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  • 2019
  • Tidskriftsartikel (refereegranskat)
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  • Abe, O, et al. (författare)
  • Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials
  • 2005
  • Ingår i: The Lancet. - 1474-547X. ; 365:9472, s. 1687-1717
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Quinquennial overviews (1985-2000) of the randomised trials in early breast cancer have assessed the 5-year and 10-year effects of various systemic adjuvant therapies on breast cancer recurrence and survival. Here, we report the 10-year and 15-year effects. Methods Collaborative meta-analyses were undertaken of 194 unconfounded randomised trials of adjuvant chemotherapy or hormonal therapy that began by 1995. Many trials involved CMF (cyclophosphamide, methotrexate, fluorouracil), anthracycline-based combinations such as FAC (fluorouracil, doxombicin, cyclophosphamide) or FEC (fluorouracil, epirubicin, cyclophosphamide), tamoxifen, or ovarian suppression: none involved taxanes, trastuzumab, raloxifene, or modem aromatase inhibitors. Findings Allocation to about 6 months of anthracycline-based polychemotherapy (eg, with FAC or FEC) reduces the annual breast cancer death rate by about 38% (SE 5) for women younger than 50 years of age when diagnosed and by about 20% (SE 4) for those of age 50-69 years when diagnosed, largely irrespective of the use of tamoxifen and of oestrogen receptor (ER) status, nodal status, or other tumour characteristics. Such regimens are significantly (2p=0 . 0001 for recurrence, 2p<0 . 00001 for breast cancer mortality) more effective than CMF chemotherapy. Few women of age 70 years or older entered these chemotherapy trials. For ER-positive disease only, allocation to about 5 years of adjuvant tamoxifen reduces the annual breast cancer death rate by 31% (SE 3), largely irrespective of the use of chemotherapy and of age (<50, 50-69, &GE; 70 years), progesterone receptor status, or other tumour characteristics. 5 years is significantly (2p<0 . 00001 for recurrence, 2p=0 . 01 for breast cancer mortality) more effective than just 1-2 years of tamoxifen. For ER-positive tumours, the annual breast cancer mortality rates are similar during years 0-4 and 5-14, as are the proportional reductions in them by 5 years of tamoxifen, so the cumulative reduction in mortality is more than twice as big at 15 years as at 5 years after diagnosis. These results combine six meta-analyses: anthracycline-based versus no chemotherapy (8000 women); CMF-based versus no chemotherapy (14 000); anthracycline-based versus CMF-based chemotherapy (14 000); about 5 years of tamoxifen versus none (15 000); about 1-2 years of tamoxifen versus none (33 000); and about 5 years versus 1-2 years of tamoxifen (18 000). Finally, allocation to ovarian ablation or suppression (8000 women) also significantly reduces breast cancer mortality, but appears to do so only in the absence of other systemic treatments. For middle-aged women with ER-positive disease (the commonest type of breast cancer), the breast cancer mortality rate throughout the next 15 years would be approximately halved by 6 months of anthracycline-based chemotherapy (with a combination such as FAC or FEC) followed by 5 years of adjuvant tamoxifen. For, if mortality reductions of 38% (age <50 years) and 20% (age 50-69 years) from such chemotherapy were followed by a further reduction of 31% from tamoxifen in the risks that remain, the final mortality reductions would be 57% and 45%, respectively (and, the trial results could well have been somewhat stronger if there had been full compliance with the allocated treatments). Overall survival would be comparably improved, since these treatments have relatively small effects on mortality from the aggregate of all other causes. Interpretation Some of the widely practicable adjuvant drug treatments that were being tested in the 1980s, which substantially reduced 5-year recurrence rates (but had somewhat less effect on 5-year mortality rates), also substantially reduce 15-year mortality rates. Further improvements in long-term survival could well be available from newer drugs, or better use of older drugs.
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  • Palmer, Nicholette D, et al. (författare)
  • A genome-wide association search for type 2 diabetes genes in African Americans.
  • 2012
  • Ingår i: PloS one. - San Francisco : Public Library of Science (PLoS). - 1932-6203. ; 7:1, s. e29202-
  • Tidskriftsartikel (refereegranskat)abstract
    • African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.
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  • Carvalho, E. de, et al. (författare)
  • EU FP7 INFSO-ICT-317669 METIS, D3.1 Positioning of multi-node/multi-antenna technologies
  • 2013
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • This document describes the research activity in multi-node/multi-antenna technologies within METIS and positions it with respect to the state-of-the-art in the academic literature and in the standardization bodies. Based on the state-of-the-art and as well as on the METIS objectives,we set the research objectives and we group the different activities (or technology components) into research clusters with similar research objectives. The technologycomponents and the research objectives have been set to achieve an ambidextrous purpose. On one side we aim at providing the METIS system with those technological components that are a natural but non-trivial evolution of 4G. On the other side, we aim at seeking for disruptivetechnologies that could radically change 5G with respect to 4G. Moreover, we mapped the different technology components to METIS’ other activities and to the overall goals of theproject.
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  • Bhavadharini, B., et al. (författare)
  • Association of dairy consumption with metabolic syndrome, hypertension and diabetes in 147 812 individuals from 21 countries
  • 2020
  • Ingår i: Bmj Open Diabetes Research & Care. - : BMJ. - 2052-4897. ; 8:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective Our aims were to assess the association of dairy intake with prevalence of metabolic syndrome (MetS) (cross-sectionally) and with incident hypertension and incident diabetes (prospectively) in a large multinational cohort study. Methods The Prospective Urban Rural Epidemiology (PURE) study is a prospective epidemiological study of individuals aged 35 and 70 years from 21 countries on five continents, with a median follow-up of 9.1 years. In thecross-sectional analyses, we assessed the association of dairy intake with prevalent MetS and its components among individuals with information on the five MetS components (n=112 922). Forthe prospective analyses, we examined the association of dairy with incident hypertension (in 57 547 individuals free of hypertension) and diabetes (in 131 481 individuals free of diabetes). Results In cross-sectional analysis, higher intake of total dairy (at least two servings/day compared with zero intake; OR 0.76, 95% CI 0.71 to 0.80, p-trend<0.0001) was associated with a lower prevalence of MetS after multivariable adjustment. Higher intakes of whole fat dairy consumed alone (OR 0.72, 95% CI 0.66 to 0.78, p-trend<0.0001), or consumed jointly with low fat dairy (OR 0.89, 95% CI 0.80 to 0.98, p-trend=0.0005), were associated with a lower MetS prevalence. Low fat dairy consumed alone was not associated with MetS (OR 1.03, 95% CI 0.77 to 1.38, p-trend=0.13). In prospective analysis, 13 640 people with incident hypertension and 5351 people with incident diabetes were recorded. Higher intake of total dairy (at least two servings/day vs zero serving/day) was associated with a lower incidence of hypertension (HR 0.89, 95% CI 0.82 to 0.97, p-trend=0.02) and diabetes (HR 0.88, 95% CI 0.76 to 1.02, p-trend=0.01). Directionally similar associations were found for whole fat dairy versus each outcome. Conclusions Higher intake of whole fat (but not low fat) dairy was associated with alower prevalenceof MetS and most of its component factors, and with alower incidenceof hypertension and diabetes. Our findings should be evaluated in large randomized trials of the effects of whole fat dairy on the risks of MetS, hypertension, and diabetes.
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  • Dehghan, M., et al. (författare)
  • Association of dairy intake with cardiovascular disease and mortality in 21 countries from five continents (PURE): a prospective cohort study
  • 2018
  • Ingår i: Lancet. - : Elsevier BV. - 0140-6736. ; 392:10161, s. 2288-2297
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Dietary guidelines recommend minimising consumption of whole-fat dairy products, as they are a source of saturated fats and presumed to adversely affect blood lipids and increase cardiovascular disease and mortality. Evidence for this contention is sparse and few data for the effects of dairy consumption on health are available from low-income and middle-income countries. Therefore, we aimed to assess the associations between total dairy and specific types of dairy products with mortality and major cardiovascular disease. Methods The Prospective Urban Rural Epidemiology (PURE) study is a large multinational cohort study of individuals aged 35-70 years enrolled from 21 countries in five continents. Dietary intakes of dairy products for 136 384 individuals were recorded using country-specific validated food frequency questionnaires. Dairy products comprised milk, yoghurt, and cheese. We further grouped these foods into whole-fat and low-fat dairy. The primary outcome was the composite of mortality or major cardiovascular events (defined as death from cardiovascular causes, non-fatal myocardial infarction, stroke, or heart failure). Hazard ratios (HRs) were calculated using multivariable Cox frailty models with random intercepts to account for clustering of participants by centre. Findings Between Jan 1, 2003, and July 14, 2018, we recorded 10 567 composite events (deaths [n=6796] or major cardiovascular events [n=5855]) during the 9.1 years of follow-up. Higher intake of total dairy (>2 servings per day compared with no intake) was associated with a lower risk of the composite outcome (HR 0.84, 95% CI 0.75-0.94; p(trend) 0.0004), total mortality (0.83, 0.72-0.96; p(trend) 0.0052), non-cardiovascular mortality (0.86, 0.72-1.02; p(trend)=0.046), cardiovascular mortality (0.77, 0.58-1.01; p(trend)=0.029), major cardiovascular disease (0.78, 0.67-0.90; p(trend)=0.0001), and stroke (0.66, 0.53-0.82; p(trend)=0.0003). No significant association with myocardial infarction was observed (HR 0.89, 95% CI 0.71-1.11;p(trend)=0.163). Higher intake (>1 serving vs no intake) of milk (HR 0.90, 95% CI 0.82-0.99; p(trend)=0.0529) and yogurt (0.86, 0.75-0.99; p(trend)=0.0051) was associated with lower risk of the composite outcome, whereas cheese intake was not significantly associated with the composite outcome (0.88, 0.76-1.02; p(trend)=0.1399). Butter intake was low and was not significantly associated with clinical outcomes (HR 1.09, 95% CI 0.90-1.33; p(trend)=0.4113). Interpretation Dairy consumption was associated with lower risk of mortality and major cardiovascular disease events in a diverse multinational cohort. Copyright (c) 2018 Elsevier Ltd. All rights reserved.
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  • McMurray, J. J. V., et al. (författare)
  • Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction
  • 2019
  • Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 381:21, s. 1995-2008
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND In patients with type 2 diabetes, inhibitors of sodium-glucose cotransporter 2 (SGLT2) reduce the risk of a first hospitalization for heart failure, possibly through glucose-independent mechanisms. More data are needed regarding the effects of SGLT2 inhibitors in patients with established heart failure and a reduced ejection fraction, regardless of the presence or absence of type 2 diabetes.METHODS In this phase 3, placebo-controlled trial, we randomly assigned 4744 patients with New York Heart Association class II, III, or IV heart failure and an ejection fraction of 40% or less to receive either dapagliflozin (at a dose of 10 mg once daily) or placebo, in addition to recommended therapy. The primary outcome was a composite of worsening heart failure (hospitalization or an urgent visit resulting in intravenous therapy for heart failure) or cardiovascular death.RESULTS Over a median of 18.2 months, the primary outcome occurred in 386 of 2373 patients (16.3%) in the dapagliflozin group and in 502 of 2371 patients (21.2%) in the placebo group (hazard ratio, 0.74; 95% confidence interval [CI], 0.65 to 0.85; P<0.001). A first worsening heart failure event occurred in 237 patients (10.0%) in the dapagliflozin group and in 326 patients (13.7%) in the placebo group (hazard ratio, 0.70; 95% CI, 0.59 to 0.83). Death from cardiovascular causes occurred in 227 patients (9.6%) in the dapagliflozin group and in 273 patients (11.5%) in the placebo group (hazard ratio, 0.82; 95% CI, 0.69 to 0.98); 276 patients (11.6%) and 329 patients (13.9%), respectively, died from any cause (hazard ratio, 0.83; 95% CI, 0.71 to 0.97). Findings in patients with diabetes were similar to those in patients without diabetes. The frequency of adverse events related to volume depletion, renal dysfunction, and hypoglycemia did not differ between treatment groups.CONCLUSIONS Among patients with heart failure and a reduced ejection fraction, the risk of worsening heart failure or death from cardiovascular causes was lower among those who received dapagliflozin than among those who received placebo, regardless of the presence or absence of diabetes.
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  • Fantini, R, et al. (författare)
  • EU FP7 INFSO-ICT-317669 METIS, D3.2 First performance results for multi-node/multi-antenna transmission technologies
  • 2014
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • This deliverable describes the current results of the multi-node/multi-antenna technologies investigated within METIS and analyses the interactions within and outside Work Package 3. Furthermore, it identifies the most promising technologies based on the current state of obtained results. This document provides a brief overview of the results in its first part. The second part, namely the Appendix, further details the results, describes the simulation alignment efforts conducted in the Work Package and the interaction of the Test Cases. The results described here show that the investigations conducted in Work Package 3 are maturing resulting in valuable innovative solutions for future 5G systems.
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  • Langefeld, Carl D., et al. (författare)
  • Transancestral mapping and genetic load in systemic lupus erythematosus
  • 2017
  • Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (similar to 50% of these regions have multiple independent associations); these include 24 novel SLE regions (P < 5 x 10(-8)), refined association signals in established regions, extended associations to additional ancestries, and a disentangled complex HLA multigenic effect. The risk allele count (genetic load) exhibits an accelerating pattern of SLE risk, leading us to posit a cumulative hit hypothesis for autoimmune disease. Comparing results across the three ancestries identifies both ancestry-dependent and ancestry-independent contributions to SLE risk. Our results are consistent with the unique and complex histories of the populations sampled, and collectively help clarify the genetic architecture and ethnic disparities in SLE.
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  • Narula, N., et al. (författare)
  • Association of ultra-processed food intake with risk of inflammatory bowel disease: prospective cohort study
  • 2021
  • Ingår i: Bmj-British Medical Journal. - : BMJ. - 1756-1833. ; 374
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE To evaluate the relation between intake of ultra processed food and risk of inflammatory bowel disease (IBD). DESIGN Prospective cohort study. SETTING 21 low, middle, and high income countries across seven geographical regions (Europe and North America, South America, Africa, Middle East, south Asia, South East Asia, and China). PARTICIPANTS 116 087 adults aged 35-70 years with at least one cycle of follow-up and complete baseline food frequency questionnaire (FFQ) data (country specific validated FFQs were used to document baseline dietary intake). Participants were followed prospectively at least every three years. MAIN OUTCOME MEASURES The main outcome was development of IBD, including Crohn & rsquo;s disease or ulcerative colitis. Associations between ultra-processed food intake and risk of IBD were assessed using Cox proportional hazard multivariable models. Results are presented as hazard ratios with 95% confidence intervals. RESULTS Participants were enrolled in the study between 2003 and 2016. During the median follow-up of 9.7 years (interquartile range 8.9-11.2 years), 467 participants developed incident IBD (90 with Crohn & rsquo;s disease and 377 with ulcerative colitis). After adjustment for potential confounding factors, higher intake of ultra-processed food was associated with a higher risk of incident IBD (hazard ratio 1.82, 95% confidence interval 1.22 to 2.72 for >= 5 servings/day and 1.67, 1.18 to 2.37 for 1-4 servings/day compared with <1 serving/day, P=0.006 for trend). Different subgroups of ultra-processed food, including soft drinks, refined sweetened foods, salty snacks, and processed meat, each were associated with higher hazard ratios for IBD. Results were consistent for Crohn & rsquo;s disease and ulcerative colitis with low heterogeneity. Intakes of white meat, red meat, dairy, starch, and fruit, vegetables, and legumes were not associated with incident IBD. CONCLUSIONS Higher intake of ultra-processed food was positively associated with risk of IBD. Further studies are needed to identify the contributory factors within ultra processed foods.
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  • Pihl, E., et al. (författare)
  • Ten new insights in climate science 2020- A horizon scan
  • 2020
  • Ingår i: Global Sustainability. - : Cambridge University Press. - 2059-4798.
  • Tidskriftsartikel (refereegranskat)abstract
    • Non-technical summary We summarize some of the past year's most important findings within climate change-related research. New research has improved our understanding of Earth's sensitivity to carbon dioxide, finds that permafrost thaw could release more carbon emissions than expected and that the uptake of carbon in tropical ecosystems is weakening. Adverse impacts on human society include increasing water shortages and impacts on mental health. Options for solutions emerge from rethinking economic models, rights-based litigation, strengthened governance systems and a new social contract. The disruption caused by COVID-19 could be seized as an opportunity for positive change, directing economic stimulus towards sustainable investments. Technical summary A synthesis is made of ten fields within climate science where there have been significant advances since mid-2019, through an expert elicitation process with broad disciplinary scope. Findings include: (1) a better understanding of equilibrium climate sensitivity; (2) abrupt thaw as an accelerator of carbon release from permafrost; (3) changes to global and regional land carbon sinks; (4) impacts of climate change on water crises, including equity perspectives; (5) adverse effects on mental health from climate change; (6) immediate effects on climate of the COVID-19 pandemic and requirements for recovery packages to deliver on the Paris Agreement; (7) suggested long-term changes to governance and a social contract to address climate change, learning from the current pandemic, (8) updated positive cost-benefit ratio and new perspectives on the potential for green growth in the short- A nd long-term perspective; (9) urban electrification as a strategy to move towards low-carbon energy systems and (10) rights-based litigation as an increasingly important method to address climate change, with recent clarifications on the legal standing and representation of future generations. Social media summary Stronger permafrost thaw, COVID-19 effects and growing mental health impacts among highlights of latest climate science. 
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  • Wilking, N., et al. (författare)
  • Long-term follow-up of the SBG 9401 study comparing tailored FEC-based therapy versus marrow-supported high-dose therapy
  • 2007
  • Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 18:4, s. 694-700
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The purpose was to investigate adjuvant marrow-supportive high-dose chemotherapy compared with an equitoxicity-tailored comparator arm. Patients and methods: Five hundred and twenty-five women below theage of 60 years with operated high-risk primary breast cancer were randomised to nine cycles of granulocyte colony-stimulating factor supported and individually tailored FEC (5-fluorouracil, epirubicin, cyclophosphamide), (n = 251) or standard FEC followed by marrow-supported high-dose therapy with CTCb (cyclophosphamide, thiotepa, carboplatin) therapy (n = 274), followed by locoregional radiotherapy and tamoxifen for 5 years. Results: There were 104 breast cancer relapses in the tailored FEC group versus 139 in the CTCb group (double triangular method by Whitehead, P = 0.046), with a median follow-up of all included patients of 60.8 months. The event-free survival demonstrated 121 and 150 events in the tailored FEC- and CTCb group, respectively [P = 0.074, hazard ratio (HR) 0.804, 95% confidence interval (CI) 0.633-1.022]. Ten patients in the tailored FEC regimen developed acute myeloid leukaemia (AML)/myelodysplasia (MDS). One hundred deaths occurred in the tailored FEC group and 121 in the CTCb group (P = 0.287, HR 0.866, 95% CI 0.665-1.129). Conclusion: The update of this study shows an improved outcome linked to the tailored FEC treatment in relation to breast cancer relapse, but also an increased incidence of AML/MDS. © 2007 Oxford University Press.
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29.
  • Maroju, P. K., et al. (författare)
  • Analysis of two-color photoelectron spectroscopy for attosecond metrology at seeded free-electron lasers
  • 2021
  • Ingår i: New Journal of Physics. - : IOP Publishing. - 1367-2630. ; 23:4
  • Tidskriftsartikel (refereegranskat)abstract
    • The generation of attosecond pulse trains at free-electron lasers opens new opportunities in ultrafast science, as it gives access, for the first time, to reproducible, programmable, extreme ultraviolet (XUV) waveforms with high intensity. In this work, we present a detailed analysis of the theoretical model underlying the temporal characterization of the attosecond pulse trains recently generated at the free-electron laser FERMI. In particular, the validity of the approximations used for the correlated analysis of the photoelectron spectra generated in the two-color photoionization experiments are thoroughly discussed. The ranges of validity of the assumptions, in connection with the main experimental parameters, are derived.
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  • Nilsson, R. Henrik, 1976, et al. (författare)
  • Taxonomic annotation of public fungal ITS sequences from the built environment - a report from an April 10-11, 2017 workshop (Aberdeen, UK)
  • 2018
  • Ingår i: Mycokeys. - : Pensoft Publishers. - 1314-4057 .- 1314-4049. ; :28, s. 65-82
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent DNA-based studies have shown that the built environment is surprisingly rich in fungi. These indoor fungi - whether transient visitors or more persistent residents - may hold clues to the rising levels of human allergies and other medical and building-related health problems observed globally. The taxonomic identity of these fungi is crucial in such pursuits. Molecular identification of the built mycobiome is no trivial undertaking, however, given the large number of unidentified, misidentified, and technically compromised fungal sequences in public sequence databases. In addition, the sequence metadata required to make informed taxonomic decisions - such as country and host/substrate of collection - are often lacking even from reference and ex-type sequences. Here we report on a taxonomic annotation workshop (April 10-11, 2017) organized at the James Hutton Institute/University of Aberdeen (UK) to facilitate reproducible studies of the built mycobiome. The 32 participants went through public fungal ITS bar-code sequences related to the built mycobiome for taxonomic and nomenclatural correctness, technical quality, and metadata availability. A total of 19,508 changes - including 4,783 name changes, 14,121 metadata annotations, and the removal of 99 technically compromised sequences - were implemented in the UNITE database for molecular identification of fungi (https://unite.ut.ee/) and shared with a range of other databases and downstream resources. Among the genera that saw the largest number of changes were Penicillium, Talaromyces, Cladosporium, Acremonium, and Alternaria, all of them of significant importance in both culture-based and culture-independent surveys of the built environment.
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31.
  • Bahram, Mohammad, et al. (författare)
  • Structure and function of the global topsoil microbiome
  • 2018
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 560:7717, s. 233-7
  • Tidskriftsartikel (refereegranskat)abstract
    • Soils harbour some of the most diverse microbiomes on Earth and are essential for both nutrient cycling and carbon storage. To understand soil functioning, it is necessary to model the global distribution patterns and functional gene repertoires of soil microorganisms, as well as the biotic and environmental associations between the diversity and structure of both bacterial and fungal soil communities(1-4). Here we show, by leveraging metagenomics and metabarcoding of global topsoil samples (189 sites, 7,560 subsamples), that bacterial, but not fungal, genetic diversity is highest in temperate habitats and that microbial gene composition varies more strongly with environmental variables than with geographic distance. We demonstrate that fungi and bacteria show global niche differentiation that is associated with contrasting diversity responses to precipitation and soil pH. Furthermore, we provide evidence for strong bacterial-fungal antagonism, inferred from antibiotic-resistance genes, in topsoil and ocean habitats, indicating the substantial role of biotic interactions in shaping microbial communities. Our results suggest that both competition and environmental filtering affect the abundance, composition and encoded gene functions of bacterial and fungal communities, indicating that the relative contributions of these microorganisms to global nutrient cycling varies spatially.
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32.
  • Inzucchi, S. E., et al. (författare)
  • Dapagliflozin and the incidence of type 2 diabetes in patients with heart failure and reduced ejection fraction: An exploratory analysis from DAPA-HF
  • 2021
  • Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 44:2, s. 586-594
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE The sodium–glucose cotransporter 2 inhibitor dapagliflozin reduced the risk of cardiovascular mortality and worsening heart failure in the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) trial. This report explores the effect of dapagliflozin on incident type 2 diabetes (T2D) in the cohort without diabetes enrolled in the trial. RESEARCH DESIGN AND METHODS The subgroup of 2,605 patients with heart failure and reduced ejection fraction (HFrEF), no prior history of diabetes, and an HbA1c of <6.5% at baseline was randomized to dapagliflozin 10 mg daily or placebo. In this exploratory analysis, surveillance for new-onset diabetes was accomplished through periodic HbA1c testing as part of the study protocol and comparison between the treatment groups assessed through a Cox proportional hazards model. RESULTS At baseline, the mean HbA1c was 5.8%. At 8 months, there were minimal changes, withaplacebo-adjusted change inthedapagliflozin groupof20.04%. Over a median follow-up of 18 months, diabetes developed in 93 of 1,307 patients (7.1%) in the placebogroup and 64 of 1,298 (4.9%) in the dapagliflozingroup. Dapagliflozin led to a 32% reduction in diabetes incidence (hazard ratio 0.68, 95% CI 0.50–0.94; P 5 0.019). More than 95% of the participants who developed T2D had prediabetes at baseline (HbA1c 5.7–6.4%). Participants who developed diabetes in DAPA-HF had a higher subsequent mortality than those who did not. CONCLUSIONS In this exploratory analysis among patients with HFrEF, treatment with dapagliflozin reduced the incidence of new diabetes. This potential benefit needs confirmation in trials of longer duration and in people without heart failure. © 2020 by the American Diabetes Association.
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33.
  • Lundtoft, Christian, et al. (författare)
  • Strong Association of Combined Genetic Deficiencies in the Classical Complement Pathway With Risk of Systemic Lupus Erythematosus and Primary Sjogren's Syndrome
  • 2022
  • Ingår i: Arthritis & Rheumatology. - : Wiley. - 2326-5191 .- 2326-5205. ; 74:11, s. 1842-1850
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective Complete genetic deficiency of the complement component C2 is a strong risk factor for monogenic systemic lupus erythematosus (SLE), but whether heterozygous C2 deficiency adds to the risk of SLE or primary Sjogren's syndrome (SS) has not been studied systematically. This study was undertaken to investigate potential associations of heterozygous C2 deficiency and C4 copy number variation with clinical manifestations in patients with SLE and patients with primary SS. Methods The presence of the common 28-bp C2 deletion rs9332736 and C4 copy number variation was examined in Scandinavian patients who had received a diagnosis of SLE (n = 958) or primary SS (n = 911) and in 2,262 healthy controls through the use of DNA sequencing. The concentration of complement proteins in plasma and classical complement function were analyzed in a subgroup of SLE patients. Results Heterozygous C2 deficiency-when present in combination with a low C4A copy number-substantially increased the risk of SLE (odds ratio [OR] 10.2 [95% confidence interval (95% CI) 3.5-37.0]) and the risk of primary SS (OR 13.0 [95% CI 4.5-48.4]) when compared to individuals with 2 C4A copies and normal C2. For patients heterozygous for rs9332736 with 1 C4A copy, the median age at diagnosis was 7 years earlier in patients with SLE and 12 years earlier in patients with primary SS when compared to patients with normal C2. Reduced C2 levels in plasma (P = 2 x 10(-9)) and impaired function of the classical complement pathway (P = 0.03) were detected in SLE patients with heterozygous C2 deficiency. Finally, in a primary SS patient homozygous for C2 deficiency, we observed low levels of anti-Scl-70, which suggests a risk of developing systemic sclerosis or potential overlap between primary SS and other systemic autoimmune diseases. Conclusion We demonstrate that a genetic pattern involving partial deficiencies of C2 and C4A in the classical complement pathway is a strong risk factor for SLE and for primary SS. Our results emphasize the central role of the complement system in the pathogenesis of both SLE and primary SS.
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34.
  • Trainer, P J, et al. (författare)
  • Treatment of acromegaly with the growth hormone-receptor antagonist pegvisomant.
  • 2000
  • Ingår i: The New England journal of medicine. - 0028-4793. ; 342:16, s. 1171-7
  • Tidskriftsartikel (refereegranskat)abstract
    • Patients with acromegaly are currently treated with surgery, radiation therapy, and drugs to reduce hypersecretion of growth hormone, but the treatments may be ineffective and have adverse effects. Pegvisomant is a genetically engineered growth hormone-receptor antagonist that blocks the action of growth hormone.We conducted a 12-week, randomized, double-blind study of three daily doses of pegvisomant (10 mg, 15 mg, and 20 mg) and placebo, given subcutaneously, in 112 patients with acromegaly.The mean (+/-SD) serum concentration of insulin-like growth factor I (IGF-I) decreased from base line by 4.0+/-16.8 percent in the placebo group, 26.7+/-27.9 percent in the group that received 10 mg of pegvisomant per day, 50.1+/-26.7 percent in the group that received 15 mg of pegvisomant per day, and 62.5+/-21.3 percent in the group that received 20 mg of pegvisomant per day (P<0.001 for the comparison of each pegvisomant group with placebo), and the concentrations became normal in 10 percent, 54 percent, 81 percent, and 89 percent of patients, respectively (P<0.001 for each comparison with placebo). Among patients treated with 15 mg or 20 mg of pegvisomant per day, there were significant decreases in ring size, soft-tissue swelling, the degree of excessive perspiration, and fatigue. The score fortotal symptoms and signs of acromegaly decreased significantly in all groups receiving pegvisomant (P< or =0.05). The incidence of adverse effects was similar in all groups.On the basis of these preliminary results, treatment of patients who have acromegaly with a growth hormone-receptor antagonist results in a reduction in serum IGF-I concentrations and in clinical improvement.
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35.
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36.
  • Makos, I., et al. (författare)
  • Attosecond photoelectron spectroscopy using high-harmonic generation and seeded free-electron lasers
  • 2023
  • Ingår i: 2023 Photonics North, PN 2023. - 9798350326734
  • Konferensbidrag (refereegranskat)abstract
    • In this work, we use attosecond time-resolved techniques to investigate photoionization dynamics on its natural timescale, employing both high harmonic generation and seeded free-electron lasers to generate extreme ultraviolet attosecond pulse trains for our studies. With the former approach, we examine the role of nuclear motion in molecular photoionization dynamics, while with the latter we introduce a novel attosecond timing tool for single-shot characterization of the relative phase between the XUV and the infrared field.
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37.
  • Wormser, David, et al. (författare)
  • Adult height and the risk of cause-specific death and vascular morbidity in 1 million people : individual participant meta-analysis
  • 2012
  • Ingår i: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 41:5, s. 1419-1433
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundThe extent to which adult height, a biomarker of the interplay of genetic endowment and early-life experiences, is related to risk of chronic diseases in adulthood is uncertain.MethodsWe calculated hazard ratios (HRs) for height, assessed in increments of 6.5 cm, using individual-participant data on 174 374 deaths or major non-fatal vascular outcomes recorded among 1 085 949 people in 121 prospective studies.ResultsFor people born between 1900 and 1960, mean adult height increased 0.5-1 cm with each successive decade of birth. After adjustment for age, sex, smoking and year of birth, HRs per 6.5 cm greater height were 0.97 (95% confidence interval: 0.96-0.99) for death from any cause, 0.94 (0.93-0.96) for death from vascular causes, 1.04 (1.03-1.06) for death from cancer and 0.92 (0.90-0.94) for death from other causes. Height was negatively associated with death from coronary disease, stroke subtypes, heart failure, stomach and oral cancers, chronic obstructive pulmonary disease, mental disorders, liver disease and external causes. In contrast, height was positively associated with death from ruptured aortic aneurysm, pulmonary embolism, melanoma and cancers of the pancreas, endocrine and nervous systems, ovary, breast, prostate, colorectum, blood and lung. HRs per 6.5 cm greater height ranged from 1.26 (1.12-1.42) for risk of melanoma death to 0.84 (0.80-0.89) for risk of death from chronic obstructive pulmonary disease. HRs were not appreciably altered after further adjustment for adiposity, blood pressure, lipids, inflammation biomarkers, diabetes mellitus, alcohol consumption or socio-economic indicators.ConclusionAdult height has directionally opposing relationships with risk of death from several different major causes of chronic diseases.
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38.
  • Bengtsson-Palme, Johan, 1985, et al. (författare)
  • Towards monitoring of antimicrobial resistance in the environment: For what reasons, how to implement it, and what are the data needs?
  • 2023
  • Ingår i: Environment International. - 0160-4120 .- 1873-6750. ; 178
  • Tidskriftsartikel (refereegranskat)abstract
    • Antimicrobial resistance (AMR) is a global threat to human and animal health and well-being. To understand AMR dynamics, it is important to monitor resistant bacteria and resistance genes in all relevant settings. How-ever, while monitoring of AMR has been implemented in clinical and veterinary settings, comprehensive monitoring of AMR in the environment is almost completely lacking. Yet, the environmental dimension of AMR is critical for understanding the dissemination routes and selection of resistant microorganisms, as well as the human health risks related to environmental AMR. Here, we outline important knowledge gaps that impede implementation of environmental AMR monitoring. These include lack of knowledge of the 'normal' background levels of environmental AMR, definition of high-risk environments for transmission, and a poor understanding of the concentrations of antibiotics and other chemical agents that promote resistance selection. Furthermore, there is a lack of methods to detect resistance genes that are not already circulating among pathogens. We conclude that these knowledge gaps need to be addressed before routine monitoring for AMR in the environment can be implemented on a large scale. Yet, AMR monitoring data bridging different sectors is needed in order to fill these knowledge gaps, which means that some level of national, regional and global AMR surveillance in the envi-ronment must happen even without all scientific questions answered. With the possibilities opened up by rapidly advancing technologies, it is time to fill these knowledge gaps. Doing so will allow for specific actions against environmental AMR development and spread to pathogens and thereby safeguard the health and wellbeing of humans and animals.
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39.
  • Jackson, Alice M., et al. (författare)
  • Dapagliflozin and Diuretic Use in Patients With Heart Failure and Reduced Ejection Fraction in DAPA-HF.
  • 2020
  • Ingår i: Circulation. - 1524-4539. ; 142:11, s. 1040-1054
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: In the DAPA-HF trial (Dapagliflozin and Prevention of Adverse-Outcomes in Heart Failure), the sodium-glucose cotransporter 2 inhibitor dapagliflozin reduced the risk of worsening heart failure and death in patients with heart failure and reduced ejection fraction. We examined the efficacy and tolerability of dapagliflozin in relation to background diuretic treatment and change in diuretic therapy after randomization to dapagliflozin or placebo. METHODS: We examined the effects of study treatment in the following subgroups: no diuretic and diuretic dose equivalent to furosemide $<$40, 40, and $>$40 mg daily at baseline. We examined the primary composite end point of cardiovascular death or a worsening heart failure event and its components, all-cause death and symptoms. RESULTS: Of 4616 analyzable patients, 736 (15.9%) were on no diuretic, 1311 (28.4%) were on $<$40 mg, 1365 (29.6%) were on 40 mg, and 1204 (26.1%) were taking $>$40 mg. Compared with placebo, dapagliflozin reduced the risk of the primary end point across each of these subgroups: hazard ratios were 0.57 (95% CI, 0.36-0.92), 0.83 (95% CI, 0.63-1.10), 0.77 (95% CI, 0.60-0.99), and 0.78 (95% CI, 0.63-0.97), respectively (P for interaction=0.61). The hazard ratio in patients taking any diuretic was 0.78 (95% CI, 0.68-0.90). Improvements in symptoms and treatment toleration were consistent across the diuretic subgroups. Diuretic dose did not change in most patients during follow- up, and mean diuretic dose did not differ between the dapagliflozin and placebo groups after randomization. CONCLUSIONS: The efficacy and safety of dapagliflozin were consistent across the diuretic subgroups examined in DAPA-HF. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03036124.
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40.
  • Kindmark, Andreas, et al. (författare)
  • Genome-wide pharmacogenetic investigation of a hepatic adverse event without clinical signs of immunopathology suggests an underlying immune pathogenesis
  • 2008
  • Ingår i: The Pharmacogenomics Journal. - : Springer Science and Business Media LLC. - 1470-269X .- 1473-1150. ; 8:3, s. 186-195
  • Tidskriftsartikel (refereegranskat)abstract
    • One of the major goals of pharmacogenetics is to elucidate mechanisms and identify patients at increased risk of adverse events (AEs). To date, however, there have been only a few successful examples of this type of approach. In this paper, we describe a retrospective case–control pharmacogenetic study of an AE of unknown mechanism, characterized by elevated levels of serum alanine aminotransferase (ALAT) during long-term treatment with the oral direct thrombin inhibitor ximelagatran. The study was based on 74 cases and 130 treated controls and included both a genome-wide tag single nucleotide polymorphism and large-scale candidate gene analysis. A strong genetic association between elevated ALAT and the MHC alleles DRB1*07 and DQA1*02 was discovered and replicated, suggesting a possible immune pathogenesis. Consistent with this hypothesis, immunological studies suggest that ximelagatran may have the ability to act as a contact sensitizer, and hence be able to stimulate an adaptive immune response.
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41.
  • Kjaergaard, M., et al. (författare)
  • Demonstration of Density Matrix Exponentiation Using a Superconducting Quantum Processor
  • 2022
  • Ingår i: Physical Review X. - 2160-3308. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Quantum computers hold the potential to outperform classical supercomputers at certain tasks. To implement algorithms on a quantum computer, programmers use conventional computers and hardware to create a set of classical control signals that implement a desired quantum algorithm. However, feeding the quantum information forward requires an inefficient conversion: extraction of quantum information, conversion to classical control signals, and reinjection of those signals into the system to implement quantum operations. Here, we demonstrate a more natively quantum strategy to programming quantum computers. Our approach uses the density matrix exponentiation (DME) protocol, a general technique for using a quantum state to enact a quantum operation. It can be thought of as a subroutine with which programmers can turn multiple copies of a quantum state into instructions for next steps in a quantum algorithm.We implement DME using two qubits in a superconducting quantum processor. Our implementation relies on a high-fidelity two-qubit gate and a novel technique called quantum measurement emulation to approximately reset a known quantum state. These developments enable us to demonstrate the DME protocol for the first time on a small-scale quantum processor and benchmark its performance.While DME was originally proposed in the context of a specific quantum machine-learning algorithm, it may also represent a fundamentally different approach to quantum programming. It allows the possibility of encoding quantum algorithms directly into quantum states and executing those algorithms on other quantum states, enabling a new class of efficient quantum algorithms.
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42.
  • Petrie, Mark C, et al. (författare)
  • Effect of Dapagliflozin on Worsening Heart Failure and Cardiovascular Death in Patients With Heart Failure With and Without Diabetes.
  • 2020
  • Ingår i: JAMA. - : American Medical Association (AMA). - 1538-3598 .- 0098-7484. ; 323:14, s. 1353-1368
  • Tidskriftsartikel (refereegranskat)abstract
    • Additional treatments are needed for heart failure with reduced ejection fraction (HFrEF). Sodium-glucose cotransporter 2 (SGLT2) inhibitors may be an effective treatment for patients with HFrEF, even those without diabetes.To evaluate the effects of dapagliflozin in patients with HFrEF with and without diabetes.Exploratory analysis of a phase 3 randomized trial conducted at 410 sites in 20 countries. Patients with New York Heart Association classification II to IV with an ejection fraction less than or equal to 40% and elevated plasma N-terminal pro B-type natriuretic peptide were enrolled between February 15, 2017, and August 17, 2018, with final follow-up on June 6, 2019.Addition of once-daily 10 mg of dapagliflozin or placebo to recommended therapy.The primary outcome was the composite of an episode of worsening heart failure or cardiovascular death. This outcome was analyzed by baseline diabetes status and, in patients without diabetes, by glycated hemoglobin level less than 5.7% vs greater than or equal to 5.7%.Among 4744 patients randomized (mean age, 66 years; 1109 [23%] women; 2605 [55%] without diabetes), 4742 completed the trial. Among participants without diabetes, the primary outcome occurred in 171 of 1298 (13.2%) in the dapagliflozin group and 231 of 1307 (17.7%) in the placebo group (hazard ratio, 0.73 [95% CI, 0.60-0.88]). In patients with diabetes, the primary outcome occurred in 215 of 1075 (20.0%) in the dapagliflozin group and 271 of 1064 (25.5%) in the placebo group (hazard ratio, 0.75 [95% CI, 0.63-0.90]) (P value for interaction=.80). Among patients without diabetes and a glycated hemoglobin level less than 5.7%, the primary outcome occurred in 53 of 438 patients (12.1%) in the dapagliflozin group and 71 of 419 (16.9%) in the placebo group (hazard ratio, 0.67 [95% CI, 0.47-0.96]). In patients with a glycated hemoglobin of at least 5.7%, the primary outcome occurred in 118 of 860 patients (13.7%) in the dapagliflozin group and 160 of 888 (18.0%) in the placebo group (hazard ratio, 0.74 [95% CI, 0.59-0.94]) (P value for interaction=.72). Volume depletion was reported as an adverse event in 7.3% of patients in the dapagliflozin group and 6.1% in the placebo group among patients without diabetes and in 7.8% of patients in the dapagliflozin group and 7.8% in the placebo group among patients with diabetes. A kidney adverse event was reported in 4.8% of patients in the dapagliflozin group and 6.0% in the placebo group among patients without diabetes and in 8.5% of patients in the dapagliflozin group and 8.7% in the placebo group among patients with diabetes.In this exploratory analysis of a randomized trial of patients with HFrEF, dapagliflozin compared with placebo, when added to recommended therapy, significantly reduced the risk of worsening heart failure or cardiovascular death independently of diabetes status.ClinicalTrials.gov Identifier: NCT03036124.
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43.
  • Serenelli, Matteo, et al. (författare)
  • Effect of dapagliflozin according to baseline systolic blood pressure in the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure trial (DAPA-HF).
  • 2020
  • Ingår i: European heart journal. - : Oxford University Press (OUP). - 1522-9645 .- 0195-668X. ; 41:36, s. 3402-3418
  • Tidskriftsartikel (refereegranskat)abstract
    • Concern about hypotension often leads to withholding of beneficial therapy in patients with heart failure and reduced ejection fraction (HFrEF). We evaluated the efficacy and safety of dapagliflozin, which lowers systolic blood pressure (SBP),according to baseline SBP in Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure trial (DAPA-HF).Key inclusion criteria were: New York Heart Association Class II-IV, left ventricular ejection fraction ≤ 40%, elevated N-terminal pro-B-type natriuretic peptide level, and SBP ≥95mmHg. The primary outcome was a composite of worsening heart failure or cardiovascular death. The efficacy and safety of dapagliflozin were examined using SBP as both a categorical and continuous variable. A total of 1205 patients had a baseline SBP <110mmHg; 981≥110<120; 1149≥120<130; and 1409≥130mmHg. The placebo-corrected reduction in SBP from baseline to 2weeks with dapagliflozin was -2.54 (-3.33 to -1.76) mmHg (P<0.001), with a smaller between-treatment difference in patients in the lowest compared to highest SBP category. Patients in the lowest SBP category had a much higher rate (per 100 person-years) of the primary outcome [20.6, 95% confidence interval (95% CI) 17.6-24.2] than those in the highest SBP category (13.8, 11.7-16.4). The benefit and safety of dapagliflozin was consistent across the range of SBP; hazard ratio (95% CI) in each SBP group, lowest to highest: 0.76 (0.60-0.97), 0.76 (0.57-1.02), 0.81 (0.61-1.08), and 0.67 (0.51-0.87), P interaction = 0.78. Study drug discontinuation did not differ between dapagliflozin and placebo across the SBP categories examined.Dapagliflozin had a small effect on SBP in patients with HFrEF and was superior to placebo in improving outcomes, and well tolerated, across the range of SBP included in DAPA-HF.ClinicalTrials.gov NCT03036124.
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44.
  • Weinreich, I. D., et al. (författare)
  • Scandiatransplant Exchange Program (STEP): Development and Results From an International Kidney Exchange Program
  • 2023
  • Ingår i: Transplantation Direct. - 2373-8731. ; 9:11
  • Tidskriftsartikel (refereegranskat)abstract
    • Background. Kidney transplant candidates may be incompatible with their intended living donors because of the presence of antibodies against HLA and/or ABO. To increase the possibility of finding an acceptable kidney donor for these patients, the Scandiatransplant Exchange Program (STEP) program within Scandiatransplant was launched in 2019.Methods. This is a retrospective review of our experiences from the first 4 y of the STEP program, including details about the match runs, performed transplantations, and recipient outcomes within the program.Results. During 2019-2022, 11 match runs and 4 reruns were performed. In total, 114 pairs and 6 anonymous donors participated in these match runs. Fifty-one pairs (45%) participated in 1 match run, 31 pairs (27%) participated in 2 match runs, and 32 pairs (29%) participated in >= 3 match runs. Seventy-two individuals (63%) participated because of HLA incompatibility, 19 (17%) because of ABO incompatibility, and 7 (6%) because of both HLA and ABO incompatibility. Forty percent of the patients enrolled in the program underwent transplantation. In total, 49 transplantations have so far been performed within the program, and 46 (94%) of the recipients had a functioning kidney graft at follow-up in February 2023.Results. During 2019-2022, 11 match runs and 4 reruns were performed. In total, 114 pairs and 6 anonymous donors participated in these match runs. Fifty-one pairs (45%) participated in 1 match run, 31 pairs (27%) participated in 2 match runs, and 32 pairs (29%) participated in >= 3 match runs. Seventy-two individuals (63%) participated because of HLA incompatibility, 19 (17%) because of ABO incompatibility, and 7 (6%) because of both HLA and ABO incompatibility. Forty percent of the patients enrolled in the program underwent transplantation. In total, 49 transplantations have so far been performed within the program, and 46 (94%) of the recipients had a functioning kidney graft at follow-up in February 2023.Conclusions. The STEP program offers sensitized patients an enlarged pool of living donors and a chance of a compatible international living donor, resulting in an increased number of total transplantations. Currently, STEP is one of the largest transnational kidney exchange programs and has improved the situation for patients waiting for kidney transplantation in Scandiatransplant.
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45.
  • Yadav, R. B., et al. (författare)
  • Identification of triaxial strongly deformed bands in Hf-168
  • 2008
  • Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 78:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Possible decay pathways associated with three candidates for triaxial strongly deformed (TSD) bands in Hf-168 have been investigated. The spin and excitation energy of the strongest band, TSD1, were determined approximately based on gamma-ray coincidence relationships. Discrete links were established for the second band. The overall agreement between the observed properties of the bands and cranking calculations using the ULTIMATE CRANKER code provides strong support for an interpretation where band TSD1 is associated with a TSD minimum, (epsilon(2),gamma)similar to(0.43,20(degrees)), involving the pi(i(13/2))(2) and the nu(j(15/2)) high-j orbitals. This constitutes the first identification of a TSD band in Hf isotopes, which has been long-predicted by theoretical studies. The second band is understood as being associated with a near-prolate shape and a deformation enhanced with respect to the normal deformed bands. It is proposed to be built on the pi(i(13/2)h(9/2))circle times nu(i(13/2))(2) configuration.
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46.
  • Bengtsson, L, et al. (författare)
  • Using mobile phone data to predict the spatial spread of cholera
  • 2015
  • Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 5, s. 8923-
  • Tidskriftsartikel (refereegranskat)abstract
    • Effective response to infectious disease epidemics requires focused control measures in areas predicted to be at high risk of new outbreaks. We aimed to test whether mobile operator data could predict the early spatial evolution of the 2010 Haiti cholera epidemic. Daily case data were analysed for 78 study areas from October 16 to December 16, 2010. Movements of 2.9 million anonymous mobile phone SIM cards were used to create a national mobility network. Two gravity models of population mobility were implemented for comparison. Both were optimized based on the complete retrospective epidemic data, available only after the end of the epidemic spread. Risk of an area experiencing an outbreak within seven days showed strong dose-response relationship with the mobile phone-based infectious pressure estimates. The mobile phone-based model performed better (AUC 0.79) than the retrospectively optimized gravity models (AUC 0.66 and 0.74, respectively). Infectious pressure at outbreak onset was significantly correlated with reported cholera cases during the first ten days of the epidemic (p < 0.05). Mobile operator data is a highly promising data source for improving preparedness and response efforts during cholera outbreaks. Findings may be particularly important for containment efforts of emerging infectious diseases, including high-mortality influenza strains.
  •  
47.
  • Bengtsson, S., et al. (författare)
  • Space–time control of free induction decay in the extreme ultraviolet
  • 2017
  • Ingår i: Nature Photonics. - : Springer Science and Business Media LLC. - 1749-4885 .- 1749-4893. ; 11:4, s. 252-258
  • Tidskriftsartikel (refereegranskat)abstract
    • Ultrafast extreme-ultraviolet (XUV) and X-ray sources are revolutionizing our ability to follow femtosecond processes with ångström-scale resolution. The next frontier is to simultaneously control the direction, duration and timing of such radiation. Here, we demonstrate a fully functional opto-optical modulator for XUV light, similar to modulators available at infrared (IR) and visible wavelengths. It works by using an IR pulse to control the spatial and spectral phase of the free induction decay that results from using attosecond pulses to excite a gas. The modulator allows us to send the XUV light in a direction of our choosing at a time of our choosing. The inherent synchronization of the XUV emission to the control pulse will allow laser-pump/X-ray probe experiments with sub-femtosecond time resolution.
  •  
48.
  • Birkhofer, Klaus, et al. (författare)
  • Relationships between multiple biodiversity components and ecosystem services along a landscape complexity gradient
  • 2018
  • Ingår i: Biological Conservation. - : Elsevier BV. - 0006-3207 .- 1873-2917. ; 218, s. 247-253
  • Tidskriftsartikel (refereegranskat)abstract
    • The assessment of effects of anthropogenic disturbance on biodiversity (BD) and ecosystem services (ES) and their relationships are key priorities of the Intergovernmental Panel for Biodiversity and Ecosystem Services. Agricultural landscapes and their associated BD provide multiple ES and it is crucial to understand how relationships between ES and BD components change along gradients of landscape complexity. In this study, we related eight ES potentials to the species richness of five invertebrate, vertebrate and plant taxonomic groups in cereal farming systems. The landscape complexity gradient ranged from areas dominated by annually tilled arable land to areas with high proportions of unfertilized, non-rotational pastures and uncultivated field borders. We show that after accounting for landscape complexity relationships between yield and bird richness or biological control became more positive, but relationships between bird richness and biological control became less positive. The relationship between bird and plant richness turned from positive to negative. Multidiversity (overall biodiversity), was positively related to landscape complexity, whereas multifunctionality (overall ES provision), was not significantly related to either one of these. Our results suggest that multidiversity can be promoted by increasing landscape complexity; however; we found no support for a simultaneous increase of several individual ES, BD components or multifunctionality. These results challenge the assumption that bio-diversity-friendly landscape management will always simultaneously promote multiple ES in agricultural landscapes. Future studies need to verify this pattern by using multi-year data, larger sets of ES and BD components and a study design that is appropriate to address larger spatial scales and relationships in several regions.
  •  
49.
  • Blystad, A K, et al. (författare)
  • High-dose therapy with autologous stem cell transplantation in patients with peripheral T cell lymphomas.
  • 2001
  • Ingår i: Bone Marrow Transplantation. - : Springer Science and Business Media LLC. - 0268-3369 .- 1476-5365. ; 27:7, s. 711-6
  • Tidskriftsartikel (refereegranskat)abstract
    • Peripheral T cell lymphomas (PTCL) have a poorer prognosis after conventional treatment than do high-grade B cell lymphomas. The place for high-dose therapy (HDT) with autologous stem cell support in these patients is still not clear. Forty patients, 10 women and 30 men, median age 41.5 years (range 16-61) with PTCL were treated with HDT and autologous stem cell support at The Norwegian Radium Hospital, Oslo, Norway and The University Hospital, Uppsala, Sweden, between February 1990 and September 1999. The histologic subtypes were: PTCL unspecified, 20 patients; intestinal, two patients; angioimmunoblastic (AILD), two patients; angiocentric, two patients and anaplastic large cell lymphoma (ALCL), 14 patients. All patients had chemosensitive disease and had received anthracycline-containing regimens prior to transplantation. At the time of HDT, 17 patients were in first PR or CR and 23 were in second or third PR or CR. Conditioning regimens were BEAM in 15 patients, BEAC in 14 patients, cyclophosphamide and total body irradiation (TBI) in eight patients, BEAC, without etoposide and TBI in one patient and mitoxantrone and melphalan in two patients. There were three (7.5%) treatment-related deaths. The estimated overall survival (OS) at 3 years was 58%, the event-free survival (EFS) 48% and the relapse-free survival (RFS) 56%, with a median follow-up of 36 months (range 7-100) for surviving patients. The patients with ALCL tended to have a better prognosis compared to those with other PTCL subtypes, OS 79% vs 44%, respectively. In conclusion, patients with chemosensitive PTCL who are failing to achieve CR with first-line chemotherapy or are in relapse can successfully be treated with HDT and autologous stem cell support.
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50.
  • Bäckström, Torbjörn, et al. (författare)
  • Paradoxical effects of GABA-A modulators may explain sex steroid induced negative mood symptoms in some persons
  • 2011
  • Ingår i: Neuroscience. - Oxford : Elsevier BV. - 0306-4522 .- 1873-7544. ; 191:Special issue, s. 46-54
  • Forskningsöversikt (refereegranskat)abstract
    • Some women have negative mood symptoms, caused by progestagens in hormonal contraceptives or sequential hormone therapy or by progesterone in the luteal phase of the menstrual cycle, which may be attributed to metabolites acting on the GABA-A receptor. The GABA system is the major inhibitory system in the adult CNS and most positive modulators of the GABA-A receptor (benzodiazepines, barbiturates, alcohol, GABA steroids), induce inhibitory (e.g. anesthetic, sedative, anticonvulsant, anxiolytic) effects. However, some individuals have adverse effects (seizures, increased pain, anxiety, irritability, aggression) upon exposure. Positive GABA-A receptor modulators induce strong paradoxical effects including negative mood in 3%-8% of those exposed, while up to 25% have moderate symptoms. The effect is biphasic: low concentrations induce an adverse anxiogenic effect while higher concentrations decrease this effect and show inhibitory, calming properties. The prevalence of premenstrual dysphoric disorder (PMDD) is also 3%-8% among women in fertile ages, and up to 25% have more moderate symptoms of premenstrual syndrome (PMS). Patients with PMDD have severe luteal phase-related symptoms and show changes in GABA-A receptor sensitivity and GABA concentrations. Findings suggest that negative mood symptoms in women with PMDD are caused by the paradoxical effect of allopregnanolone mediated via the GABA-A receptor, which may be explained by one or more of three hypotheses regarding the paradoxical effect of GABA steroids on behavior: (1) under certain conditions, such as puberty, the relative fraction of certain GABA-A receptor subtypes may be altered, and at those subtypes the GABA steroids may act as negative modulators in contrast to their usual role as positive modulators; (2) in certain brain areas of vulnerable women the transmembrane C1(-) gradient may be altered by factors such as estrogens that favor excitability; (3) inhibition of inhibitory neurons may promote disinhibition, and hence excitability. This article is part of a Special Issue entitled: Neuroactive Steroids: Focus on Human Brain. (C) 2011 Published by Elsevier Ltd on behalf of IBRO.
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