SwePub - search: WFRF:(Carlsson Peter)

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1.	Klionsky, Daniel J, et al. (author) Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). 2016 In: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 12:1, s. 1-222 Journal article (peer-reviewed)
2.	Bentham, James, et al. (author) A century of trends in adult human height 2016 In: eLIFE. - 2050-084X. ; 5 Journal article (peer-reviewed)abstract Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.522.7) and 16.5 cm (13.319.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
3.	Bentham, James, et al. (author) A century of trends in adult human height 2016 In: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 5 Journal article (peer-reviewed)abstract Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3– 19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8– 144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
4.	Zhou, Bin, et al. (author) Worldwide trends in diabetes since 1980: A pooled analysis of 751 population-based studies with 4.4 million participants 2016 In: The Lancet. - : Elsevier B.V.. - 0140-6736 .- 1474-547X. ; 387:10027, s. 1513-1530 Journal article (peer-reviewed)abstract Background: One of the global targets for non-communicable diseases is to halt, by 2025, the rise in the age standardised adult prevalence of diabetes at its 2010 levels. We aimed to estimate worldwide trends in diabetes, how likely it is for countries to achieve the global target, and how changes in prevalence, together with population growth and ageing, are aff ecting the number of adults with diabetes.Methods: We pooled data from population-based studies that had collected data on diabetes through measurement of its biomarkers. We used a Bayesian hierarchical model to estimate trends in diabetes prevalence-defined as fasting plasma glucose of 7.0 mmol/L or higher, or history of diagnosis with diabetes, or use of insulin or oral hypoglycaemic drugs-in 200 countries and territories in 21 regions, by sex and from 1980 to 2014. We also calculated the posterior probability of meeting the global diabetes target if post-2000 trends continue.Findings: We used data from 751 studies including 4372000 adults from 146 of the 200 countries we make estimates for. Global age-standardised diabetes prevalence increased from 4.3% (95% credible interval 2.4-17.0) in 1980 to 9.0% (7.2-11.1) in 2014 in men, and from 5.0% (2.9-7.9) to 7.9% (6.4-9.7) in women. The number of adults with diabetes in the world increased from 108 million in 1980 to 422 million in 2014 (28.5% due to the rise in prevalence, 39.7% due to population growth and ageing, and 31.8% due to interaction of these two factors). Age-standardised adult diabetes prevalence in 2014 was lowest in northwestern Europe, and highest in Polynesia and Micronesia, at nearly 25%, followed by Melanesia and the Middle East and north Africa. Between 1980 and 2014 there was little change in age-standardised diabetes prevalence in adult women in continental western Europe, although crude prevalence rose because of ageing of the population. By contrast, age-standardised adult prevalence rose by 15 percentage points in men and women in Polynesia and Micronesia. In 2014, American Samoa had the highest national prevalence of diabetes (>30% in both sexes), with age-standardised adult prevalence also higher than 25% in some other islands in Polynesia and Micronesia. If post-2000 trends continue, the probability of meeting the global target of halting the rise in the prevalence of diabetes by 2025 at the 2010 level worldwide is lower than 1% for men and is 1% for women. Only nine countries for men and 29 countries for women, mostly in western Europe, have a 50% or higher probability of meeting the global target.Interpretation: Since 1980, age-standardised diabetes prevalence in adults has increased, or at best remained unchanged, in every country. Together with population growth and ageing, this rise has led to a near quadrupling of the number of adults with diabetes worldwide. The burden of diabetes, both in terms of prevalence and number of adults aff ected, has increased faster in low-income and middle-income countries than in high-income countries.
5.	Åberg, N David, 1970, et al. (author) Insulin-like growth factor-I increases astrocyte intercellular gap junctional communication and connexin43 expression in vitro. 2003 In: Journal of neuroscience research. - : Wiley. - 0360-4012. ; 74:1, s. 12-22 Journal article (peer-reviewed)abstract Connexin43 (cx43) forms gap junctions in astrocytes, and these gap junctions mediate intercellular communication by providing transport of low-molecular-weight metabolites and ions. We have recently shown that systemic growth hormone increases cx43 in the brain. One possibility was that local brain insulin-like growth factor-I (IGF-I) could mediate the effect by acting directly on astrocytes. In the present study, we examined the effects of direct application of recombinant human IGF-I (rhIGF-I) on astrocytes in primary culture concerning cx43 protein expression and gap junctional communication (GJC). After 24 hr of stimulation with rhIGF-I under serum-free conditions, the GJC and cx43 protein were analyzed. Administration of 30 ng/ml rhIGF-I increased the GJC and the abundance of cx43 protein. Cell proliferation of the astrocytes was not significantly increased by rhIGF-I at this concentration. However, a higher concentration of rhIGF-I (150 ng/ml) had no effect on GJC/cx43 but increased cell proliferation. Because of the important modulatory role of IGF binding proteins (IGFBPs) on IGF-I action, we analyzed IGFBPs in conditioned media. In cultures with a low abundance of IGFBPs (especially IGFBP-2), the GJC response to 30 ng/ml rhIGF-I was 81%, compared with the average of 25%. Finally, as a control, insulin was given in equimolar concentrations. However, GJC was not affected, which suggests that rhIGF-I acted via IGF-I receptors. In summary, the data show that rhIGF-I may increase GJC/cx43, whereas a higher concentration of rhIGF-I--at which stimulation of proliferation occurred--did not affect GJC/cx43. Furthermore, IGFBP-2 appeared to modulate the action of rhIGF-I on GJC in astrocytes by a paracrine mechanism.
6.	Adlerberth, Ingegerd, 1959, et al. (author) Intestinal colonization with Enterobacteriaceae in Pakistani and Swedish hospital-delivered infants. 1991 In: Acta paediatrica Scandinavica. - 0001-656X. ; 80:6-7, s. 602-10 Journal article (peer-reviewed)abstract Rectal cultures from Swedish and Pakistani hospital-delivered newborn infants were analysed regarding the early acquisition of enterobacteria. Swedish infants were delivered vaginally, Pakistani infants were delivered either vaginally or by caesarean section. The Swedish infants were all breast-fed, whereas breastfeeding was incomplete and often started late among the Pakistani infants. Both groups of Pakistani infants were more rapidly colonized with enterobacteria than were the Swedish infants. Cultures from Swedish infants seldom yielded more than one kind of enterobacteria; E. coli and Klebsiella were most frequently isolated. E. coli dominated in both Pakistani groups, but especially caesarean section delivered infants were in addition often colonized with Proteus, Klebsiella, Enterobacter or Citrobacter species. Breastfeeding from the first day of life reduced colonization with Klebsiella/Enterobacter/Citrobacter. The results suggest that environmental exposure, delivery mode and early feeding habits all influence the early intestinal colonization with enterobacteria.
7.	Adolfsson, Emelie, 1985- (author) Lithium formate EPR dosimetry for accurate measurements of absorbed dose in radiotherapy 2014 Doctoral thesis (other academic/artistic)abstract Lithium formate has shown to be a material with properties suitable for electron paramagnetic resonance (EPR) dosimetry, among them up to 7 times higher sensitivity compared to alanine, which is a well-established EPR detector material for dose determinations in radiotherapy.The aim of this thesis was to further investigate the properties of lithium formate and develop the dosimetry system towards applications in radiotherapy. The intrinsic efficiency for energies of relevance to brachytherapy and the signal stability were investigated. The dosimetry system was expanded to include a smaller dosimeter model, suitable for measurements in dose gradient regions. An individual sensitivity correction method was applied to the smaller dosimeters to be able to perform dose determinations with the same precision as for the larger ones. EPR dosimetry in general is time consuming and effort was spent to optimize the signal readout procedure regarding measurement time and measurement precision.The system was applied in two clinical applications chosen for their high demands on the dosimetry system: 1) a dosimetry audit for external photon beam therapy and 2) dose verification measurements around a low energy HDR brachytherapy source.The conclusions drawn from this thesis were: dose determinations can be performed with a standard uncertainty of 1.8-2.5% using both the original size dosimeters and the new developed smaller ones. The dosimetry system is robust and useful for applications when high measurement precision and accuracy is prioritized. It is a good candidate for dosimetry audits, both in external beam therapy and brachytherapy.
8.	Ahlqvist, Emma, et al. (author) Novel subgroups of adult-onset diabetes and their association with outcomes : a data-driven cluster analysis of six variables 2018 In: The Lancet Diabetes and Endocrinology. - 2213-8587 .- 2213-8595. ; 6:5, s. 361-369 Journal article (peer-reviewed)abstract BackgroundDiabetes is presently classiﬁed into two main forms, type 1 and type 2 diabetes, but type 2 diabetes in particular is highly heterogeneous. A reﬁned classiﬁcation could provide a powerful tool to individualise treatment regimens and identify individuals with increased risk of complications at diagnosis.MethodsWe did data-driven cluster analysis (k-means and hierarchical clustering) in patients with newly diagnosed diabetes (n=8980) from the Swedish All New Diabetics in Scania cohort. Clusters were based on six variables (glutamate decarboxylase antibodies, age at diagnosis, BMI, HbA1c, and homoeostatic model assessment 2 estimates of β-cell function and insulin resistance), and were related to prospective data from patient records on development of complications and prescription of medication. Replication was done in three independent cohorts: the Scania Diabetes Registry (n=1466), All New Diabetics in Uppsala (n=844), and Diabetes Registry Vaasa (n=3485). Cox regression and logistic regression were used to compare time to medication, time to reaching the treatment goal, and risk of diabetic complications and genetic associations.FindingsWe identiﬁed ﬁve replicable clusters of patients with diabetes, which had signiﬁcantly different patient characteristics and risk of diabetic complications. In particular, individuals in cluster 3 (most resistant to insulin) had signiﬁcantly higher risk of diabetic kidney disease than individuals in clusters 4 and 5, but had been prescribed similar diabetes treatment. Cluster 2 (insulin deﬁcient) had the highest risk of retinopathy. In support of the clustering, genetic associations in the clusters differed from those seen in traditional type 2 diabetes.InterpretationWe stratiﬁed patients into ﬁve subgroups with differing disease progression and risk of diabetic complications. This new substratiﬁcation might eventually help to tailor and target early treatment to patients who would beneﬁt most, thereby representing a ﬁrst step towards precision medicine in diabetes.
9.	Ainegren, Mats, 1963-, et al. (author) Design and development of a climatic wind tunnel for physiological sports experimentation 2019 In: Proceedings of the Institution of Mechanical Engineers, Part P. - : SAGE Publications. - 1754-3371. ; 233:1, s. 86-100 Journal article (peer-reviewed)abstract The aim of this project was to develop a wind tunnel that enables the study of human performance during various types ofsports and physical activities by examining the influence of aerodynamic drag, precipitation, frictional forces and gravitationalforces on uphill and downhill travel on a moving substrate. An overall design for a wind tunnel and working section containinga large treadmill was drafted, followed by computational fluid dynamics simulations of flow conditions to assess thedesign’s feasibility and select from different geometries prior to its construction. The flow conditions in the completed windtunnel were validated using different flows, speeds and treadmill inclinations. Pilot experiments were carried out using across-country skier to investigate the effect of aerodynamic drag on oxygen uptake during double poling and the maximalachieved speed when rolling on a declined treadmill. The purpose was to validate the usefulness of the tunnel. The resultsshowed that flow conditions are acceptable for experiments even in worst-case scenarios with maximal inclined and declinedtreadmill. Results also showed that aerodynamic drag has a significant impact on the skier’s energy expenditure.
10.	Andersson-Assarsson, Johanna C., 1974, et al. (author) Evolution of age-related mutation-driven clonal haematopoiesis over 20 years is associated with metabolic dysfunction in obesity 2023 In: Ebiomedicine. - 2352-3964. ; 92 Journal article (peer-reviewed)abstract Background Haematopoietic clones caused by somatic mutations with >= 2% variant allele frequency (VAF) increase with age and are linked to risk of haematological malignancies and cardiovascular disease. Recent observations suggest that smaller clones (VAF<2%) are also associated with adverse outcomes. Our aims were to determine the prevalence of clonal haematopoiesis driven by clones of variable sizes in individuals with obesity treated by usual care or bariatric surgery (a treatment that improves metabolic status), and to examine the expansion of clones in relation to age and metabolic dysregulation over up to 20 years.Methods Clonal haematopoiesis-driver mutations (CHDMs) were identified in blood samples from participants of the Swedish Obese Subjects intervention study. Using an ultrasensitive assay, we analysed single-timepoint samples from 1050 individuals treated by usual care and 841 individuals who had undergone bariatric surgery, and multiple-timepoint samples taken over 20 years from a subset (n = 40) of the individuals treated by usual care.Findings In this explorative study, prevalence of CHDMs was similar in the single-timepoint usual care and bariatric surgery groups (20.6% and 22.5%, respectively, P = 0.330), with VAF ranging from 0.01% to 31.15%. Clone sizes increased with age in individuals with obesity, but not in those who underwent bariatric surgery. In the multiple-timepoint analysis, VAF increased by on average 7% (range -4% to 24%) per year and rate of clone growth was negatively associated with HDL-cholesterol (R = -0.68, 1.74 E-04).Interpretation Low HDL-C was associated with growth of haematopoietic clones in individuals with obesity treated by usual care.
11.	Bednar, Peter, et al. (author) Supporting Business Decision-making: One Professional at a Time 2014 In: DSS 2.0 – Supporting Decision Making with New Technologies. - 9781614993988 - 9781614993995 ; 261, s. 471-482 Book chapter (peer-reviewed)abstract This paper discusses the potential for personalized, user-owned decision-support systems. It can be readily seen that there are benefits from analysis of ‘Big Data’ that could not be attained through more traditional means, e.g. insurance and credit card fraud can be detected more readily when it is possible to analyze integrated data across multiple servers owned and controlled by separate organizations. However, high-level data analysis, though useful, cannot be trusted to provide all the answers to organizational ‘questions’. Individuals need to be able to inform themselves in complex decision situations and for this purpose there can be no substitute for ‘little data’ from wherever this is to be drawn. We explore a potential type of support that could overcome the barriers to professional creativity arising through lack of trust in decision-support systems owned and controlled from senior management. The Virtual Personal Assistant described uses natural language processing to interact with a professional user in the context of messy, situated problems, and in private. It has capability to learn from user-interactions and therefore to co-evolve contextually. A ‘little data’ system such as this can therefore help to improve relevance of user understandings in a relatively risk free environment.
12.	Benzinou, Michael, et al. (author) Common nonsynonymous variants in PCSK1 confer risk of obesity. 2008 In: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 40:8, s. 943-5 Journal article (peer-reviewed)abstract Mutations in PCSK1 cause monogenic obesity. To assess the contribution of PCSK1 to polygenic obesity risk, we genotyped tag SNPs in a total of 13,659 individuals of European ancestry from eight independent case-control or family-based cohorts. The nonsynonymous variants rs6232, encoding N221D, and rs6234-rs6235, encoding the Q665E-S690T pair, were consistently associated with obesity in adults and children (P = 7.27 x 10(-8) and P = 2.31 x 10(-12), respectively). Functional analysis showed a significant impairment of the N221D-mutant PC1/3 protein catalytic activity.
13.	Bergman, Lina, 1982, et al. (author) Study for Improving Maternal Pregnancy And Child ouTcomes (IMPACT): a study protocol for a Swedish prospective multicentre cohort study 2020 In: BMJ Open. - : BMJ. - 2044-6055 .- 2044-6055. ; 10:9, s. e033851-e033851 Journal article (peer-reviewed)abstract Introduction First-trimester pregnancy risk evaluation facilitates individualised antenatal care, as well as application of preventive strategies for pre-eclampsia or birth of a small for gestational age infant. A range of early intervention strategies in pregnancies identified as high risk at the end of the first trimester has been shown to decrease the risk of preterm pre-eclampsia (<37 gestational weeks). The aim of this project is to create the Improving Maternal Pregnancy And Child ouTcomes (IMPACT) database; a nationwide database with individual patient data, including predictors recorded at the end of the first trimester and later pregnancy outcomes, to identify women at high risk of pre-eclampsia. A second aim is to link the IMPACT database to a biobank with first-trimester blood samples. Methods and analysis This is a Swedish prospective multicentre cohort study. Women are included between the 11th and 14th weeks of pregnancy. At inclusion, pre-identified predictors are retrieved by interviews and medical examinations. Blood samples are collected and stored in a biobank. Additional predictors and pregnancy outcomes are retrieved from the Swedish Pregnancy Register. Inclusion in the study began in November 2018 with a targeted sample size of 45 000 pregnancies by end of 2021. Creation of a new risk prediction model will then be developed, validated and implemented. The database and biobank will enable future research on prediction of various pregnancy-related complications. Ethics and dissemination Confidentiality aspects such as data encryption and storage comply with the General Data Protection Regulation and with ethical committee requirements. This study has been granted national ethical approval by the Swedish Ethical Review Authority (Uppsala 2018-231) and national biobank approval at Uppsala Biobank (18237 2 2018 231). Results from the current as well as future studies using information from the IMPACT database will be published in peer-reviewed journals.
14.	Carlsson, Axel C, et al. (author) Endostatin, cathepsin S, and cathepsin L, and their association with inflammatory markers and mortality in patients undergoing hemodialysis 2015 In: Blood Purification. - : S. Karger AG. - 0253-5068 .- 1421-9735. ; 39:4, s. 259-265 Journal article (peer-reviewed)abstract Background/Aims: Although both endostatin and cathepsins S have been associated with higher mortality, data in patients with end-stage renal disease (ESRD) are scarce.Methods: A longitudinal cohort study of 207 prevalent patients undergoing hemodialysis.Results: Cathepsins S and L were associated with soluble receptors for tumor necrosis factor (sTNFR1 and sTNFR2, rho between 0.28 and 0.43, p < 0.001 for all). Weaker or absent associations between endostatin, cathepsins S and L were seen with other inflammatory biomarkers, that is, CRP, interleukin 6, pentraxin 3, and TNF. In Cox and Laplace regression models adjusted for age, sex, dialysis vintage, and diabetes: standard deviation increments of endostatin was associated with a lower mortality (hazard ratio 0.75, 95% confidence interval (CI) 0.57-0.98), and with 6.8 months longer median survival.Conclusions: The high levels of endostatin, cathepsins S and L, and their associations with sTNFR1 and sTNFR2 warrant further studies exploring mortality, and the angiogenic and inflammatory pathways in ESRD. (C) 2015 S. Karger AG, Basel
15.	Carlsson, Axel C, et al. (author) High levels of soluble tumor necrosis factor receptors 1 and 2 and their association with mortality in patients undergoing hemodialysis 2015 In: CardioRenal Medicine. - : S. Karger AG. - 1664-3828 .- 1664-5502. ; 5:2, s. 89-95 Journal article (peer-reviewed)abstract Objective: Circulating soluble tumor necrosis factor receptors 1 and 2 (sTNFR1 and 5TNFR2) are associated with chronic kidney disease (CKD) progression in patients with CKD or diabetes, and with higher mortality. However, data in patients with end-stage renal disease are scarce. Therefore, we analyzed serum levels of sTNFR1 and sTNFR2 and investigated their association with inflammatory markers and mortality in dialysis patients. Research Design and Methods: This was a longitudinal cohort study of 207 prevalent patients (median age 66 years, 56% men) undergoing hemodialysis in Stockholm, Sweden. Demographics, clinical characteristics, including comorbidities and laboratory data, were obtained at baseline, together with prospective follow-up for mortality.Results: The median sTNFR1 and sTNFR2 levels were 17,680 ng/l [95% confidence interval (CI) 17,023-18,337] and 24,450 ng/l (95% CI 23,721-25,179), respectively. During a follow-up of 31 months (interquartile range, 21-38), 77 patients died. There was no association between the levels of sTNFRs and mortality in Cox regression models, and no consistent trend towards higher or lower mortality was seen in Laplace regression models. sTNFR1 and sTNFR2 levels were highly associated with other inflammatory markers including interleukin-6, pentraxin 3 and TNF-alpha. Conclusions:Prevalent hemodialysis patients have several-fold higher levels of sTNFRs compared to previous studies in CKD stage 4 patients. As no consistent association between TNFR and mortality was observed, clinical implications of measuring these receptors to predict outcome end-stage renal disease patients provide limited results.
16.	Carlsson, Erik F., 1968, et al. (author) Experimental Study of Thin Film HTS/Ferroelectric CPW Phase Shifters for Microwave Applications 1997 In: Institute of Physics Conference Series. - 0951-3248. ; 158, s. 339-342 Journal article (peer-reviewed)
17.	Carlsson, Lena M S, 1957, et al. (author) Bariatric surgery and prevention of type 2 diabetes in Swedish obese subjects. 2012 In: The New England journal of medicine. - : Massachusetts Medical Society. - 1533-4406 .- 0028-4793. ; 367:8, s. 695-704 Journal article (other academic/artistic)abstract Weight loss protects against type 2 diabetes but is hard to maintain with behavioral modification alone. In an analysis of data from a nonrandomized, prospective, controlled study, we examined the effects of bariatric surgery on the prevention of type 2 diabetes.
18.	Carlsson, Lena M S, 1957, et al. (author) Life expectancy after bariatric surgery or usual care in patients with or without baseline type 2 diabetes in Swedish Obese Subjects. 2023 In: International journal of obesity (2005). - 1476-5497. ; 47, s. 931-8 Journal article (peer-reviewed)abstract To determine life expectancy and causes of death after bariatric surgery in relation to baseline type 2 diabetes (T2D) in the prospective, Swedish Obese Subjects study.The study included 2010 patients with obesity who underwent bariatric surgery and 2037 matched controls, eligible for surgery. The surgery group underwent gastric bypass (n=265), banding (n=376), or vertical banded gastroplasty (n=1369). The control group (n=2037) received usual obesity care. Causes of death were obtained from the Swedish Cause of Death Register, case sheets and autopsy reports, in patients with baseline T2D (n=392 surgery patients/n=305 controls) or non-T2D (n=1609 surgery patients/n=1726 controls) during a median follow-up 26 years.In T2D and non-T2D subgroups, bariatric surgery was associated with increased life expectancy (2.1, 95% confidence interval (95% CI) 0.2-4.0; and 1.6, 0.5-2.7 years, respectively) and reduced overall mortality (adjusted hazard ratio (adjHR)=0.77, 95% CI: 0.61-0.97; and 0.82, 0.72-0.94, respectively), and the treatment benefit was similar (interaction p=0.615). Bariatric surgery was associated with reduced cardiovascular mortality in both subgroups (adjHR=0.65, 95% CI: 0.46-0.91; and 0.70, 0.55-0.88, respectively (interaction p=0.516)).Bariatric surgery is associated with similar reduction of overall and cardiovascular mortality and increased life expectancy regardless of baseline diabetes status.
19.	Carlsson, Lena M S, 1957, et al. (author) Long-term incidence of microvascular disease after bariatric surgery or usual care in patients with obesity, stratified by baseline glycaemic status: a post-hoc analysis of participants from the Swedish Obese Subjects study. 2017 In: The lancet. Diabetes & endocrinology. - 2213-8595. ; 5:4, s. 271-279 Journal article (peer-reviewed)abstract Bariatric surgery is associated with remission of diabetes and prevention of diabetic complications in patients with obesity and type 2 diabetes. Long-term effects of bariatric surgery on microvascular complications in patients with prediabetes are unknown. The aim of this study was to examine the effects of bariatric surgery on incidence of microvascular complications in patients with obesity stratified by baseline glycaemic status.Patients were recruited to the Swedish Obese Subjects (SOS) study between Sept 1, 1987, and Jan 31, 2001. Inclusion criteria were age 37-60 years and BMI of 34 kg/m(2) or greater in men and 38 kg/m(2) or greater in women. Exclusion criteria were identical in surgery and control groups and designed to exclude patients not suitable for surgery. The surgery group (n=2010) underwent gastric bypass (265 [13%]), gastric banding (376 [19%]), or vertical-banded gastroplasty (1369 [68%]). Participants in the control group (n=2037) received usual care. Bodyweight was measured and questionnaires were completed at baseline and at 0·5 years, 1 year, 2 years, 3 years, 4 years, 6 years, 8 years, 10 years, 15 years, and 20 years. Biochemical variables were measured at baseline and at 2 years, 10 years, and 15 years. We categorised participants into subgroups on the basis of baseline glycaemic status (normal [fasting blood glucose concentration <5·0 mmol/L], prediabetes [5·0-6·0 mmol/L], screen-detected diabetes [≥6·1 mmol/L at baseline visit without previous diagnosis], and established diabetes [diagnosis of diabetes before study inclusion]). We obtained data about first incidence of microvascular disease from nationwide registers and about diabetes incidence at study visits at 2 years, 10 years, and 15 years. We did the main analysis by intention to treat, and subgroup analyses after stratification by baseline glycaemic status and by diabetes status at the 15 year follow-up. The SOS study is registered with ClinicalTrials.gov, NCT01479452.4032 of the 4047 participants in the SOS study were included in this analysis. We excluded four patients with suspected type 1 diabetes, and 11 patients with unknown glycaemic status at baseline. At baseline, 2838 patients had normal blood glucose, 591 had prediabetes, 246 had screen-detected diabetes, and 357 had established diabetes. Median follow-up was 19 years (IQR 16-21). We identified 374 incident cases of microvascular disease in the control group and 224 in the surgery group (hazard ratio [HR] 0·56, 95% CI 0·48-0·66; p<0·0001). Interaction between baseline glycaemic status and effect of treatment on incidence of microvascular disease was significant (p=0·0003). Unadjusted HRs were lowest in the subgroup with prediabetes (0·18, 95% CI 0·11-0·30), followed by subgroups with screen-detected diabetes (0·39, 0·24-0·65), established diabetes (0·54, 0·40-0·72), and normoglycaemia (0·63, 0·48-0·81). Surgery was associated with reduced incidence of microvascular events in people with prediabetes regardless of whether they developed diabetes during follow-up.Bariatric surgery was associated with reduced risk of microvascular complications in all subgroups, but the greatest relative risk reduction was observed in patients with prediabetes at baseline. Our results suggest that prediabetes should be treated aggressively to prevent future microvascular events, and effective non-surgical treatments need to be developed for this purpose.US National Institutes of Health, Swedish Research Council, Sahlgrenska University Hospital Regional Agreement on Medical Education and Research, and Swedish Diabetes Foundation.
20.	Carlsson, Lena M S, 1957, et al. (author) Long-term incidence of serious fall-related injuries after bariatric surgery in Swedish obese subjects. 2019 In: International journal of obesity (2005). - : Springer Science and Business Media LLC. - 1476-5497 .- 0307-0565. ; 43:4, s. 933-937 Journal article (peer-reviewed)abstract Obesity increases risk of falling, but the effect of bariatric surgery on fall-related injuries is unknown. The aim of this study was therefore to study the association between bariatric surgery and long-term incidence of fall-related injuries in the prospective, controlled Swedish Obese Subjects study. At inclusion, body mass index was≥34kg/m2 in men and ≥38kg/m2 in women. The surgery per-protocol group (n=2007) underwent gastric bypass (n=266), banding (n=376), or vertical banded gastroplasty (n=1365), and controls (n=2040) received usual care. At the time of analysis (31 December 2013), median follow-up was 19 years (maximal 26 years). Fall-related injuries requiring hospital treatment were captured using data from the Swedish National Patient Register. During follow-up, there were 617 first-time fall-related injuries in the surgery group and 513 in the control group (adjusted hazard ratio 1.21, 95% CI, 1.07-1.36; P=0.002). The incidence differed between treatment groups (P<0.001, log-rank test) and was higher after gastric bypass than after usual care, banding and vertical banded gastroplasty (adjusted hazard ratio 0.50-0.52, P<0.001 for all three comparisons). In conclusion, gastric bypass surgery was associated with increased risk of serious fall-related injury requiring hospital treatment.
21.	Carlsson, Maria L., 1959, et al. (author) The 5-HT2A receptor antagonist M100907 is more effective in counteracting NMDA antagonist- than dopamine agonist-induced hyperactivity in mice 1999 In: J Neural Transm. - 0300-9564. ; 106:2, s. 123-9 Journal article (peer-reviewed)abstract The purpose of the present study was to compare the effectiveness of the selective 5-HT2A antagonist M100907 in different psychosis models. The classical neuroleptic haloperidol was used as reference compound. Two hyperdopaminergia and two hypoglutamatergia mouse models were used. Hyperdopaminergia was produced by the DA releaser d-amphetamine or the DA uptake inhibitor GBR 12909. Hypoglutamatergia was produced by the un-competitive NMDA receptor antagonist MK-801 or the competitive NMDA receptor antagonist D-CPPene. M100907 was found to counteract the locomotor stimulant effects of the NMDA receptor antagonists MK-801 and D-CPPene, but spontaneous locomotion, d-amphetamine- and GBR-12909-induced hyperactivity were not significantly affected. Haloperidol, on the other hand, antagonized both NMDA antagonist- and DA agonist-induced hyperactivity, as well as spontaneous locomotion in the highest dose used. Based on the present and previous results we draw the conclusion that 5-HT2A receptor antagonists are particularly effective against behavioural anomalies resulting from hypoglutamatergia of various origins. The clinical implications of our results and conclusions would be that a 5-HT2A receptor antagonist, due to i a the low side effect liability, could be the preferable treatment strategy in various disorders associated with hypoglutamatergia; such conditions might include schizophrenia, childhood autism and dementia disorders.
22.	CARLSSON, STEFAN, 1987, et al. (author) Age at surgery, educational level and long-term urinary incontinence after radical prostatectomy 2011 In: BJU International. - 1464-4096 .- 1464-410X. ; 108:10, s. 1572-1577 Journal article (peer-reviewed)abstract OBJECTIVE To identify predictors for long-term urinary leakage after radical prostatectomy. PATIENTS AND METHODS A consecutive series of 1411 patients who underwent radical prostatectomy (open surgery or robot-assisted laparoscopic surgery) at Karolinska University Hospital between 2002 and 2006 were invited to complete a study-specific questionnaire. Urinary leakage was defined as use of two or more pads per day. RESULTS Questionnaires were received from 1288 (91%) patients with a median follow-up of 2.2 years. Age at surgery predicts in an exponential manner long-term urinary incontinence at follow-up with an estimated relative increase of 6% per year. Among the oldest patients, 19% had urinary incontinence compared with 6% in the youngest age group, translating to a prevalence ratio of 2.4 (95% confidence interval [CI], 1.5-8.1). Low educational level, as compared with high, yielded an increased age-adjusted prevalence ratio of 2.5 (95% CI, 1.7-3.9). Patients who had undergone salvage radiation therapy had an increased prevalence of urinary incontinence (2.5; 95% CI, 1.6-3.8), as did those with respiratory disease (2.4; 95% CI, 1.3-4.4). Body mass index, prostate weight, presence of diabetes or previous transurethral resection did not appear to influence the prevalence of urinary incontinence. CONCLUSIONS In this series, a patient's age at radical prostatectomy influenced, in an exponential manner, his risk of long-term urinary incontinence. Other predictors are low educational level, salvage radiation therapy and respiratory disease. Intervention studies are needed to understand if these data are relevant to the prevalence of urinary leakage if a radical prostatectomy is postponed in an active monitoring programme.
23.	CARLSSON, STEFAN, 1987, et al. (author) Orgasm-Associated Urinary Incontinence and Sexual Life after Radical Prostatectomy. 2011 In: The journal of sexual medicine. - : Oxford University Press (OUP). - 1743-6109 .- 1743-6095. Journal article (peer-reviewed)abstract Introduction. Involuntary release of urine during sexual climax, orgasm-associated urinary incontinence, occurs frequently after radical prostatectomy. We know little about its prevalence and its effect on sexual satisfaction. Aim. To determine the prevalence of orgasm-associated incontinence after radical prostatectomy and its effect on sexual satisfaction. Methods. Consecutive series, follow-up at one point in calendar time of men having undergone radical prostatectomy (open surgery or robot-assisted laparoscopic surgery) at Karolinska University Hospital, Stockholm, Sweden, 2002-2006. Of the 1,411 eligible men, 1,288 (91%) men completed a study-specific questionnaire. Main Outcome Measure. Prevalence rate of orgasm-associated incontinence. Results. Of the 1,288 men providing information, 691 were sexually active. Altogether, 268 men reported orgasm-associated urinary incontinence, of whom 230 (86%) were otherwise continent. When comparing them with the 422 not reporting the symptom but being sexually active, we found a prevalence ratio (with 95% confidence interval) of 1.5 (1.2-1.8) for not being able to satisfy the partner, 2.1 (1.1-3.5) for avoiding sexual activity because of fear of failing, 1.5 (1.1-2.1) for low orgasmic satisfaction, and 1.4 (1.2-1.7) for having sexual intercourse infrequently. Prevalence ratios increase in prostate-cancer survivors with a higher frequency of orgasm-associated urinary incontinence. Conclusion. We found orgasm-associated urinary incontinence to occur among a fifth of prostate cancer survivors having undergone radical prostatectomy, most of whom are continent when not engaged in sexual activity. The symptom was associated with several aspects of sexual life. Nilsson AE, Carlsson S, Johansson E, Jonsson MN, Adding C, Nyberg T, Steineck G, and Wiklund NP. Orgasm-associated urinary incontinence and sexual life after radical prostatectomy. J Sex Med ;:-.
24.	Carlsson, Sigrid, 1982, et al. (author) Who and when should we screen for prostate cancer? Interviews with key opinion leaders. 2015 In: BMC medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 13 Journal article (peer-reviewed)abstract Prostate cancer screening using prostate-specific antigen (PSA) is highly controversial. In this Q & A, Guest Editors for BMC Medicine's 'Spotlight on Prostate Cancer' article collection, Sigrid Carlsson and Andrew Vickers, invite some of the world's key opinion leaders to discuss who, and when, to screen for prostate cancer. In response to the points of view from the invited experts, the Guest Editors summarize the experts' views and give their own personal opinions on PSA screening.
25.	Carlsson, Ylva, 1975, et al. (author) Comparing the results from a Swedish pregnancy cohort using data from three automated placental growth factor immunoassay platforms intended for first-trimester preeclampsia prediction. 2023 In: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; :8, s. 1084-1091 Journal article (peer-reviewed)abstract INTRODUCTION: Risk evaluation for preeclampsia in early pregnancy allows identification of women at high risk. Prediction models for preeclampsia often include circulating concentrations of placental growth factor (PlGF); however, the models are usually limited to a specific PlGF method of analysis. The aim of this study was to compare three different PlGF methods of analysis in a Swedish cohort to assess their convergent validity and appropriateness for use in preeclampsia risk prediction models in the first trimester of pregnancy.MATERIAL AND METHODS: First-trimester blood samples were collected in gestational week 11+0 to 13+6 from 150 pregnant women at Uppsala University Hospital during November 2018 until November 2020. These samples were analyzed using the different PlGF methods from Perkin Elmer, Roche Diagnostics, and Thermo Fisher Scientific.RESULTS: There were strong correlations between the PlGF results obtained with the three methods, but the slopes of the correlations clearly differed from 1.0: PlGFPerkinElmer = 0.553 (95% confidence interval [CI] 0.518-0.588) * PlGFRoche -1.112 (95% CI -2.773 to 0.550); r = 0.966, mean difference -24.6 (95% CI -26.4 to -22.8). PlGFPerkinElmer = 0.673 (95% CI 0.618-0.729) * PlGFThermoFisher -0.199 (95% CI -2.292 to 1.894); r = 0.945, mean difference -13.8 (95% CI -15.1 to -12.6). PlGFRoche = 1.809 (95% CI 1.694-1.923) * PlGFPerkinElmer +2.010 (95% CI -0.877 to 4.897); r = 0.966, mean difference 24.6 (95% CI 22.8-26.4). PlGFRoche = 1.237 (95% CI 1.113-1.361) * PlGFThermoFisher +0.840 (95% CI -3.684 to 5.363); r = 0.937, mean difference 10.8 (95% CI 9.4-12.1). PlGFThermoFisher = 1.485 (95% CI 1.363-1.607) * PlGFPerkinElmer +0.296 (95% CI -2.784 to 3.375); r = 0.945, mean difference 13.8 (95% CI 12.6-15.1). PlGFThermoFisher = 0.808 (95% CI 0.726-0.891) * PlGFRoche -0.679 (95% CI -4.456 to 3.099); r = 0.937, mean difference -10.8 (95% CI -12.1 to -9.4).CONCLUSION: The three PlGF methods have different calibrations. This is most likely due to the lack of an internationally accepted reference material for PlGF. Despite different calibrations, the Deming regression analysis indicated good agreement between the three methods, which suggests that results from one method may be converted to the others and hence used in first-trimester prediction models for preeclampsia.
26.	Chen, Yun, 1966, et al. (author) Neonatal losartan treatment suppresses renal expression of molecules involved in cell-cell and cell-matrix interactions 2004 In: Journal of the American Society of Nephrology. - : Lippincott Williams & Wilkins. - 1046-6673 .- 1533-3450. ; 15:5, s. 1232-43 Journal article (peer-reviewed)abstract Lack of neonatal angiotensin II type 1 receptor (AT(1)) stimulation produces renal abnormalities characterized by papillary atrophy and impaired urinary concentrating ability, but the mechanisms involved are still unclear. DNA microarray was used to identify genes that are differentially expressed in renal medulla in response to neonatal treatment with AT(1) receptor antagonist losartan (30 mg/kg per d), which commenced within 24 h after birth. The data showed that losartan treatment for 48 h downregulated 68 genes, approximately 30% of which encode various components of cytoskeleton and cytoskeleton-associated proteins, extracellular matrix, and enzymes involved in extracellular matrix maturation or turnover. With the use of immunohistochemistry and Western immunoblot, the microarray data were confirmed and it was demonstrated that losartan suppressed renal expression of syndecan 2, alpha-smooth muscle actin, MHC class II, and leukocyte type 12-lipoxygenase by day 4. In addition, losartan inhibited medullary expression of integrin alpha6 and caused relocalization of integrins alpha6 and alpha3. Moreover, losartan inhibited cell proliferation in medullary tubules by day 9, as detected by Ki-67 immunostaining. This study provides new data supporting the contention that a lack of AT(1) receptor stimulation results in abnormal matrix assembly, disturbed cell-cell and cell-matrix interactions, and subsequent abnormal tubular maturation. Moreover, regulation of the expression of leukocyte type 12-lipoxygenase and alpha-smooth muscle actin by the renin-angiotensin system in the immature kidney adds new knowledge toward the understanding of renal vascular development.
27.	Cortés-González, Jeff R, et al. (author) Early salvage radiation therapy combined with short-term hormonal therapy in recurrent prostate cancer after radical prostatectomy: Single-institution 4-year data on outcome, toxicity, health-related quality of life and co-morbidities from 184 consecutive patients treated with 70 Gy. 2013 In: International journal of oncology. - : Spandidos Publications. - 1791-2423 .- 1019-6439. ; 42:1, s. 109-17 Journal article (peer-reviewed)abstract The aim of this study was to investigate the role of 70Gy salvage radiotherapy (SRT) combined with short-term neoadjuvant hormonal therapy (NHT) in the treatment of recurrent disease after radical prostatectomy (RP), and to consider quality of life (QoL), survival outcomes and impact of co-morbidities on treatment-related rectal-genitourinary toxicity. Electronic records of 184 SRT patients treated consecutively between October 2001 and February 2007 were analyzed. Median age was 64 years (median follow-up 48months). NHT was given to 165 patients (median 3 months). Pre-RP and pre-SRT PSA, PSA doubling time, Gleason score (GS), seminal vesicle invasion (SVI) and detectable post-SRT PSA were recorded. Any detectable PSA or PSA >0.1 ng/ml + nadir was considered biochemical failure (BcF). The Charlson co-morbidity index was used to correlate co-morbidities and rectal-genitourinary toxicity. Scores from the health-related QoL EORTC QLQ-C30 and PR-25 questionnaires were also evaluated. In 116 (63%) patients, a long-lasting curative effect was indicated by undetectable PSA levels. In univariate analysis, using BcF as an outcome variable, p<0.001 was found for GS, pre-SRT PSA, SVI and detectable post-SRT PSA. Multivariate analysis showed p=0.01 for SVI, p=0.09 for GS, and detectable post-SRT PSA (p=0.01); with metastases as an outcome variable, only SVI was significant (p=0.007). Cancer-specific and overall survival were 99 and 95%, respectively. Although microscopy showed SVI or GS 8-10 in the prostatectomy specimens 17/40(43%) and 13/29 (45%), respectively, of patients still showed undetectable PSA at long-term follow-up (median 55 months) after SRT. Likewise, 11/31 (36%) patients with pre-SRT PSA >1.0 ng/ml and 80/134 (60%) patients with PSA doubling time (PSADT) <10 still showed undetectable PSA after 50 months. Slightly elevated acute and late rectal-genitourinary grade 3-4 toxicity was observed. No association with co-morbidity/toxicity was found. EORTC QLQ-C30 scores were similar to or slightly better than reference values. SRT with 70 Gy combined with 3-month NHT results in long-term undetectable PSA in >50% of patients with recurrence after RP with acceptable rectal-genitourinary toxicity and without negatively affecting long-term QoL. Non-metastatic patients should not be disqualified from receiving SRT although presenting with poor prognostic factors at surgery.
28.	Davidsson, P., et al. (author) No effect of sleep on the generalization of fear learning 2014 In: Journal of sleep research. - : Wiley-Blackwell. - 1365-2869. ; 23, s. 7- Journal article (other academic/artistic)abstract Objectives: Sleep has been shown to be involved both in emotion regulation and in the active processing of information. We combined these two concepts and tested if sleep affected the generalization of fear learning.Methods: In a fear conditioning paradigm, participants were shown images of a small and a big circle where one of them was paired with an aversive sound, making it the CS+. Fear was measured with skin conductance responses. Participants were then randomly divided into a sleep or a wake group. The sleep group took a 2 h nap while the wake group rested for 2 h. Participants were then exposed to the two circles seen before, combined with 8 novel circles that gradually varied in size from the small one to the big one. We looked at how many circle sizes away from the CS+ that participants still exhibited a fear response, and if this differed between the sleep and the wake group.Results: We found no effect of sleep on the slope of the generalization across the different circles. There was a main effect of circle size, F(1,25) = 10.42, P = 0.01, but no main effect of sleep/wake, F (1,25) = 0.40, P = 0.54, and no interaction between sleep/wake X circle size, F(1,25) = 0.62, P = 0.44.Conclusions: The fear conditioning manipulation worked, with a gradual increase of fear depending on the stimuli’s similarity to the CS+. However, there was no effect of sleep or wake, which could possibly be explained by that just a 2 h nap not being a sufficient sleep manipulation to detect any differences.
29.	Dina, Christian, et al. (author) Variation in FTO contributes to childhood obesity and severe adult obesity. 2007 In: Nature genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 39:6, s. 724-6 Journal article (peer-reviewed)abstract We identified a set of SNPs in the first intron of the FTO (fat mass and obesity associated) gene on chromosome 16q12.2 that is consistently strongly associated with early-onset and severe obesity in both adults and children of European ancestry with an experiment-wise P value of 1.67 x 10(-26) in 2,900 affected individuals and 5,100 controls. The at-risk haplotype yields a proportion of attributable risk of 22% for common obesity. We conclude that FTO contributes to human obesity and hence may be a target for subsequent functional analyses.
30.	Försth, Peter, et al. (author) A Randomized, Controlled Trial of Fusion Surgery for Lumbar Spinal Stenosis 2016 In: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 374:15, s. 1413-1423 Journal article (peer-reviewed)abstract BACKGROUND The efficacy of fusion surgery in addition to decompression surgery in patients who have lumbar spinal stenosis, with or without degenerative spondylolisthesis, has not been substantiated in controlled trials.METHODS We randomly assigned 247 patients between 50 and 80 years of age who had lumbar spinal stenosis at one or two adjacent vertebral levels to undergo either decompression surgery plus fusion surgery (fusion group) or decompression surgery alone (decompression-alone group). Randomization was stratified according to the presence of preoperative degenerative spondylolisthesis (in 135 patients) or its absence. Outcomes were assessed with the use of patient-reported outcome measures, a 6-minute walk test, and a health economic evaluation. The primary outcome was the score on the Oswestry Disability Index (ODI; which ranges from 0 to 100, with higher scores indicating more severe disability) 2 years after surgery. The primary analysis, which was a per-protocol analysis, did not include the 14 patients who did not receive the assigned treatment and the 5 who were lost to follow-up.RESULTS There was no significant difference between the groups in the mean score on the ODI at 2 years (27 in the fusion group and 24 in the decompression-alone group, P = 0.24) or in the results of the 6-minute walk test (397 m in the fusion group and 405 m in the decompression- alone group, P = 0.72). Results were similar between patients with and those without spondylolisthesis. Among the patients who had 5 years of follow-up and were eligible for inclusion in the 5-year analysis, there were no significant differences between the groups in clinical outcomes at 5 years. The mean length of hospitalization was 7.4 days in the fusion group and 4.1 days in the decompression-alone group (P< 0.001). Operating time was longer, the amount of bleeding was greater, and surgical costs were higher in the fusion group than in the decompression-alone group. During a mean follow-up of 6.5 years, additional lumbar spine surgery was performed in 22% of the patients in the fusion group and in 21% of those in the decompression-alone group.CONCLUSIONS Among patients with lumbar spinal stenosis, with or without degenerative spondylolisthesis, decompression surgery plus fusion surgery did not result in better clinical outcomes at 2 years and 5 years than did decompression surgery alone.
31.	Hallersund, Peter, 1975, et al. (author) Correction: Gastric Bypass Surgery Is Followed by Lowered Blood Pressure and Increased Diuresis - Long Term Results from the Swedish Obese Subjects (SOS) Study. 2013 In: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 8:5 Journal article (other academic/artistic)abstract [This corrects the article on p. e49696 in vol. 7.].
32.	Hallersund, Peter, 1975, et al. (author) Gastric Bypass Surgery Is Followed by Lowered Blood Pressure and Increased Diuresis - Long Term Results from the Swedish Obese Subjects (SOS) Study. 2012 In: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 7:11 Journal article (peer-reviewed)abstract To compare two bariatric surgical principles with regard to effects on blood pressure and salt intake.
33.	Hälso- och sjukvårdens förmåga att hantera en allvarlig händelse med många skadade : erfarenheter och lärdomar av Övning TYKO 2016 Reports (other academic/artistic)abstract Den 3 mars 2016 fick Socialstyrelsen i uppdrag av regeringen att öva hälsooch sjukvårdens förmåga att hantera en allvarlig händelse med många skadade. Myndigheten beslutade att genomföra övningen som en funktionell simuleringsövning med motspel. De övade utvärderades med hjälp av mätbara kvalitetsindikatorer som tidigare identifierats inom ramen för Socialstyrelsens arbete med att ta fram en gemensam modell för särskild sjukvårdsledning vid allvarlig händelse. Inför övningen skapades ett scenario som var utmanande för hälso- och sjukvården men, för att möjliggöra genomförandet inte innefattade alla potentiella komplexa faktorer. En kritisk observation är att analysen utifrån en övning bör vara restriktiv med slutsatser ifall dessa inte samtidigt kan styrkas utifrån tidigare övningar eller verkliga händelser. Övningens scenario samt patienternas skadepanorama och utfall visualiserades med hjälp av simuleringsverktyget Emergo Train System® och dess instruktörer vid Katastrofmedicinskt Centrum i Linköping. Ett väsentligt mål med övningen var att den ska utgöra ett underlag för att stärka förmågan inom hälso- och sjukvården genom att identifiera utvecklingsområden. I rapporten redovisas under övningen identifierade förmågor och utvecklingsområden som myndigheten bedömer som viktiga för att upprätthålla, säkra och förbättra förmågan att hantera allvarliga händelser: • Dokumentation och lägesbild • Kommunikation och terminologi • Mobilisering och dirigering av resurser • Fördelningsstrategi och gränssättande kapacitet • Nationell samordning • Övningsteknisk utveckling En gemensam lägesbild är viktig efter som det stödjer de involverade aktörerna i arbetet med att värdera behovet av stöd under pågående händelse. Därför var en viktig del i övningens utvärdering huruvida påverkade landsting hade förmågan att snabbt skapa sig en uppfattning om aktuellt behov, tillgängliga resurser och hur ytterligare pre- hospitala samt hospitala resurser skulle kunna mobiliseras. Dessa kritiska faktorer skapar förutsättningar för att korrekta fördelningsstrategier för de skadande patienterna ska kunna utarbetas. Övning Tyko visade att staber med hög upplevd arbetsbelastning och låg upplevd situationsmedvetenhet hade svårt att värdera sitt eget behov av stöd från andra aktörer. Att i förväg ha kännedom om vilken typ av stöd man behöver och kan förvänta sig i olika situationer kräver ett arbete för att identifiera detta redan i före-perspektivet. Det går inte att utesluta att en annan överblick av tillgängliga resurser och en annan förutsägbarhet i vad som kan förväntas av andra hade föranlett en annan fördelningsstrategi som hade förbättrat patientfallet i övningen. För att avgöra effektiviteten av fattade beslut i enlighet med framtagna strategier behövs även en förmåga till 8 HÄLSO- OCH SJUKVÅRDENS FÖRMÅGA ATT HANTERA EN ALLVARLIG HÄNDELSE MED MÅNGA SKADADE SOCIALSTYRELSEN uppföljning huruvida tagna beslut får förväntad effekt inom rimlig tid, under övningen observerades kommunikationsproblem gällande kvittens, förfrågan och bekräftelse. En viktig sammanfattande slutsats som Socialstyrelsen drar inför fortsatt arbete är att myndigheten ska verka för att etablera en funktion för nationell samordning med syfte att ge förutsättningar till en bättre behovs- och resursmatchning vid stora skadeutfall. Inom ramen för en sådan samordning bör gemensamma triage och larmkriterier, medicinska bedömningskriterier och skadeklassificeringar, gemensamma rapportmallar och system för distribution av diagnostiskt material samt gemensam terminologi m.m. inkluderas. Metoder och teknik för framtagandet och kommunikationen av fördelningsnycklar och aktuella kapacitetsbedömningar över tid behöver tas fram för att skapa förutsättningar för en aktuell bild av resurstillgången. Socialstyrelsen vill skapa förutsättningar för ett nationellt kompetenscentrum med inriktning på ökad förmåga och samordning i hela traumavårskedjan. I detta arbete kan även arbetet med Socialstyrelsens förmåga till nationell samordning under pågående händelse utarbetas, definieras och implementeras. Myndigheten vill slutligen lyfta fram att en samlad nationell plan för både trauma- och katastrofmedicinsk utbildning och övning ger ytterligare förutsättningar att upprätthålla och öka förmågan att hantera allvarliga händelser. Dessa viktiga slutsatser avser myndigheten ta med sig in i sitt fortsatta arbete med att stärka hälso-och sjukvårdens förmåga vid allvarlig händelse.
34.	Jacobson, Peter, 1962, et al. (author) 9p21.3 Coronary Artery Disease Locus Identifies Patients With Treatment Benefit From Bariatric Surgery in the Nonrandomized Prospective Controlled Swedish Obese Subjects Study. 2020 In: Circulation. Genomic and precision medicine. - 2574-8300. ; 13:5, s. 460-465 Journal article (peer-reviewed)abstract Sequence variation at chromosome 9p21.3 accounts for 20% of myocardial infarctions (MIs) in several populations. Whereas the risk conferred by the 9p21.3 locus appears to act independently of traditional risk factors, studies suggest that the association between 9p21.3 and MI is modified by glucose homeostasis and lifestyle. We examined if the 9p21.3 variant rs1333049, along with the previously identified predictor fasting insulin, modifies the preventive effect of bariatric surgery on MI incidence.rs1333049 was genotyped in 1852 patients treated by bariatric surgery and 1803 controls given usual care in the SOS study (Swedish Obese Subjects). MI incidence was determined using national registers. Median follow-up was 21 years (interquartile range 18-24 years).Overall, 366 MIs occurred during follow-up. Among rs1333049 risk-allele carriers (CC+GC), the incidence of MI was reduced in the surgery group compared with the control group (hazard ratio=0.72 [95% CI, 0.57-0.92], P=0.008). By contrast, noncarriers (GG) showed no significant differences in MI incidence between the treatment groups (hazard ratio=1.28 [0.86-1.90], P=0.227; interaction between treatment and the risk-allele P=0.016). In addition, carriers with higher fasting insulin (above the median [17 mmol/L]) experienced significantly higher MI incidence than carriers with lower fasting insulin (hazard ratio=0.58 [0.42-0.78], P<0.001, interaction P=0.031).In the SOS cohort, patients with the chromosome 9p21.3 rs1333049 risk allele together with high fasting insulin levels benefitted from bariatric surgery in terms of reduced incidence of MI. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01479452.
35.	Jantunen, Esa, et al. (author) Autologous Stem Cell Transplantation (ASCT) for Enteropathy-Associated T-Cell Lymphoma (EATL) : Final Analysis of a Retrospective Study On the Behalf of Lymphoma Working Party (LWP) of the European Group for Blood and Marrow Transplantation (EBMT). 2012 In: Blood. - 0006-4971 .- 1528-0020. ; 120:21, s. 3105- Journal article (peer-reviewed)
36.	Jernås, Margareta, 1961, et al. (author) Regulation of carboxylesterase 1 (CES1) in human adipose tissue. 2009 In: Biochemical and biophysical research communications. - : Elsevier BV. - 1090-2104 .- 0006-291X. ; 383:1, s. 63-7 Journal article (peer-reviewed)abstract Carboxylesterase 1 (CES1) has recently been suggested to play a role in lipolysis. Our aim was to study the regulation of CES1 expression in human adipose tissue. In the SOS Sib Pair Study, CES1 expression was higher in obese compared with lean sisters (n=78 pairs, P=8.7x10(-18)) and brothers (n=12 pairs, P=0.048). CES1 expression was higher in subcutaneous compared with omental adipose tissue in lean (P=0.027) and obese subjects (P=0.00036), and reduced during diet-induced weight loss (n=24, weeks 8, 16, and 18 compared to baseline, P<0.0001 for all time points). CES1 expression was higher in isolated adipocytes compared with intact adipose tissue (P=0.0018) and higher in large compared with small adipocytes (P=4.1x10(-6)). Basal and stimulated lipolysis was not different in individuals with high, intermediate, and low expression of CES1. Thus, CES1 expression was linked to body fat and adipocyte fat content but not to lipolytic activity.
37.	Johnson, Magnus S.C. 1969, et al. (author) Interaction of scavenger receptor class B type I with peroxisomal targeting receptor Pex5p. 2003 In: Biochemical and biophysical research communications. - 0006-291X. ; 312:4, s. 1325-34 Journal article (peer-reviewed)abstract Scavenger receptor class B type I (SR-BI) is an HDL receptor that mediates selective HDL lipid uptake. Peroxisomes play an important role in lipid metabolism and peroxisomal targeting signal type 1 (PTS1)-containing proteins are translocated to peroxisomes by the peroxisomal targeting import receptor, Pex5p. We have previously identified a PTS1 motif in the intracellular domain of rat SR-BI. Here, we examine the possible interaction between Pex5p and SR-BI. Expression of a Flag-tagged intracellular domain of SR-BI resulted in translocation to the peroxisome as demonstrated by double labeling with anti-Flag IgG and anti-catalase IgG analyzed by confocal microscopy. Immunoprecipitation experiments with anti-SR-BI antibody showed that Pex5p co-precipitated with SR-BI. However, when an antibody against Pex5p was used for immunoprecipitation, only the 57kDa, non-glycosylated form, of SR-BI co-precipitated. We conclude that the PTS1 domain of SR-BI is functional and can mediate peroxisomal interaction via Pex5p, in vitro.
38.	Lena, Carlsson, et al. (author) Life Expectancy after Bariatric Surgery in the Swedish Obese Subjects Study. 2020 In: The New England journal of medicine. - 1533-4406. ; 383:16, s. 1535-1543 Journal article (peer-reviewed)abstract Obesity shortens life expectancy. Bariatric surgery is known to reduce the long-term relative risk of death, but its effect on life expectancy is unclear.We used the Gompertz proportional hazards regression model to compare mortality and life expectancy among patients treated with either bariatric surgery (surgery group) or usual obesity care (control group) in the prospective, controlled Swedish Obese Subjects (SOS) study and participants in the SOS reference study (reference cohort), a random sample from the general population.In total, 2007 and 2040 patients were included in the surgery group and the control group, respectively, and 1135 participants were included in the reference cohort. At the time of the analysis (December 31, 2018), the median duration of follow-up for mortality was 24 years (interquartile range, 22 to 27) in the surgery group and 22 years (interquartile range, 21 to 27) in the control group; data on mortality were available for 99.9% of patients in the study. In the SOS reference cohort, the median duration of follow-up was 20 years (interquartile range, 19 to 21), and data on mortality were available for 100% of participants. In total, 457 patients (22.8%) in the surgery group and 539 patients (26.4%) in the control group died (hazard ratio, 0.77; 95% confidence interval [CI], 0.68 to 0.87; P<0.001). The corresponding hazard ratio was 0.70 (95% CI, 0.57 to 0.85) for death from cardiovascular disease and 0.77 (95% CI, 0.61 to 0.96) for death from cancer. The adjusted median life expectancy in the surgery group was 3.0 years (95% CI, 1.8 to 4.2) longer than in the control group but 5.5 years shorter than in the general population. The 90-day postoperative mortality was 0.2%, and 2.9% of the patients in the surgery group underwent repeat surgery.Among patients with obesity, bariatric surgery was associated with longer life expectancy than usual obesity care. Mortality remained higher in both groups than in the general population. (Funded by the Swedish Research Council and others; SOS ClinicalTrials.gov number, NCT01479452.).
39.	Moller, Peter, et al. (author) Global calculations of ground-state axial shape asymmetry of nuclei 2006 In: Physical Review Letters. - 1079-7114. ; 97:16 Journal article (peer-reviewed)abstract Important insight into the symmetry properties of the nuclear ground-state (gs) shape is obtained from the characteristics of low-lying collective energy-level spectra. In the 1950s, experimental and theoretical studies showed that in the gs many nuclei are spheroidal in shape rather than spherical. Later, a hexadecapole component of the gs shape was identified. In the 1970-1995 time frame, a consensus that reflection symmetry of the gs shape was broken for some nuclei emerged. Here we present the first calculation across the nuclear chart of axial symmetry breaking in the nuclear gs. We show that we fulfill a necessary condition: Where we calculate axial symmetry breaking, characteristic gamma bands are observed experimentally. Moreover, we find that, for those nuclei where axial asymmetry is found, a systematic deviation between calculated and measured masses is removed.
40.	Movérare, Robert, et al. (author) Purification and characterization of the major oak pollen allergen Que a 1 for component-resolved diagnostics using ImmunoCAP 2008 In: International Archives of Allergy and Immunology. - : S. Karger AG. - 1018-2438 .- 1423-0097. ; 146:3, s. 203-211 Journal article (peer-reviewed)abstract BACKGROUND: The aim of this study was to purify the major oak pollen allergen, Que a 1, to perform biochemical and immunological characterization of the allergen and to develop an experimental native (n) Que a 1 ImmunoCAP(R). METHODS: Que a 1 was purified from oak pollen extract using affinity chromatography and characterized by SDS-PAGE, two-dimensional (2D) PAGE, mass spectrometry (MS), N-terminal sequencing and specific IgE inhibition on ImmunoCAP. Samples from 16 subjects sensitized to oak pollen were analyzed by ImmunoCAP for IgE reactivity to nQue a 1, and recombinant (r)Bet v 1 and 2 (profilin). They were also studied in IgE immunoblotting. RESULTS: The purity of nQue a 1 was >95%, since a single band was observed on silver-stained SDS-PAGE. The identity was verified by MS analysis, and 2D-PAGE revealed several isoforms. The obtained N-terminal sequence of 50-amino-acid residues from nQue a 1 showed a 58-74% sequence identity with other pathogenesis-related class 10 allergens. Specific IgE inhibition verified a preserved immunoreactivity (70-92% inhibition). All subjects were sensitized to Que a 1 and Bet v 1, and two to profilin. The IgE antibody levels to nQue a 1 were generally lower than to rBet v 1. The obtained results correlated well with IgE immunoblotting. CONCLUSIONS: We present a highly purified and extensively characterized preparation of nQue a 1. Que a 1 seems to be an allergen of equal importance in oak pollen as Bet v 1 in birch pollen. An nQue a 1 ImmunoCAP will be useful in component-resolved diagnostics.
41.	Nelldal, Bo-Lennart, 1946-, et al. (author) Utvärdering av intermodala transportkedjor : Sammanfattande rapport, SiR-C 2010 2010 Reports (other academic/artistic)abstract Syftet med detta projekt har varit att identifiera de svagaste länkarna i en intermodal transportkedja. Detta ska ge underlag för förslag till hur dessa elimineras så att kombitrafiken kan bli mer attraktiv på transportmarknaden. I detta projekt har givetvis inte allt kunnat analyseras. En målsättning har varit att undersöka sådant som är mindre känt tidigare och där det också går att utveckla metoder. Projektet har delats in i följande delar:Fallstudier av ett antal transportkedjorUtveckling av kostnadsmodeller för terminaler och transportkedjorFältmätningar av stötar och vibrationer i terminaler och vid transportStöt- och vibrationssimulering med skakbord i laboratoriumDjupanalys av skadestatistik från ett företag med bra statistikRiskanalys för oönskade händelser i ett antal transportkedjorUtvärdering av resultat och identifiering av svaga länkarFörslag till åtgärder för att eliminera svaga länkar.Urvalet av transportkedjor, för fältmätningar av accelerationer och för simulering med skakbord framgår av tabell på nästa sida.Det som är det främsta bidraget ur kvantitativt vetenskaplig synvinkel är mätningarna av stötar och vibrationer i fält och de efterföljande simuleringarna och analyserna med skakbord. Något sådant har inte gjorts tidigare för denna typ av transporter. Dessa visar att påkänningarna vid normal hantering och transport inte är kritiska. Detta är också en viktig slutsats som kanske kan slå hål på myten att man inte kan använda kombitrafik p.g.a. risk för godsskador.Fallstudier av transportkedjorFör de som har valt kombitransport gäller i regel att kostnaden är lägre med kombitransport än med direkt lastbilstransport. Dock är oftast transporttiden med kombitransport betydligt längre än med lastbil i de studerade transportkedjorna. Vid granskning av transporttiderna på järnväg så är den passiva tiden ofta en stor del av transporttiden. Om den passiva tiden räknas bort så kommer järnvägstransporten upp i konkurrenskraft gentemot lastbilen. För terminaltiderna finns troligen även där viss potential för förbättring. Vissa kunder förhandlar till sig något tidigare utlämning än vad tidtabellen anger. Transporttiden med lastbil används i kombitransportkedjorna som bufferttid mot förseningar. Transportfrekvensen anses ibland otillräcklig med kombitransport, ibland önskas fler avgångar per vecka och ibland fler per dag. I flera transportkedjor körs lastbil parallellt med kombitransport beroende på den leveranstid och frekvens som kombitransporten erbjuder. Punktligheten är relativt god och det finns en acceptans för mindre förseningar. Deadline för bokning av kombitransport anses ofta vara för tidig. Skaderisken i samtliga transportkedjor anses vara väldigt låg, och därför förs sällan någon statistik över dessa. Vissa kunder upplever en viss brist på materiel och spårkapacitet. Kostnadsmodeller för transporter och terminalerKostnaden utgör enligt många undersökningar den viktigaste faktorn för valet av transportmedel givet att de grundläggande kvalitetskraven kan uppfyllas. Kostnaden för en kombitransport kan därför utgöra ett hinder för att kunden ska välja kombitransport.Det som skiljer kombitransporter från direkta lastbilstransporter är de höga kostnaderna för terminalhantering och matartransporter. Detta i kombination med att det oftast ryms mindre gods i en lastbärare än i en lastbil eller järnvägsvagn innebär att kostnaden per m3 ofta blir högre. Det är också svårare att köra returgods med kombi än med direkt lastbilstrafik.För att analysera kostnaderna för kombitransporter har två modeller utvecklas: En modell för att beräkna kostnaden för hela transportkedjan och en särskild terminalkostnadsmodell.Transportkedjemodellen är översiktlig. För att skatta modellens tillförlitlighet jämfördes modellens resultat med typvärden för en kombitransport med CargoNets priser, se figur. En slutsats som kan dras är att kostnadsmodellen ligger i rätt storleksordning vid beräkning av kostnaden för en kombitransport och att modellen tycks uppskatta kostnaden för transport av container relativt nära verkligheten. Modellens kostnad är linjär mot avståndet men börjar med en språngkostnad som följd av terminalkostnaden. Detsamma gäller i stort för CargoNets priser.Modellen ger en högre kostnad för trailern än för containern medan CargoNet har ungefär samma pris för container och semitrailer vilket är marknadspriset. Man kan diskutera vad som är rätt men det pekar samtidigt på ett problem; trailers dimensionerar systemet och gör att kostnaderna blir höga men de får inte betala kostnaderna fullt ut för tung lyftutrustning och specialvagnar. Trailers innebär med dagens teknik ett sämre längdutnyttjande av tågen än containers och växelflak. I ett långsiktigt perspektiv ger inte denna affärsmodell incitament till att utveckla effektiva kombilösningar transporttekniskt sett. Å andra sidan så efterfrågar kunderna kombitransporter med trailer, så ur marknadsperspektivet är de kanske effektiva. Den samlade bedömningen är att modellen kräver en del justering och kompletterande uppgifter för att vara tillförlitlig. Dessa uppgifter är av grundläggande karaktär vilket gör det relativt lätt att ta fram dessa uppgifter. Modellen ger en uppfattning om i vilka aktiviteter som kostnader orsakas och dess storleksordning. Den kan därmed vara ett verktyg i inledande analys och bedömning av olika upplägg av transportkedjor. Det bör hållas i minnet att kostnad och pris är två skilda saker. Terminalkostnadsmodellen har fyra fördefinierade terminaler utifrån svenska förhållanden. Tre av dem är traditionella kombiterminaler av olika storlek och den fjärde är en linjeterminal. Terminalkostnadsmodellen har använts till att analysera vad som driver kostnader i terminalen och terminaltypernas effektivitet utifrån ansatta värden. Terminalkostnadsmodellen ger en överblick av de kostnader som förekommer i en traditionell kombiterminal samt kostnadernas storleksordning.Med ansatta värden så visar sig den stora ändpunktsterminalen vara effektivast. De har dock behov av snabb hantering för att inte hanteringsspåren ska vara låsta en längre tid. De mindre terminalerna har däremot mindre behov av rangering av tågset till och från hanteringsspåren.Kostnaden för infrastrukturen ligger runt 60 kr per lyft eller 20 – 25 %. Kostnaden för truckhanteringen ligger på 90 – 150 kr eller 37 – 47 % för ändpunktsterminalerna och kostnaden för växling 73 – 86 kr eller 25 – 32 %. Linjeterminalen har ingen växling utan där står truckkostnaden för 68 % av lyftkostnaden. Administrationskostnaderna hamnar runt 20 kr per lyft och står för 7- 8 % av lyftkostnaden.Fältmätningar av stötar och vibrationer i terminaler och vid transportEtt stort antal mätningar har genomförts av de påkänningar, i form av stötar och vibrationer, som gods upplever vid intermodala transporter. Mätutrustning som registrerat och lagrat accelerationer har satts in i lastbärarna och rörelserna har samtidigt följts upp m.h.a. GPS. Mätningar har utförts både vid hantering av lastbärarna i terminaler och hamnar samt vid själva transporten på järnväg och landsväg. Resultaten har dels använts för att jämföra transportmiljön mellan olika transportkedjor, dels för att genom skakbordstester kunna bestämma vilka nivåer på accelerationer som medför risk för godsskador, till följd av att godset skakar sönder eller kommer i rörelse. Generellt sett kan man från resultaten av dessa mätningar sluta sig till att hantering av lastbärarna ger de största amplituderna på accelerationer, t.ex. vid nedslag mot mark och järnvägsvagnar, men att transporter och interna förflyttningar ger upphov till större impulser då markanta påkänningar tillåts verka under längre tid vid t.ex. kurvtagningar och tvära inbromsningar. Dock visar analysen av mätningarna att påkänningarna vid normal hantering inte är kritiska, men att det finns en teknisk utvecklingspotential i vagnar och hanteringsteknik. En slutsats är att hanteringen av containers och växelflak ger upphov till större impulser än motsvarande hantering av trailers oavsett hanteringsutrustning. Detta beror på att hjulen på trailrarna dämpar stötarna. Hantering med portalkran och hamnkran är i jämförelse med hantering med reach-stacker och containertruck mycket skonsammare mot godset och lastbäraren.Mätningarna vid interna förflyttningar av lastbärare inom terminal och hamnområden visar tydligt inverkan av hjulupphängningen hos de fordon varmed förflyttningen sker. Framför allt för stötar med korta varaktigheter syns tydliga skillnader i amplituder hos de uppmätta accelerationerna. Vidare noterades att de kraftigaste stötarna uppmättes vid transporter in och ut ur fartyg. Vid landsvägs och järnvägstransporter uppträder generellt stötar med lägre amplitud men längre varaktighet än vid hanteringar och interna förflyttningar inom terminalområden, men inga större skillnader i impulsmönster i horisontalplanet har noterats mellan de två tranportslagen. Nämnas bör dock att rangeringar av kombitåg förekommer nästan inte och därför inte har registrerats under mätningarna. Den företeelse som ger upphov till godsvandring, vibrationer i vertikalled, är naturligtvis mycket beroende av underlag, hjultyp, hjulupphängning och hastigheten varmed fordonet framförs. Vid transport på järnväg har de typiska vibrationerna i vertikalled cirka dubbelt så stor amplitud men lägre frekvens än motsvarande vibrationer vid landsvägstransport.De data som samlats in har kommit till användning vid framtagning av internationella standarder för beskrivning av transportmiljöer och testprocedurer för stötkänsligt gods. Det är s
42.	Nyberg, Martin, et al. (author) Functional and Oncologic Outcomes Between Open and Robotic Radical Prostatectomy at 24-month Follow-up in the Swedish LAPPRO Trial 2018 In: European urology oncology. - : Elsevier BV. - 2588-9311 .- 0302-2838. ; 1:5, s. 353-360 Journal article (peer-reviewed)
43.	Nyberg, Martin, et al. (author) Risk of Recurrent Disease 6 Years After Open or Robotic-assisted Radical Prostatectomy in the Prospective Controlled Trial LAPPRO 2020 In: European Urology Open Science. - : Elsevier BV. - 2666-1691 .- 2666-1683. ; 20, s. 54-61 Journal article (peer-reviewed)abstract Background: Conclusive evidence of superiority in oncological outcome for robotassisted laparoscopic prostatectomy (RALP) over retropubic radical prostatectomy (RRP) is lacking. Objective: To compare RALP and RRP regarding recurrent disease and to report the mortality rate 6 yr after surgery. Design, setting, and participants: A total of 4003 men with localized prostate cancer were enrolled between 2008 and 2011 in Laparoscopic Prostatectomy Robot Open (LAPPRO)- a prospective, controlled, nonrandomized trial performed at 14 Swedish centers. Outcome measurements and statistical analysis: Data were collected at visits and by patient questionnaires at 3, 12, and 24 mo, and through a structured telephone interview at 6 yr. Cause of death was retrieved from the National Cause of Death Register in Sweden. The modified Poisson regression approach was used for analyses. Results and limitations: After adjustment for patient-, tumor-, and surgeon-related confounders, no statistically significant difference was observed between RALP and RRP in biochemical recurrence rate (14 vs 16%, relative risk [RR] 0.77, 95% confidence interval [CI] 0.56-1.06) or in not cured endpoint (22% vs 23%, RR 0.82, 95% CI 0.6-1.11). Stratified by D'Amico risk group, a significant benefit for RALP existed for recurrent disease in high-risk patients (RR 0.47, 95% CI 0.26-0.86, p = 0.02). All-cause mortality was 3% (n = 96). Prostate cancer-specific mortality was 0.6% (n = 21) overall, 0.3% (n = 8) after RALP, and 1.5% (n = 13) after RRP. The nonrandomized design is a limitation. Conclusions: No significant difference was observed for cancer recurrence rate between RALP and RRP 6 yr after surgery. However, in a subgroup analysis, we found a significant benefit for RALP regarding recurrence rate in the high-risk group. Larger studies with longer follow-up are needed to make a firm conclusion and to evaluate a possible survival benefit. Patient summary: In general, the oncological outcome is comparable between robotic and open radical prostatectomy 6 yr after surgery. For high-risk patients, our findings indicate that there is an advantage for robotics, but further studies with longer follow-up time is needed to make a firm conclusion. (c) 2020 Published by Elsevier B.V. on behalf of European Association of Urology. This is an open access article under the CC BY-NC-ND license (http://creativecommons. org/licenses/by-nc-nd/4.0/).
44.	Nyberg, Martin, et al. (author) Surgeon heterogeneity significantly affects functional and oncological outcomes after radical prostatectomy in the Swedish LAPPRO trial 2021 In: BJU International. - : Wiley. - 1464-4096 .- 1464-410X. ; 127:3, s. 361-368 Journal article (peer-reviewed)abstract Objectives To evaluate how surgeon heterogeneity - the variation in outcomes between individual surgeons - influences functional and oncological outcomes after robot-assisted laparoscopic prostatectomy (RALP) and retropubic radical prostatectomy (RRP), and to assess whether surgeon heterogeneity affects the comparison between RALP and RRP. Patients and Methods Laparoscopic Prostatectomy Robot Open (LAPPRO) is a prospective, controlled, non-randomized trial performed at 14 Swedish centres with 68 operating surgeons. A total of 4003 men with localized prostate cancer were enrolled between 2008 and 2011. The endpoints were urinary incontinence, erectile dysfunction (ED) and recurrence at 24 months after surgery. Logistic regression models were built to evaluate surgeon heterogeneity and, secondarily, surgeon-specific factors were added to the models to investigate their influence on heterogeneity and the comparison between RALP and RRP. Results Among surgeons who performed at least 20 surgeries during the study period (n=25), we observed statistically significant heterogeneity for incontinence (P= 0.001), ED (P< 0.001) and rate of recurrent disease (P< 0.001). The significant heterogeneity remained when analysing only experienced surgeons with a stated experience of at least 250 radical prostatectomies (n=12). Among all participating surgeons (n=68), differences in surgeon volume explained 42% of the observed heterogeneity for incontinence (P= 0.003), 11% for ED (P= 0.03) and 19% for recurrence (P= 0.01). Taking surgeon volume into account when comparing RALP and RRP had a significant impact on the results. The effect was greatest for functional outcomes, and the additional adjustments for the surgeons' previous experience changed whether the difference between techniques was statistically significant or not. The surgeons' annual volume had the greatest effect on the recurrence rate. Conclusions There was a large degree of heterogeneity among surgeons regarding both functional and oncological outcomes and this had a significant impact on the results when comparing RALP and RRP. Some of the observed heterogeneity was explained by differences in surgeon volume. Efforts to decrease heterogeneity are warranted and variation among surgeons must be accounted for when conducting comparative analyses between surgical techniques.
45.	Olofsson, Louise, 1977, et al. (author) Preliminary report: Zn-alpha2-glycoprotein genotype and serum levels are associated with serum lipids. 2010 In: Metabolism. - : Elsevier BV. - 1532-8600 .- 0026-0495. ; 59:9, s. 1316-1318 Journal article (peer-reviewed)abstract Zn-alpha2-glycoprotein (ZAG) is a serum protein implicated in cancer cachexia and lipolysis. Our aim was to investigate serum levels of ZAG and polymorphisms in the ZAG gene in relation to serum lipids in man. Serum levels of ZAG correlated with serum levels of cholesterol (P = .00088) in healthy subjects and during weight loss (P = .059). The ZAG genotype was associated with total cholesterol (P = .014) and low-density lipoprotein cholesterol (P = .026) in healthy subjects, and the associations were replicated in an additional cohort (P = .0017 and P = .060, respectively). Our data indicate that ZAG plays a role in lipid metabolism.
46.	Rodriguez-Espigares, Ismael, et al. (author) GPCRmd uncovers the dynamics of the 3D-GPCRome 2020 In: Nature Methods. - : Springer Nature. - 1548-7091 .- 1548-7105. ; 17:8, s. 777-787 Journal article (peer-reviewed)abstract G-protein-coupled receptors (GPCRs) are involved in numerous physiological processes and are the most frequent targets of approved drugs. The explosion in the number of new three-dimensional (3D) molecular structures of GPCRs (3D-GPCRome) over the last decade has greatly advanced the mechanistic understanding and drug design opportunities for this protein family. Molecular dynamics (MD) simulations have become a widely established technique for exploring the conformational landscape of proteins at an atomic level. However, the analysis and visualization of MD simulations require efficient storage resources and specialized software. Here we present GPCRmd (http://gpcrmd.org/), an online platform that incorporates web-based visualization capabilities as well as a comprehensive and user-friendly analysis toolbox that allows scientists from different disciplines to visualize, analyze and share GPCR MD data. GPCRmd originates from a community-driven effort to create an open, interactive and standardized database of GPCR MD simulations.
47.	Rudholm Feldreich, Tobias, et al. (author) Circulating proteins as predictors of cardiovascular mortality in end-stage renal disease 2019 In: JN. Journal of Nephrology (Milano. 1992). - Stockholm : Springer Science and Business Media LLC. - 1121-8428 .- 1724-6059. ; 32:1, s. 111-119 Journal article (peer-reviewed)abstract Proteomic profiling of end-stage renal disease (ESRD) patients could lead to improved risk prediction and novel insights into cardiovascular disease mechanisms. Plasma levels of 92 cardiovascular disease-associated proteins were assessed by proximity extension assay (Proseek Multiplex CVD-1, Olink Bioscience, Uppsala, Sweden) in a discovery cohort of dialysis patients, the Mapping of Inflammatory Markers in Chronic Kidney disease cohort [MIMICK; n=183, 55% women, mean age 63years, 46 cardiovascular deaths during follow-up (mean 43months)]. Significant results were replicated in the incident and prevalent hemodialysis arm of the Salford Kidney Study [SKS dialysis study, n=186, 73% women, mean age 62years, 45 cardiovascular deaths during follow-up (mean 12months)], and in the CKD5-LD-RTxcohort with assessments of coronary artery calcium (CAC)-score by cardiac computed tomography (n=89, 37% women, mean age 46years).ResultsIn age and sex-adjusted Cox regression in MIMICK, 11 plasma proteins were nominally associated with cardiovascular mortality (in order of significance: Kidney injury molecule-1 (KIM-1), Matrix metalloproteinase-7, Tumour necrosis factor receptor 2, Interleukin-6, Matrix metalloproteinase-1, Brain-natriuretic peptide, ST2 protein, Hepatocyte growth factor, TNF-related apoptosis inducing ligand receptor-2, Spondin-1, and Fibroblast growth factor 25). Only plasma KIM-1 was associated with cardiovascular mortality after correction for multiple testing, but also after adjustment for dialysis vintage, cardiovascular risk factors and inflammation (hazard ratio) per standard deviation (SD) increase 1.84, 95% CI 1.26-2.69, p=0.002. Addition of KIM-1, or nine of the most informative proteins to an established risk-score (modified AROii CVM-score) improved discrimination of cardiovascular mortality risk from C=0.777 to C=0.799 and C=0.823, respectively. In the SKS dialysis study, KIM-1 predicted cardiovascular mortality in age and sex adjusted models (hazard ratio per SD increase 1.45, 95% CI 1.03-2.05, p=0.034) and higher KIM-1 was associated with higher CACscores in the CKD5-LD-RTx-cohort.ConclusionsOur proteomics approach identified plasma KIM-1 as a risk marker for cardiovascular mortality and coronary artery calcification in three independent ESRD-cohorts. The improved risk prediction for cardiovascular mortality by plasma proteomics merit further studies.
48.	Saiki, Atsuhito, et al. (author) Tenomodulin is highly expressed in adipose tissue, increased in obesity, and down-regulated during diet-induced weight loss. 2009 In: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 94:10, s. 3987-94 Journal article (peer-reviewed)abstract CONTEXT: Tenomodulin (TNMD), a putative angiogenesis inhibitor, is expressed in hypovascular connective tissues. Global gene expression scans show that the TNMD gene also is expressed in human adipose tissue and that its expression is regulated in response to weight reduction; however, more detailed information is lacking. OBJECTIVE: The aim of this study was to investigate TNMD tissue distribution and TNMD gene expression in human adipose tissue in relation to obesity and metabolic disease. DESIGN, PATIENTS, AND INTERVENTIONS: TNMD gene expression, tissue distribution, and TNMD gene expression in adipose tissue from different depots, from lean and obese subjects, and during diet-induced weight reduction were analyzed by DNA microarray and real-time PCR. MAIN OUTCOME MEASURE: We primarily measured TNMD gene expression. RESULTS: The TNMD gene was predominantly expressed in sc adipose tissue. TNMD gene expression was higher in sc than omental adipose tissue both in lean (P = 0.002) and obese subjects (P = 0.014). In both women and men, TNMD gene expression was significantly higher in the obese subjects compared to the lean subjects (P = 1.1 x 10(-26) and P = 0.010, respectively). In a multiple linear regression analysis, BMI was a significant independent predictor of TNMD gene expression. TNMD gene expression was down-regulated during diet-induced weight loss, with a 65% decrease after 18 wk of diet (P < 0.0001). CONCLUSIONS: We conclude that human adipose tissue TNMD gene expression is highly affected by obesity, adipose tissue location, and weight loss, indicating that TNMD may play a role in adipose tissue function.
49.	Sarzynski, M. A., et al. (author) Changes in Uric Acid Levels following Bariatric Surgery Are Not Associated with SLC2A9 Variants in the Swedish Obese Subjects Study 2012 In: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 7:12 Journal article (peer-reviewed)abstract Context and Objective: Obesity and SLC2A9 genotype are strong determinants of uric acid levels. However, data on SLC2A9 variants and weight loss induced changes in uric acid levels are missing. We examined whether the changes in uric acid levels two- and ten-years after weight loss induced by bariatric surgery were associated with SLC2A9 single nucleotide polymorphisms (SNPs) in the Swedish Obese Subjects study. Methods: SNPs (N = 14) identified by genome-wide association studies and exonic SNPs in the SLC2A9 gene locus were genotyped. Cross-sectional associations were tested before (N = 1806), two (N = 1664) and ten years (N = 1201) after bariatric surgery. Changes in uric acid were compared between baseline and Year 2 (N = 1660) and years 2 and 10 (N = 1172). A multiple testing corrected threshold of P = 0.007 was used for statistical significance. Results: Overall, 11 of the 14 tested SLC2A9 SNPs were significantly associated with cross-sectional uric acid levels at all three time points, with rs13113918 showing the strongest association at each time point (R-2 = 3.725.2%, 3.9 x 10-(22)<= p <= 7.7 x 10(-11)). One SNP (rs737267) showed a significant association (R-2 = 0.60%, P = 0.002) with change in uric acid levels from baseline to Year 2, as common allele homozygotes (C/C, N = 957) showed a larger decrease in uric acid (-61.4 mu mol/L) compared to minor allele carriers (A/X: -51.7 mu mol/L, N = 702). No SNPs were associated with changes in uric acid from years 2 to 10. Conclusions: SNPs in the SLC2A9 locus contribute significantly to uric acid levels in obese individuals, and the associations persist even after considerable weight loss due to bariatric surgery. However, we found little evidence for an interaction between genotype and weight change on the response of uric acid to bariatric surgery over ten years. Thus, the fluctuations in uric acid levels among the surgery group appear to be driven by the weight losses and gains, independent of SLC2A9 genotypes. Citation: Sarzynski MA, Jacobson P, Rankinen T, Carlsson B, Sjostrom L, et al. (2012) Changes in Uric Acid Levels following Bariatric Surgery Are Not Associated with SLC2A9 Variants in the Swedish Obese Subjects Study.
50.	Sarzynski, MA, et al. (author) Associations of markers in 11 obesity candidate genes with maximal weight loss and weight regain in the SOS bariatric surgery cases 2011 In: INTERNATIONAL JOURNAL OF OBESITY. - 0307-0565. ; 35:5, s. 676-683 Journal article (peer-reviewed)abstract Abstract: Purpose: To test whether DNA sequence variation in 11 obesity genes is associated with maximum weight loss and weight regain over 6 years of follow-up in bariatric surgery patients of the Swedish obese subjects (SOS) intervention study. Methods: A total of 1443 subjects were available for analysis (vertical banded gastroplasty: n = 966, banding: n = 293 and gastric bypass: n 184). Single-nucleotide polymorphisms (SNPs) from the following 11 genes were included: ADIPOQ, BDNF, FTO, GNB3, LEP, LEPR, MC4R, NR3C1, PPARG, PPARGC1A and TNF. General linear models were used to analyze associations between the SNPs and maximum weight loss and weight regain. Results: The average maximum weight loss was 33.7 kg (s.d. 13.3; min -95.5 kg, max + 2.0 kg), which was reached 2.2 (s.d. 1.6) years after the surgery. Subjects regained approximately 12 kg (range 0.0-51.4 kg) by year 6. After correcting for multiple testing, the FTO SNP rs16945088 remained significantly associated with maximum weight loss (P = 0.0002), as minor allele carriers lost approximately 3 kg less compared with common allele homozygotes. This association was particularly evident in the banding surgery patients (P < 0.0001), whereas no significant association was found in the gastric bypass subjects. No other SNPs were associated with maximum weight loss. Furthermore, no SNPs were significantly associated with weight regain. Conclusion: The FTO SNP rs16945088 was associated with maximum weight loss after banding surgery. We found no evidence that obesity-risk SNPs in FTO or other obesity candidate genes derived from genome-wide association studies are associated with maximum weight loss or weight regain over 6 years of follow-up in bariatric surgery patients. The potential role of other obesity genes remains to be investigated. International Journal of Obesity (2011) 35, 676-683; doi: 10.1038/ijo.2010.166; published online 24 August 2010

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