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Sökning: WFRF:(Graf Tobias)

  • Resultat 1-6 av 6
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1.
  • Miehe, Georg, et al. (författare)
  • The Kobresia pygmaea ecosystem of the Tibetan highlands – Origin, functioning and degradation of the world's largest pastoral alpine ecosystem: Kobresia pastures of Tibet
  • 2019
  • Ingår i: Science of the Total Environment. - : Elsevier BV. - 0048-9697. ; 648, s. 754-771
  • Tidskriftsartikel (refereegranskat)abstract
    • With 450,000 km2 Kobresia (syn. Carex) pygmaea dominated pastures in the eastern Tibetan highlands are the world's largest pastoral alpine ecosystem forming a durable turf cover at 3000–6000 m a.s.l. Kobresia's resilience and competitiveness is based on dwarf habit, predominantly below-ground allocation of photo assimilates, mixture of seed production and clonal growth, and high genetic diversity. Kobresia growth is co-limited by livestock-mediated nutrient withdrawal and, in the drier parts of the plateau, low rainfall during the short and cold growing season. Overstocking has caused pasture degradation and soil deterioration over most parts of the Tibetan highlands and is the basis for this man-made ecosystem. Natural autocyclic processes of turf destruction and soil erosion are initiated through polygonal turf cover cracking, and accelerated by soil-dwelling endemic small mammals in the absence of predators. The major consequences of vegetation cover deterioration include the release of large amounts of C, earlier diurnal formation of clouds, and decreased surface temperatures. These effects decrease the recovery potential of Kobresia pastures and make them more vulnerable to anthropogenic pressure and climate change. Traditional migratory rangeland management was sustainable over millennia, and possibly still offers the best strategy to conserve and possibly increase C stocks in the Kobresia turf.
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2.
  • Freischmidt, Axel, et al. (författare)
  • Haploinsufficiency of TBK1 causes familial ALS and fronto-temporal dementia
  • 2015
  • Ingår i: Nature Neuroscience. - : Springer Science and Business Media LLC. - 1097-6256 .- 1546-1726. ; 18:5, s. 631-
  • Tidskriftsartikel (refereegranskat)abstract
    • Amyotrophic lateral sclerosis (ALS) is a genetically heterogeneous neurodegenerative syndrome hallmarked by adult-onset loss of motor neurons. We performed exome sequencing of 252 familial ALS (fALS) and 827 control individuals. Gene-based rare variant analysis identified an exome-wide significant enrichment of eight loss-of-function (LoF) mutations in TBK1 (encoding TANK-binding kinase 1) in 13 fALS pedigrees. No enrichment of LoF mutations was observed in a targeted mutation screen of 1,010 sporadic ALS and 650 additional control individuals. Linkage analysis in four families gave an aggregate LOD score of 4.6. In vitro experiments confirmed the loss of expression of TBK1 LoF mutant alleles, or loss of interaction of the C-terminal TBK1 coiled-coil domain (CCD2) mutants with the TBK1 adaptor protein optineurin, which has been shown to be involved in ALS pathogenesis. We conclude that haploinsufficiency of TBK1 causes ALS and fronto-temporal dementia.
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3.
  • Grossmann, Igor, et al. (författare)
  • Insights into the accuracy of social scientists' forecasts of societal change
  • 2023
  • Ingår i: Nature Human Behaviour. - : Springer Nature. - 2397-3374. ; 7, s. 484-501
  • Tidskriftsartikel (refereegranskat)abstract
    • How well can social scientists predict societal change, and what processes underlie their predictions? To answer these questions, we ran two forecasting tournaments testing the accuracy of predictions of societal change in domains commonly studied in the social sciences: ideological preferences, political polarization, life satisfaction, sentiment on social media, and gender-career and racial bias. After we provided them with historical trend data on the relevant domain, social scientists submitted pre-registered monthly forecasts for a year (Tournament 1; N = 86 teams and 359 forecasts), with an opportunity to update forecasts on the basis of new data six months later (Tournament 2; N = 120 teams and 546 forecasts). Benchmarking forecasting accuracy revealed that social scientists' forecasts were on average no more accurate than those of simple statistical models (historical means, random walks or linear regressions) or the aggregate forecasts of a sample from the general public (N = 802). However, scientists were more accurate if they had scientific expertise in a prediction domain, were interdisciplinary, used simpler models and based predictions on prior data. How accurate are social scientists in predicting societal change, and what processes underlie their predictions? Grossmann et al. report the findings of two forecasting tournaments. Social scientists' forecasts were on average no more accurate than those of simple statistical models.
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4.
  • Joost, Daemen, et al. (författare)
  • Safety and efficacy of endovascular ultrasound renal denervation in resistant hypertension: 12-month results from the ACHIEVE study.
  • 2019
  • Ingår i: Journal of hypertension. - 1473-5598. ; 37:9, s. 1906-1912
  • Tidskriftsartikel (refereegranskat)abstract
    • First-generation radiofrequency renal denervation devices may have had limited efficacy due to incomplete circumferential ablation and dependence on individual operator technique. This study evaluated a next-generation catheter-based technology using ultrasound designed to maximize nerve coverage using circumferential ultrasound energy.This was a prospective, multicenter, nonrandomized, postmarket study evaluating the safety and efficacy of an endovascular ultrasound renal denervation system (Paradise) in patients who met the European Society of Hypertension/European Society of Cardiology definition of resistant hypertension. Major exclusion criteria included renal artery stenosis and renal insufficiency. Patients were followed for 12 months. Safety and efficacy endpoints included procedural safety and renal artery patency, as well as changes in systolic office and 24-h ambulatory bllod pressure (BP) measurement.A total of 96 patients from eight European sites were included. Mean age was 63.9 years and 41% of patients were female. At baseline, mean 24-h ambulatory BP was 156.2/88.4 ± 15.4/12.7 mmHg, and mean office BP was 176.2/95.0 ± 20.6/16.0 mmHg. Patients were on average on 5.1 ± 2.5 antihypertensive agents. At 12 months, the average 24-h ambulatory BP change was -7.5/-3.8 ± 18.3/10.6 mmHg (P = 0.0007; P = 0.0024) with an average office BP change of -15.0/-7.0 ± 27.0/12.3 mmHg (P < 0.0001 for both). At 12 months, there was a single patient death unrelated to the device or procedure.This single-arm study represents the largest cohort of patients treated with endovascular ultrasound renal denervation to date. Within this trial, the therapy appeared safe and resulted in sustained reductions in both office BP and 24-h ambulatory BP through 12 months.
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5.
  • Jung, Christian, et al. (författare)
  • A comparison of very old patients admitted to intensive care unit after acute versus elective surgery or intervention
  • 2019
  • Ingår i: Journal of critical care. - : W B SAUNDERS CO-ELSEVIER INC. - 0883-9441 .- 1557-8615. ; 52, s. 141-148
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: We aimed to evaluate differences in outcome between patients admitted to intensive care unit (ICU) after elective versus acute surgery in a multinational cohort of very old patients (80 years; VIP). Predictors of mortality, with special emphasis on frailty, were assessed.Methods: In total, 5063 VIPs were induded in this analysis, 922 were admitted after elective surgery or intervention, 4141 acutely, with 402 after acute surgery. Differences were calculated using Mann-Whitney-U test and Wilcoxon test. Univariate and multivariable logistic regression were used to assess associations with mortality.Results: Compared patients admitted after acute surgery, patients admitted after elective surgery suffered less often from frailty as defined as CFS (28% vs 46%; p < 0.001), evidenced lower SOFA scores (4 +/- 5 vs 7 +/- 7; p < 0.001). Presence of frailty (CFS >4) was associated with significantly increased mortality both in elective surgery patients (7% vs 12%; p = 0.01), in acute surgery (7% vs 12%; p = 0.02).Conclusions: VIPs admitted to ICU after elective surgery evidenced favorable outcome over patients after acute surgery even after correction for relevant confounders. Frailty might be used to guide clinicians in risk stratification in both patients admitted after elective and acute surgery. 
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6.
  • Reinthaler, Eva M., et al. (författare)
  • TPP2 mutation associated with sterile brain inflammation mimicking MS
  • 2018
  • Ingår i: NEUROLOGY-GENETICS. - 2376-7839. ; 4:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective To ascertain the genetic cause of a consanguineous family from Syria suffering from a sterile brain inflammation mimicking a mild nonprogressive form of MS.Methods We used homozygosity mapping and next-generation sequencing to detect the disease-causing gene in the affected siblings. In addition, we performed RNA and protein expression studies, enzymatic activity assays, immunohistochemistry, and targeted sequencing of further MS cases from Austria, Germany, Canada and Jordan.Results In this study, we describe the identification of a homozygous missense mutation (c.82T>G, p.Cys28Gly) in the tripeptidyl peptidase II (TPP2) gene in all 3 affected siblings of the family. Sequencing of all TPP2-coding exons in 826 MS cases identified one further homozygous missense variant (c.2027C>T, p.Thr676Ile) in a Jordanian MS patient. TPP2 protein expression in whole blood was reduced in the affected siblings. In contrast, TPP2 protein expression in postmortem brain tissue from MS patients without TPP2 mutations was highly upregulated.Conclusions The homozygous TPP2 mutation (p.Cys28Gly) is likely responsible for the inflammation phenotype in this family. TPP2 is an ubiquitously expressed serine peptidase that removes tripeptides from the N-terminal end of longer peptides. TPP2 is involved in various biological processes including the destruction of major histocompatibility complex Class I epitopes. Recessive loss-of-function mutations in TPP2 were described in patients with Evans syndrome, a rare autoimmune disease affecting the hematopoietic system. Based on the gene expression results in our MS autopsy brain samples, we further suggest that TPP2 may play a broader role in the inflammatory process in MS.
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