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Sökning: WFRF:(du Plessis K)

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  • Jain, R., et al. (författare)
  • Liver nucleotide biosynthesis is linked to protection from vascular complications in individuals with long-term type 1 diabetes
  • 2020
  • Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 10:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Identification of biomarkers associated with protection from developing diabetic complications is a prerequisite for an effective prevention and treatment. The aim of the present study was to identify clinical and plasma metabolite markers associated with freedom from vascular complications in people with very long duration of type 1 diabetes (T1D). Individuals with T1D, who despite having longer than 30 years of diabetes duration never developed major macro- or microvascular complications (non-progressors; NP) were compared with those who developed vascular complications within 25 years from diabetes onset (rapid progressors; RP) in the Scandinavian PROLONG (n = 385) and DIALONG (n = 71) cohorts. The DIALONG study also included 75 healthy controls. Plasma metabolites were measured using gas and/or liquid chromatography coupled to mass spectrometry. Lower hepatic fatty liver indices were significant common feature characterized NPs in both studies. Higher insulin sensitivity and residual beta-cell function (C-peptide) were also associated with NPs in PROLONG. Protection from diabetic complications was associated with lower levels of the glycolytic metabolite pyruvate and APOCIII in PROLONG, and with lower levels of thiamine monophosphate and erythritol, a cofactor and intermediate product in the pentose phosphate pathway as well as higher phenylalanine, glycine and serine in DIALONG. Furthermore, T1D individuals showed elevated levels of picolinic acid as compared to the healthy individuals. The present findings suggest a potential beneficial shunting of glycolytic substrates towards the pentose phosphate and one carbon metabolism pathways to promote nucleotide biosynthesis in the liver. These processes might be linked to higher insulin sensitivity and lower liver fat content, and might represent a mechanism for protection from vascular complications in individuals with long-term T1D.
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  • Abdalla, H., et al. (författare)
  • LMC N132D : A mature supernova remnant with a power-law gamma-ray spectrum extending beyond 8 TeV
  • 2021
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 655
  • 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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  • Abdalla, H., et al. (författare)
  • Search for Dark Matter Annihilation Signals from Unidentified Fermi-LAT Objects with HESS
  • 2021
  • Ingår i: Astrophysical Journal. - : Institute of Physics Publishing (IOPP). - 0004-637X .- 1538-4357. ; 918:1
  • 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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  • Abdalla, H., et al. (författare)
  • Searching for TeV Gamma-Ray Emission from SGR 1935+2154 during Its 2020 X-Ray and Radio Bursting Phase
  • 2021
  • Ingår i: Astrophysical Journal. - : Institute of Physics Publishing (IOPP). - 0004-637X .- 1538-4357. ; 919:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Magnetar hyperflares are the most plausible explanation for fast radio bursts (FRBs)-enigmatic powerful radio pulses with durations of several milliseconds and high brightness temperatures. The first observational evidence for this scenario was obtained in 2020 April when an FRB was detected from the direction of the Galactic magnetar and soft gamma-ray repeater SGR 1935+2154. The FRB was preceded by two gamma-ray outburst alerts by the BAT instrument aboard the Swift satellite, which triggered follow-up observations by the High Energy Stereoscopic System (H.E.S.S.). H.E.S.S. observed SGR 1935+2154 for 2 hr on 2020 April 28. The observations are coincident with X-ray bursts from the magnetar detected by INTEGRAL and Fermi-GBM, thus providing the first very high energy gamma-ray observations of a magnetar in a flaring state. High-quality data acquired during these follow-up observations allow us to perform a search for short-time transients. No significant signal at energies E > 0.6 TeV is found, and upper limits on the persistent and transient emission are derived. We here present the analysis of these observations and discuss the obtained results and prospects of the H.E.S.S. follow-up program for soft gamma-ray repeaters.
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  • Duong, M., et al. (författare)
  • Mortality and cardiovascular and respiratory morbidity in individuals with impaired FEV 1 (PURE): an international, community-based cohort study
  • 2019
  • Ingår i: The Lancet Global Health. - 2214-109X. ; 7:5, s. e613-e623
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The associations between the extent of forced expiratory volume in 1 s (FEV 1 ) impairment and mortality, incident cardiovascular disease, and respiratory hospitalisations are unclear, and how these associations might vary across populations is unknown. Methods: In this international, community-based cohort study, we prospectively enrolled adults aged 35–70 years who had no intention of moving residences for 4 years from rural and urban communities across 17 countries. A portable spirometer was used to assess FEV 1 . FEV 1 values were standardised within countries for height, age, and sex, and expressed as a percentage of the country-specific predicted FEV 1 value (FEV 1 %). FEV 1 % was categorised as no impairment (FEV 1 % ≥0 SD from country-specific mean), mild impairment (FEV 1 % <0 SD to −1 SD), moderate impairment (FEV 1 % <–1 SD to −2 SDs), and severe impairment (FEV 1 % <–2 SDs [ie, clinically abnormal range]). Follow-up was done every 3 years to collect information on mortality, cardiovascular disease outcomes (including myocardial infarction, stroke, sudden death, or congestive heart failure), and respiratory hospitalisations (from chronic obstructive pulmonary disease, asthma, pneumonia, tuberculosis, or other pulmonary conditions). Fully adjusted hazard ratios (HRs) were calculated by multilevel Cox regression. Findings: Among 126 359 adults with acceptable spirometry data available, during a median 7·8 years (IQR 5·6–9·5) of follow-up, 5488 (4·3%) deaths, 5734 (4·5%) cardiovascular disease events, and 1948 (1·5%) respiratory hospitalisation events occurred. Relative to the no impairment group, mild to severe FEV 1 % impairments were associated with graded increases in mortality (HR 1·27 [95% CI 1·18–1·36] for mild, 1·74 [1·60–1·90] for moderate, and 2·54 [2·26–2·86] for severe impairment), cardiovascular disease (1·18 [1·10–1·26], 1·39 [1·28–1·51], 2·02 [1·75–2·32]), and respiratory hospitalisation (1·39 [1·24–1·56], 2·02 [1·75–2·32], 2·97 [2·45–3·60]), and this pattern persisted in subgroup analyses considering country income level and various baseline risk factors. Population-attributable risk for mortality (adjusted for age, sex, and country income) from mildly to moderately reduced FEV 1 % (24·7% [22·2–27·2]) was larger than that from severely reduced FEV 1 % (3·7% [2·1–5·2]) and from tobacco use (19·7% [17·2–22·3]), previous cardiovascular disease (5·5% [4·5–6·5]), and hypertension (17·1% [14·6–19·6]). Population-attributable risk for cardiovascular disease from mildly to moderately reduced FEV 1 was 17·3% (14·8–19·7), second only to the contribution of hypertension (30·1% [27·6–32·5]). Interpretation: FEV 1 is an independent and generalisable predictor of mortality, cardiovascular disease, and respiratory hospitalisation, even across the clinically normal range (mild to moderate impairment). Funding: Population Health Research Institute, the Canadian Institutes of Health Research, Heart and Stroke Foundation of Ontario, Ontario Ministry of Health and Long-Term Care, AstraZeneca, Sanofi-Aventis, Boehringer Ingelheim, Servier, and GlaxoSmithKline, Novartis, and King Pharma. Additional funders are listed in the appendix. © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license
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  • Hystad, P., et al. (författare)
  • Associations of outdoor fine particulate air pollution and cardiovascular disease in 157 436 individuals from 21 high-income, middle-income, and low-income countries (PURE): a prospective cohort study
  • 2020
  • Ingår i: Lancet Planetary Health. - 2542-5196. ; 4:6, s. E235-E245
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Most studies of long-term exposure to outdoor fine particulate matter (PM5) and cardiovascular disease are from high-income countries with relatively low PM25 concentrations. It is unclear whether risks are similar in low-income and middle-income countries (LMICs) and how outdoor PM contributes to the global burden of cardiovascular disease. In our analysis of the Prospective Urban and Rural Epidemiology (PURE) study, we aimed to investigate the association between long-term exposure to come, middle-income, and low-income countries. Methods In this multinational, prospective cohort study, we studied 157 436 adults aged 35-70 years who were enrolled in the PURE study in countries with ambient PM25 estimates, for whom follow-up data were available. Cox proportional hazard frailty models were used to estimate the associations between long-term mean community outdoor PM concentrations and cardiovascular disease events ( fatal and non-fatal), cardiovascular disease mortality, and other non-accidental mortality. Findings Between Jan 1, 2003, and July 14, 2018, 157 436 adults from 747 communities in 21 high-income, middle-income, and low-income countries were enrolled and followed up, of whom 140 020 participants resided in LMICs. During a median follow-up period of 9 center dot 3 years (IQR 7 center dot 8-10 center dot 8; corresponding to 1 center dot 4 million person-years), we documented 9996 non-accidental deaths, of which 3219 were attributed to cardiovascular disease. 9152 (5 center dot 8%) of 157 436 participants had cardiovascular disease events (fatal and non-fatal incident cardiovascular disease), including 4083 myocardial infarctions and 4139 strokes. Mean 3-year PM25 at cohort baseline was 47 center dot 5 mu g/m(3) (range 6-140). In models adjusted for individual, household, and geographical factors, a 10 mu g/m(3) increase in PM25 was associated with increased risk for cardiovascular disease events (hazard ratio 1 center dot 05 [95% CI 1 center dot 03-1 center dot 07]), myocardial infarction (1 center dot 03 [1 center dot 00-1 center dot 05]), stroke (1 center dot 07 [1 center dot 04-1 center dot 10]), and cardiovascular disease mortality (1 center dot 03 [1 center dot 00-1 center dot 05]). Results were similar for LMICs and communities with high PM25 concentrations (>35 mu g/m(3)). The population attributable fraction for PM25 in the PURE cohort was 13 center dot 9% (95% CI 8 center dot 8-18 center dot 6) for cardiovascular disease events, 8 center dot 4% (0 center dot 0-15 center dot 4) for myocardial infarction, 19 center dot 6% (13 center dot 0-25 center dot 8) for stroke, and 8 center dot 3% (0 center dot 0-15 center dot 2) for cardiovascular disease mortality. We identified no consistent associations between PM25 and risk for non-cardiovascular disease deaths. Interpretation Long-term outdoor PM25 concentrations were associated with increased risks of cardiovascular disease in adults aged 35-70 years. Air pollution is an important global risk factor for cardiovascular disease and a need exists to reduce air pollution concentrations, especially in LMICs, where air pollution levels are highest. Copyright (c) 2020 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND 4.0 license.
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