| 1. |
- Afghahi, Henri, 1966, et al.
(författare)
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Long-term glycemic variability and the risk of mortality in diabetic patients receiving peritoneal dialysis.
- 2022
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- The large amount of glucose in the dialysate used in peritoneal dialysis (PD) likely affects the glycemic control. The aim of this study was to investigate the association between HbA1c variability, as a measure of long-term glycemic variability, and the risk of all-cause mortality in diabetic patients with PD.325 patients with diabetes and ESRD were followed (2008-2018) in the Swedish Renal Registry. Patients were separated in seven groups according to level of HbA1c variability. The group with the lowest variability was denoted the reference. The ratio of the standard deviation (SD) to the mean of HbA1c, HbA1c (SD)/HbA1c (mean), i.e. the coefficient of variation (CV), was defined as HbA1c variability. Hazard ratios (HR) and 95% confidence intervals (CI) were examined using Cox regression analyses.During follow-up, 170 (52%) deaths occurred. The highest mortality was among patients with the second highest HbA1c variability, CV≥2.83 [n = 44 of which 68% patients died]. In the multivariate analyses where lowest HbA1c variability (CV≤0.51) was used as the reference group, HbA1c CV 2.83-4.60 (HR 3.15, 95% CI 1.78-5.55; p<0.001) and CV> 4.6 (HR 2.48, 95% CI 1.21-5.11; p = 0.014) were associated with increased risk of death.The high risk of all-cause mortality in patients with diabetes and PD increased significantly with elevated HbA1c variability, as measure of long-term glycemic control. This indicates that stable glycemia is associated with an improvement of survival; whereas more severe glycemic fluctuations, possibly caused by radical changes in dialysis regimes or peritonitis, are associated with a higher risk of mortality in diabetic patients with PD.
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| 2. |
- Afghahi, Henri, 1966, et al.
(författare)
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The association between long-term glycemic control and all-cause mortality is different among older versus younger patients with diabetes mellitus and maintenance hemodialysis treatment.
- 2022
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Ingår i: Diabetes research and clinical practice. - : Elsevier BV. - 1872-8227 .- 0168-8227. ; 191
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Tidskriftsartikel (refereegranskat)abstract
- Knowledge about association between glycated hemoglobin (HbA1c) and risk of all-cause mortality in patients with diabetes mellitus on maintenance hemodialysis (HD)-treatment is sparse. The study aims to investigate association between HbA1c and all-cause mortality in patients with diabetes and maintenance HD-treatment, separately for two age groups- above and below 75years.2487 patients (mean age 66years, 66% men) were separated in two age groups: ≤75years (n=1810) and>75years (n=677) and followed up between 2008 and 2018. Hazard ratios (HR) and 95% confidence intervals (CI) for associations between HbA1c and all-cause mortality were calculated using Cox-regression-models.1295 (52%) patients died and 473 (70%) among the patients above 75years old. In the multivariate analysis, HbA1c5-6% was used as reference. In patients≤75years old, only increased HbA1c>9.7%, HR2.03(CI1.43-2.89) was associated with increased risk of all-cause mortality. In patients>75years, HbA1c≤5%, HR1.67(CI1.16-2.40); HbA1c6.9-7.8%, HR1.41(CI1.03-1.93) and HbA1c8.7-9.7%, HR1.79 (CI1.08-2.96) were associated with increased risk of all-cause mortality.We found a J-shaped association between HbA1c and mortality only in diabetic HD-patients>75years. This probably indicates that in an old population of diabetic HD-patients, both intensive glucose control and hyperglycemia could be harmful and associated with higher risk of death.
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| 3. |
- Andersson, Jan, 1965-, et al.
(författare)
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Regeringsuppdrag synfält : utredning om förutsättningar för undantag från de medicinska kraven för individer med synfältsbortfall
- 2022
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- I regeringsuppdraget (I2021/ 02412) framgår att VTI, i samarbete med Trafikverket och Transportstyrelsen, ska utreda förutsättningarna för undantagshantering från de medicinska föreskrifterna med avseende på synfältsbortfall (B-körkort). Vidare ska tre aspekter beaktas: hur andra länder gör, konsekvenser för den enskilde samt samhällsekonomiska konsekvenser. Slutrapporten påvisar att Sverige med gällande rättsligt ramverk inte kan genomföra de förslag som slutrapporten föreslår. Det innebär att det kommer att krävas juridiska förändringar. Givet att dessa förändringar genomförs och att ett nytt förfaringssätt nyttjas visar slutrapporten på att a) positiva effekter för den enskilde individen uppstår, b) samhällsekonomiska vinster uppstår och c) en rättssäker och rättvis prövning är möjlig. Slutrapporten redovisar dessutom hur ett urval av andra länder har hanterat handläggningen av individer med synfältsbortfall givet samma EU-direktiv som Sverige regleras av. Det framgår också av undersökningen att samtliga länder, som en förutsättning för undantag från de föreskrivna kraven avseende synfält, tillämpar krav eller rekommendationer om att ett praktiskt körprov ska utgöra del i underlaget för bedömning av körförmågan. Kunskapsläget med avseende på körförmågebedömningar för individer med synfältsbortfall redovisas och där framgår med tydlighet att perimetrin som Sverige utnyttjar som underlag för återkallelse av körkort inte kan predicera individers körförmåga. Perimetrin är dock viktig eftersom individer med synfältsbortfall som grupp kan vara olämpliga förare. Slutsatsen som forskningslitteraturen enstämmigt lyfter är att det behövs förarprov (på väg eller i en simulator) för att kunna genomföra en valid bedömning. Slutligen innehåller slutrapporten vilka problem (aktiviteter) som kvarstår för att skapa en lämplig och kvalitetssäkrad process. Dessutom presenteras den kronologiska ordning på aktiviteter som behöver genomföras. Kronologin krävs eftersom resultatet av lämplig metod och aktör påverkar det vidare arbetet med avseende på utformning av körprov och rättsligt ramverk. Slutrapportens slutsats är att Sverige har möjligheten att genomföra en förändring med avsevärda nyttor. Detta eftersom de valda aktörerna och de valda metoderna existerar idag och därför endast behöver utvecklas i viss mån för att säkerställa att individer med synfältsbortfall erbjuds en kvalitetssäkrad, rättssäker och rättvis process som dessutom bedöms vara samhällsekonomiskt lönsam.
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| 4. |
- Andersson, Jan, 1965-, et al.
(författare)
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The importance of reaction time, cognition, and meta-cognition abilities for drivers with visual deficits
- 2020
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Ingår i: Cognition, Technology & Work. - : Springer. - 1435-5558 .- 1435-5566. ; 22:4, s. 787-800
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Tidskriftsartikel (refereegranskat)abstract
- Individuals who do not fulfill required visual field standards have their driving license withdrawn in Sweden. However, understanding of the ability to compensate for this loss is limited. This study aimed to determine if reaction time and cognitive performance are important for safe driving in visual field loss (VFL) individuals. Visually demanding reaction time tasks of different complexity, for example, can help one understand why some VFL individuals drive as safely as normally sighted individuals. Twenty VFL individuals and 83 normally sighted individuals participated in a driving simulator experiment and an additional test battery. The driving task categorized VFL participants into two subgroups: passed or failed. Three reaction time tasks, four cognitive tests, and two meta-cognitive scales were completed. The passed VFL subgroup was faster than the failed subgroup in the context-dependent reaction time task and slower in the context-independent reaction time task. The passed subgroup performed equally well, or less well, on the cognitive tasks compared to the failed subgroup. The VFL participants performed less well than the normally sighted individuals on most cognitive tasks. However, VFL participants did not reflect on their driving ability (in meta-cognitive scales) in the same way as normally sighted individuals. There appear to be VFL subgroups in terms of ability to drive safely. Reaction time is important, but context dependent. Cognitive context-independent tests appear unrelated to driving test outcome for VFL individuals. The problems with context-independent testing of perceptual, cognitive, and meta-cognitive abilities when predicting safe driving capabilities are discussed. © 2019, The Author(s).
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| 5. |
- Arvidsson, Rickard, 1984, et al.
(författare)
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Using industrial default values for prospective modeling of new materials production – the case of photon upconversion materials for solar modules
- 2021
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Several approaches to upscaling of materials production processes in the context of prospective life cycle assessment (LCA) have been proposed. Often, such approaches are bottom-up, departing from laboratory-scale descriptions of production processes and from that creating a model of future large-scale production. While such approaches make use of the material-specific knowledge available at the time of the assessment, they often neglect emergent aspects that may be present at factory level. An alternative, more top-down approach is to use industrial default values, i.e. average or typical values of inputs and outputs reflecting materials production today. Since production facilities normally do not change drastically over at least 10 years, such values might be relevant in prospective LCAs, at least given modest time horizons. Such default values can also be modified based on assumptions about future changes, such as increased energy recovery or novel solvent recovery processes. We applied previously derived industrial default values for fine chemical production when modeling the production of two materials with potential use in photon upconversion applications: lead sulfide (PbS) and lead selenide (PbSe) nanoparticles. Photon upconversion means that two low-energy photons are converted into one higher-energy photon utilizable by a solar module. While we used some material-specific values, such as synthesis-specific yields, most auxiliary input and output values (e.g. solvents, inert gas, heat, electricity and emissions) instead represent factory-scale values for current fine chemical production. Considering the availability of both best- and worst-case default values, it was possible to derive ranges for the likely future environmental impacts of the two materials. We conclude that the approach is feasible, but the availability of more up-to-date industrial default values would make it even more relevant in prospective LCAs.
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| 6. |
- Broadaway, K Alaine, et al.
(författare)
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Loci for insulin processing and secretion provide insight into type 2 diabetes risk.
- 2023
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Ingår i: American Journal of Human Genetics. - : Elsevier. - 0002-9297 .- 1537-6605. ; 110:2, s. 284-299
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Tidskriftsartikel (refereegranskat)abstract
- Insulin secretion is critical for glucose homeostasis, and increased levels of the precursor proinsulin relative to insulin indicate pancreatic islet beta-cell stress and insufficient insulin secretory capacity in the setting of insulin resistance. We conducted meta-analyses of genome-wide association results for fasting proinsulin from 16 European-ancestry studies in 45,861 individuals. We found 36 independent signals at 30 loci (p value < 5 × 10-8), which validated 12 previously reported loci for proinsulin and ten additional loci previously identified for another glycemic trait. Half of the alleles associated with higher proinsulin showed higher rather than lower effects on glucose levels, corresponding to different mechanisms. Proinsulin loci included genes that affect prohormone convertases, beta-cell dysfunction, vesicle trafficking, beta-cell transcriptional regulation, and lysosomes/autophagy processes. We colocalized 11 proinsulin signals with islet expression quantitative trait locus (eQTL) data, suggesting candidate genes, including ARSG, WIPI1, SLC7A14, and SIX3. The NKX6-3/ANK1 proinsulin signal colocalized with a T2D signal and an adipose ANK1 eQTL signal but not the islet NKX6-3 eQTL. Signals were enriched for islet enhancers, and we showed a plausible islet regulatory mechanism for the lead signal in the MADD locus. These results show how detailed genetic studies of an intermediate phenotype can elucidate mechanisms that may predispose one to disease.
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| 7. |
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| 8. |
- Eriksson, Elina, 1979-, et al.
(författare)
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Addressing Students’ Eco-anxiety when Teaching Sustainability in Higher Education
- 2022
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Ingår i: Proceedings - 2022 International Conference on ICT for Sustainability, ICT4S 2022. - : Institute of Electrical and Electronics Engineers (IEEE). ; , s. 88-98
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Konferensbidrag (refereegranskat)abstract
- The widespread awareness and the sense of urgency and helplessness regarding the ongoing sustainability crisis (climate change, biodiversity loss etc.) can evoke feelings of grief, sorrow, despair and anxiety. Those emotions are seldom discussed in computing or in computing education. They can have detrimental effects on the well-being of students and others, and also lead to inaction. But concern can on the other hand also be a catalyst for learning. In this paper, we present results and reflections from a research and development project in our introductory course to sustainability and ICT focusing on emotions in sustainability education. We focus on “eco-anxiety” and ask: 1) How is eco-anxiety communicated by students and teachers?, 2) In what ways do students receive support to deal with eco-anxiety? and 3) What could be done to better address eco-anxiety in computing education? We here present an analysis of how we have responded to the phenomenon of eco-anxiety, what activities have been added to the course and an evaluation of these interventions. The results are based on joint reflections that have been guided by literature, a small-scale ethnographic study as well as a course evaluation. The paper will end with recommendations for other ICT4S educators on how they can start addressing eco-anxiety in their education.
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| 9. |
- Harlacher, Eva, et al.
(författare)
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Increased levels of a mycophenolic acid metabolite in patients with kidney failure negatively affect cardiomyocyte health.
- 2024
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Ingår i: Frontiers in cardiovascular medicine. - 2297-055X. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Chronic kidney disease (CKD) significantly increases cardiovascular risk and mortality, and the accumulation of uremic toxins in the circulation upon kidney failure contributes to this increased risk. We thus performed a screening for potential novel mediators of reduced cardiovascular health starting from dialysate obtained after hemodialysis of patients with CKD. The dialysate was gradually fractionated to increased purity using orthogonal chromatography steps, with each fraction screened for a potential negative impact on the metabolic activity of cardiomyocytes using a high-throughput MTT-assay, until ultimately a highly purified fraction with strong effects on cardiomyocyte health was retained. Mass spectrometry and nuclear magnetic resonance identified the metabolite mycophenolic acid-β-glucuronide (MPA-G) as a responsible substance. MPA-G is the main metabolite from the immunosuppressive agent MPA that is supplied in the form of mycophenolate mofetil (MMF) to patients in preparation for and after transplantation or for treatment of autoimmune and non-transplant kidney diseases. The adverse effect of MPA-G on cardiomyocytes was confirmed in vitro, reducing the overall metabolic activity and cellular respiration while increasing mitochondrial reactive oxygen species production in cardiomyocytes at concentrations detected in MMF-treated patients with failing kidney function. This study draws attention to the potential adverse effects of long-term high MMF dosing, specifically in patients with severely reduced kidney function already displaying a highly increased cardiovascular risk.
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| 10. |
- Harlid, Sophia, 1978-, et al.
(författare)
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Diabetes mellitus in relation to colorectal tumor molecular subtypes : a pooled analysis of more than 9000 cases
- 2022
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Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 151:3, s. 348-360
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Tidskriftsartikel (refereegranskat)abstract
- Diabetes is an established risk factor for colorectal cancer. However, colorectal cancer is a heterogeneous disease and it is not well understood whether diabetes is more strongly associated with some tumor molecular subtypes than others. A better understanding of the association between diabetes and colorectal cancer according to molecular subtypes could provide important insights into the biology of this association. We used data on lifestyle and clinical characteristics from the Colorectal Cancer Family Registry (CCFR) and the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), including 9756 colorectal cancer cases (with tumor marker data) and 9985 controls, to evaluate associations between reported diabetes and risk of colorectal cancer according to molecular subtypes. Tumor markers included BRAF and KRAS mutations, microsatellite instability and CpG island methylator phenotype. In the multinomial logistic regression model, comparing colorectal cancer cases to cancer-free controls, diabetes was positively associated with colorectal cancer regardless of subtype. The highest OR estimate was found for BRAF-mutated colorectal cancer, n = 1086 (ORfully adj: 1.67, 95% confidence intervals [CI]: 1.36-2.05), with an attenuated association observed between diabetes and colorectal cancer without BRAF-mutations, n = 7959 (ORfully adj: 1.33, 95% CI: 1.19-1.48). In the case only analysis, BRAF-mutation was differentially associated with diabetes (Pdifference = .03). For the other markers, associations with diabetes were similar across tumor subtypes. In conclusion, our study confirms the established association between diabetes and colorectal cancer risk, and suggests that it particularly increases the risk of BRAF-mutated tumors.
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| 11. |
- Kanoni, Stavroula, et al.
(författare)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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| 12. |
- Kleineidam, Luca, et al.
(författare)
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Midlife occupational cognitive requirements protect cognitive function in old age by increasing cognitive reserve
- 2022
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Ingår i: Frontiers in Psychology. - : Frontiers Media SA. - 1664-1078. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Several lifestyle factors promote protection against Alzheimer's disease (AD) throughout a person's lifespan. Although such protective effects have been described for occupational cognitive requirements (OCR) in midlife, it is currently unknown whether they are conveyed by brain maintenance (BM), brain reserve (BR), or cognitive reserve (CR) or a combination of them. Methods: We systematically derived hypotheses for these resilience concepts and tested them in the population-based AgeCoDe cohort and memory clinic-based AD high-risk DELCODE study. The OCR score (OCRS) was measured using job activities based on the O*NET occupational classification system. Four sets of analyses were conducted: (1) the interaction of OCR and APOE-ε4 with regard to cognitive decline (N = 2,369, AgeCoDe), (2) association with differentially shaped retrospective trajectories before the onset of dementia of the Alzheimer's type (DAT; N = 474, AgeCoDe), (3) cross-sectional interaction of the OCR and cerebrospinal fluid (CSF) AD biomarkers and brain structural measures regarding memory function (N = 873, DELCODE), and (4) cross-sectional and longitudinal association of OCR with CSF AD biomarkers and brain structural measures (N = 873, DELCODE). Results: Regarding (1), higher OCRS was associated with a reduced association of APOE-ε4 with cognitive decline (mean follow-up = 6.03 years), consistent with CR and BR. Regarding (2), high OCRS was associated with a later onset but subsequently stronger cognitive decline in individuals converting to DAT, consistent with CR. Regarding (3), higher OCRS was associated with a weaker association of the CSF Aβ42/40 ratio and hippocampal volume with memory function, consistent with CR. Regarding (4), OCR was not associated with the levels or changes in CSF AD biomarkers (mean follow-up = 2.61 years). We found a cross-sectional, age-independent association of OCRS with some MRI markers, but no association with 1-year-change. OCR was not associated with the intracranial volume. These results are not completely consistent with those of BR or BM. Discussion: Our results support the link between OCR and CR. Promoting and seeking complex and stimulating work conditions in midlife could therefore contribute to increased resistance to pathologies in old age and might complement prevention measures aimed at reducing pathology.
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| 13. |
- Mölne, Johan, et al.
(författare)
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Glomerular macrophage index (GMI) in kidney transplant biopsies is associated with graft outcome
- 2022
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Ingår i: Clinical Transplantation. - : John Wiley & Sons. - 0902-0063 .- 1399-0012. ; 36:12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Macrophages in renal transplants have been shown to participate in antibody-mediated rejection and are associated with impaired renal function. We calculated the glomerular macrophage index (GMI) in a large transplant biopsy cohort, studied its quantity in different diagnostic groups, to clarify its possible impact on graft survival.Methods: GMI, defined as the mean number of macrophages in 10 glomeruli, was prospectively quantified in 1440 renal transplant biopsies over a 10-year period. The main histopathological diagnoses were grouped into eight disease entities, and GMI was compared to normal transplant biopsies as the reference group. The impact of GMI on graft survival was analyzed.Results: GMI was highest in chronic (mean 9.4) and active (9.7) antibody mediated rejections (ABMR), mixed rejections (7.6), and recurrent or de novo glomerulonephritis (7.5) and differed significantly from normal transplants (1.3) in almost all diagnostic groups. Hazard ratios for graft loss were significantly increased for all biopsies with GMI ≥1.9 compared to GMI <.5 (reference group) in an adjusted Cox regression model and increased with higher GMI levels. Biopsies with GMI ≥ 4.6 had < 60% 10-year graft-survival, compared to > 80% with GMI ≤ 1.8.Conclusion: GMI levels were predictive of graft loss independent of histological diagnoses and may guide clinicians to decide follow-up and therapy.
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| 14. |
- Nasic, Salmir, et al.
(författare)
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Changes in numbers of glomerular macrophages between two consecutive biopsies and the association with renal transplant graft survival
- 2024
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Ingår i: Clinical Transplantation. - : John Wiley & Sons. - 0902-0063 .- 1399-0012. ; 38:7
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Tidskriftsartikel (refereegranskat)abstract
- Background: Macrophages are involved in kidney transplants. The aim of the study was to investigate if changes exist in the levels of glomerular macrophage index (GMI) between two consecutive kidney transplant biopsies, and if so to determine their potential impact on graft survival.Methods: Two consecutive biopsies were performed on the same renal graft in 623 patients. GMI was categorized into three GMI classes: ≤1.8 Low, 1.9–4.5 Medium, and ≥4.6 High. This division yielded nine possible switches between the first and second biopsies (Low-Low, Low-Medium, etc.). Cox-regressions were used and hazard ratios (HR) with 95% confidence interval (CI) are presented.Results: The worst graft survival was observed in the High-High group, and the best graft survival was observed in the Low-Low and High-Low groups. Compared to the High-High group, a reduction of risk was observed in nearly all other decreasing groups (reductions between 65% and 80% of graft loss). After adjustment for covariates, the risk for graft-loss was lower in the Low-Low (HR = 0.24, CI 0.13–0.46), Low-Medium (HR = 0.25, CI 0.11–0.55), Medium-Low (HR = 0.29, CI 0.11–0.77), and the High-Low GMI (HR = 0.31, CI 0.10–0.98) groups compared to the High-High group as the reference.Conclusions: GMI may change dynamically, and the latest finding is of most prognostic importance. GMI should be considered in all evaluations of biopsy findings since high or increasing GMI levels are associated with shorter graft survival. Future studies need to consider therapeutic strategies to lower or maintain a low GMI. A high GMI besides a vague histological finding should be considered as a warning sign requiring more frequent clinical follow up.
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| 15. |
- Nasic, Salmir, et al.
(författare)
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Changes in Numbers of Glomerular Macrophages Between Two Consecutive Biopsies and the Association With Renal Transplant Graft Survival.
- 2024
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Ingår i: Clinical transplantation. - : John Wiley & Sons. - 1399-0012 .- 0902-0063. ; 38:7
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Tidskriftsartikel (refereegranskat)abstract
- Macrophages are involved in kidney transplants. The aim of the study was to investigate if changes exist in the levels of glomerular macrophage index (GMI) between two consecutive kidney transplant biopsies, and if so to determine their potential impact on graft survival.Two consecutive biopsies were performed on the same renal graft in 623 patients. GMI was categorized into three GMI classes: ≤1.8 Low, 1.9-4.5 Medium, and ≥4.6 High. This division yielded nine possible switches between the first and second biopsies (Low-Low, Low-Medium, etc.). Cox-regressions were used and hazard ratios (HR) with 95% confidence interval (CI) are presented.The worst graft survival was observed in the High-High group, and the best graft survival was observed in the Low-Low and High-Low groups. Compared to the High-High group, a reduction of risk was observed in nearly all other decreasing groups (reductions between 65% and 80% of graft loss). After adjustment for covariates, the risk for graft-loss was lower in the Low-Low (HR = 0.24, CI 0.13-0.46), Low-Medium (HR = 0.25, CI 0.11-0.55), Medium-Low (HR = 0.29, CI 0.11-0.77), and the High-Low GMI (HR = 0.31, CI 0.10-0.98) groups compared to the High-High group as the reference.GMI may change dynamically, and the latest finding is of most prognostic importance. GMI should be considered in all evaluations of biopsy findings since high or increasing GMI levels are associated with shorter graft survival. Future studies need to consider therapeutic strategies to lower or maintain a low GMI. A high GMI besides a vague histological finding should be considered as a warning sign requiring more frequent clinical follow up.
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| 16. |
- Nasic, Salmir, et al.
(författare)
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Histological diagnosis from kidney transplant biopsy can contribute to prediction of graft survival
- 2022
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Ingår i: Nephrology. - : Wiley. - 1320-5358 .- 1440-1797. ; 27:6, s. 528-536
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Tidskriftsartikel (refereegranskat)abstract
- Aim The primary aim of this study was to in depth examine if the histological findings in a transplanted kidney biopsy can predict the prognosis for the graft and the patient. The secondary aim was to extend knowledge of the impact of time elapsed on biopsy findings. Methods Data from 1462 patients were merged from a kidney transplantation registry and a biopsy registry during 1 January 2007 and 30 September 2017. Kaplan-Meier analysis and multivariate Cox-regression analysis were performed and hazard ratios (HR) with 95% confidence intervals (CI) were presented. Results Compared to normal biopsy findings, graft survival after biopsy (gsaBiopsy) was shorter for patients with glomerular diseases (HR 8.2, CI:3.2-21.1), rejections (HR 4.2, CI:1.7-10.3), chronic changes including IFTA (HR 3.2, CI:1.3-8.0), acute tubular injuries (HR 3.0, CI:1.2-7.8), and borderline changes (HR 2.9, CI:1.1-7.6). Sub-analysis of rejections showed shorter gsaBiopsy for chronic TCMR (HR 4.7, CI:1.9-11.3), active ABMR (HR 3.6, CI:1.7-7.7) and chronic ABMR (HR 3.5, CI:2.0-6.0). Patients with TCMR Banff grade II (HR 0.35, CI:0.20-0.63) and grade I (HR 0.52, CI:0.29-0.93) had a better gsaBiopsy compared to all other types of rejections. Conclusion Shorter gsaBiopsy was noted in kidneys with glomerular diseases, rejections, acute tubular injuries and borderline changes. TCMR Banff rejections grade I and II were associated with a better prognosis.
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| 17. |
- Nasic, Salmir, et al.
(författare)
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Sex-specific time trends of long-term graft survival after kidney transplantation : a registry-based study
- 2023
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Ingår i: Renal failure. - : Taylor & Francis. - 0886-022X .- 1525-6049. ; 45:2
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Tidskriftsartikel (refereegranskat)abstract
- Background: Sex-specific trends over time with respect to kidney graft survival have scarcely been described in earlier studies. The present study aimed to examine whether kidney graft survival differs between women and men over time.Methods: This study was based on prospectively collected data extracted from a quality registry including all kidney transplant patients between January 1965 and September 2017 at the transplantation center of a university hospital in Sweden. The transplantation center serves a population of approximately 3.5 million inhabitants. Only the first graft for each patient was included in the study resulting in 4698 transplantations from unique patients (37% women, 63% men). Patients were followed-up until graft failure, death, or the end of the study. Death-censored graft survival analysis after kidney transplantation (KT) was performed using Kaplan-Meier analysis with log-rank test, and analysis adjusted for confounders was performed using multivariable Cox regression analysis.Results: Median age at transplantation was 48 years (quartiles 36–57 years) and was similar for women and men. Graft survival was analyzed separately in four transplantation periods that represented various immunosuppressive regimes (1965-1985, 1986–1995, 1996–2005, and 2006–2017). Sex differences in graft survival varied over time (sex-by-period interaction, p = 0.026). During the three first periods, there were no significant sex differences in graft survival. However, during the last period, women had shorter graft survival (p = 0.022, hazard ratio (HR) 1.71, 95% confidence interval (CI) 1.1–2.7, adjusted for covariates). Biopsy-proven rejections were more common in women.Conclusions: In this registry-based study, women had shorter graft survival than men during the last observation period (years 2006–2017).
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| 18. |
- Nasic, Salmir, et al.
(författare)
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Sex-specific time trends of long-term graft survival after kidney transplantation - a registry-based study
- 2023
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Ingår i: Renal Failure. - 0886-022X. ; 45:2
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Tidskriftsartikel (refereegranskat)abstract
- Background Sex-specific trends over time with respect to kidney graft survival have scarcely been described in earlier studies. The present study aimed to examine whether kidney graft survival differs between women and men over time.Methods This study was based on prospectively collected data extracted from a quality registry including all kidney transplant patients between January 1965 and September 2017 at the transplantation center of a university hospital in Sweden. The transplantation center serves a population of approximately 3.5 million inhabitants. Only the first graft for each patient was included in the study resulting in 4698 transplantations from unique patients (37% women, 63% men). Patients were followed-up until graft failure, death, or the end of the study. Death-censored graft survival analysis after kidney transplantation (KT) was performed using Kaplan-Meier analysis with log-rank test, and analysis adjusted for confounders was performed using multivariable Cox regression analysis.Results Median age at transplantation was 48 years (quartiles 36-57 years) and was similar for women and men. Graft survival was analyzed separately in four transplantation periods that represented various immunosuppressive regimes (1965-1985, 1986-1995, 1996-2005, and 2006-2017). Sex differences in graft survival varied over time (sex-by-period interaction, p = 0.026). During the three first periods, there were no significant sex differences in graft survival. However, during the last period, women had shorter graft survival (p = 0.022, hazard ratio (HR) 1.71, 95% confidence interval (CI) 1.1-2.7, adjusted for covariates). Biopsy-proven rejections were more common in women.Conclusions In this registry-based study, women had shorter graft survival than men during the last observation period (years 2006-2017).
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| 19. |
- Peters, Björn, 1978-, et al.
(författare)
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Clinical parameters predicting complications in native kidney biopsies
- 2020
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Ingår i: Clinical Kidney Journal. - : Oxford University Press. - 2048-8505 .- 2048-8513. ; 13:4, s. 654-659
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Tidskriftsartikel (refereegranskat)abstract
- Background: Renal biopsies are essential in nephrology but they are invasive and complications can occur. The aim of this study was to explore clinical parameters that can be used as predictors for biopsy complications.Methods: Clinical parameters such as demographics, biopsy indications, serology, comorbidities and clinical chemistry were retrieved from a regional biopsy registry between 2006 and 2015 and from a nationwide registry between 2015 and 2017. Clinical data before biopsy were compared with data on major biopsy complications. Fisher’s exact and χ2 tests were used and odds ratios (ORs) with 95% confidence intervals (CIs) were presented. Univariate and multiple binary logistic regression analyses were performed with complications as outcome. A two-sided P-value <0.05 was considered significant.Results: In total, 2835 consecutive native kidney biopsies were analysed (39% women and 61% men, median age 57 years). No death and nephrectomy due to biopsy complications were registered. The frequency of major biopsy complications was 5.65%. In the multiple logistic regression, the risk for complications increased in women [OR 1.51 (95% CI 1.08–2.11)] and decreased with age: 45–64 years age group [OR 0.66 (95% CI 0.44–0.99)] and >74 years age group [OR 0.51 (95% CI 0.27–0.96)]. Among comorbidities, patients with diabetes mellitus type 2 [OR 2.07 (95% CI 1.15–3.72)] and non-ischaemic heart disease [OR 3.20 (95% CI 1.64–6.25)] had a higher risk for major biopsy complications.Conclusions: Female gender, younger age (≤44 years), diabetes mellitus type 2 and non-ischaemic heart disease were found as risk factors for major biopsy complications.
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| 20. |
- Peters, Björn, et al.
(författare)
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Clinical parameters predicting complications in native kidney biopsies
- 2021
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Ingår i: Clinical Kidney Journal. - 2048-8505. ; 13:4, s. 654-659
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Tidskriftsartikel (refereegranskat)abstract
- Background. Renal biopsies are essential in nephrology but they are invasive and complications can occur. The aim of this study was to explore clinical parameters that can be used as predictors for biopsy complications. Methods. Clinical parameters such as demographics, biopsy indications, serology, comorbidities and clinical chemistry were retrieved from a regional biopsy registry between 2006 and 2015 and from a nationwide registry between 2015 and 2017. Clinical data before biopsy were compared with data on major biopsy complications. Fisher's exact and v2 tests were used and odds ratios (ORs) with 95% confidence intervals (CIs) were presented. Univariate and multiple binary logistic regression analyses were performed with complications as outcome. A two-sided P-value <0.05 was considered significant. Results. In total, 2835 consecutive native kidney biopsies were analysed (39% women and 61% men, median age 57 years). No death and nephrectomy due to biopsy complications were registered. The frequency of major biopsy complications was 5.65%. In the multiple logistic regression, the risk for complications increased in women [OR 1.51 (95% CI 1.08-2.11)] and decreased with age: 45-64 years age group [OR 0.66 (95% CI 0.44-0.99)] and >74 years age group [OR 0.51 (95% CI 0.27-0.96)]. Among comorbidities, patients with diabetes mellitus type 2 [OR 2.07 (95% CI 1.15-3.72)] and non-ischaemic heart disease [OR 3.20 (95% CI 1.64-6.25)] had a higher risk for major biopsy complications. Conclusions. Female gender, younger age (<44 years), diabetes mellitus type 2 and non-ischaemic heart disease were found as risk factors for major biopsy complications.
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| 21. |
- Peters, Björn, et al.
(författare)
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Dynamics of urine proteomics biomarker and disease progression in patients with IgA nephropathy
- 2023
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Ingår i: Nephrology, Dialysis and Transplantation. - : Oxford University Press. - 0931-0509 .- 1460-2385. ; 38:12, s. 2826-2834
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Tidskriftsartikel (refereegranskat)abstract
- Background: Immunoglobulin A nephropathy (IgAN) frequently leads to kidney failure. The urinary proteomics-based classifier IgAN237 may predict disease progression at the time of kidney biopsy. We studied whether IgAN237 also predicts progression later in the course of IgAN.Methods: Urine from patients with biopsy-proven IgAN was analyzed using capillary electrophoresis-mass spectrometry at baseline (IgAN237-1, n = 103) and at follow-up (IgAN237-2, n = 89). Patients were categorized as "non-progressors" (IgAN237 ≤0.38) and "progressors" (IgAN237 >0.38). Estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio slopes were calculated.Results: Median age at biopsy was 44 years, interval between biopsy and IgAN237-1 was 65 months and interval between IgAN237-1 and IgAN237-2 was 258 days (interquartile range 71-531). IgAN237-1 and IgAN237-2 values did not differ significantly and were correlated (rho = 0.44, P < .001). Twenty-eight percent and 26% of patients were progressors based on IgAN237-1 and IgAN237-2, respectively. IgAN237 inversely correlated with chronic eGFR slopes (rho = -0.278, P = .02 for score-1; rho = -0.409, P = .002 for score-2) and with ±180 days eGFR slopes (rho = -0.31, P = .009 and rho = -0.439, P = .001, respectively). The ±180 days eGFR slopes were worse for progressors than for non-progressors (median -5.98 versus -1.22 mL/min/1.73 m2 per year for IgAN237-1, P < .001; -3.02 vs 1.08 mL/min/1.73 m2 per year for IgAN237-2, P = .0047). In multiple regression analysis baseline progressor/non-progressor according to IgAN237 was an independent predictor of eGFR180days-slope (P = .001).Conclusion: The urinary IgAN237 classifier represents a risk stratification tool in IgAN also later in the course of the dynamic disease. It may guide patient management in an individualized manner.
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| 22. |
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| 23. |
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| 24. |
- Peters, Björn, et al.
(författare)
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Renal transplant biopsy complications: assessment of risk factors and potential of desmopressin to decrease risk of hemorrhage
- 2020
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Ingår i: Acta Radiologica. - : SAGE Publications. - 0284-1851 .- 1600-0455. ; 61:12, s. 1717-1723
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Tidskriftsartikel (refereegranskat)abstract
- Background Renal transplant biopsies are essential in nephrology; however, they are invasive and complications can occur. Purpose To explore the risk of transplant kidney biopsy (TxB) complications in relation to possible preventive effects of desmopressin prophylaxis. Material and Methods A total of 515 consecutive TxB (375 patients, median age 53 years) were analyzed. In 252 TxB, the Resistive Index (RI) was measured right before the biopsy. A total of 282 patients had serum creatinine >150 mu mol/L. In one of the six hospitals 39/282 patients consecutively received desmopressin (dose 0.3 mu g/kg subcutaneously) as prophylaxis within 1 h before the biopsy. Fisher's exact and chi(2) test were used (odds ratio [OR], 95% confidence interval [CI]). Univariate and multiple binary logistic regression analyses were performed. A two-sided P value Results RI >= 0.8 was a risk factor for major TxB complications (OR 4.2, 95% CI 1.13-15.76). The risk for minor complications decreased with mean arterial blood pressure (MAP) (97.9 vs. 89.5 mmHg, OR 0.97, 95% CI 0.95-0.997). In a multiple regression analysis for overall biopsy complications, the risk remained increased for patients with RI >= 0.8 (OR 4.45, 95% CI 1.32-15.04). No patients (0/39) with desmopressin prophylaxis had a major complication versus 8/243 in the other group. In patients with serum creatinine >150 mu mol/L, those with a higher MAP had more overall TxB complications (104.5 vs. 98.2 mmHg, OR 1.05, 95% CI 1.004-1.1). Conclusion RI >= 0.8 was a risk factor for major and overall complications and a lower MAP for minor biopsy complications. Desmopressin prophylaxis showed yet no verified benefit as prophylaxis in TxB.
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| 25. |
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| 26. |
- Peters, Björn, et al.
(författare)
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Risk factors for biopsy complications in initial versus subsequent biopsies in native and transplant kidneys.
- 2021
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Ingår i: Acta radiologica. - : SAGE Publications. - 1600-0455 .- 0284-1851. ; 62:10, s. 1426-1432
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Tidskriftsartikel (refereegranskat)abstract
- Few studies exist about risk factors for complications in subsequent biopsies.To explore risk factors for complications in initial versus subsequent biopsies in native and transplant kidneys, which may predict biopsy complications.In a multicenter study, 2830 native kidney biopsies (4.3% subsequent) were analyzed for major complications (1251 of these were also analyzed for minor) and 667 transplant kidney biopsies (29% subsequent) were analyzed for major and minor complications. No death or nephrectomy were described. Fisher's exact test, Student's t-test, chi-square analyses, and univariate and multiple binary logistic regression analyses were employed; P<0.05 was considered significant.In initial native kidney biopsies, the frequency of major complications was higher in women compared to men (odds ratio 1.6, 95% confidence interval 1.1-2.2), in younger patients (50 vs. 54 years, P=0.007), and in patients with lower weight (78 vs. 82 kg, P=0.005). In subsequent native kidney biopsies, patients with major complications had a higher systolic blood pressure (145 vs. 132mmHg, P=0.03). In initial transplant kidney biopsies, biopsies with major complications had less glomeruli in the biopsy (17 vs. 24, P=0.046). In subsequent transplant kidney biopsies, patients with major complications had a higher mean arterial pressure (112 vs. 98mmHg, P=0.002). In subsequent native kidney biopsies, there was a higher number of SLE-nephritis (12% vs. 4.6%, P=0.001) compared to initial biopsies.The different types of risk factors for complications in initial versus subsequent renal biopsies could be important for the clinicians to improve patients' safety.
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| 27. |
- Pierre, Jon, 1953, et al.
(författare)
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Back to Basics: A Comparative Analysis of Government Performance in Governing
- 2024
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Ingår i: International Journal of Public Administration. - 0190-0692.
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Tidskriftsartikel (refereegranskat)abstract
- While the positive aspects, but also pathologies, of performance measurement and management are today well known, we know less about the impact of NPM reform on governance. Using Bertelsmann SGI data (2009 and 2022) from 30 advanced democracies and a unique dataset measuring NPM reform in 14 countries, we study how core aspects of governing capacity have been impacted by, or triggered as responses to, public management reform. While the executive capacity of government has increased, NPM has not increased the accountability of executive government. Corruption prevention has increased between 2009 and 2022, while legal certainty has improved only marginally.
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| 28. |
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| 29. |
- Rudnicki, Michael, et al.
(författare)
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Urine proteomics for prediction of disease progression in patients with IgA nephropathy
- 2022
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Ingår i: Nephrology, Dialysis and Transplantation. - : Oxford University Press. - 0931-0509 .- 1460-2385. ; 37:1, s. 42-52
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Tidskriftsartikel (refereegranskat)abstract
- Background: Risk of kidney function decline in immunoglobulin A (IgA) nephropathy (IgAN) is significant and may not be predicted by available clinical and histological tools. To serve this unmet need, we aimed at developing a urinary biomarker-based algorithm that predicts rapid disease progression in IgAN, thus enabling a personalized risk stratification.Methods: In this multicentre study, urine samples were collected in 209 patients with biopsy-proven IgAN. Progression was defined by tertiles of the annual change of estimated glomerular filtration rate (eGFR) during follow-up. Urine samples were analysed using capillary electrophoresis coupled mass spectrometry. The area under the receiver operating characteristic curve (AUC) was used to evaluate the risk prediction models.Results: Of the 209 patients, 64% were male. Mean age was 42 years, mean eGFR was 63 mL/min/1.73 m2 and median proteinuria was 1.2 g/day. We identified 237 urine peptides showing significant difference in abundance according to the tertile of eGFR change. These included fragments of apolipoprotein C-III, alpha-1 antitrypsin, different collagens, fibrinogen alpha and beta, titin, haemoglobin subunits, sodium/potassium-transporting ATPase subunit gamma, uromodulin, mucin-2, fractalkine, polymeric Ig receptor and insulin. An algorithm based on these protein fragments (IgAN237) showed a significant added value for the prediction of IgAN progression [AUC 0.89; 95% confidence interval (CI) 0.83-0.95], as compared with the clinical parameters (age, gender, proteinuria, eGFR and mean arterial pressure) alone (0.72; 95% CI 0.64-0.81).Conclusions: A urinary peptide classifier predicts progressive loss of kidney function in patients with IgAN significantly better than clinical parameters alone.
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| 30. |
- Siwy, Justyna, et al.
(författare)
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CD99 and polymeric immunoglobulin receptor peptides deregulation in critical COVID-19 : A potential link to molecular pathophysiology?
- 2021
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Ingår i: Proteomics. - : John Wiley & Sons. - 1615-9853 .- 1615-9861. ; 21:20
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Tidskriftsartikel (refereegranskat)abstract
- Identification of significant changes in urinary peptides may enable improved understanding of molecular disease mechanisms. We aimed towards identifying urinary peptides associated with critical course of COVID-19 to yield hypotheses on molecular pathophysiological mechanisms in disease development. In this multicentre prospective study urine samples of PCR-confirmed COVID-19 patients were collected in different centres across Europe. The urinary peptidome of 53 patients at WHO stages 6–8 and 66 at WHO stages 1–3 COVID-19 disease was analysed using capillary electrophoresis coupled to mass spectrometry. 593 peptides were identified significantly affected by disease severity. These peptides were compared with changes associated with kidney disease or heart failure. Similarities with kidney disease were observed, indicating comparable molecular mechanisms. In contrast, convincing similarity to heart failure could not be detected. The data for the first time showed deregulation of CD99 and polymeric immunoglobulin receptor peptides and of known peptides associated with kidney disease, including collagen and alpha-1-antitrypsin. Peptidomic findings were in line with the pathophysiology of COVID-19. The clinical corollary is that COVID-19 induces specific inflammation of numerous tissues including endothelial lining. Restoring these changes, especially in CD99, PIGR and alpha-1-antitripsin, may represent a valid and effective therapeutic approach in COVID-19, targeting improvement of endothelial integrity.
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| 31. |
- Staessen, Jan A., et al.
(författare)
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Predictive performance and clinical application of COV50, a urinary proteomic biomarker in early COVID-19 infection : a prospective multicentre cohort study
- 2022
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Ingår i: The Lancet Digital Health. - : Elsevier. - 2589-7500. ; 4:10, s. e727-e737
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Tidskriftsartikel (refereegranskat)abstract
- Background: The SARS-CoV-2 pandemic is a worldwide challenge. The CRIT-CoV-U pilot study generated a urinary proteomic biomarker consisting of 50 peptides (COV50), which predicted death and disease progression from SARS-CoV-2. After the interim analysis presented for the German Government, here, we aimed to analyse the full dataset to consolidate the findings and propose potential clinical applications of this biomarker.Methods: CRIT-CoV-U was a prospective multicentre cohort study. In eight European countries (Austria, France, Germany, Greece, North Macedonia, Poland, Spain, and Sweden), 1012 adults with PCR-confirmed COVID-19 were followed up for death and progression along the 8-point WHO scale. Capillary electrophoresis coupled with mass spectrometry was used for urinary proteomic profiling. Statistical methods included logistic regression and receiver operating characteristic curve analysis with a comparison of the area under curve (AUC) between nested models. Hospitalisation costs were derived from the care facility corresponding with the Markov chain probability of reaching WHO scores ranging from 3 to 8 and flat-rate hospitalisation costs adjusted for the gross per capita domestic product of each country.Findings: From June 30 to Nov 19, 2020, 228 participants were recruited, and from April 30, 2020, to April 14, 2021, 784 participants were recruited, resulting in a total of 1012 participants. The entry WHO scores were 1–3 in 445 (44%) participants, 4–5 in 529 (52%) participants, and 6 in 38 (4%) participants; and of all participants, 119 died and 271 had disease progression. The odds ratio (OR) associated with COV50 in all 1012 participants for death was 2·44 (95% CI 2·05–2·92) unadjusted and 1·67 (1·34–2·07) when adjusted for sex, age, BMI, comorbidities, and baseline WHO score; and for disease progression, the OR was 1·79 (1·60–2·01) when unadjusted and 1·63 (1·41–1·91) when adjusted (p<0·0001 for all). The predictive accuracy of the optimised COV50 thresholds was 74·4% (71·6–77·1%) for mortality (threshold 0·47) and 67·4% (64·4–70·3%) for disease progression (threshold 0·04). When adjusted for covariables and the baseline WHO score, these thresholds improved AUCs from 0·835 to 0·853 (p=0·033) for death and from 0·697 to 0·730 (p=0·0008) for progression. Of 196 participants who received ambulatory care, 194 (99%) did not reach the 0·04 threshold. The cost reductions associated with 1 day less hospitalisation per 1000 participants were million Euro (M€) 0·887 (5–95% percentile interval 0·730–1·039) in participants at a low risk (COV50 <0·04) and M€2·098 (1·839-2·365) in participants at a high risk (COV50 ≥0·04).Interpretation: The urinary proteomic COV50 marker might be predictive of adverse COVID-19 outcomes. Even in people with mild-to-moderate PCR-confirmed infections (WHO scores 1–4), the 0·04 COV50 threshold justifies earlier drug treatment, thereby potentially reducing the number of days in hospital and associated costs. Funding: German Federal Ministry of Health.
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| 32. |
- Wendt, Ralph, et al.
(författare)
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A urinary peptidomic profile predicts outcome in SARS-CoV-2-infected patients.
- 2021
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Ingår i: Lancet EClinicalMedicine. - : Elsevier BV. - 2589-5370. ; 36
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Tidskriftsartikel (refereegranskat)abstract
- COVID-19 prediction models based on clinical characteristics, routine biochemistry and imaging, have been developed, but little is known on proteomic markers reflecting the molecular pathophysiology of disease progression.he multicentre (six European study sites) Prospective Validation of a Proteomic Urine Test for Early and Accurate Prognosis of Critical Course Complications in Patients with SARS-CoV-2 Infection Study (Crit-COV-U) is recruiting consecutive patients (≥ 18 years) with PCR-confirmed SARS-CoV-2 infection. A urinary proteomic biomarker (COV50) developed by capillary-electrophoresis-mass spectrometry (CE-MS) technology, comprising 50 sequenced peptides and identifying the parental proteins, was evaluated in 228 patients (derivation cohort) with replication in 99 patients (validation cohort). Death and progression along the World Health Organization (WHO) Clinical Progression Scale were assessed up to 21 days after the initial PCR test. Statistical methods included logistic regression, receiver operating curve (ROC) analysis and comparison of the area under the curve (AUC).in the derivation cohort, 23 patients died, and 48 developed worse WHO scores. The odds ratios (OR) for death per 1 standard deviation (SD) increment in COV50 were 3·52 (95% CI, 2·02-6·13, p<0·0001) unadjusted and 2·73 (1·25-5·95, p = 0·012) adjusted for sex, age, baseline WHO score, body mass index (BMI) and comorbidities. For WHO scale progression, the corresponding OR were 2·63 (1·80-3·85, p<0·0001) and 3·38 (1·85-6·17, p<0·0001), respectively. The area under the curve (AUC) for COV50 as a continuously distributed variable was 0·80 (0·72-0·88) for mortality and 0·74 (0·66-0·81) for worsening WHO score. The optimised COV50 thresholds for mortality and worsening WHO score were 0·47 and 0·04 with sensitivity/specificity of 87·0 (74·6%) and 77·1 (63·9%), respectively. On top of covariates, COV50 improved the AUC, albeit borderline for death, from 0·78 to 0·82 (p = 0·11) and 0·84 (p = 0·052) for mortality and from 0·68 to 0·78 (p = 0·0097) and 0·75 (p = 0·021) for worsening WHO score. The validation cohort findings were confirmatory.this first CRIT-COV-U report proves the concept that urinary proteomic profiling generates biomarkers indicating adverse COVID-19 outcomes, even at an early disease stage, including WHO stages 1-3. These findings need to be consolidated in an upcoming final dataset.
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| 33. |
- Wickerts, Sanna, 1992, et al.
(författare)
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Prospective Life-Cycle Modeling of Quantum Dot Nanoparticles for Use in Photon Upconversion Devices
- 2021
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Ingår i: ACS Sustainable Chemistry & Engineering. - : American Chemical Society (ACS). - 2168-0485. ; 9:14, s. 5187-5195
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Tidskriftsartikel (refereegranskat)abstract
- Quantum dot nanoparticles (NPs) can be used in several applications, for example, photon upconversion devices that increase the electricity output of solar modules. In order to facilitate life cycle assessment (LCA) studies of such applications, this study provides ready-to-use LCA unit process data for four NPs suitable for photon upconversion applications: cadmium selenide, cadmium sulfide, lead selenide, and lead sulfide. The data is provided for two prospective scenarios: one optimistic and one pessimistic. An impact assessment is conducted in order to assess the NPs’ climate change performance, where solvent-related processes such as steam production for recycling and hazardous waste treatment are shown to be hotspots. To show the applicability of the data, a prospective assessment of a solar module with an upconversion layer is conducted to investigate whether it is preferable from a climate perspective to install more solar modules or equip existing ones with upconversion devices, leading to more electricity produced in both cases. The assessment shows that solar modules need to become 0.05–2 percentage points more efficient per gram of NPs applied, depending on the scenario, in order for the upconversion layer to be preferable.
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| 34. |
- Williamson, Alice, et al.
(författare)
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Genome-wide association study and functional characterization identifies candidate genes for insulin-stimulated glucose uptake
- 2023
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 55:6, s. 973-983
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Tidskriftsartikel (refereegranskat)abstract
- Distinct tissue-specific mechanisms mediate insulin action in fasting and postprandial states. Previous genetic studies have largely focused on insulin resistance in the fasting state, where hepatic insulin action dominates. Here we studied genetic variants influencing insulin levels measured 2 h after a glucose challenge in >55,000 participants from three ancestry groups. We identified ten new loci (P < 5 × 10-8) not previously associated with postchallenge insulin resistance, eight of which were shown to share their genetic architecture with type 2 diabetes in colocalization analyses. We investigated candidate genes at a subset of associated loci in cultured cells and identified nine candidate genes newly implicated in the expression or trafficking of GLUT4, the key glucose transporter in postprandial glucose uptake in muscle and fat. By focusing on postprandial insulin resistance, we highlighted the mechanisms of action at type 2 diabetes loci that are not adequately captured by studies of fasting glycemic traits.
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