstract
- Eight manufacturing facilities participating in the National Institutes of Health-sponsored Clinical Islet Transplantation (CIT) Consortium jointly developed and implemented a harmonized process for the manufacture of allogeneic purified human pancreatic islet (PHPI) product evaluated in a phase 3 trial in subjects with type 1 diabetes. Manufacturing was controlled by a common master production batch record, standard operating procedures that included acceptance criteria for deceased donor organ pancreata and critical raw materials, PHPI product specifications, certificate of analysis, and test methods. The process was compliant with Current Good Manufacturing Practices and Current Good Tissue Practices. This report describes the manufacturing process for 75 PHPI clinical lots and summarizes the results, including lot release. The results demonstrate the feasibility of implementing a harmonized process at multiple facilities for the manufacture of a complex cellular product. The quality systems and regulatory and operational strategies developed by the CIT Consortium yielded product lots that met the prespecified characteristics of safety, purity, potency, and identity and were successfully transplanted into 48 subjects. No adverse events attributable to the product and no cases of primary nonfunction were observed.
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| 8. |
- Hering, Bernhard J., et al.
(författare)
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Phase 3 Trial of Transplantation of Human Islets in Type 1 Diabetes Complicated by Severe Hypoglycemia
- 2016
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 39:7, s. 1230-1240
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE Impaired awareness of hypoglycemia (IAH) and severe hypoglycemic events (SHEs) cause substantial morbidity and mortality in patients with type 1 diabetes (T1D). Current therapies are effective in preventing SHEs in 50-80% of patients with IAH and SHEs, leaving a substantial number of patients at risk. We evaluated the effectiveness and safety of a standardized human pancreatic islet product in subjects in whom IAH and SHEs persisted despite medical treatment. RESEARCH DESIGN AND METHODS This multicenter, single-arm, phase 3 study of the investigational product purified human pancreatic islets (PHPI) was conducted at eight centers in North America. Forty-eight adults with T1D for >5 years, absent stimulated C-peptide, and documented IAH and SHEs despite expert care were enrolled. Each received immunosuppression and one or more transplants of PHPI, manufactured on-site under good manufacturing practice conditions using a common batch record and standardized lot release criteria and test methods. The primary end point was the achievement of HbA(1c) <7.0% (53 mmol/mol) at day 365 and freedom from SHEs from day 28 to day 365 after the first transplant. RESULTS The primary end point was successfully met by 87.5% of subjects at 1 year and by 71% at 2 years. The median HbA(1c) level was 5.6% (38 mmol/mol) at both 1 and 2 years. Hypoglycemia awareness was restored, with highly significant improvements in Clarke and HYPO scores (P > 0.0001). No study-related deaths or disabilities occurred. Five of the enrollees (10.4%) experienced bleeds requiring transfusions (corresponding to 5 of 75 procedures), and two enrollees (4.1%) had infections attributed to immunosuppression. Glomerular filtration rate decreased significantly on immunosuppression, and donor-specific antibodies developed in two patients. CONCLUSIONS Transplanted PHPI provided glycemic control, restoration of hypoglycemia awareness, and protection from SHEs in subjects with intractable IAH and SHEs. Safety events occurred related to the infusion procedure and immunosuppression, including bleeding and decreased renal function. Islet transplantation should be considered for patients with T1D and IAH in whom other, less invasive current treatments have been ineffective in preventing SHEs.
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- Markmann, James F., et al.
(författare)
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Phase 3 trial of human islet-after-kidney transplantation in type 1 diabetes
- 2021
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Ingår i: American Journal of Transplantation. - : John Wiley & Sons. - 1600-6135 .- 1600-6143. ; 21:4, s. 1477-1492
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Tidskriftsartikel (refereegranskat)abstract
- Allogeneic islet transplant offers a minimally invasive option for beta cell replacement in the treatment of type 1 diabetes (T1D). The CIT consortium trial of purified human pancreatic islets (PHPI) in patients with T1D after kidney transplant (CIT06), a National Institutes of Health-sponsored phase 3, prospective, open-label, single-arm pivotal trial of PHPI, was conducted in 24 patients with impaired awareness of hypoglycemia while receiving intensive insulin therapy. PHPI were manufactured using standardized processes. PHPI transplantation was effective with 62.5% of patients achieving the primary endpoint of freedom from severe hypoglycemic events and HbA(1c) <= 6.5% or reduced by >= 1 percentage point at 1 year posttransplant. Median HbA(1c)declined from 8.1% before to 6.0% at 1 year and 6.3% at 2 and 3 years following transplant (P < .001 for all vs baseline), with related improvements in hypoglycemia awareness and glucose variability. The improved metabolic control was associated with better health-related and diabetes-related quality of life. The procedure was safe and kidney allograft function remained stable after 3 years. These results add to evidence establishing allogeneic islet transplant as a safe and effective treatment for patients with T1D and unstable glucose control despite intensive insulin treatment, supporting the indication for PHPI in the post-renal transplant setting.
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