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1.	Lindgren, Johan, et al. (författare) Molecular composition and ultrastructure of Jurassic paravian feathers 2015 Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 5 Tidskriftsartikel (refereegranskat)abstract Feathers are amongst the most complex epidermal structures known, and they have a well-documented evolutionary trajectory across non-avian dinosaurs and basal birds. Moreover, melanosome-like microbodies preserved in association with fossil plumage have been used to reconstruct original colour, behaviour and physiology. However, these putative ancient melanosomes might alternatively represent microorganismal residues, a conflicting interpretation compounded by a lack of unambiguous chemical data. We therefore used sensitive molecular imaging, supported by multiple independent analytical tests, to demonstrate that the filamentous epidermal appendages in a new specimen of the Jurassic paravian Anchiornis comprise remnant eumelanosomes and fibril-like microstructures, preserved as endogenous eumelanin and authigenic calcium phosphate. These results provide novel insights into the early evolution of feathers at the sub-cellular level, and unequivocally determine that melanosomes can be preserved in fossil feathers.
2.	Locke, Adam E, et al. (författare) Genetic studies of body mass index yield new insights for obesity biology. 2015 Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401 Tidskriftsartikel (refereegranskat)abstract Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
3.	Shungin, Dmitry, et al. (författare) New genetic loci link adipose and insulin biology to body fat distribution. 2015 Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 187-378 Tidskriftsartikel (refereegranskat)abstract Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
4.	Sundström, Johan, Professor, 1971-, et al. (författare) Are there lost opportunities in chronic kidney disease? A region-wide cohort study 2024 Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 14:4 Tidskriftsartikel (refereegranskat)abstract OBJECTIVES: Identify the windows of opportunity for the diagnosis of chronic kidney disease (CKD) and the prevention of its adverse outcomes and quantify the potential population gains of such prevention.DESIGN AND SETTING: Observational, population-wide study of residents in the Stockholm and Skåne regions of Sweden between 1 January 2015 and 31 December 2020.PARTICIPANTS: All patients who did not yet have a diagnosis of CKD in healthcare but had CKD according to laboratory measurements of CKD biomarkers available in electronic health records.OUTCOME MEASURES: We assessed the proportions of the patient population that received a subsequent diagnosis of CKD in healthcare, that used guideline-directed pharmacological therapy (statins, renin-angiotensin aldosterone system inhibitors (RAASi) and/or sodium-glucose cotransporter-2 inhibitors (SGLT2i)) and that experienced adverse outcomes (all-cause mortality, cardiovascular mortality or major adverse cardiovascular events (MACE)). The potential to prevent adverse outcomes in CKD was assessed using simulations of guideline-directed pharmacological therapy in untreated subsets of the study population.RESULTS: We identified 99 382 patients with undiagnosed CKD during the study period. Only 33% of those received a subsequent diagnosis of CKD in healthcare after 5 years. The proportion that used statins or RAASi was of similar size to the proportion that didn't, regardless of how advanced their CKD was. The use of SGLT2i was negligible. In simulations of optimal treatment, 22% of the 21 870 deaths, 27% of the 14 310 cardiovascular deaths and 39% of the 22 224 MACE could have been avoided if every patient who did not use an indicated medication for their laboratory-confirmed CKD was treated with guideline-directed pharmacological therapy for CKD.CONCLUSIONS: While we noted underdiagnosis and undertreatment of CKD in this large contemporary population, we also identified a substantial realisable potential to improve CKD outcomes and reduce its burden by treating patients early with guideline-directed pharmacological therapy.
5.	Sundström, Johan, et al. (författare) Heart failure outcomes by left ventricular ejection fraction in a contemporary region-wide patient cohort 2024 Ingår i: ESC Heart Failure. - 2055-5822. ; 11:3, s. 1377-1388 Tidskriftsartikel (refereegranskat)abstract AIMS: This study aimed to characterize a contemporary population with subtypes of incident or prevalent heart failure (HF) based on reduced (HFrEF), mildly reduced, or preserved (HFpEF) left ventricular ejection fraction (LVEF) and to assess how outcomes, healthcare, treatments, and healthcare costs vary between each subtype of incident HF.METHODS AND RESULTS: Using Swedish data from the CardioRenal and Metabolic disease Heart Failure (CaReMe HF) study, updated to cover a more recent time period, this population-based study characterized patients from Stockholm County, Sweden, with incident HF (patients with a first HF diagnosis between 1 January 2015 and 31 December 2019) or prevalent HF (patients with a first HF diagnosis before 1 January 2020). Patients with incident HF had LVEF measured by echocardiography within ±90 days of their first HF diagnosis, and patients with prevalent HF within 5 years prior to the index date. The 13 375 patients with prevalent HF (39.2% women, mean age 73.9 years) had multiple comorbidities (cardiovascular diseases, chronic kidney disease, diabetes, and cancer). These were already highly prevalent at the time of the first HF diagnosis in the 8042 patients with incident HF (40.5% women, mean age 72.3 years). Patients with incident HFpEF received less specialist HF care at outpatient secondary care facilities following their first HF diagnosis than those with incident HFrEF. Patients with HFrEF had higher risks of complications and exerted a higher burden, in terms of care for and costs of HF, on the healthcare system.CONCLUSIONS: This study of contemporary patients with incident HF demonstrates that those with HFpEF and HFrEF differ considerably in terms of clinical presentation, prognosis, and care, highlighting a potential to improve HF outcomes.
6.	Ahlén, Ingemar, et al. (författare) Nya järnvägen hotar unikt naturområde 2002 Ingår i: Aftonbladet. - 1103-9000. Tidskriftsartikel (populärvet., debatt m.m.)
7.	Ahlén, Ingemar, et al. (författare) Nya järnvägen hotar unikt naturområde 2002 Ingår i: Aftonbladet. - 1103-9000. Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
8.	Bilberg, Johan, 1646-1717 (författare) Dissertatio de asylis autoritate amplissimi ordinis philosophici moderante ... Johanne Bilberg ... ad diem XXV Feb. anno adsertæ salutis M DC LXXXII in audit. Gust. publico examini oblata ab autore Gustavo Carlholm Vermelando 1682 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)
9.	Bonagas, Nadilly, et al. (författare) Pharmacological targeting of MTHFD2 suppresses acute myeloid leukemia by inducing thymidine depletion and replication stress 2022 Ingår i: NATURE CANCER. - : Springer Science and Business Media LLC. - 2662-1347. ; 3:2, s. 156- Tidskriftsartikel (refereegranskat)abstract The folate metabolism enzyme MTHFD2 (methylenetetrahydrofolate dehydrogenase/cyclohydrolase) is consistently overexpressed in cancer but its roles are not fully characterized, and current candidate inhibitors have limited potency for clinical development. In the present study, we demonstrate a role for MTHFD2 in DNA replication and genomic stability in cancer cells, and perform a drug screen to identify potent and selective nanomolar MTHFD2 inhibitors; protein cocrystal structures demonstrated binding to the active site of MTHFD2 and target engagement. MTHFD2 inhibitors reduced replication fork speed and induced replication stress followed by S-phase arrest and apoptosis of acute myeloid leukemia cells in vitro and in vivo, with a therapeutic window spanning four orders of magnitude compared with nontumorigenic cells. Mechanistically, MTHFD2 inhibitors prevented thymidine production leading to misincorporation of uracil into DNA and replication stress. Overall, these results demonstrate a functional link between MTHFD2-dependent cancer metabolism and replication stress that can be exploited therapeutically with this new class of inhibitors. Helleday and colleagues describe a nanomolar MTHFD2 inhibitor that causes replication stress and DNA damage accumulation in cancer cells via thymidine depletion, demonstrating a potential therapeutic strategy in AML tumors in vivo.
10.	Bremer, Johan, 1991, et al. (författare) Analysis of Lateral Thermal Coupling for GaN MMIC Technologies 2018 Ingår i: IEEE Transactions on Microwave Theory and Techniques. - 0018-9480 .- 1557-9670. ; 66:10, s. 4430-4438 Tidskriftsartikel (refereegranskat)abstract This paper presents a study of the lateral heat propagation in an aluminum gallium nitride/gallium nitride (AlGaN/GaN) heterostructure grown on a silicon carbide substrate. The study is enabled by the design of a temperature sensor that utilizes the temperature-dependent I-V characteristic of a semiconductor resistor, making it suitable for integration in GaN monolithic microwave integrated circuit technologies. Using the sensor, we are able to characterize the thermal transient response and extract lateral thermal time constants from the measurements. Time constants in the range from 25 mu s to 1.2 ms are identified. Furthermore, the heat propagation properties are characterized for heat source-to-sensor distances of 86-484 mu m, resulting in delay times from 3.5 to 111 mu s. It is shown that both the time constants and propagation delay increase with temperature. An empirical model of the sensor current versus temperature and voltage is proposed and used to predict the junction temperature of the sensor. The study provides knowledge for heat management design and proposes an integrated temperature measurement solution for future highly integrated GaN applications.
11.	Broadaway, K Alaine, et al. (författare) Loci for insulin processing and secretion provide insight into type 2 diabetes risk. 2023 Ingår i: American Journal of Human Genetics. - : Elsevier. - 0002-9297 .- 1537-6605. ; 110:2, s. 284-299 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.
12.	Carlsson, Axel C., et al. (författare) Use of a proximity extension assay proteomics chip to discover new biomarkers associated with albuminuria 2017 Ingår i: European Journal of Preventive Cardiology. - : Oxford University Press (OUP). - 2047-4873 .- 2047-4881. ; :4, s. 340-348 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: The underlying mechanisms for the development of albuminuria and the increased cardiovascular risk in patients with elevated albuminuria levels are incompletely understood. We therefore investigated the associations between 80 cardiovascular proteins and the urinary albumin to creatinine ratio (ACR).METHODS: We used a discovery/replication approach in two independent community-based cohorts of elderly patients: the Uppsala Longitudinal Study of Adult Men (n = 662; mean age 78 years) and the Prospective Investigation of the Vasculature in Uppsala Seniors (n = 757; mean age 75 years; 51% women). A proteomic chip with a panel of 80 plasma proteins associated with different aspects of cardiovascular disease was analysed. In the discovery cohort, we used a false discovery rate of 5% to take into account the multiple statistical testing. Nominal p values were used in the replication.RESULTS: Higher levels of T-cell immunoglobulin mucin-1, placenta growth factor, growth/differentiation factor-15, urokinase plasminogen activator surface receptor and kallikrein-11 were robustly associated with a higher ACR in both cohorts in multivariable linear regression models adjusted for sex, established cardiovascular risk factors, antihypertensive treatment, prevalent cardiovascular disease and glomerular filtration rate (p < 0.02 for all). All associations were also significant in separate analyses of patients without diabetes.CONCLUSIONS: We discovered and replicated associations between ACR and five cardiovascular proteins involved in tubular injury, atherosclerosis, endothelial function, heart failure, inflammation, glomerulosclerosis and podocyte injury. Our findings put forward multiplex proteomics as a promising approach to explore novel aspects of the complex detrimental interplay between kidney function and the cardiovascular system.
13.	Carlsson, Axel C, et al. (författare) Use of proteomics to investigate kidney function decline over 5 years 2017 Ingår i: American Society of Nephrology. Clinical Journal. - 1555-9041 .- 1555-905X. ; 12:8, s. 1226-1235 Tidskriftsartikel (refereegranskat)abstract BACKGROUND AND OBJECTIVES: Using a discovery/replication approach, we investigated associations between a multiplex panel of 80 circulating proteins associated with cardiovascular pathology or inflammation, and eGFR decline per year and CKD incidence.DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We used two cohorts, the Prospective Investigation of the Vasculature in Uppsala Seniors Study (PIVUS; n=687, mean age of 70 years, 51% women) and the Uppsala Longitudinal Study of Adult Men (ULSAM; n=360 men, mean age of 78 years), with 5-year follow-up data on eGFR. There were 231 and 206 incident cases of CKD during follow-up in the PIVUS and ULSAM studies, respectively. Proteomic profiling of 80 proteins was assessed by a multiplex assay (proximity extension assay). The assay uses two antibodies for each protein and a PCR step to achieve a high-specific binding and the possibility to measure multiple proteins in parallel, but gives no absolute concentrations.RESULTS: In the discovery cohort from the PIVUS Study, 28 plasma proteins were significantly associated with eGFR decline per year, taking into account the multiple testing. Twenty of these proteins were significantly associated with eGFR decline per year in the replication cohort from the ULSAM Study after adjustment for age, sex, cardiovascular risk factors, medications, and urinary albumin-to-creatinine ratio (in order of significance: TNF-related apoptosis-inducing ligand receptor 2, CD40L receptor, TNF receptor 1, placenta growth factor, thrombomodulin, urokinase plasminogen activator surface receptor, growth/differentiation factor 15, macrophage colony-stimulating factor 1, fatty acid-binding protein, cathepsin D, resistin, kallikrein 11, C-C motif chemokine 3, proteinase-activated receptor 1, cathepsin L, chitinase 3-like protein 1, TNF receptor 2, fibroblast growth factor 23, monocyte chemotactic protein 1, and kallikrein 6). Moreover, 11 of the proteins predicted CKD incidence (marked with above). No protein consistently predicted eGFR decline per year independently of baseline eGFR in both cohorts.CONCLUSIONS: Several circulating proteins involved in phosphate homeostasis, inflammation, apoptosis, extracellular matrix remodeling, angiogenesis, and endothelial dysfunction were associated with worsening kidney function. Multiplex proteomics appears to be a promising way of discovering novel aspects of kidney disease pathology.
14.	Christersson, Malin, et al. (författare) Usefulness of Heart Failure Categories Based on Left Ventricular Ejection Fraction 2024 Ingår i: Journal of the American Heart Association. - : John Wiley & Sons. - 2047-9980. ; 13:8 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Heart failure guidelines have recently introduced a narrow category with mildly reduced left ventricular ejection fraction (LVEF) (heart failure with mildly reduced ejection fraction; LVEF 41%-49%) between the previous categories of reduced (heart failure with reduced ejection fraction; LVEF <= 40%) and preserved (heart failure with preserved ejection fraction; LVEF >= 50%) ejection fraction. Grouping of continuous measurements into narrow categories can be questioned if their variability is high. METHODS AND RESULTS: We constructed a cohort of all 9716 new cases of chronic heart failure with an available LVEF in Stockholm, Sweden, from January 1, 2015, until December 31, 2020. All values of LVEF were collected over time, and patients were followed up until death, moving out of Stockholm, or end of study. Mixed models were used to quantify within-person variance in LVEF, and multistate Markov models, with death as an absorbing state, to quantify the stability of LVEF categories. LVEF values followed a normal distribution. The SD of the within-person variance in LVEF over time was 7.4%. The mean time spent in any LVEF category before transition to another category was on average <1 year for heart failure with mildly reduced ejection fraction. Probabilities of transitioning between categories during the first year were substantial; patients with heart failure with mildly reduced ejection fraction had a probability of <25% of remaining in that category 1 year later. CONCLUSIONS: LVEF follows a normal distribution and has considerable variability over time, which may impose a risk for under-use of efficient treatment. The heart failure with mildly reduced ejection fraction category is especially inconstant. Assumptions of a patient's current LVEF should take this variability and the normal distribution of LVEF into account.
15.	Conrad, Sarah, et al. (författare) Distribution of Fe isotopes in particles and colloids in the salinity gradient along the Lena River plume, Laptev Sea 2019 Ingår i: Biogeosciences. - : European Geosciences Union (EGU). - 1726-4170 .- 1726-4189. ; 16:6, s. 1305-1319 Tidskriftsartikel (refereegranskat)abstract Riverine Fe input is the primary Fe source for the ocean. This study is focused on the distribution of Fe along the Lena River freshwater plume in the Laptev Sea using samples from a 600 km long transect in front of the Lena River mouth. Separation of the particulate ( > 0.22 μm), colloidal (0.22 μm–1 kDa), and truly dissolved (< 1 kDa) fractions of Fe was carried out. The total Fe concentrations ranged from 0.2 to 57μM with Fe dominantly as particulate Fe. The loss of > 99% of particulate Fe and about 90% of the colloidal Fe was observed across the shelf, while the truly dissolved phase was almost constant across the Laptev Sea. Thus, the truly dissolved Fe could be an important source of bioavailable Fe for plankton in the central Arctic Ocean, together with the colloidal Fe. Fe-isotope analysis showed that the particulate phase and the sediment below the Lena River freshwater plume had negative δ56Fe values (relative to IRMM-14). The colloidal Fe phase showed negative δ56Fe values close to the river mouth (about -0.20 ‰) and positive δ56Fe values in the outermost stations (about +0.10 ‰). We suggest that the shelf zone acts as a sink for Fe particles and colloids with negative δ56Fe values, representing chemically reactive ferrihydrites. The positive δ56Fe values of the colloidal phase within the outer Lena River freshwater plume might represent Fe oxyhydroxides, which remain in the water column, and will be the predominant δ56Fe composition in the Arctic Ocean.
16.	Cornelis, Marilyn C, et al. (författare) Targeted proteomic analysis of habitual coffee consumption 2018 Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 283:2, s. 200-211 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Coffee drinking has been implicated in mortality and a variety of diseases but potential mechanisms underlying these associations are unclear. Large-scale systems epidemiological approaches may offer novel insights to mechanisms underlying associations of coffee with health.OBJECTIVE: We performed an analysis of known and novel protein markers linked to cardiovascular disease and their association with habitual coffee intake in the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS, n=816) and followed-up top proteins in the Uppsala Longitudinal Study of Adult Men (ULSAM, n=635) and EpiHealth (n=2418).METHODS: In PIVUS and ULSAM, coffee intake was measured by 7-day dietary records while a computer-based food frequency questionnaire was used in EpiHealth. Levels of up to 80 proteins were assessed in plasma by a proximity extension assay.RESULTS: Four protein-coffee associations adjusted for age, sex, smoking and BMI, met statistical significance in PIVUS (FDR<5%, P<2.31×10(-3) ): leptin (LEP), chitinase-3-like protein 1 (CHI3L), Tumor necrosis factor (TNF) receptor 6 and TNF-related apoptosis-inducing ligand. The inverse association between coffee intake and LEP replicated in ULSAM (β, -0.042 SD per cup of coffee, P=0.028) and EpiHealth (β, -0.025 SD per time of coffee, P=0.004). The negative coffee-CHI3L association replicated in EpiHealth (β, -0.07, P=1.15×10(-7) ), but not in ULSAM (β, -0.034, P=0.16).CONCLUSIONS: The current study supports an inverse association between coffee intake and plasma LEP and CHI3L1 levels. The coffee-CHI3L1 association is novel and warrants further investigation given links between CHI3L1 and health conditions that are also potentially influenced by coffee.
17.	Figarska, Sylwia M., et al. (författare) Associations of circulating protein levels with lipid fractions in the general population 2018 Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - : Lippincott Williams & Wilkins. - 1079-5642 .- 1524-4636. ; 38:10, s. 2505-2518 Tidskriftsartikel (refereegranskat)abstract Objective: Revealing patterns of associations between circulating protein and lipid levels could improve biological understanding of cardiovascular disease (CVD). In this study, we investigated the associations between proteins related to CVD and triglyceride (TG), total cholesterol, LDL (low-density lipoprotein), and HDL (high-density lipoprotein) cholesterol levels in individuals from the general population.Approach and Results: We measured plasma protein levels using the Olink ProSeek CVD I or II+III arrays and analyzed 57 proteins available in 3 population-based cohorts: EpiHealth (n=2029; 52% women; median age, 61 years), PIVUS (Prospective Study of the Vasculature in Uppsala Seniors; n=790; 51% women; all aged 70 years), and ULSAM (Uppsala Longitudinal Study of Adult Men; n=551; all men aged 77 years). A discovery analysis was performed in EpiHealth in a regression framework (adjusted for sex, age, body mass index, smoking, glucose levels, systolic blood pressure, blood pressure medication, diabetes mellitus medication, and CVD history), and associations with false discovery rate <0.05 were further tested in PIVUS and ULSAM, where a P value of 0.05 was considered a successful replication (validation false discovery rate of 0.1%). We used summary statistics from a genome-wide association study on each protein biomarker (meta-analysis of EpiHealth, PIVUS, ULSAM, and IMPROVE [Carotid Intima-Media Thickness and IMT-Progression as Predictors of Vascular Events in a High-Risk European Population]) and publicly available data from Global Lipids Genetics Consortium to perform Mendelian randomization analyses to address possible causality of protein levels. Of 57 tested proteins, 42 demonstrated an association with at least 1 lipid fraction; 35 were associated with TG, 15 with total cholesterol, 9 with LDL cholesterol, and 24 with HDL cholesterol. Among these associations, we found KIM-1 (kidney injury molecule-1), TNFR (TNF [tumor necrosis factor] receptor) 1 and 2, TRAIL-R2 (TRAIL [TNF-related apoptosis-inducing ligand] receptor 2), and RETN (resistin) to be associated with all 4 lipid fractions. Further, 15 proteins were related to both TG and HDL cholesterol in a consistent and biologically expected manner, that is, higher TG and lower HDL cholesterol or vice versa. Another common pattern of associations was concomitantly higher TG, total cholesterol, and LDL cholesterol, which is associated with higher CVD risk. We did not find evidence of causal links for protein levels.Conclusions: Our comprehensive analysis of plasma proteins and lipid fractions of 3370 individuals from the general population provides new information about lipid metabolism.
18.	Folkersen, Lasse, et al. (författare) Genomic and drug target evaluation of 90 cardiovascular proteins in 30,931 individuals. 2020 Ingår i: Nature metabolism. - : Springer Science and Business Media LLC. - 2522-5812. ; 2:10, s. 1135-1148 Tidskriftsartikel (refereegranskat)abstract Circulating proteins are vital in human health and disease and are frequently used as biomarkers for clinical decision-making or as targets for pharmacological intervention. Here, we map and replicate protein quantitative trait loci (pQTL) for 90 cardiovascular proteins in over 30,000 individuals, resulting in 451 pQTLs for 85 proteins. For each protein, we further perform pathway mapping to obtain trans-pQTL gene and regulatory designations. We substantiate these regulatory findings with orthogonal evidence for trans-pQTLs using mouse knockdown experiments (ABCA1 and TRIB1) and clinical trial results (chemokine receptors CCR2 and CCR5), with consistent regulation. Finally, we evaluate known drug targets, and suggest new target candidates or repositioning opportunities using Mendelian randomization. This identifies 11 proteins with causal evidence of involvement in human disease that have not previously been targeted, including EGF, IL-16, PAPPA, SPON1, F3, ADM, CASP-8, CHI3L1, CXCL16, GDF15 and MMP-12. Taken together, these findings demonstrate the utility of large-scale mapping of the genetics of the proteome and provide a resource for future precision studies of circulating proteins in human health.
19.	Franke, Ulrik, et al. (författare) EAF(2) - A Framework for Categorizing Enterprise Architecture Frameworks 2009 Ingår i: SNPD 2009. - LOS ALAMITOS : IEEE COMPUTER SOC. ; , s. 327-332 Konferensbidrag (refereegranskat)abstract What constitutes an enterprise architecture framework is a contested subject. The contents of present enterprise architecture frameworks thus differ substantially. This paper aims to alleviate the confusion regarding which framework contains what by proposing a meta framework for enterprise architecture frameworks. By using this meta framework, decision makers are able to express their requirements on what their enterprise architecture framework must contain and also to evaluate whether the existing frameworks meets these requirements. An example classification of common EA frameworks illustrates the approach.
20.	Gustafsson, Erik, 1993-, et al. (författare) Comparison of Design Automation and Machine Learning algorithms for creation of easily modifiable splines 2020 Ingår i: Proceedings of NordDesign 2020, Lyngby, Denmark, 12th - 14th August 2020. - : The Design Society. - 9781912254088 Konferensbidrag (refereegranskat)abstract In order to enable easy modification of results from a design optimization process in a CAD tool, a flexible representation of the geometry is needed. This is not always trivial however, since many file formats are not importable as modifiable geometry into the CAD tool, and if they are, they might not represent the geometry in a way that enables easy modification. To mitigate this problem a design automation (DA) and a machine learning (ML) approach are developed and compared using a test case from an optimization process used to optimize hose routing in tight spaces. In the test case used, the geometry from the optimization process consists of center curves represented as a large number of points. To enable easy modification a more flexible representation is needed such as a spline with a few well-placed control points. Both the DA and ML approach can approximate center curves from the optimization process as splines containing a varying number of control points but do show different properties. The DA approach is considerably slower than the ML but adds a lot of flexibility regarding accuracy and the number of control points used.
21.	Gustafsson, Erik, 1993- (författare) Exploring Data-Driven Methods to Enhance Usability of Design Optimization 2022 Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract Developing high-performing products at a low cost while keeping development time down is increasingly important in today’s competitive market. The current state presents a need for efficient product development processes. One of the challenges is knowledge often being limited in early stages where the cost of making changes is still relatively low. As the process progresses more knowledge is gained to better support decisions; however the cost of making changes increases, limiting the design freedom. To increase knowledge while retaining design freedom, several computer-based tools are available to both generate and evaluate designs in order to make iterations faster and more accurate.Design Optimization (DO) can be utilized to explore the design space and find optimal designs. A Computer-Aided Design (CAD) model is often required as input to analysis tools evaluating the designs. By utilizing Design Automation (DA) several tasks involved in creation and modification of CAD models can be automated. For this reason, DA is sometimes considered an enabler for DO although its use is far wider, covering several aspects of the design process mainly focusing on automating repetitive and routine tasks.Machine Learning and other data-driven methods are becoming increasingly viable in the context of DO and DA. This thesis explores the use of data-driven methods to enhance the usability of DO in different ways such as a faster process, new use-cases, or a more integrated and automated process. Literature in the area is reviewed, identifying applications, trends and challenges. Furthermore, two support tools are developed, incorporating data-driven methods tied to an industrial case. The applications focus on parameterizing geometry and predicting design performance respectively. Potential benefits, limitations, and challenges are discussed based on the literature review and insights from the two support tools. The focus of the thesis is mainly on how data-driven methods can facilitate automation and integration in the design process, specifically for complex products requiring significant engineering efforts.
22.	Gustafsson, Johan, 1993-, et al. (författare) Earnings Dynamics in Sweden : The Recent Evolution of Permanent Inequality and Earnings Volatility 2019 Rapport (övrigt vetenskapligt/konstnärligt)abstract This paper analyzes the dynamics of earnings over the life-cycle, based on Swedish data, and the evolution of permanent and transitory earnings inequality for 2002-2015. We use data on earnings from administrative records gathered in the ASTRID database. We find that features of the data does not match the predictions of the heterogeneous or restricted income profile models commonly applied in the earning dynamics literature and estimate an alternative permanent- transitory (PT) error components model. Analyzing the covariance structure of both male and female earnings, controlling for educational background, we find that the upward trend in permanent earnings inequality observed in Sweden during the 1990s does not seem to continue during the 2000s, and the financial crisis of 2008 did not have any major impact on the variability of earnings. We further simulate the accumulation of income pension entitlements and find that variations in pension entitlements is smaller among college educated workers.
23.	Gustafsson, Johan, 1993-, et al. (författare) Permanent and transitory earnings dynamics and lifetime income inequality in Sweden 2023 Ingår i: Labour Economics. - : Elsevier. - 0927-5371 .- 1879-1034. ; 85 Tidskriftsartikel (refereegranskat)abstract This paper studies the role of permanent- and transitory earnings variability for lifetime income inequality in Sweden. We fit a permanent–transitory error component model to the autocovariance structure of earnings using administrative data for 2002–2015 and minimum distance estimation. We find that permanent earnings inequality increased during the first decade and that the financial crisis of 2008 temporarily heightened earnings volatility. Using this model, we simulate pension entitlements and study lifetime income inequality conditional on the pre- and post-1990’s pension system. We find that permanent earnings differences generally contribute the most to lifetime income inequality. We conclude that the Swedish pension system provides some insurance against earnings risk, but accentuates the role of permanent earnings differences in explaining lifetime inequality.
24.	Gustafsson, Per-Johan, et al. (författare) Characterisation of Tensile Fracture Properties of Paper 1998 Rapport (övrigt vetenskapligt/konstnärligt)
25.	Gustafsson, Per-Johan, et al. (författare) Tests and test results on mechanical properties of adhesive bond lines 2002 Ingår i: Wood adhesion and glued products : state of the art. ; 2, s. 7-24 Bokkapitel (övrigt vetenskapligt/konstnärligt)
26.	Hindorf, Cecilia, et al. (författare) Traceable calibration with 177Lu and comparison of activity meters at hospitals in Norway and Sweden 2023 Ingår i: Physica medica (Testo stampato). - : Elsevier. - 1120-1797 .- 1724-191X. ; 116 Tidskriftsartikel (refereegranskat)abstract Introduction: The activity meter is used to determine the activity of delivered radiopharmaceuticals, administered activity to patients and reference activity when gamma-cameras are calibrated prior to imaged-based dosimetry. The aim is to describe a procedure for cross-calibration of activity meters at different clinical sites, and report on 177Lu activity results when using factory-set calibration factors compared to when calibration is performed with traceability to a primary standard.Methods: Thirty activity meters placed at seven hospitals in Norway and Sweden from four manufacturers: Capintec, Commecer, NuviaTech and Veenstra were included. A stock solution with 177Lu was prepared at the local sites and measured in each activity meter with factory settings. The solution was shipped to the reference site at Lund University for measurements in a secondary standard activity meter. Deviations between local and reference activity measurements were determined for three geometries: 25-mL vial, 10-mL syringe and 1-mL syringe.Results: The median of the deviations was 6.4 % for the 25 mL vial, 5.9 % for the 10 mL syringe and 6.8 % for the 1 mL syringe. The median of the deviations for the 25 mL vial, was 1.5 % for activity meters from Capintec, 7.0 % for Comecer, 11.0 % for NuviaTech and 2.4 % for Veenstra. The majority of the deviations were positive and the maximum deviation was 14.5 %.Conclusion: The activity of 177Lu measured in an activity meter with factory-set dial settings may yield deviations up to 14.5%, compared to activities measured with traceability to a primary standard. This would imply an undertreatment of patients.
27.	Hultman, Johan, et al. (författare) A Resourcification Manifesto: Understanding the Social Process of Resources Becoming Resources 2021 Ingår i: Research Policy. - : Elsevier BV. - 0048-7333. ; 50:9 Tidskriftsartikel (refereegranskat)abstract In times of major global interconnectedness and environmental change, the pressure to identify, create, and exploit new resources is certain to intensify. Given that there are unavoidable trade-offs, conflicts, and arenas for violence involved when increasingly more material and immaterial things are turned into resources, we call for explicit research on the very process – a process that we label resourcification. The concept of resourcification shifts attention from essentialist queries about the nature of resources to a focus on the social processes through which things are turned into resources. In search of a better understanding of resources in the Anthropocene and, in particular, an understanding about the way resources emerge and are used, resourcification offers a new conceptual framework that allows for a systematic search for knowledge about the diversity of contexts, conditions, modes, and temporalities of resourcification. This Resourcification Manifesto offers a theoretical and empirical framework for a radical and disruptive approach to innovation, sustainability, and management studies and policies.
28.	Idborg, Helena, et al. (författare) STRATIFICATION OF SLE PATIENTS FOR IMPROVED DIAGNOSIS AND TREATMENT 2013 Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 72, s. A80-A80 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract Background. Systemic autoimmune diseases (SAIDs) affect about 2% of the population in Western countries. Sufficient diagnostic criteria are lacking due to the heterogeneity within diagnostic categories and apparent overlap regarding symptoms and patterns of autoantibodies between different diagnoses. Systemic lupus erythematosus (SLE) is regarded as a prototype for SAIDs and we hypothesise that subgroups of patients with SLE may have different pathogenesis and should consequently be subject to different treatment strategies.Objectives. Our goal is to find new biomarkers to be used for the identification of more homogenous patient populations for clinical trials and to identify sub-groups of patients with high risk of for example cardiovascular events.Methods. In this study we have utilised 320 SLE patients from the Karolinska lupus cohort and 320 age and gender matched controls. The SLE cohort was characterised based on clinical, genetic and serological data and combined by multivariate data analysis in a systems biology approach to study possible subgroups. A pilot study was designed to verify and investigate suggested subgroups of SLE. Two main subgroups were defined: One group was defined as having SSA and SSB antibodies and a negative lupus anticoagulant test (LAC), i.e., a “Sjögren-like” group. The other group was defined as being negative for SSA and SSB antibodies but positive in the LAC test.i.e. an “APS-like” group. EDTA-plasma from selected patients in these two groups and controls were analysed using a mass spectrometry (MS) based proteomic and metabolomic approach. Pathway analysis was then performed on the obtained data.Results. Our pilot study showed that differences in levels of proteins and metabolites could separate disease groups from population controls. The profile/pattern of involved factors in the complement system supported a division of SLE in two major subgroups, although each individual factor was not significantly different between subgroups. Complement factor 2 (C2) and membrane attack complex (MAC) were analysed in the entire cohort with complementary methods and C2 verifies our results while the levels of MAC did not differ between SLE subgroups. The generated metabolomics data clearly separated SLE patients from controls in both gas chromatography (GC)-MS and liquid chromatography (LC)-MS data. We found for example that tryptophan was lower in the SLE patients compared to controls.Conclusions. Our systems biology approach may lead to a better understanding of the disease and its pathogenesis, and assigning patients into subgroups will result in improved diagnosis and better outcome measures of SLE.
29.	Idborg, Helena, et al. (författare) Systems biology of SLE : biochemical characterisation of subgroups within SLE for improved diagnosis and treatment 2012 Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 71, s. A12- Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
30.	Ingri, Johan, et al. (författare) Fractionation of iron isotopes during estuarine mixing in Ob, Yenisey and Lena freshwater plumes 2009 Ingår i: Geochimica et Cosmochimica Acta. - 0016-7037 .- 1872-9533. ; 73:13, Suppl. S, s. A569- Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract Iron isotopes were measured in suspended matter (>0.2 µm) in the Ob, Yenisey and Lena River freshwater plumes during the International Siberian Shelf Study 2008 (ISSS-08). The δ56Fe value was around zero within the Lena River and close to the river mouth, but changed to more negative values in the outer parts of the plume. In both the Ob and Yenisey plumes suspended matter in the surface water had clearly negative values whereas samples close to the bottom showed values close to zero.It has previously been suggested that total Fe in river suspended matter (>0.2µm) in boreal regions is roughly a mixture of three phases, detrital particles (δ56Fe around zero), oxyhydroxide particles (δ56Fe positive) and C-Fe particles (δ56Fe negative). We suggest that the δ56Fe pattern observed in this study is the result of relatively rapid removal of detrital particles and Fe-oxyhydroxides, leaving a suspended fraction with negative values in the surface water in the outer parts of the freshwater plumes. Hence, during estuarine mixing of suspended particles heavy iron isotopes are deposited close to the river mouth, whereas light isotopes are exported to open ocean water.
31.	Kleman, Johan, et al. (författare) Rubbat förtroende för forskarna 2010 Ingår i: Svenska Dagbladet. - 1101-2412. ; :25 maj Tidskriftsartikel (populärvet., debatt m.m.)
32.	Lind, Lars, et al. (författare) Plasma Protein Profiling of Incident Cardiovascular Diseases : A Multisample Evaluation 2023 Ingår i: CIRCULATION-GENOMIC AND PRECISION MEDICINE. - : Wolters Kluwer. - 2574-8300. ; 16:6 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Proteomic profiling could potentially disclose new pathophysiological pathways for cardiovascular diseases (CVD) and improve prediction at the individual level. We therefore aimed to study the plasma protein profile associated with the incidence of different CVDs.METHODS: Plasma levels of 245 proteins suspected to be linked to CVD or metabolism were measured in 4 Swedish prospective population-based cohorts (SIMPLER [Swedish Infrastructure for Medical Population-Based Life-Course and Environmental Research], ULSAM (Uppsala Longitudinal Study of Adult Men), EpiHealth, and POEM [Prospective Investigation of Obesity, Energy Production, and Metabolism]) comprising 11 869 individuals, free of CVD diagnoses at baseline. Our primary CVD outcome was defined by a combined end point that included either incident myocardial infarction, stroke, or heart failure.RESULTS: Using a discovery/validation approach, 42 proteins were associated with our primary composite end point occurring in 1163 subjects. In separate meta-analyses for each of the 3 CVD outcomes, 49 proteins were related to myocardial infarction, 34 to ischemic stroke, and 109 to heart failure. Thirteen proteins were related to all 3 outcomes. Of those, urokinase plasminogen activator surface receptor, adrenomedullin, and KIM-1 (kidney injury molecule 1) were also related to several markers of subclinical CVD in Prospective Investigation of Obesity, Energy production and Metabolism, reflecting myocardial or arterial pathologies. In prediction analysis, a lasso selection of 11 proteins in ULSAM improved the discrimination of CVD by 3.3% (P<0.0001) in SIMPLER when added to traditional risk factors.CONCLUSIONS: Protein profiling in multiple samples disclosed several new proteins to be associated with subsequent myocardial infarction, stroke, and heart failure, suggesting common pathophysiological pathways for these diseases. KIM-1, urokinase plasminogen activator surface receptor, and adrenomedullin were novel early markers of CVD. A selection of 11 proteins improved the discrimination of CVD.
33.	Lindstedt, Sandra, et al. (författare) Lung transplant after 6 months on ECMO support for SARS-CoV-2-induced ARDS complicated by severe antibody-mediated rejection 2021 Ingår i: BMJ Open Respiratory Research. - : BMJ. - 2052-4439. ; 8, s. 1-4 Tidskriftsartikel (refereegranskat)abstract There have been a few reports of successful lung transplantation (LTx) in patients with SARS-CoV-2-induced acute respiratory distress syndrome (ARDS); however, all reports were with rather short follow-up. Here we present a 62-year-old man without prior lung diseases. Following SARS-CoV-2-induced ARDS and 6 months of extracorporeal membrane oxygenation, he underwent LTx. 3 months post-transplantation he developed acute hypoxia requiring emergency intubation. Chest imaging showed acute rejection, and de novo DQ8-DSA was discovered. He was treated with a high dose of corticosteroids and plasmapheresis and was extubated 4 days later, yet the de novo DQ8-DSA remained. After sessions of plasmapheresis and rituximab, the levels of de novo DQ8-DSA remained unchanged. Nine months post-transplantation the patient died of respiratory failure. We herein discuss the decision to transplant, the transplantation itself and the postoperative course with severe antibody-mediated rejection. In addition, we evaluated the histological changes of the explanted lungs and compared these with end-stage idiopathic pulmonary fibrosis tissue, where both similarities and differences are seen. With the current case experience, one might consider close monitoring regarding DSA, and gives further support that LTx should only be considered for very carefully selected patients.
34.	Malmqvist, Johan, 1964, et al. (författare) Ten Years of CDIO - Experiences from a Long-Term Education Development Process 2010 Ingår i: Proceedings of the 6th International CDIO Conference, Montreal, Canada. Konferensbidrag (refereegranskat)abstract The paper describes and analyses a long-term education development process – the CDIO-based reform of Chalmers University of Technology’s M.Sc. in Mechanical Engineering programme. The initial goals of the reform programme and the changes that it has lead to are reviewed. The results of various kinds of evaluations – CDIO self-evaluations, external evaluations, student and faculty views and costs – are reviewed. A number of critical success factors for sustainable educational development process are identified.
35.	Mokhtari, Arash, et al. (författare) Haemodynamic effects of -75 mmHg negative pressure therapy in a porcine sternotomy wound model. 2009 Ingår i: International Wound Journal. - 1742-481X. ; 6:1, s. 48-54 Tidskriftsartikel (refereegranskat)abstract Previous research has shown -125 mmHg to be the optimal negative pressure for creating an environment that promotes wound healing, and this has therefore been adopted as a standard pressure for patients with deep sternal wound infection. However, it has not yet been clearly shown that -125 mmHg is the optimal pressure from a haemodynamic point of view. Furthermore, there have been reports of cardiac rupture during -125 mmHg negative pressure therapy. We therefore studied the effects of a lower pressure: -75 mmHg. Twelve pigs were used. After median sternotomy, sealed negative pressure therapy of -75 mmHg was applied. Baseline measurements were made and continuous recording of the cardiac output, end-tidal CO(2) production, mean arterial pressure, mean pulmonary pressure (pulmonary artery pressure), systemic vascular resistance, pulmonary vascular resistance, left atrial pressure and central venous pressure was started. Six pigs served as controls. No statistically significant difference was observed in any of the haemodynamic parameters studied, compared with the controls. The present study shows that, with a suitable foam application technique, -75 mmHg can be applied without compromising the central haemodynamics.
36.	Mokhtari, Arash, et al. (författare) The cost of vacuum-assisted closure therapy in treatment of deep sternal wound infection. 2008 Ingår i: Scandinavian Cardiovascular Journal. - : Informa UK Limited. - 1651-2006 .- 1401-7431. ; 42:1, s. 85-89 Tidskriftsartikel (refereegranskat)abstract Objectives. Surgical sites infections are very expensive and the total costs for coronary artery bypass grafting (CABG) surgery followed by deep sternal wound infection (DSWI) with conventional therapy are estimated to be 2.8 times that for normal, CABG surgery. Promising results have been reported with vacuum-assisted closure (VAC) therapy in patients with DSWI. This study presents the cost of VAC therapy in patients with DSWI after CABG surgery. Design. Thirty-eight CABG patients with DSWI, between 2001 and 2005, were treated with VAC therapy. The cost of surgery, intensive care, ward care, laboratory tests and other costs were analyzed. Results. No three-month mortality or recurrent infection was observed. The average cost of CABG procedure and treatment of DSWI was 2.5 times higher than the mean cost of CABG alone. No significant correlations were found between the preoperative EuroSCORE and the cost of DSWI therapy. Conclusions. VAC therapy for patients who underwent CABG surgery followed by DSWI seems to be cost effective, and has low mortality rate.
37.	Nyholm, Tufve, et al. (författare) A national approach for automated collection of standardized and population-based radiation therapy data in Sweden 2016 Ingår i: Radiotherapy and Oncology. - : Elsevier BV. - 0167-8140 .- 1879-0887. ; 119:2, s. 344-350 Tidskriftsartikel (refereegranskat)abstract Purpose: To develop an infrastructure for structured and automated collection of interoperable radiation therapy (RT) data into a national clinical quality registry. Materials and methods: The present study was initiated in 2012 with the participation of seven of the 15 hospital departments delivering RT in Sweden. A national RT nomenclature and a database for structured unified storage of RT data at each site (Medical Information Quality Archive, MIQA) have been developed. Aggregated data from the MIQA databases are sent to a national RT registry located on the same IT platform (INCA) as the national clinical cancer registries. Results: The suggested naming convention has to date been integrated into the clinical workflow at 12 of 15 sites, and MIQA is installed at six of these. Involvement of the remaining 3/15 RT departments is ongoing, and they are expected to be part of the infrastructure by 2016. RT data collection from ARIA (R), Mosaiq (R), Eclipse (TM), and Oncentra (R) is supported. Manual curation of RT-structure information is needed for approximately 10% of target volumes, but rarely for normal tissue structures, demonstrating a good compliance to the RT nomenclature. Aggregated dose/volume descriptors are calculated based on the information in MIQA and sent to INCA using a dedicated service (MIQA2INCA). Correct linkage of data for each patient to the clinical cancer registries on the INCA platform is assured by the unique Swedish personal identity number. Conclusions: An infrastructure for structured and automated prospective collection of syntactically inter operable RT data into a national clinical quality registry for RT data is under implementation. Future developments include adapting MIQA to other treatment modalities (e.g. proton therapy and brachytherapy) and finding strategies to harmonize structure delineations. How the RT registry should comply with domain-specific ontologies such as the Radiation Oncology Ontology (ROO) is under discussion.
38.	Rubin, Johanna, et al. (författare) Intrathecal chemoprophylaxis after HSCT in children 2008 Ingår i: Pediatric Transplantation. - : Wiley. - 1397-3142 .- 1399-3046. ; 12:8, s. 889-895 Tidskriftsartikel (refereegranskat)abstract At present, the literature on the efficacy and risks of i.t. chemotherapy to children after HSCT is scarce. Current practices to reduce the risk of leukemic relapse in the CNS after HSCT differ between centers of transplantation. We compared 74 patients (56 ALL/18 AML), who received i.t. therapy post-HSCT with 46 patients (36 ALL/10 AML) who did not receive post-HSCT i.t. therapy. The patients were transplanted at the University Children's Hospital, Uppsala or the Karolinska University Hospital, Huddinge, two Swedish transplantation units with different routines concerning i.t. therapy after HSCT. The primary end-point was the number of isolated CNS relapses. Secondary end-points were other types of relapse, death, and neurological complications. There was no statistically significant difference in the incidence of CNS relapses between the groups (p > 0.05). I.t. therapy did not reduce the overall incidence of isolated CNS relapse or mortality. Our study did not demonstrate a protective effect of i.t. therapy indicating that post-HSCT i.t. therapy may only be of limited use in the treatment of acute childhood leukemia. We conclude that with the risks present, i.t. therapy should be carefully evaluated, and only considered in high-risk cases.
39.	Räftegård, Oskar, et al. (författare) Energin under mark ska upp till ytan : Strategisk innovationsagenda för geoenergi 2016 Rapport (övrigt vetenskapligt/konstnärligt)abstract The Swedish Strategic Innovation Agenda for Geoenergy develops a strategy for highlighting the need for geoenergy research, development and innovation in relation to the business community and authorities. Sweden has a strong global position in the field. Geothermal energy is the thirdlargest renewable energy source in Sweden, along with wind power. Currently, approximately 18 TWh of renewable heat per year is supplied to household, industrial and commercial buildings. In addition, there is 12 TWh of cooling. There is a great need for a longterm strategy and financial plan for geoenergy research and innovation in Sweden, in order to maintain and further develop research groups and the country's leading position in the field. Today, Swedish research in this field comprises about 14 fulltime positions at universities, institutes and companies. This is little compared to the existing use of geothermal energy, about 19 TWh, which is worth about 15 billion SEK in consumer sales. It is also little in relation to possible future contributions to sustainable development in Sweden and abroad. The agenda is divided into short independent chapters that are tailored to different target groups/ applications. Each chapter consists of an introduction to the current situation, how geoenergy can strategically contribute to a sustainable society, and what actions/needs are a priority.
40.	Räftegård, Oskar, et al. (författare) Energin under markska upp till ytan - Strategisk innovationsagenda för geoenergi 2016 Rapport (övrigt vetenskapligt/konstnärligt)
41.	Sjödin, Johan, 1977- (författare) Strength and Moisture Aspects of Steel Timber Dowel Joints in Glulam Structures : An Experimental and Numerical Study 2008 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Joints are critical parts of timber structures, transmitting static and dynamic forces between structural members. The ultimate behavior of e.g. a building depends strongly on the structural configuration and the capacity of its joints. The complete collapse of a building or other less extensive accidents that may occur usually start as a local failure inside or in the vicinity of a joint. Such serious failures have recently occurred in the Nordic countries. Especially the collapses of two large glued-laminated timber (glulam) structures clearly indicate the need of an improved joint design. The trend toward larger and more complex structures even further increases the importance of a safer design of the joints.One aim of this partly experimentally and partly numerically based work has been to investigate if the short term capacity of steel-timber dowel joints loaded parallel to the grain is affected by an initial drying exposure. The experimental results showed that the load-bearing capacity of the joints is indeed reduced by such moisture changes. Moisture induced stresses was mentioned to be the explanation. The key point is that the climates chosen in the present work (20°C / 65% RH and 20°C / 20% RH) are equivalent to service class 1 according to EC5 (Eurocode 5 2004). Thus, EC5 predicts no decrease in load-bearing capacity, in relation to the standard climate used during testing. A decrease in load-bearing capacity in the range of 5-20%, which was found in the present work, is of course not negligible and, therefore, there could be a need to introduce the effect of drying in design codes. Because similar results were also observed for a double-tapered glulam beam, further work should consider timber structures in general.Two numerical methods in order to predict the capacity of multiple steel-timber dowel joints loaded parallel to the grain were tested in the thesis. For the first method, where fracture mechanics (LEFM) concepts were implemented, a good correlation with the experimental results was seen. Also for the second method, where the capacity for a single dowel-type joint as given in EC5 was used as a failure criterion, a good correlation to traditional EC5 calculations of multiple dowel-type joints was seen. One advantage of using numerical methods in design is that the capacity of the joint can be calculated also for cases when the dowels are placed in more complex patterns. From both a structural and an architectural point of view this can be very important. In addition, such numerical methods are effective tools for the structural engineer when considering complicated loading situations in joints, i.e. eccentric loading giving moments in the joint.
42.	Sjögren, Johan, et al. (författare) Clinical outcome after poststernotomy mediastinitis: Vacuum-assisted closure versus conventional treatment 2005 Ingår i: Annals of Thoracic Surgery. - : Elsevier BV. - 1552-6259 .- 0003-4975. ; 79:6, s. 2049-2055 Tidskriftsartikel (refereegranskat)abstract Background. The conventional treatment for poststernotomy mediastinitis usually involves surgical revision, closed irrigation, or reconstruction with omentum or pectoral muscle flaps. Recently, vacuum-assisted closure has been successfully used in poststernotomy mediastinitis. The aim of the present study was to compare the clinical outcome and survival in 101 patients undergoing vacuum-assisted closure therapy or conventional treatment for poststernotomy mediastinitis. Methods. One hundred one consecutive patients underwent treatment for poststernotomy mediastinitis: vacuum-assisted closure therapy (January 1999 through December 2003, n = 61) or conventional treatment (July 1994 through December 1998, n = 40). Follow-up was made in April 2004 and was 100% complete. Actuarial statistics were used to calculate the survival rates. Results. The 90-days mortality was 0% in the vacuum-assisted closure group and 15% in the conventional treatment group (p < 0.01). The failure rate to first-line treatment with vacuum-assisted closure and conventional treatment were 0% and 37.5%, respectively (p < 0.001). There was no statistically significant difference in the recurrence of sternal fistulas after vacuum-assisted closure therapy or conventional treatment: 6.6% versus 5.0%, respectively. Overall survival in the vacuum-assisted closure group was significantly better (p < 0.05) than in the conventional treatment group: 97% versus 84% (6 months), 93% versus 82% (1 year), and 83% versus 59% (5 years). Conclusions. Our findings support that vacuum-assisted closure therapy is a safe and reliable option in poststernotomy mediastinitis with excellent survival and a very low failure rate compared with conventional treatment.
43.	Sjögren, Johan, et al. (författare) Negative-pressure wound therapy following cardiac surgery: bleeding complications and 30-days mortality in 176 patients with deep sternal wound infection. 2011 Ingår i: Interactive Cardiovascular and Thoracic Surgery. - : Oxford University Press (OUP). - 1569-9285 .- 1569-9293. ; 12:2, s. 117-120 Tidskriftsartikel (refereegranskat)abstract Negative-pressure wound therapy (NPWT) has been used for the treatment of deep sternal wound infection (DSWI) with promising results. However, questions have been raised regarding the potential risk of right ventricle (RV) rupture during treatment. In the present study, we evaluate our clinical experience of NPWT focusing on RV rupture and major bleeding complications and its potentially negative impact on 30-day mortality during an 11-year period. Serious bleeding complications during NPWT were reviewed for 176 patients treated for DSWI between January 1999 and April 2010. The 30-day mortality following DSWI was 1.1% (2/176). Four patients (2.3%) suffered bleeding from the RV rupture during NPWT of the sternal wound (two spontaneous and two debridement related). Furthermore, two patients had debridement-related bleedings from the venous bypass grafts during wound dressing change. The very low 30-day mortality (1.1%) following DSWI supports the use of NPWT. Overall, even if major bleeding complications may occur, the risk of RV rupture seems to be outweighed by the benefit of superior infection control. However, surgical experience is recommended when debriding sternal wounds and we recommend the use of a wound dressing, such as paraffin gauze, in order to protect the RV from direct contact with the polyurethane foam. Keywords: Wound infection; Sternum; Negative-pressure wound therapy; Outcome.
44.	Sjögren, Johan, et al. (författare) The impact of vacuum-assisted closure on long-term survival after post-sternotomy mediastinitis. 2005 Ingår i: Annals of Thoracic Surgery. - : Elsevier BV. - 1552-6259 .- 0003-4975. ; 80:4, s. 1270-1275 Tidskriftsartikel (refereegranskat)
45.	Sjögren, Johan, et al. (författare) Vacuum-assisted closure therapy for deep sternal wound infections: the impact of learning curve on survival and predictors for late mortality. 2008 Ingår i: International Wound Journal. - 1742-481X. ; 5:2, s. 216-223 Tidskriftsartikel (refereegranskat)abstract The aim of this study was to evaluate the possible learning curve effects on survival during the introduction of vacuum-assisted closure (VAC) therapy in patients with deep sternal wound infection (DSWI). Furthermore, predictors of late mortality were analysed and causes of late death were examined. Fifty-three patients (early Group, n = 26, January 1999 to July 2001 versus late group, n = 27, August 2001 to March 2003) were all treated with VAC for DSWI. A follow-up was carried out in September 2006. Multivariate analyses were used to evaluate the predictors of late mortality. The 90-day mortality was 0% in both groups. The survival rates at 5 years were 69.2 +/- 9.1% (early group) versus 58.5 +/- 11.7% (late group), P = ns (non significant). The time interval from cardiac surgery to diagnosis of DSWI and prolonged VAC therapy were identified as independent predictors of late mortality. Our concept for VAC therapy in DSWI seems to be readily introduced in clinical practice. There was no difference in survival between our initial cases and later cases. Late diagnosis and prolonged wound therapy were identified as predictors for late mortality.
46.	Sommar, Carl-Johan, 1989- (författare) Inramningar av lömska problem : Fallstudier av lokala förvaltningars möte med hållbarhet i sjukvård och under pandemin 2023 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Everything should come together, and everything should permeate everything. Trends in governance and policy areas have come to encompass increasingly broader and more diverse issues. For example, sustainable development should guide all parts of government, but there is often little guidance on what this means in practice and how organizations should tackle the diverse issues and challenges of sustainability. Overall, much indicates that the challenges and problems faced by decision-makers in public administration have become increasingly difficult to manage. Some of these problems are particularly challenging and cannot be solved with a short term solution, by a single actor, or by an established method. These problems can only be managed and are referred to as "wicked problems" in the literature.The dissertation focuses on two wicked problems: sustainability and a pandemic. The analysis address how these wicked problems are handled by local public authorities in Sweden. Both problems have an unclear scope, a vague definition, and no definitive solution within reach. The overshadowing argument is that wicked problems need to be framed to be managed through policy mechanisms and implementation processes. The thesis argues that a frame determines and delimits the issue at hand, thus configuring what becomes manageable or not in practice.The dissertation is based on a selection of empirical case studies aimed at observing how governments translate the problems they face by handling both the need to become more sustainable and balancing the needs during a pandemic through changes and modifying the discourse. The study employs an interpretive and constructivist analysis of document studies and interviews with key stakeholders.The overarching conclusions indicate that framing is a central process necessary to move wicked problems forward on the political agenda and make them manageable. In this way, framing helps to delimit the problems; the framing becomes crucial for what becomes manageable and what is left out. Frames have different characteristics, which then influence how the problem is addressed. The conclusions suggest a continued need to make the wickedness of policy problems visible, to consider the larger and more complex aspects of certain political issues, and to strive to identify different mechanisms for managing them. We can see that framing is not just about coping with wicked issues but also about redefining the understanding of wicked problems to align more closely with an organization's limitations and possibilities. Framing offers the possibility to bridge, merge, or even transform our understanding of the wicked problem through the social reality of the organization.
47.	Strawbridge, Rona J., et al. (författare) Identification of a novel proinsulin-associated SNP and demonstration that proinsulin is unlikely to be a causal factor in subclinical vascular remodelling using Mendelian randomisation 2017 Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150 .- 1879-1484. ; 266, s. 196-204 Tidskriftsartikel (refereegranskat)abstract Background and aims: Increased proinsulin relative to insulin levels have been associated with subclinical atherosclerosis (measured by carotid intima-media thickness (cIMT)) and are predictive of future cardiovascular disease (CVD), independently of established risk factors. The mechanisms linking proinsulin to atherosclerosis and CVD are unclear. A genome-wide meta-analysis has identified nine loci associated with circulating proinsulin levels. Using proinsulin-associated SNPs, we set out to use a Mendelian randomisation approach to test the hypothesis that proinsulin plays a causal role in subclinical vascular remodelling.Methods: We studied the high CVD-risk IMPROVE cohort (n = 3345), which has detailed biochemical phenotyping and repeated, state-of-the-art, high-resolution carotid ultrasound examinations. Genotyping was performed using Illumina Cardio-Metabo and Immuno arrays, which include reported proinsulin-associated loci. Participants with type 2 diabetes (n = 904) were omitted from the analysis. Linear regression was used to identify proinsulin-associated genetic variants.Results: We identified a proinsulin locus on chromosome 15 (rs8029765) and replicated it in data from 20,003 additional individuals. An 11-SNP score, including the previously identified and the chromosome 15 proinsulin-associated loci, was significantly and negatively associated with baseline IMTmean and IMTmax (the primary cIMT phenotypes) but not with progression measures. However, MR-Eggers refuted any significant effect of the proinsulin-associated 11-SNP score, and a non-pleiotropic SNP score of three variants (including rs8029765) demonstrated no effect on baseline or progression cIMT measures.Conclusions: We identified a novel proinsulin-associated locus and demonstrated that whilst proinsulin levels are associated with cIMT measures, proinsulin per se is unlikely to have a causative effect on cIMT.
48.	Surakka, Ida, et al. (författare) The impact of low-frequency and rare variants on lipid levels. 2015 Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 47:6, s. 589-597 Tidskriftsartikel (refereegranskat)abstract Using a genome-wide screen of 9.6 million genetic variants achieved through 1000 Genomes Project imputation in 62,166 samples, we identify association to lipid traits in 93 loci, including 79 previously identified loci with new lead SNPs and 10 new loci, 15 loci with a low-frequency lead SNP and 10 loci with a missense lead SNP, and 2 loci with an accumulation of rare variants. In six loci, SNPs with established function in lipid genetics (CELSR2, GCKR, LIPC and APOE) or candidate missense mutations with predicted damaging function (CD300LG and TM6SF2) explained the locus associations. The low-frequency variants increased the proportion of variance explained, particularly for low-density lipoprotein cholesterol and total cholesterol. Altogether, our results highlight the impact of low-frequency variants in complex traits and show that imputation offers a cost-effective alternative to resequencing.
49.	Tryding, Johan, et al. (författare) Analysis of Notched Newsprint Sheet in Mode I Fracture 2001 Ingår i: Journal of Pulp and Paper Science. - 0826-6220. ; 27:3, s. 103-109 Tidskriftsartikel (refereegranskat)abstract A new approach to analyze notched paper sheet loaded in mode I, based on cohesive crack modelling, is investigated. The method predicts final failure of the sheet, regardless of the sheet size and initial crack length. Onset of crack growth, stable crack growth and onset of unstable crack growth are predicted. The simulations of the notched paper sheet reveal that the concept of autonomy, i.e. independence of specimen geometry and load configuration, in a region near the crack edge does not in general prevail, except at small-scale yielding. The method is confirmed by a large number of experimental tests. Different sheet sizes are tested. In the experiments, 45 g/m2 newsprint was used.
50.	Tryding, Johan, et al. (författare) Characterization of tensile fracture properties of paper 2000 Ingår i: Tappi Journal. - 0734-1415. ; 83:2, s. 84-89 Tidskriftsartikel (refereegranskat)abstract A relationship between stress and deformation can be evaluated from the load and elongation recorded in the tensile test of a strip of paper. This relationship characterizes the fracture properties of the paper. It shows how the stress acting across a fracture region decreases as the deformation increases.The relationship can be used in strength analysis by the finite element method and for the determination of various conventional fracture parameters such as fracture energy.The theory of characterization, a test method, and test results for three papers are presented.

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