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1.	Klionsky, Daniel J, et al. (författare) Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). 2016 Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 12:1, s. 1-222 Tidskriftsartikel (refereegranskat)
2.	Palmer, Nicholette D, et al. (författare) A genome-wide association search for type 2 diabetes genes in African Americans. 2012 Ingår i: PloS one. - San Francisco : Public Library of Science (PLoS). - 1932-6203. ; 7:1, s. e29202- Tidskriftsartikel (refereegranskat)abstract African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.
3.	Kanoni, Stavroula, et al. (författare) Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis. 2022 Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1 Tidskriftsartikel (refereegranskat)abstract Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
4.	Kleineidam, Luca, et al. (författare) Midlife occupational cognitive requirements protect cognitive function in old age by increasing cognitive reserve 2022 Ingår i: Frontiers in Psychology. - : Frontiers Media SA. - 1664-1078. ; 13 Tidskriftsartikel (refereegranskat)abstract Introduction: Several lifestyle factors promote protection against Alzheimer's disease (AD) throughout a person's lifespan. Although such protective effects have been described for occupational cognitive requirements (OCR) in midlife, it is currently unknown whether they are conveyed by brain maintenance (BM), brain reserve (BR), or cognitive reserve (CR) or a combination of them. Methods: We systematically derived hypotheses for these resilience concepts and tested them in the population-based AgeCoDe cohort and memory clinic-based AD high-risk DELCODE study. The OCR score (OCRS) was measured using job activities based on the O*NET occupational classification system. Four sets of analyses were conducted: (1) the interaction of OCR and APOE-ε4 with regard to cognitive decline (N = 2,369, AgeCoDe), (2) association with differentially shaped retrospective trajectories before the onset of dementia of the Alzheimer's type (DAT; N = 474, AgeCoDe), (3) cross-sectional interaction of the OCR and cerebrospinal fluid (CSF) AD biomarkers and brain structural measures regarding memory function (N = 873, DELCODE), and (4) cross-sectional and longitudinal association of OCR with CSF AD biomarkers and brain structural measures (N = 873, DELCODE). Results: Regarding (1), higher OCRS was associated with a reduced association of APOE-ε4 with cognitive decline (mean follow-up = 6.03 years), consistent with CR and BR. Regarding (2), high OCRS was associated with a later onset but subsequently stronger cognitive decline in individuals converting to DAT, consistent with CR. Regarding (3), higher OCRS was associated with a weaker association of the CSF Aβ42/40 ratio and hippocampal volume with memory function, consistent with CR. Regarding (4), OCR was not associated with the levels or changes in CSF AD biomarkers (mean follow-up = 2.61 years). We found a cross-sectional, age-independent association of OCRS with some MRI markers, but no association with 1-year-change. OCR was not associated with the intracranial volume. These results are not completely consistent with those of BR or BM. Discussion: Our results support the link between OCR and CR. Promoting and seeking complex and stimulating work conditions in midlife could therefore contribute to increased resistance to pathologies in old age and might complement prevention measures aimed at reducing pathology.
5.	Solmi, Marco, et al. (författare) Physical and mental health impact of COVID-19 on children, adolescents, and their families : 2022 Ingår i: Journal of Affective Disorders. - : Elsevier. - 0165-0327 .- 1573-2517. ; 299, s. 367-376 Tidskriftsartikel (refereegranskat)abstract Background: The COVID-19 pandemic has altered daily routines and family functioning, led to closing schools, and dramatically limited social interactions worldwide. Measuring its impact on mental health of vulnerable children and adolescents is crucial. Methods: The Collaborative Outcomes study on Health and Functioning during Infection Times (COH-FIT - www. coh-fit.com) is an on-line anonymous survey, available in 30 languages, involving >230 investigators from 49 countries supported by national/international professional associations. COH-FIT has thee waves (until the pandemic is declared over by the WHO, and 6-18 months plus 24-36 months after its end). In addition to adults, COH-FIT also includes adolescents (age 14-17 years), and children (age 6-13 years), recruited via nonprobability/snowball and representative sampling and assessed via self-rating and parental rating. Nonmodifiable/modifiable risk factors/treatment targets to inform prevention/intervention programs to promote health and prevent mental and physical illness in children and adolescents will be generated by COH-FIT. Co primary outcomes are changes in well-being (WHO-5) and a composite psychopathology P-Score. Multiple behavioral, family, coping strategy and service utilization factors are also assessed, including functioning and quality of life. Results: Up to June 2021, over 13,000 children and adolescents from 59 countries have participated in the COHFIT project, with representative samples from eleven countries. Limitations: Cross-sectional and anonymous design. Conclusions: Evidence generated by COH-FIT will provide an international estimate of the COVID-19 effect on childrens, adolescents and families, mental and physical health, well-being, functioning and quality of life, informing the formulation of present and future evidence-based interventions and policies to minimize adverse effects of the present and future pandemics on youth.
6.	Solmi, Marco, et al. (författare) The collaborative outcomes study on health and functioning during infection times in adults (COH-FIT-Adults) : Design and methods of an international online survey targeting physical and mental health effects of the COVID-19 pandemic 2022 Ingår i: Journal of Affective Disorders. - : Elsevier. - 0165-0327 .- 1573-2517. ; 299, s. 393-407 Tidskriftsartikel (refereegranskat)abstract Background: . High-quality comprehensive data on short-/long-term physical/mental health effects of the COVID-19 pandemic are needed. Methods: . The Collaborative Outcomes study on Health and Functioning during Infection Times (COH-FIT) is an international, multi-language (n=30) project involving >230 investigators from 49 countries/territories/regions, endorsed by national/international professional associations. COH-FIT is a multi-wave, on-line anonymous, cross-sectional survey [wave 1: 04/2020 until the end of the pandemic, 12 months waves 2/3 starting 6/24 months threreafter] for adults, adolescents (14-17), and children (6-13), utilizing non-probability/snowball and representative sampling. COH-FIT aims to identify non-modifiable/modifiable risk factors/treatment targets to inform prevention/intervention programs to improve social/health outcomes in the general population/vulnerable subgrous during/after COVID-19. In adults, co-primary outcomes are change from pre-COVID-19 to intra-COVID-19 in well-being (WHO-5) and a composite psychopathology P-Score. Key secondary outcomes are a P-extended score, global mental and physical health. Secondary outcomes include health-service utilization/ functioning, treatment adherence, functioning, symptoms/behaviors/emotions, substance use, violence, among others. Results: . Starting 04/26/2020, up to 14/07/2021 >151,000 people from 155 countries/territories/regions and six continents have participated. Representative samples of >= 1,000 adults have been collected in 15 countries. Overall, 43.0% had prior physical disorders, 16.3% had prior mental disorders, 26.5% were health care workers, 8.2% were aged >= 65 years, 19.3% were exposed to someone infected with COVID-19, 76.1% had been in quarantine, and 2.1% had been COVID 19-positive. Limitations: . Cross-sectional survey, preponderance of non-representative participants. Conclusions: . Results from COH-FIT will comprehensively quantify the impact of COVID-19, seeking to identify high-risk groups in need for acute and long-term intervention, and inform evidence-based health policies/strategies during this/future pandemics.
7.	Baumeister, Hannah, et al. (författare) A generalizable data-driven model of atrophy heterogeneity and progression in memory clinic settings 2024 Ingår i: Brain : a journal of neurology. - 1460-2156. ; 147:7, s. 2400-2413 Tidskriftsartikel (refereegranskat)abstract Memory clinic patients are a heterogeneous population representing various aetiologies of pathological aging. It is unknown if divergent spatiotemporal progression patterns of brain atrophy, as previously described in Alzheimer's disease (AD) patients, are prevalent and clinically meaningful in this group of older adults. To uncover distinct atrophy subtypes, we applied the Subtype and Stage Inference (SuStaIn) algorithm to baseline structural MRI data from 813 participants enrolled in the DELCODE cohort (mean ± SD age = 70.67 ± 6.07 years, 52% females). Participants were cognitively unimpaired (CU; n = 285) or fulfilled diagnostic criteria for subjective cognitive decline (SCD; n = 342), mild cognitive impairment (MCI; n = 118), or dementia of the Alzheimer's type (n = 68). Atrophy subtypes were compared in baseline demographics, fluid AD biomarker levels, the Preclinical Alzheimer Cognitive Composite (PACC-5), as well as episodic memory and executive functioning. PACC-5 trajectories over up to 240 weeks were examined. To test if baseline atrophy subtype and stage predicted clinical trajectories before manifest cognitive impairment, we analysed PACC-5 trajectories and MCI conversion rates of CU and SCD participants. Limbic-predominant and hippocampal-sparing atrophy subtypes were identified. Limbic-predominant atrophy first affected the medial temporal lobes, followed by further temporal and, finally, the remaining cortical regions. At baseline, this subtype was related to older age, more pathological AD biomarker levels, APOE ε4 carriership, and an amnestic cognitive impairment. Hippocampal-sparing atrophy initially occurred outside the temporal lobe with the medial temporal lobe spared up to advanced atrophy stages. This atrophy pattern also affected individuals with positive AD biomarkers and was associated with more generalised cognitive impairment. Limbic-predominant atrophy, in all and in only unimpaired participants, was linked to more negative longitudinal PACC-5 slopes than observed in participants without or with hippocampal-sparing atrophy and increased the risk of MCI conversion. SuStaIn modelling was repeated in a sample from the Swedish BioFINDER-2 cohort. Highly similar atrophy progression patterns and associated cognitive profiles were identified. Cross-cohort model generalizability, both on the subject and group level, were excellent, indicating reliable performance in previously unseen data. The proposed model is a promising tool for capturing heterogeneity among older adults at early at-risk states for AD in applied settings. The implementation of atrophy subtype- and stage-specific end-points may increase the statistical power of pharmacological trials targeting early AD.
8.	Ingelsson, Erik, et al. (författare) Detailed physiologic characterization reveals diverse mechanisms for novel genetic Loci regulating glucose and insulin metabolism in humans 2010 Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 59:5, s. 1266-1275 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE Recent genome-wide association studies have revealed loci associated with glucose and insulin-related traits. We aimed to characterize 19 such loci using detailed measures of insulin processing, secretion, and sensitivity to help elucidate their role in regulation of glucose control, insulin secretion and/or action. RESEARCH DESIGN AND METHODS We investigated associations of loci identified by the Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) with circulating proinsulin, measures of insulin secretion and sensitivity from oral glucose tolerance tests (OGTTs), euglycemic clamps, insulin suppression tests, or frequently sampled intravenous glucose tolerance tests in nondiabetic humans (n = 29,084). RESULTS The glucose-raising allele in MADD was associated with abnormal insulin processing (a dramatic effect on higher proinsulin levels, but no association with insulinogenic index) at extremely persuasive levels of statistical significance (P = 2.1 x 10(-71)). Defects in insulin processing and insulin secretion were seen in glucose-raising allele carriers at TCF7L2, SCL30A8, GIPR, and C2CD4B. Abnormalities in early insulin secretion were suggested in glucose-raising allele carriers at MTNR1B, GCK, FADS1, DGKB, and PROX1 (lower insulinogenic index; no association with proinsulin or insulin sensitivity). Two loci previously associated with fasting insulin (GCKR and IGF1) were associated with OGTT-derived insulin sensitivity indices in a consistent direction. CONCLUSIONS Genetic loci identified through their effect on hyperglycemia and/or hyperinsulinemia demonstrate considerable heterogeneity in associations with measures of insulin processing, secretion, and sensitivity. Our findings emphasize the importance of detailed physiological characterization of such loci for improved understanding of pathways associated with alterations in glucose homeostasis and eventually type 2 diabetes.
9.	Pandi-Perumal, Seithikurippu R., et al. (författare) Scientists Against War : A Plea to World Leaders for Better Governance 2022 Ingår i: Sleep and Vigilance. - : Springer Science and Business Media LLC. - 2510-2265. ; 6:1, s. 1-6 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
10.	Smith, Gustav, et al. (författare) Discovery of Genetic Variation on Chromosome 5q22 Associated with Mortality in Heart Failure 2016 Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 12:5 Tidskriftsartikel (refereegranskat)abstract Failure of the human heart to maintain sufficient output of blood for the demands of the body, heart failure, is a common condition with high mortality even with modern therapeutic alternatives. To identify molecular determinants of mortality in patients with new-onset heart failure, we performed a meta-analysis of genome-wide association studies and follow-up genotyping in independent populations. We identified and replicated an association for a genetic variant on chromosome 5q22 with 36% increased risk of death in subjects with heart failure (rs9885413, P = 2.7x10-9). We provide evidence from reporter gene assays, computational predictions and epigenomic marks that this polymorphism increases activity of an enhancer region active in multiple human tissues. The polymorphism was further reproducibly associated with a DNA methylation signature in whole blood (P = 4.5x10-40) that also associated with allergic sensitization and expression in blood of the cytokine TSLP (P = 1.1x10-4). Knockdown of the transcription factor predicted to bind the enhancer region (NHLH1) in a human cell line (HEK293) expressing NHLH1 resulted in lower TSLP expression. In addition, we observed evidence of recent positive selection acting on the risk allele in populations of African descent. Our findings provide novel genetic leads to factors that influence mortality in patients with heart failure.
11.	Williamson, Alice, et al. (författare) Genome-wide association study and functional characterization identifies candidate genes for insulin-stimulated glucose uptake 2023 Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 55:6, s. 973-983 Tidskriftsartikel (refereegranskat)abstract Distinct tissue-specific mechanisms mediate insulin action in fasting and postprandial states. Previous genetic studies have largely focused on insulin resistance in the fasting state, where hepatic insulin action dominates. Here we studied genetic variants influencing insulin levels measured 2 h after a glucose challenge in >55,000 participants from three ancestry groups. We identified ten new loci (P < 5 × 10-8) not previously associated with postchallenge insulin resistance, eight of which were shown to share their genetic architecture with type 2 diabetes in colocalization analyses. We investigated candidate genes at a subset of associated loci in cultured cells and identified nine candidate genes newly implicated in the expression or trafficking of GLUT4, the key glucose transporter in postprandial glucose uptake in muscle and fat. By focusing on postprandial insulin resistance, we highlighted the mechanisms of action at type 2 diabetes loci that are not adequately captured by studies of fasting glycemic traits.
12.	Allenström, Björn, et al. (författare) The interaction of large and high-speed vessels with the environment in archipelagos - Final report.” SSPA Research Report No 122 2003 Rapport (övrigt vetenskapligt/konstnärligt)
13.	Bao, Erik L, et al. (författare) Inherited myeloproliferative neoplasm risk affects haematopoietic stem cells 2020 Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 586:7831, s. 769-775 Tidskriftsartikel (refereegranskat)abstract Myeloproliferative neoplasms (MPNs) are blood cancers that are characterized by the excessive production of mature myeloid cells and arise from the acquisition of somatic driver mutations in haematopoietic stem cells (HSCs). Epidemiological studies indicate a substantial heritable component of MPNs that is among the highest known for cancers1. However, only a limited number of genetic risk loci have been identified, and the underlying biological mechanisms that lead to the acquisition of MPNs remain unclear. Here, by conducting a large-scale genome-wide association study (3,797 cases and 1,152,977 controls), we identify 17 MPN risk loci (P < 5.0 × 10-8), 7 of which have not been previously reported. We find that there is a shared genetic architecture between MPN risk and several haematopoietic traits from distinct lineages; that there is an enrichment for MPN risk variants within accessible chromatin of HSCs; and that increased MPN risk is associated with longer telomere length in leukocytes and other clonal haematopoietic states-collectively suggesting that MPN risk is associated with the function and self-renewal of HSCs. We use gene mapping to identify modulators of HSC biology linked to MPN risk, and show through targeted variant-to-function assays that CHEK2 and GFI1B have roles in altering the function of HSCs to confer disease risk. Overall, our results reveal a previously unappreciated mechanism for inherited MPN risk through the modulation of HSC function.
14.	Bartek, Jiri, Jr., et al. (författare) Scandinavian Multicenter Acute Subdural Hematoma (SMASH) Study : Study Protocol for a Multinational Population-Based Consecutive Cohort 2019 Ingår i: Neurosurgery. - : Ovid Technologies (Wolters Kluwer Health). - 0148-396X .- 1524-4040. ; 84:3, s. 799-803 Tidskriftsartikel (refereegranskat)abstract BACKGROUNDTraumatic acute subdural hematomas (ASDHs) are associated with high rate of morbidity and mortality, especially in elderly individuals. However, recent reports indicate that the morbidity and mortality rates might have improved.OBJECTIVETo evaluate postoperative (30-d) mortality in younger vs elderly (70 yr) patients with ASDH. Comparing younger and elderly patients, the secondary objectives are morbidity patterns of care and 6 mo outcome according to Glasgow outcome scale (GOS). Finally, in patients with traumatic ASDH, we aim to provide prognostic variables.METHODS This is a large-scale population-based Scandinavian study including all neurosurgical departments in Denmark and Sweden. All adult (18 yr) patients surgically treated between 2010 and 2014 for a traumatic ASDH in Denmark and Sweden will be included. Identification at clinicaltrials.gov is NCT03284190.EXPECTED OUTCOMESWe expect to provide data on potential differences between younger vs elderly patients in terms of mortality and morbidity. We hypothesize that elderly patients selected for surgery have a similar pattern of care as compared with younger patients. We will provide functional outcome in terms of GOS at 6 mo in younger vs elderly patients undergoing ASDH evacuation. Finally, clinical useful prognostic factors for favorable (GOS 4-5) vs unfavorable (GOS 1-3) will be identified.DISCUSSION An improved understanding of the clinical outcome, treatment and resource allocation, clinical course, and the prognostic factors of traumatic ASDH will allow neurosurgeons to make better treatment decisions.
15.	Bergmann, Michael Alexander, 1989, et al. (författare) Electrochemical etching of AlGaN for the realization of thin-film devices 2019 Ingår i: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 115:18, s. 182103- Tidskriftsartikel (refereegranskat)abstract Heterogeneously integrated AlGaN epitaxial layers will be essential for future optical and electrical devices like thin-film flip-chip ultraviolet (UV) light-emitting diodes, UV vertical-cavity surface-emitting lasers, and high-electron mobility transistors on efficient heat sinks. Such AlGaN-membranes will also enable flexible and micromechanical devices. However, to develop a method to separate the AlGaN-device membranes from the substrate has proven to be challenging, in particular, for high-quality device materials, which require the use of a lattice-matched AlGaN sacrificial layer. We demonstrate an electrochemical etching method by which it is possible to achieve complete lateral etching of an AlGaN sacrificial layer with up to 50% Al-content. The influence of etching voltage and the Al-content of the sacrificial layer on the etching process is investigated. The etched N-polar surface shows the same macroscopic topography as that of the as-grown epitaxial structure, and the root-mean square roughness is 3.5 nm for 1 µm x 1 µm scan areas. Separated device layers have a well-defined thickness and smooth etched surfaces. Transferred multi-quantum-well structures were fabricated and investigated by time-resolved photoluminescence measurements. The quantum wells showed no sign of degradation caused by the thin-film process.
16.	Bjørnsbo, Kirsten Schroll, et al. (författare) Protocol for the combined cardiometabolic deep phenotyping and registry-based 20-year follow-up study of the Inter99 cohort 2024 Ingår i: BMJ Open. - 2044-6055. ; 14:1 Tidskriftsartikel (refereegranskat)abstract Introduction The population-based Inter99 cohort has contributed extensively to our understanding of effects of a systematic screening and lifestyle intervention, as well as the multifactorial aetiology of type 2 diabetes (T2D) and cardiovascular disease. To understand causes, trajectories and patterns of early and overt cardiometabolic disease manifestations, we will perform a combined clinical deep phenotyping and registry follow-up study of the now 50–80 years old Inter99 participants. Methods and analysis The Inter99 cohort comprises individuals aged 30–60 years, who lived in a representative geographical area of greater Copenhagen, Denmark, in 1999. Age-stratified and sex-stratified random subgroups were invited to participate in either a lifestyle intervention (N=13 016) or questionnaires (N=5264), while the rest served as a reference population (N=43 021). Of the 13 016 individuals assigned to the lifestyle intervention group, 6784 (52%) accepted participation in a baseline health examination in 1999, including screening for cardiovascular risk factors and prediabetic conditions. In total, 6004 eligible participants, who participated in the baseline examination, will be invited to participate in the deep phenotyping 20-year follow-up clinical examination including measurements of anthropometry, blood pressure, arterial stiffness, cardiometabolic biomarkers, coronary artery calcification, heart rate variability, heart rhythm, liver stiffness, fundus characteristics, muscle strength and mass, as well as health and lifestyle questionnaires. In a subsample, 10-day monitoring of diet, physical activity and continuous glucose measurements will be performed. Fasting blood, urine and faecal samples to be stored in a biobank. The established database will form the basis of multiple analyses. A main purpose is to investigate whether low birth weight independent of genetics, lifestyle and glucose tolerance predicts later common T2D cardiometabolic comorbidities. Ethics and dissemination The study was approved by the Medical Ethics Committee, Capital Region, Denmark (H-20076231) and by the Danish Data Protection Agency through the Capital Region of Denmark’s registration system (P-2020-1074). Informed consent will be obtained before examinations. Findings will be disseminated in peer-reviewed journals, at conferences and via presentations to stakeholders, including patients and public health policymakers.
17.	Broadaway, K Alaine, et al. (författare) Loci for insulin processing and secretion provide insight into type 2 diabetes risk. 2023 Ingår i: American Journal of Human Genetics. - : Elsevier. - 0002-9297 .- 1537-6605. ; 110:2, s. 284-299 Tidskriftsartikel (refereegranskat)abstract Insulin secretion is critical for glucose homeostasis, and increased levels of the precursor proinsulin relative to insulin indicate pancreatic islet beta-cell stress and insufficient insulin secretory capacity in the setting of insulin resistance. We conducted meta-analyses of genome-wide association results for fasting proinsulin from 16 European-ancestry studies in 45,861 individuals. We found 36 independent signals at 30 loci (p value < 5 × 10-8), which validated 12 previously reported loci for proinsulin and ten additional loci previously identified for another glycemic trait. Half of the alleles associated with higher proinsulin showed higher rather than lower effects on glucose levels, corresponding to different mechanisms. Proinsulin loci included genes that affect prohormone convertases, beta-cell dysfunction, vesicle trafficking, beta-cell transcriptional regulation, and lysosomes/autophagy processes. We colocalized 11 proinsulin signals with islet expression quantitative trait locus (eQTL) data, suggesting candidate genes, including ARSG, WIPI1, SLC7A14, and SIX3. The NKX6-3/ANK1 proinsulin signal colocalized with a T2D signal and an adipose ANK1 eQTL signal but not the islet NKX6-3 eQTL. Signals were enriched for islet enhancers, and we showed a plausible islet regulatory mechanism for the lead signal in the MADD locus. These results show how detailed genetic studies of an intermediate phenotype can elucidate mechanisms that may predispose one to disease.
18.	Broomé, Michael, et al. (författare) Pressure-independent cardiac effects of angiotensin II in pigs. 2004 Ingår i: Acta Anaesthesiol Scand. - 0001-6772 .- 1365-201X. ; 182:2, s. 111-9 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Angiotensin II (Ang II) is a potent vasoconstrictor with an important role in the development of cardiovascular disease. Earlier results have shown a positive acute inotropic effect of Ang II in anaesthetized pigs together with significant vasoconstriction. This investigation was designed to study cardiac effects of Ang II, when blood pressure was maintained constant by experimental means. METHODS: Ang II (200 microg h(-1)) was infused in anaesthetized pigs (n = 10) at two different arterial blood pressures, the first determined by the effects of Ang II alone, and the second maintained at baseline blood pressure with nitroprusside. Cardiac systolic and diastolic function was evaluated by analysis of left ventricular pressure-volume relationships. RESULTS: Heart rate, end-systolic elastance (Ees) and pre-load adjusted maximal power (PWRmax EDV(-2)) increased at both blood pressure levels, although less when blood pressure was kept constant with nitroprusside. The time constant for isovolumetric relaxation (tau(1/2)) was prolonged with Ang II alone and shortened with Ang II infused together with nitroprusside. CONCLUSION: Ang II infusion in the pig has inotropic and chronotropic properties independent of arterial blood pressure levels, although the effects seem to be blunted by pharmacological actions of the nitric oxide donor nitroprusside.
19.	Börsbo, Björn, 1952-, et al. (författare) Catastrophizing, depression, and pain : Correlation with and influence on quality of life and health - A study of chronic whiplash-associated disorders 2008 Ingår i: Journal of Rehabilitation Medicine. - : Medical Journals Sweden AB. - 1650-1977 .- 1651-2081. ; 40:7, s. 562-569 Tidskriftsartikel (refereegranskat)abstract Objective: The aims of this study were: (i) to classify subgroups according to the degree of pain intensity, depression, and catastrophizing, and investigate distribution in a group of patients with chronic whiplash-associated disorders; and (h) to investigate how these subgroups were distributed and inter-related multivariately with respect to consequences such as health and quality of life outcome measures. Design: Descriptive cross-sectional study. Patients: A total of 275 consecutive chronic pain patients with whiplash-associated disorders who were referred to a university hospital. Methods: The following data were obtained by means of self-report questionnaires: pain intensity in neck and shoulders, background history, Beck Depression Inventory, the catastrophizing scale of Coping Strategy Questionnaire, Life Satisfaction Checklist, the SF-36 Health Survey, and the EuroQol. Results: Principal component analysis was used to recognize subgroups according to the degree of pain intensity, depression, and catastrophizing. These subgroups have specific characteristics according to perceived health and quality of life, and the degree of depression appears to be the most important influencing factor. Conclusion: From a clinical point of view, these findings indicate that it is important to assess patients for intensity of pain, depression, and catastrophizing when planning a rehabilitation programme. Such an evaluation will help individualize therapy and intervention techniques so as to optimize the efficiency of the programme.
20.	Börsbo, Björn, 1952-, et al. (författare) Impact of the interaction between selfefficacy, symptoms and catastrophizing on disability, quality of life and health in chronic pain patients 2010 Ingår i: Disability and Rehabilitation. - : Informa Healthcare. - 0963-8288 .- 1464-5165. ; 32:17, s. 1387-1396 Tidskriftsartikel (refereegranskat)abstract This study investigates the interactions between self-efficacy–including subcomponents–and symptoms (pain, depression, and anxiety), catastrophizing, disability, quality of life, and health in a population of chronic pain patients. The study used 433 chronic pain patients including 47 patients with spinal cord injuryrelated pain, 150 with chronic whiplash-associated disorders, and 236 with fibromyalgia. The participants answered a postal questionnaire that provided background data, pain intensity and duration, and psychological- and health-related items. In the multivariate context, depression, anxiety, catastrophizing, and disability were intercorrelated. Self-efficacy correlated positively with variables of quality of life and general health. These two groups of variables were negatively correlated. The pain variables–duration of pain, pain intensity, and spreading of pain–formed a third group of variables. Self-efficacy function was negatively correlated to these three pain variables. When regressing disability, quality of life, and health, we found that self-efficacy had a positive impact whereas symptoms, catastrophizing, and pain had a negative influence on these aspects. Different patterns of influencing variables were discerned for the three different analyses, and specific patterns of the subscales of self-efficacy corresponded to specific patterns of negative factors for the outcome of disability, quality of life, and health. Perspective: This article presents the complex interaction of psychological factors and symptoms and their positive and negative influence on disability, quality of life, and health. The results indicate that it might be important to assess and influence both enhancing and detoriating factors to ensure an effective pain management programme.
21.	Börsbo, Björn, 1952- (författare) Relationships between Psychological Factors, Disability, Quality of Life and Health in Chronic Pain Disorders 2008 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Chronic pain is a very common condition with a prevalence of 40-65% in the community. The high prevalence of chronic pain causes a lot of human suffering but also high societal costs. The development and maintenance of chronic pain constitutes a complex interplay between neurobiological, psychosocial and genetic factors. A biopsychosocial model of chronic pain has been suggested to make a comprehensive context of the understanding of this issue.The main aims of this thesis were to analyze the relationships of the different components of the biopsychosocial model of pain and to study the relative importance of pain, stress and different psychological factors on disability and health related quality of life.The thesis is based on two groups of patients. One group consists of 275 patients with chronic Whiplash Associated Disorder (WAD) and one group comprise 433 patients with WAD, fibromyalgia (FM) and patients with chronic pain related to Spinal Cord Injury (SCI). The patients were investigated by questionnaires assessing different aspects of pain, depression, anxiety, catastrophizing, self-efficacy, disability and Health Related Quality of Life (HRQL).The main results were that psychological factors (especially depression) correlated relatively strongly with perceived HRQL and disability. The degree of depression appeared to have the most important relationship to perceived HRQL. Despite the fact that the patients rated depression just mild or moderate, depression had a great importance for the outcome of HQRL and disability. Pain intensity and duration played, in the cross-sectional perspective, a minor role for perceived HRQL, whereas pain intensity related more to the outcome of perceived disability.From a clinical point of view it is important to assess the complex and unique situation of each individual with respect to depression, anxiety, self-efficacy and pain when planning treatment and rehabilitation in order to optimise the outcome of such programmes.
22.	Börsbo, Björn, 1952-, et al. (författare) The complex interplay between pain intensity, depression, anxiety and catastrophising with respect to quality of life and disability 2009 Ingår i: Disability and Rehabilitation. - : Informa UK Limited. - 0963-8288 .- 1464-5165. ; 31:19, s. 1605-1613 Tidskriftsartikel (refereegranskat)abstract Purpose. To identify subgroups of patients with chronic pain based on the occurrence of depression, anxiety and catastrophising and the duration of pain and pain intensity. In addition to this, the relationship between the subgroups with respect to background variables, diagnosis, pain-related disability and perceived quality of life are investigated. Methods. This study used 433 patients with chronic pain including 47 patients with spinal cord injury-related pain, 150 with chronic whiplash associated disorders and 236 with fibromyalgia. The participants answered a postal questionnaire that provided background data, pain intensity and duration and psychological and health-related items. Results. On the basis of depression, anxiety, catastrophising, pain intensity and duration, we identified subgroups of patients with chronic pain that differed with respect to perceived quality of life, disability and diagnosis. The psychological factors, especially depression, significantly influenced perceived quality of life and disability. Pain intensity and duration play a minor role with respect to quality of life, although pain intensity is associated to perceived disability. Conclusions. The results of this study highlight the importance of not looking at patients with chronic pain as a homogenous entity. A detailed assessment, including psychological factors with emphasis on depressive symptoms, might be essential for planning and carrying through treatment and rehabilitation.
23.	Cox, Zachary L, et al. (författare) Guideline-Directed Medical Therapy Tolerability in Patients With Heart Failure and Mitral Regurgitation: The COAPT Trial. 2023 Ingår i: JACC. Heart failure. - 2213-1787. ; 11:7, s. 791-805 Tidskriftsartikel (refereegranskat)abstract In the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for HeartFailure Patients With Functional Mitral Regurgitation) trial, a central committee of heart failure (HF) specialists optimized guideline-directed medical therapies (GDMT) and documented medication and goal dose intolerances before patient enrollment.The authors sought to assess the rates, reasons, and predictors of GDMT intolerance in the COAPT trial.Baseline use, dose, and intolerances of angiotensin-converting enzyme inhibitors (ACEIs) angiotensin IIreceptor blockers (ARBs), angiotensin receptor neprilysin inhibitors (ARNIs), beta-blockers, and mineralocorticoid receptor antagonists (MRAs) were analyzed in patients with left ventricular ejection fraction (LVEF)≤40%, in whom maximally tolerated doses of these agents as assessed by an independent HF specialist were required before enrollment.A total of 464 patients had LVEF≤40% and complete medication information. At baseline, 38.8%, 39.4%, and 19.8% of patients tolerated 3, 2, and 1 GDMT classes, respectively (any dose); only 1.9% could not tolerate any GDMT. Beta-blockers were the most frequently tolerated GDMT (93.1%), followed by ACEIs/ARBs/ARNIs (68.5%), and then MRAs (55.0%). Intolerances differed by GDMT class, but hypotension and kidney dysfunction were most common. Goal doses were uncommonly achieved for beta-blockers (32.3%) and ACEIs/ARBs/ARNIs (10.2%) due to intolerances limiting titration. Only 2.2% of patients tolerated goal doses of all 3 GDMT classes.In a contemporary trial population with HF, severe mitral regurgitation, and systematic HF specialist-directed GDMT optimization, most patients had medical intolerances prohibiting 1 or more GDMT classes and achieving goal doses. The specific intolerances noted and methods used for GDMT optimization provide important lessons for the implementation of GDMT optimization in future clinical trials. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for HeartFailure Patients With Functional Mitral Regurgitation [The COAPT Trial] [COAPT]; NCT01626079).
24.	Crossfield, Ian J. M., et al. (författare) 197 CANDIDATES AND 104 VALIDATED PLANETS IN K2's FIRST FIVE FIELDS 2016 Ingår i: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 226:1 Tidskriftsartikel (refereegranskat)abstract We present 197 planet candidates discovered using data from the first year of the NASA K2 mission (Campaigns 0-4), along with the results of an intensive program of photometric analyses, stellar spectroscopy, high-resolution imaging, and statistical validation. We distill these candidates into sets of 104 validated planets (57 in multi-planet systems), 30 false positives, and 63 remaining candidates. Our validated systems span a range of properties, with median values of R-P = 2.3 R-circle plus, P = 8.6 days, T-eff = 5300 K, and Kp = 12.7 mag. Stellar spectroscopy provides precise stellar and planetary parameters for most of these systems. We show that K2 has increased by 30% the number of small planets known to orbit moderately bright stars (1-4 R-circle plus, Kp = 9-13. mag). Of particular interest are 76 planets smaller than 2 R-circle plus, 15 orbiting stars brighter than Kp = 11.5. mag, 5 receiving Earth-like irradiation levels, and several multi-planet systems-including 4 planets orbiting the M dwarf K2-72 near mean-motion resonances. By quantifying the likelihood that each candidate is a planet we demonstrate that our candidate sample has an overall false positive rate of 15%-30%, with rates substantially lower for small candidates (<2 R-circle plus) and larger for candidates with radii >8 R-circle plus and/or with P < 3 days. Extrapolation of the current planetary yield suggests that K2 will discover between 500 and 1000 planets in its planned four-year mission, assuming sufficient follow-up resources are available. Efficient observing and analysis, together with an organized and coherent follow-up strategy, are essential for maximizing the efficacy of planet-validation efforts for K2, TESS, and future large-scale surveys.
25.	Davidsson, Björn J. R., et al. (författare) Thermal inertia and surface roughness of Comet 9P/Tempel 1 2013 Ingår i: Icarus. - : Elsevier BV. - 0019-1035 .- 1090-2643. ; 224:1, s. 154-171 Tidskriftsartikel (refereegranskat)abstract Re-calibrated near-infrared spectroscopy of the resolved nucleus of Comet 9P/Tempel 1 acquired by the Deep Impact spacecraft has been analyzed by utilizing the post-Stardust-NExT nucleus shape model and spin pole solution, as well as a novel thermophysical model that explicitly accounts for small-scale surface roughness and thermal inertia. We find that the thermal inertia varies measurably across the surface, and that thermal emission from certain regions only can be reproduced satisfactory if surface roughness is accounted for. Particularly, a scarped/pitted terrain that experienced morning sunrise during the flyby is measurably rough (Hapke mean slope angle similar to 45 degrees) and has a thermal inertia of at most 50J m(-2) K-1 s(-1/2), but probably much lower. However, thick layered terrain and thin layered terrain experiencing local noon during the flyby have a substantially larger thermal inertia, reaching 150J m(-2) K-1 s(-1/2) if the surface is as rough as the scarped/pitted terrain, but 200J m(-2) K-1 s(-1/2) if the terrain is considered locally flat. Furthermore, the reddening of the nucleus near-infrared 1.5-2.2 gm spectrum varies between morphological units, being reddest for thick layered terrain (median value 3.4% k angstrom(-1)) and most neutral for the smooth terrain known to contain surface water ice (median value 3.1% k angstrom(-1)). Thus, Comet 9P/Tempel 1 is heterogeneous in terms of both thermophysical and optical properties, due to formation conditions and/or post-formation processing.
26.	Feinberg, Alexandra J., et al. (författare) X-ray diffractive imaging of highly ionized helium nanodroplets 2022 Ingår i: Physical Review Research. - 2643-1564. ; 4:2 Tidskriftsartikel (refereegranskat)abstract Finding the lowest energy configuration of N unit charges on a sphere, known as Thomson's problem, is a long-standing query which has only been studied via numerical simulations. We present its physical realization using multiply charged He nanodroplets. The charge positions are determined by x-ray coherent diffractive imaging with Xe as a contrast agent. In neutral droplets, filaments resulting from Xe atoms condensing on quantum vortices are observed. Unique to charged droplets, however, Xe clusters that condense on charges are distributed on the surface in lattice-like structures, introducing He droplets as experimental model systems for the study of Thomson's problem.
27.	Försth, Michael, et al. (författare) STATUS SUMMARY OF CABLE REACTION TO FIRE REGULATIONS IN EUROPE 2013 Ingår i: Proceedings of the 62nd IWCS Conference, International Wire & Cable Symposium. Konferensbidrag (övrigt vetenskapligt/konstnärligt)
28.	Harlid, Sophia, 1978-, et al. (författare) Diabetes mellitus in relation to colorectal tumor molecular subtypes : a pooled analysis of more than 9000 cases 2022 Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 151:3, s. 348-360 Tidskriftsartikel (refereegranskat)abstract Diabetes is an established risk factor for colorectal cancer. However, colorectal cancer is a heterogeneous disease and it is not well understood whether diabetes is more strongly associated with some tumor molecular subtypes than others. A better understanding of the association between diabetes and colorectal cancer according to molecular subtypes could provide important insights into the biology of this association. We used data on lifestyle and clinical characteristics from the Colorectal Cancer Family Registry (CCFR) and the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), including 9756 colorectal cancer cases (with tumor marker data) and 9985 controls, to evaluate associations between reported diabetes and risk of colorectal cancer according to molecular subtypes. Tumor markers included BRAF and KRAS mutations, microsatellite instability and CpG island methylator phenotype. In the multinomial logistic regression model, comparing colorectal cancer cases to cancer-free controls, diabetes was positively associated with colorectal cancer regardless of subtype. The highest OR estimate was found for BRAF-mutated colorectal cancer, n = 1086 (ORfully adj: 1.67, 95% confidence intervals [CI]: 1.36-2.05), with an attenuated association observed between diabetes and colorectal cancer without BRAF-mutations, n = 7959 (ORfully adj: 1.33, 95% CI: 1.19-1.48). In the case only analysis, BRAF-mutation was differentially associated with diabetes (Pdifference = .03). For the other markers, associations with diabetes were similar across tumor subtypes. In conclusion, our study confirms the established association between diabetes and colorectal cancer risk, and suggests that it particularly increases the risk of BRAF-mutated tumors.
29.	Hatti, Neelambar, et al. (författare) Cooperatives in Rural Development in India : Modern Inputs, Production Structure and Stratification 1989. - 1989 Ingår i: State, Cooperatives and Rural Change. - 0076-1478. - 9179660835 ; 53, s. 130-149 Bokkapitel (refereegranskat)
30.	Hirscher, Michael, et al. (författare) Materials for hydrogen-based energy storage - past, recent progress and future outlook 2020 Ingår i: Journal of Alloys and Compounds. - : Elsevier BV. - 0925-8388 .- 1873-4669. ; 827 Tidskriftsartikel (refereegranskat)abstract Globally, the accelerating use of renewable energy sources, enabled by increased efficiencies and reduced costs, and driven by the need to mitigate the effects of climate change, has significantly increased research in the areas of renewable energy production, storage, distribution and end-use. Central to this discussion is the use of hydrogen, as a clean, efficient energy vector for energy storage. This review, by experts of Task 32, Hydrogen-based Energy Storage of the International Energy Agency, Hydrogen TCP, reports on the development over the last 6 years of hydrogen storage materials, methods and techniques, including electrochemical and thermal storage systems. An overview is given on the background to the various methods, the current state of development and the future prospects. The following areas are covered; porous materials, liquid hydrogen carriers, complex hydrides, intermetallic hydrides, electrochemical storage of energy, thermal energy storage, hydrogen energy systems and an outlook is presented for future prospects and research on hydrogen-based energy storage.
31.	Jones, Geraint H., et al. (författare) The Comet Interceptor Mission 2024 Ingår i: Space Science Reviews. - : Springer Nature. - 0038-6308 .- 1572-9672. ; 220:1 Tidskriftsartikel (refereegranskat)abstract Here we describe the novel, multi-point Comet Interceptor mission. It is dedicated to the exploration of a little-processed long-period comet, possibly entering the inner Solar System for the first time, or to encounter an interstellar object originating at another star. The objectives of the mission are to address the following questions: What are the surface composition, shape, morphology, and structure of the target object? What is the composition of the gas and dust in the coma, its connection to the nucleus, and the nature of its interaction with the solar wind? The mission was proposed to the European Space Agency in 2018, and formally adopted by the agency in June 2022, for launch in 2029 together with the Ariel mission. Comet Interceptor will take advantage of the opportunity presented by ESA’s F-Class call for fast, flexible, low-cost missions to which it was proposed. The call required a launch to a halo orbit around the Sun-Earth L2 point. The mission can take advantage of this placement to wait for the discovery of a suitable comet reachable with its minimum Δ V capability of 600 ms − 1 . Comet Interceptor will be unique in encountering and studying, at a nominal closest approach distance of 1000 km, a comet that represents a near-pristine sample of material from the formation of the Solar System. It will also add a capability that no previous cometary mission has had, which is to deploy two sub-probes – B1, provided by the Japanese space agency, JAXA, and B2 – that will follow different trajectories through the coma. While the main probe passes at a nominal 1000 km distance, probes B1 and B2 will follow different chords through the coma at distances of 850 km and 400 km, respectively. The result will be unique, simultaneous, spatially resolved information of the 3-dimensional properties of the target comet and its interaction with the space environment. We present the mission’s science background leading to these objectives, as well as an overview of the scientific instruments, mission design, and schedule.
32.	Klawonn, Anna, 1985-, et al. (författare) Motivational valence is determined by striatal melanocortin 4 receptors 2018 Ingår i: Journal of Clinical Investigation. - : AMER SOC CLINICAL INVESTIGATION INC. - 0021-9738 .- 1558-8238. ; 128:7, s. 3160-3170 Tidskriftsartikel (refereegranskat)abstract It is critical for survival to assign positive or negative valence to salient stimuli in a correct manner. Accordingly, harmful stimuli and internal states characterized by perturbed homeostasis are accompanied by discomfort, unease, and aversion. Aversive signaling causes extensive suffering during chronic diseases, including inflammatory conditions, cancer, and depression. Here, we investigated the role of melanocortin 4 receptors (MC4Rs) in aversive processing using genetically modified mice and a behavioral test in which mice avoid an environment that they have learned to associate with aversive stimuli. In normal mice, robust aversions were induced by systemic inflammation, nausea, pain, and. opioid receptorinduced dysphoria. In sharp contrast, mice lacking MC4Rs displayed preference or indifference toward the aversive stimuli. The unusual flip from aversion to reward in mice lacking MC4Rs was dopamine dependent and associated with a change from decreased to increased activity of the dopamine system. The responses to aversive stimuli were normalized when MC4Rs were reexpressed on dopamine D1 receptor-expressing cells or in the striatum of mice otherwise lacking MC4Rs. Furthermore, activation of arcuate nucleus proopiomelanocortin neurons projecting to the ventral striatum increased the activity of striatal neurons in an MC4R-dependent manner and elicited aversion. Our findings demonstrate that melanocortin signaling through striatal MC4Rs is critical for assigning negative motivational valence to harmful stimuli.
33.	Kosmidou, Ioanna, et al. (författare) Sex-Specific Outcomes of Transcatheter Mitral-Valve Repair and Medical Therapy for Mitral Regurgitation in Heart Failure. 2021 Ingår i: JACC. Heart failure. - 2213-1787. Tidskriftsartikel (refereegranskat)abstract This study sought to assess the sex-specific outcomes in patients with heart failure (HF) with 3+ and 4+ secondary mitral regurgitation (SMR) treated with transcatheter mitral valve repair (TMVr) plus guideline-directed medical therapy (GDMT) versus GDMT alone in the COAPT trial.The impact of sex in patients with HF and severe SMR treated with TMVr with the MitraClip compared with GDMT alone is unknown.Patients were randomized 1:1 to TMVr versus GDMT alone. Two-year outcomes were examined according to sex.Among 614 patients, 221 (36.0%) were women. Women were younger than men and had fewer comorbidities, but reduced quality of life and functional capacity at baseline. In a joint frailty model accounting for the competing risk of death, the 2-year cumulative incidence of the primary endpoint of all HF hospitalizations (HFH) was higher in men compared with women treated with GDMT alone. However, the relative reduction in HFHs with TMVr was greater in men (HR: 0.43; 95% CI: 0.34-0.54) than women (HR: 0.78; 95% CI: 0.57-1.05) (Pinteraction = 0.002). A significant interaction between TMVr versus GDMT alone treatment and time was present for all HFHs in women (HR: 0.57; 95% CI: 0.39-0.84, and HR: 1.39; 95% CI: 0.83-2.33 between 0-1 year and 1-2 years after randomization, respectively, Pinteraction = 0.007) but not in men (HR: 0.48; 95% CI: 0.36-0.64, and HR: 0.33; 95% CI: 0.21-0.51; Pinteraction = 0.16). Female sex was independently associated with a lower adjusted risk of death at 2 years (HR: 0.64; 95% CI: 0.46-0.90; P = 0.011). TMVr consistently reduced 2-year mortality compared with GDMT alone, irrespective of sex (Pinteraction = 0.99).In the COAPT trial, TMVr with the MitraClip resulted in improved clinical outcomes compared with GDMT alone, irrespective of sex. However, the impact of TMVr in reducing HFH was less pronounced in women compared with men beyond the first year after treatment. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation [The COAPT Tria] [COAPT]) NCT01626079.
34.	Kressner, Marit, et al. (författare) The impact of hospital volume on surgical outcome in patients with rectal cancer. 2009 Ingår i: Diseases of the colon and rectum. - 1530-0358 .- 0012-3706. ; 52:9, s. 1542-9 Tidskriftsartikel (refereegranskat)abstract PURPOSE: This study was designed to investigate, in a population-based setting, the surgical outcome in patients with rectal cancer according to the hospital volume. METHODS: Since 1995 all patients with rectal cancer have been registered in the Swedish Rectal Cancer Registry. Hospitals were classified, according to number treated per year, as low-volume, intermediate-volume, or high-volume hospitals (<11, 11-25, or >25 procedures per year). Postoperative mortality, reoperation rate within 30 days, local recurrence rate, and overall five-year survival were studied. For postoperative morbidity and mortality the whole cohort from 1995 to 2003 (n = 10,425) was used. For cancer-related outcome only, those with five-year follow-ups, from 1995 to 1998, were used (n = 4,355). RESULTS: In this registry setting the postoperative mortality rate was 3.6% in low-volume hospitals, and 2.2% in intermediate-volume and high-volume hospitals (P = 0.002). The reoperation rate was 10%, with no differences according to volume. The overall local recurrence rates were 9.4%, 9.3%, and 7.5%, respectively (P = 0.06). Significant difference was found among the nonirradiated patients (P = 0.004), but not among the irradiated patients (P = 0.45). No differences were found according to volume in the absolute five-year survival. CONCLUSION: Postoperative mortality and local recurrence in nonirradiated patients were lower in high-volume hospitals. No difference was seen between volumes in reoperation rates, overall local recurrence, or absolute five-year survival.
35.	Lai, Ian-Lin, et al. (författare) Gas outflow and dust transport of comet 67P/Churyumov-Gerasimenko 2016 Ingår i: Monthly notices of the Royal Astronomical Society. - : OXFORD UNIV PRESS. - 0035-8711 .- 1365-2966. ; 462, s. S533-S546 Tidskriftsartikel (refereegranskat)abstract Because of the diurnal thermal cycle and the irregular shape of the nucleus, gas outflow of comet 67P/Churyumov-Gerasimenko could be highly anisotropic as indicated by the colliminated dust jet structures on the sunlit side. Based on the OSIRIS imaging observations of the outgassing effect, a simple model of surface sublimation can be constructed by taking into account the dependence on the solar insolation. With preliminary information on the time variability of the global gas production rate, a sequence of gas coma models can be generated at different epochs before and after perihelion. We also investigate different patterns of dust particle dynamics under the influences of nuclear rotation and gas drag. From these considerations, a consistent picture of the spatial distribution of dusty materials across the surface of comet 67P as it moves around the perihelion can be developed. It is found that because of the redeposition of the ejected dust from the Southern hemisphere to the Northern hemisphere during the southern summer season the Hapi region could gain up to 0.4 m while the Wosret region would lose up to 1.8 m of dust mantle per orbit.
36.	Lee, Jui-Chi, et al. (författare) Geomorphological mapping of comet 67P/Churyumov-Gerasimenko's Southern hemisphere 2016 Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 462, s. S573-S592 Tidskriftsartikel (refereegranskat)abstract In 2015 May, the Southern hemisphere of comet 67P/Churyumov-Gerasimenko became visible by the OSIRIS cameras on-board the Rosetta spacecraft. The resolution was high enough to carry out a detailed analysis of the surface morphology, which is quite different from the Northern hemisphere. Previous works show that fine particle deposits are the most extensive geological unit in the Northern hemisphere. In contrast, the Southern hemisphere is dominated by outcropping consolidated terrain. In this work, we provide geomorphological maps of the Southern hemisphere with the distinction of both geological units and linear features. The geomorphological maps described in this study allow us to gain a better understanding of the processes shaping the comet nucleus and the distribution of primary structures such as fractures and strata.
37.	Ludwig, Sebastian, et al. (författare) Transcatheter Mitral Valve Replacement versus Medical Therapy for Secondary Mitral Regurgitation: A Propensity Score-Matched Comparison. 2023 Ingår i: Circulation. Cardiovascular interventions. - 1941-7632. ; 16:6 Tidskriftsartikel (refereegranskat)abstract Background: Transcatheter mitral valve replacement (TMVR) is an emerging therapeutic alternative for patients with secondary mitral regurgitation (MR). Outcomes of TMVR versus guideline-directed medical therapy (GDMT) have not been investigated for this population. This study aimed to compare clinical outcomes of patients with secondary MR undergoing TMVR versus GDMT alone. Methods: The CHOICE-MI registry included patients with MR undergoing TMVR using dedicated devices. Patients with MR etiologies other than secondary MR were excluded. Patients treated with GDMT alone were derived from the control arm of the COAPT trial. We compared outcomes between the TMVR and GDMT groups, using propensity score (PS)-matching to adjust for baseline differences. Results: After PS-matching, 97 patient pairs undergoing TMVR (72.9±8.7 years, 60.8% male, transapical access 91.8%) versus GDMT (73.1±11.0 years, 59.8% male) were compared. At 1 and 2 years, residual MR was ≤1+ in all patients of the TMVR group compared to 6.9% and 7.7%, respectively, in those receiving GDMT alone (both p<0.001). The 2-year rate of HF hospitalization was significantly lower in the TMVR group (32.8% vs. 54.4%, HR 0.59, 95% CI 0.35-0.99; p=0.04). Among survivors, a higher proportion of patients were in NYHA functional class I or II in the TMVR group at 1 year (78.2% vs. 59.7%, p=0.03) and at 2 years (77.8% vs. 53.2%, p=0.09). Two-year mortality was similar in the two groups (TMVR vs. GDMT, 36.8% vs. 40.8%, HR 1.01, 95% CI 0.62-1.64; p=0.98). Conclusions: In this observational comparison, over 2-year follow-up, TMVR using mostly transapical devices in patients with secondary MR was associated with significant reduction of MR, symptomatic improvement, less frequent hospitalizations for HF and similar mortality compared with GDMT.
38.	Massironi, Matteo, et al. (författare) Two independent and primitive envelopes of the bilobate nucleus of comet 67P 2015 Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 526:7573, s. 402-405 Tidskriftsartikel (refereegranskat)abstract The factors shaping cometary nuclei are still largely unknown, but could be the result of concurrent effects of evolutionary(1,2) and primordial processes(3,4). The peculiar bilobed shape of comet 67P/Churyumov-Gerasimenko may be the result of the fusion of two objects that were once separate or the result of a localized excavation by outgassing at the interface between the two lobes(5). Here we report that the comet's major lobe is enveloped by a nearly continuous set of strata, up to 650 metres thick, which are independent of an analogous stratified envelope on the minor lobe. Gravity vectors computed for the two lobes separately are closer to perpendicular to the strata than those calculated for the entire nucleus and adjacent to the neck separating the two lobes. Therefore comet 67P/Churyumov-Gerasimenko is an accreted body of two distinct objects with 'onion-like' stratification, which formed before they merged. We conclude that gentle, low-velocity collisions occurred between two fully formed kilometre-sized cometesimals in the early stages of the Solar System. The notable structural similarities between the two lobes of comet 67P/Churyumov-Gerasimenko indicate that the early-forming cometesimals experienced similar primordial stratified accretion, even though they formed independently.
39.	McGinn, Steven, et al. (författare) New Technologies for DNA analysis-A review of the READNA Project. 2016 Ingår i: New Biotechnology. - : Elsevier BV. - 1876-4347 .- 1871-6784. Forskningsöversikt (refereegranskat)abstract The REvolutionary Approaches and Devices for Nucleic Acid analysis (READNA) project received funding from the European Commission for 4 1/2 years. The objectives of the project revolved around technological developments in nucleic acid analysis. The project partners have discovered, created and developed a huge body of insights into nucleic acid analysis, ranging from improvements and implementation of current technologies to the most promising sequencing technologies that constitute a 3(rd) and 4(th) generation of sequencing methods with nanopores and in situ sequencing, respectively.
40.	Pajola, Maurizio, et al. (författare) Size-frequency distribution of boulders >= 7 m on comet 67P/Churyumov-Gerasimenko 2015 Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 583 Tidskriftsartikel (refereegranskat)abstract Aims. We derive for the first time the size-frequency distribution of boulders on a comet, 67P/Churyumov-Gerasimenko (67P), computed from the images taken by the Rosetta/OSIRIS imaging system. We highlight the possible physical processes that lead to these boulder size distributions. Methods. We used images acquired by the OSIRIS Narrow Angle Camera, NAC. on 5 and 6 August 2014. The scale of these images (2.44-2.03 m/px) is such that boulders >= 7 m can be identified and manually extracted from the datasets with the software ArcGIS. We derived both global and localized size-frequency distributions. The three-pixel sampling detection, coupled with the favorable shadowine of the surface (observation phase angle ranging from 48 to 53), enables unequivocally detecting boulders scattered all over the illuminated side of 67P. Results. We identify 3546 boulders larger than 7 m on the imaged surface (36.4 km(2)), with a global number density of nearly 100/km(2) and a cumulative size-frequency distribution represented by a power-law with index of -3.6 +0.2/-0.3. The two lobes of 67P appear to have slightly different distributions, with an index of -3.5 +0.2/-0.3 for the main lobe (body) and -4.0 +0.31-0.2 for the small lobe (head). The steeper distribution of the small lobe might be due to a more pervasive fracturing. The difference of the distribution for the connecting region (neck) is much more significant, with an index value of -2.2 +0.2/-0.2. We propose that the boulder field located in the neck area is the result of blocks falling from the contiguous Hathor cliff. The lower slope of the size-frequency distribution we see today in the neck area might be due to the concurrent processes acting on the smallest boulders, such as i) disintegration or fragmentation and vanishing through sublimation; ii) uplifting by gas drag and consequent redistribution; and iii) burial beneath a debris blanket. We also derived the cumulative size-frequency distribution per km(2) of localized areas on 67P. By comparing the cumulative size-frequency distributions of similar geomorphological settings, we derived similar power-law index values. This suggests that despite the selected locations on different and often opposite sides of the comet, similar sublimation or activity processes, pit formation or collapses, as well as thermal stresses or fracturing events occurred on multiple areas of the comet, shaping its surface into the appearance we see today.
41.	Peolsson, Michael, et al. (författare) Generalized pain is associated with more negative consequences than local or regional pain : A study of chronic whiplash-associated disorders 2007 Ingår i: Journal of Rehabilitation Medicine. - : Medical Journals Sweden AB. - 1650-1977 .- 1651-2081 .- 0001-5555. ; 39:3, s. 260-268 Tidskriftsartikel (refereegranskat)abstract Objective: The main aims of this study were: (i) to determine, for chronic whiplash-associated disorders, whether widespread pain has more severe consequences for other symptoms and different aspects of perceived health than does local/regional pain; (ii) to investigate whether pain, depression, and symptoms not directly related to pain are intercorrelated and to what extent these symptoms correlate with catastrophizing according to the Coping Strategy Questionnaire. Design: Descriptive cross-sectional study. Patients: A total of 275 consecutive chronic pain patients with whiplash-associated disorders who were referred to a university hospital. Methods: Background history, Beck Depression Inventory, Coping Strategy Questionnaire, Life Satisfaction Checklist, the SF-36 Health Survey and EuroQol were used to collect data. Results: Spreading of pain was associated with negative consequences with respect to pain intensity and prevalence of other symptoms, life satisfaction/quality and general health. The subjects differ with respect to the presence of symptoms not directly related to pain. A minor part of the variation in Back Depression Inventory was explained by direct aspects of pain, indicating that, to some extent, generalization of pain is related to catastrophizing thoughts. Conclusion: Widespread pain was associated with negative consequences with respect to pain intensity, prevalence of other symptoms including depressive symptoms, some aspects of coping, life satisfaction and general health.
42.	Proletov, Ian, et al. (författare) Primary and secondary glomerulonephritides 1. 2014 Ingår i: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. - : Oxford University Press (OUP). - 1460-2385. ; 29 Suppl 3:May, s. 186-200 Tidskriftsartikel (refereegranskat)
43.	Quandt, Dagmar, et al. (författare) Implementing liquid biopsies into clinical decision making for cancer immunotherapy 2017 Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 8:29, s. 48507-48520 Forskningsöversikt (refereegranskat)abstract During the last decade, novel immunotherapeutic strategies, in particular antibodies directed against immune checkpoint inhibitors, have revolutionized the treatment of different malignancies leading to an improved survival of patients. Identification of immune-related biomarkers for diagnosis, prognosis, monitoring of immune responses and selection of patients for specific cancer immunotherapies is urgently required and therefore areas of intensive research. Easily accessible samples in particular liquid biopsies (body fluids), such as blood, saliva or urine, are preferred for serial tumor biopsies. Although monitoring of immune and tumor responses prior, during and post immunotherapy has led to significant advances of patients' outcome, valid and stable prognostic biomarkers are still missing. This might be due to the limited capacity of the technologies employed, reproducibility of results as well as assay stability and validation of results. Therefore solid approaches to assess immune regulation and modulation as well as to follow up the nature of the tumor in liquid biopsies are urgently required to discover valuable and relevant biomarkers including sample preparation, timing of the collection and the type of liquid samples. This article summarizes our knowledge of the well-known liquid material in a new context as liquid biopsy and focuses on collection and assay requirements for the analysis and the technical developments that allow the implementation of different high-throughput assays to detect alterations at the genetic and immunologic level, which could be used for monitoring treatment efficiency, acquired therapy resistance mechanisms and the prognostic value of the liquid biopsies.
44.	Rotundi, Alessandra, et al. (författare) Dust measurements in the coma of comet 67P/Churyumov-Gerasimenko inbound to the Sun 2015 Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 347:6220 Tidskriftsartikel (refereegranskat)abstract Critical measurements for understanding accretion and the dust/gas ratio in the solar nebula, where planets were forming 4.5 billion years ago, are being obtained by the GIADA (Grain Impact Analyser and Dust Accumulator) experiment on the European Space Agency's Rosetta spacecraft orbiting comet 67P/Churyumov-Gerasimenko. Between 3.6 and 3.4 astronomical units inbound, GIADA and OSIRIS (Optical, Spectroscopic, and Infrared Remote Imaging System) detected 35 outflowing grains of mass 10(-10) to 10(-7) kilograms, and 48 grains of mass 10(-5) to 10(-2) kilograms, respectively. Combined with gas data from the MIRO (Microwave Instrument for the Rosetta Orbiter) and ROSINA (Rosetta Orbiter Spectrometer for Ion and Neutral Analysis) instruments, we find a dust/gas mass ratio of 4 +/- 2 averaged over the sunlit nucleus surface. A cloud of larger grains also encircles the nucleus in bound orbits from the previous perihelion. The largest orbiting clumps are meter-sized, confirming the dust/gas ratio of 3 inferred at perihelion from models of dust comae and trails.
45.	Rudnicki, Michael, et al. (författare) Urine proteomics for prediction of disease progression in patients with IgA nephropathy 2022 Ingår i: Nephrology, Dialysis and Transplantation. - : Oxford University Press. - 0931-0509 .- 1460-2385. ; 37:1, s. 42-52 Tidskriftsartikel (refereegranskat)abstract Background: Risk of kidney function decline in immunoglobulin A (IgA) nephropathy (IgAN) is significant and may not be predicted by available clinical and histological tools. To serve this unmet need, we aimed at developing a urinary biomarker-based algorithm that predicts rapid disease progression in IgAN, thus enabling a personalized risk stratification.Methods: In this multicentre study, urine samples were collected in 209 patients with biopsy-proven IgAN. Progression was defined by tertiles of the annual change of estimated glomerular filtration rate (eGFR) during follow-up. Urine samples were analysed using capillary electrophoresis coupled mass spectrometry. The area under the receiver operating characteristic curve (AUC) was used to evaluate the risk prediction models.Results: Of the 209 patients, 64% were male. Mean age was 42 years, mean eGFR was 63 mL/min/1.73 m2 and median proteinuria was 1.2 g/day. We identified 237 urine peptides showing significant difference in abundance according to the tertile of eGFR change. These included fragments of apolipoprotein C-III, alpha-1 antitrypsin, different collagens, fibrinogen alpha and beta, titin, haemoglobin subunits, sodium/potassium-transporting ATPase subunit gamma, uromodulin, mucin-2, fractalkine, polymeric Ig receptor and insulin. An algorithm based on these protein fragments (IgAN237) showed a significant added value for the prediction of IgAN progression [AUC 0.89; 95% confidence interval (CI) 0.83-0.95], as compared with the clinical parameters (age, gender, proteinuria, eGFR and mean arterial pressure) alone (0.72; 95% CI 0.64-0.81).Conclusions: A urinary peptide classifier predicts progressive loss of kidney function in patients with IgAN significantly better than clinical parameters alone.
46.	Thomas, Nicolas, et al. (författare) The morphological diversity of comet 67P/Churyumov-Gerasimenko 2015 Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 347:6220 Tidskriftsartikel (refereegranskat)abstract Images of comet 67P/Churyumov-Gerasimenko acquired by the OSIRIS (Optical, Spectroscopic and Infrared Remote Imaging System) imaging system onboard the European Space Agency's Rosetta spacecraft at scales of better than 0.8 meter per pixel show a wide variety of different structures and textures. The data show the importance of airfall, surface dust transport, mass wasting, and insolation weathering for cometary surface evolution, and they offer some support for subsurface fluidization models and mass loss through the ejection of large chunks of material.
47.	Wayne, Greg, et al. (författare) Principles of Systems Biology, No. 11 2016 Ingår i: CELL SYSTEMS. - : CELL PRESS. - 2405-4712. ; 3:5, s. 406-410 Tidskriftsartikel (refereegranskat)abstract This month: AI that learns patterns and facts, new protein-RNA and protein-protein relationships, engineering signaling and metabolism, and more variants of Cas9.
48.	Wilson, Stephen A., et al. (författare) New materials for micro-scale sensors and actuators An engineering review 2007 Ingår i: Materials science & engineering. R, Reports. - : Elsevier BV. - 0927-796X .- 1879-212X. ; 56:06-jan, s. 1-129 Forskningsöversikt (refereegranskat)abstract This paper provides a detailed overview of developments in transducer materials technology relating to their current and future applications in micro-scale devices. Recent advances in piezoelectric, magnetostrictive and shape-memory alloy systems are discussed and emerging transducer materials such as magnetic nanoparticles, expandable micro-spheres and conductive polymers are introduced. Materials properties, transducer mechanisms and end applications are described and the potential for integration of the materials with ancillary systems components is viewed as an essential consideration. The review concludes with a short discussion of structural polymers that are extending the range of micro-fabrication techniques available to designers and production engineers beyond the limitations of silicon fabrication technology.
49.	Åkerblom, Björn, et al. (författare) Heterogeneity among RIP-Tag2 insulinomas allows vascular endothelial growth factor-A independent tumor expansion as revealed by studies in Shb mutant mice : implications for tumor angiogenesis 2012 Ingår i: Molecular Oncology. - : Wiley. - 1574-7891 .- 1878-0261. ; 6:3, s. 333-346 Tidskriftsartikel (refereegranskat)abstract The Shb adapter protein is a signaling intermediate that operates downstream of vascular endothelial growth factor receptor-2 (VEGFR-2) in endothelial cells. The Shb knockout mouse displays a dysfunctional microvasculature and impaired growth of subcutaneously implanted tumor cells. We decided to investigate tumor growth and angiogenesis in the absence of Shb in an inheritable tumor model, the RIP-Tag2 mouse, which produces insulinomas in a manner highly dependent on de novo angiogenesis. We observed a reduced tumor incidence and burden in both RIP-Tag2 Shb-/- and RIP-Tag2 Shb+/- mice. This correlated with a reduced microvascular density, measured as percentage of insulinoma area positive for CD31 staining, and altered vascular morphology. However, treatment with a VEGF-A blocking antibody was without effect on the Shb mutant tumor volume whereas it significantly inhibited tumor volume in the wild-type mice, suggesting that in mice with reduced Shb expression tumor angiogenesis was primarily sustained by VEGF-A independent pathway(s). This notion was further substantiated by gene expression analysis of angiogenic markers showing reduced VEGF-A expression in Shb deficient tumors. Considerable heterogeneity with respect to the gene expression profiles of other angiogenic markers and the signal-transduction characteristics was observed between different tumors, suggesting that multiple “rescue” pathways could be operating. The numbers of invasive tumors or metastases were unchanged in the Shb mutant. It is concluded that the Shb mutant background reduces tumor frequency by chronically suppressing VEGF-A dependent angiogenesis. However, VEGF-A independent angiogenesis supports a significant degree of tumor expansion in Shbdeficient mice, indicating heterogeneity in the mechanisms by which tumor expansion is promoted. Interference with Shb signaling may provide novel means for future cancer therapy.
50.	Aboyans, Victor, et al. (författare) Measurement and interpretation of the ankle-brachial index : a scientific statement from the Ammerican Heart Association 2012 Ingår i: Circulation. - : American Heart Association. - 0009-7322 .- 1524-4539. Tidskriftsartikel (refereegranskat)

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