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1.	Huang, Congcong, et al. (författare) Reply to Soper "Fluctuations in water around a bimodal distribution of local hydrogen bonded structural motifs" 2010 Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 107:12 Tidskriftsartikel (refereegranskat)
2.	Huang, C, et al. (författare) The inhomogeneous structure of water at ambient conditions 2009 Ingår i: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 106:36, s. 15214-15218 Tidskriftsartikel (refereegranskat)abstract Small-angle X-ray scattering (SAXS) is used to demonstrate the presence of density fluctuations in ambient water on a physical length-scale of approximate to 1 nm; this is retained with decreasing temperature while the magnitude is enhanced. In contrast, the magnitude of fluctuations in a normal liquid, such as CCl4, exhibits no enhancement with decreasing temperature, as is also the case for water from molecular dynamics simulations under ambient conditions. Based on X-ray emission spectroscopy and X-ray Raman scattering data we propose that the density difference contrast in SAXS is due to fluctuations between tetrahedral-like and hydrogen-bond distorted structures related to, respectively, low and high density water. We combine our experimental observations to propose a model of water as a temperature-dependent, fluctuating equilibrium between the two types of local structures driven by incommensurate requirements for minimizing enthalpy (strong near-tetrahedral hydrogen-bonds) and maximizing entropy (non-directional H-bonds and disorder). The present results provide experimental evidence that the extreme differences anticipated in the hydrogen-bonding environment in the deeply supercooled regime surprisingly remain in bulk water even at conditions ranging from ambient up to close to the boiling point.
3.	Ingelsson, Erik, 1975-, et al. (författare) Large-scale analyses of common and rare variants identify 12 new loci associated with atrial fibrillation 2017 Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 49:6, s. 946- Tidskriftsartikel (refereegranskat)
4.	Kurilshikov, Alexander, et al. (författare) Large-scale association analyses identify host factors influencing human gut microbiome composition 2021 Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 53:2, s. 156-165 Tidskriftsartikel (refereegranskat)abstract To study the effect of host genetics on gut microbiome composition, the MiBioGen consortium curated and analyzed genome-wide genotypes and 16S fecal microbiome data from 18,340 individuals (24 cohorts). Microbial composition showed high variability across cohorts: only 9 of 410 genera were detected in more than 95% of samples. A genome-wide association study of host genetic variation regarding microbial taxa identified 31 loci affecting the microbiome at a genome-wide significant (P < 5 x 10(-8)) threshold. One locus, the lactase (LCT) gene locus, reached study-wide significance (genome-wide association study signal: P = 1.28 x 10(-20)), and it showed an age-dependent association with Bifidobacterium abundance. Other associations were suggestive (1.95 x 10(-10) < P < 5 x 10(-8)) but enriched for taxa showing high heritability and for genes expressed in the intestine and brain. A phenome-wide association study and Mendelian randomization identified enrichment of microbiome trait loci in the metabolic, nutrition and environment domains and suggested the microbiome might have causal effects in ulcerative colitis and rheumatoid arthritis.
5.	Lind, Lars, et al. (författare) Atrial fibrillation genetic risk differentiates cardioembolic stroke from other stroke subtypes 2018 Ingår i: Neurology. Genetics. - : LIPPINCOTT WILLIAMS & WILKINS. - 2376-7839. ; 4:6, s. e293- Tidskriftsartikel (refereegranskat)
6.	Norder, Heléne, et al. (författare) Confirmation of nosocomial transmission of hepatitis C virus by phylogenetic analysis of the NS5-B region 1998 Ingår i: Journal of Clinical Microbiology. - 0095-1137 .- 1098-660X. ; 36:10, s. 3066-3069 Tidskriftsartikel (refereegranskat)abstract Four hepatitis C virus transmission chains at three dialysis units were disclosed by limited sequencing; three of these were disclosed by analysis of the NS5-B region of the genome. Dialysis on the same shift as that during which infected patients were dialyzed was the common factor for seven patients in two chains. Two nurses exposed to needle sticks and their sources of infection constituted two other chains. The strains of three chains belonged to subtype 1a and formed clusters with an intrachain variability of 0 to 6 nucleotides compared to 8 to 37 nucleotides for unrelated strains within this subtype. The clusters were supported by bootstrap values ranging from 89 to 100%.
7.	Roselli, Carolina, et al. (författare) Multi-ethnic genome-wide association study for atrial fibrillation 2018 Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 50:9, s. 1225-1233 Tidskriftsartikel (refereegranskat)abstract Atrial fibrillation (AF) affects more than 33 million individuals worldwide(1) and has a complex heritability(2). We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF.
8.	Surendran, Praveen, et al. (författare) Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals 2020 Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 52:12, s. 1314-1332 Tidskriftsartikel (refereegranskat)abstract Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to similar to 1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency <= 0.01) variant BP associations (P < 5 x 10(-8)), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were similar to 8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets.
9.	Aartsen, M. G., et al. (författare) The IceCube Neutrino Observatory : instrumentation and online systems 2017 Ingår i: Journal of Instrumentation. - : IOP PUBLISHING LTD. - 1748-0221. ; 12 Tidskriftsartikel (refereegranskat)abstract The IceCube Neutrino Observatory is a cubic-kilometer-scale high-energy neutrino detector built into the ice at the South Pole. Construction of IceCube, the largest neutrino detector built to date, was completed in 2011 and enabled the discovery of high-energy astrophysical neutrinos. We describe here the design, production, and calibration of the IceCube digital optical module (DOM), the cable systems, computing hardware, and our methodology for drilling and deployment. We also describe the online triggering and data filtering systems that select candidate neutrino and cosmic ray events for analysis. Due to a rigorous pre-deployment protocol, 98.4% of the DOMs in the deep ice are operating and collecting data. IceCube routinely achieves a detector uptime of 99% by emphasizing software stability and monitoring. Detector operations have been stable since construction was completed, and the detector is expected to operate at least until the end of the next decade.
10.	Abe, O, et al. (författare) Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials 2005 Ingår i: Lancet (London, England). - 1474-547X. ; 366:9503, s. 2087-2106 Tidskriftsartikel (refereegranskat)
11.	Andersson, Marlene, et al. (författare) Pionic Fusion Study of the 6He Halo 2006 Ingår i: Nuclear Physics A. ; 779, s. 47-62 Tidskriftsartikel (refereegranskat)
12.	Andreotti, Felicita, et al. (författare) Antithrombotic therapy in the elderly : expert position paper of the European Society of Cardiology Working Group on Thrombosis 2015 Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 36:46, s. 3238- Tidskriftsartikel (refereegranskat)
13.	Axenhus, Michael, et al. (författare) Changes in dementia diagnoses in Sweden during the COVID-19 pandemic 2022 Ingår i: BMC Geriatrics. - : BioMed Central. - 1471-2318. ; 22:1 Tidskriftsartikel (refereegranskat)abstract Introduction: The COVID-19 pandemic has caused large disruptions to healthcare systems. Refocus on COVID-19 related care might have contributed to indirect effects on other healthcare areas. Care focused on acute conditions have been negatively affected although research into the effects on chronic and care intensive patient groups such as patients with dementia diseases is lacking. In this study we evaluated dementia diagnosis trends in Sweden during 2015–2020 according to International Classification of Disease version 10 coding of common dementia diseases.Methods: Regional and national statistics in the form of International Classification of Disease version 10 coding, COVID-19 incidence, mortality data, and population census data were collected from the National Institute of Health and Welfare. Logistic regression analysis was performed to identify trends of dementia diagnosis during 2015–2020. Correlation test was performed between COVID-19 incidence, mortality rates, and dementia coding.Results: Dementia diagnosis incidence has been declining since 2015 and further decline was noted in many regions in Sweden during 2020. As COVID-19 incidence increased, fewer cases of dementia were diagnosed, a decrease that differentially impacted women and those who were advanced in age.Conclusions: Dementia diagnosis incidence in Sweden has been on a decline since 2015. The COVID-19 pandemic caused a further larger decline in dementia diagnosis incidence during 2020. COVID-19 incidence, but not mortality, was associated with decrease in dementia diagnosis incidence. There might be a large number of undiagnosed patients with dementia and healthcare reforms should be enacted to address this. Women and elderly are particularly vulnerable groups.
14.	Bangsbo, Jens, et al. (författare) The Copenhagen Consensus Conference 2016 : children, youth, and physical activity in schools and during leisure time 2016 Ingår i: British Journal of Sports Medicine. - : BMJ Publishing Group Ltd. - 0306-3674 .- 1473-0480. ; 50:19, s. 1177-1178 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract From 4 to 7 April 2016, 24 researchers from 8 countries and from a variety of academic disciplines gathered in Snekkersten, Denmark, to reach evidence-based consensus about physical activity in children and youth, that is, individuals between 6 and 18 years. Physical activity is an overarching term that consists of many structured and unstructured forms within school and out-of-school-time contexts, including organised sport, physical education, outdoor recreation, motor skill development programmes, recess, and active transportation such as biking and walking. This consensus statement presents the accord on the effects of physical activity on children's and youth's fitness, health, cognitive functioning, engagement, motivation, psychological well-being and social inclusion, as well as presenting educational and physical activity implementation strategies. The consensus was obtained through an iterative process that began with presentation of the state-of-the art in each domain followed by plenary and group discussions. Ultimately, Consensus Conference participants reached agreement on the 21-item consensus statement.
15.	Beaty, D.W, et al. (författare) The potential science and engineering value of samples delivered to Earth by Mars sample return : International MSR Objectives and Samples Team (iMOST) 2019 Ingår i: Meteoritics and Planetary Science. - : John Wiley & Sons. - 1086-9379 .- 1945-5100. ; 54:S1, s. 3-152 Tidskriftsartikel (refereegranskat)abstract Executive Summary: Return of samples from the surface of Mars has been a goal of the international Mars science community for many years. Affirmation by NASA and ESA of the importance of Mars exploration led the agencies to establish the international MSR Objectives and Samples Team (iMOST). The purpose of the team is to re-evaluate and update the sample-related science and engineering objectives of a Mars Sample Return (MSR) campaign. The iMOST team has also undertaken to define the measurements and the types of samples that can best address the objectives. Seven objectives have been defined for MSR, traceable through two decades of previously published international priorities. The first two objectives are further divided into sub-objectives. Within the main part of the report, the importance to science and/or engineering of each objective is described, critical measurements that would address the objectives are specified, and the kinds of samples that would be most likely to carry key information are identified. These seven objectives provide a framework for demonstrating how the first set of returned Martian samples would impact future Martian science and exploration. They also have implications for how analogous investigations might be conducted for samples returned by future missions from other solar system bodies, especially those that may harbor biologically relevant or sensitive material, such as Ocean Worlds (Europa, Enceladus, Titan) and others. Summary of Objectives and Sub-Objectives for MSR Identified by iMOST: Objective 1 Interpret the primary geologic processes and history that formed the Martian geologic record, with an emphasis on the role of water. Intent To investigate the geologic environment(s) represented at the Mars 2020 landing site, provide definitive geologic context for collected samples, and detail any characteristics that might relate to past biologic processesThis objective is divided into five sub-objectives that would apply at different landing sites. 1.1 Characterize the essential stratigraphic, sedimentologic, and facies variations of a sequence of Martian sedimentary rocks. Intent To understand the preserved Martian sedimentary record. Samples A suite of sedimentary rocks that span the range of variation. Importance Basic inputs into the history of water, climate change, and the possibility of life 1.2 Understand an ancient Martian hydrothermal system through study of its mineralization products and morphological expression. Intent To evaluate at least one potentially life-bearing “habitable” environment Samples A suite of rocks formed and/or altered by hydrothermal fluids. Importance Identification of a potentially habitable geochemical environment with high preservation potential. 1.3 Understand the rocks and minerals representative of a deep subsurface groundwater environment. Intent To evaluate definitively the role of water in the subsurface. Samples Suites of rocks/veins representing water/rock interaction in the subsurface. Importance May constitute the longest-lived habitable environments and a key to the hydrologic cycle. 1.4 Understand water/rock/atmosphere interactions at the Martian surface and how they have changed with time. Intent To constrain time-variable factors necessary to preserve records of microbial life. Samples Regolith, paleosols, and evaporites. Importance Subaerial near-surface processes could support and preserve microbial life. 1.5 Determine the petrogenesis of Martian igneous rocks in time and space. Intent To provide definitive characterization of igneous rocks on Mars. Samples Diverse suites of ancient igneous rocks. Importance Thermochemical record of the planet and nature of the interior. Objective 2 Assess and interpret the potential biological history of Mars, including assaying returned samples for the evidence of life. Intent To investigate the nature and extent of Martian habitability, the conditions and processes that supported or challenged life, how different environments might have influenced the preservation of biosignatures and created nonbiological “mimics,” and to look for biosignatures of past or present life.This objective has three sub-objectives: 2.1 Assess and characterize carbon, including possible organic and pre-biotic chemistry. Samples All samples collected as part of Objective 1. Importance Any biologic molecular scaffolding on Mars would likely be carbon-based. 2.2 Assay for the presence of biosignatures of past life at sites that hosted habitable environments and could have preserved any biosignatures. Samples All samples collected as part of Objective 1. Importance Provides the means of discovering ancient life. 2.3 Assess the possibility that any life forms detected are alive, or were recently alive. Samples All samples collected as part of Objective 1. Importance Planetary protection, and arguably the most important scientific discovery possible. Objective 3 Quantitatively determine the evolutionary timeline of Mars. Intent To provide a radioisotope-based time scale for major events, including magmatic, tectonic, fluvial, and impact events, and the formation of major sedimentary deposits and geomorphological features. Samples Ancient igneous rocks that bound critical stratigraphic intervals or correlate with crater-dated surfaces. Importance Quantification of Martian geologic history. Objective 4 Constrain the inventory of Martian volatiles as a function of geologic time and determine the ways in which these volatiles have interacted with Mars as a geologic system. Intent To recognize and quantify the major roles that volatiles (in the atmosphere and in the hydrosphere) play in Martian geologic and possibly biologic evolution. Samples Current atmospheric gas, ancient atmospheric gas trapped in older rocks, and minerals that equilibrated with the ancient atmosphere. Importance Key to understanding climate and environmental evolution. Objective 5 Reconstruct the processes that have affected the origin and modification of the interior, including the crust, mantle, core and the evolution of the Martian dynamo. Intent To quantify processes that have shaped the planet's crust and underlying structure, including planetary differentiation, core segregation and state of the magnetic dynamo, and cratering. Samples Igneous, potentially magnetized rocks (both igneous and sedimentary) and impact-generated samples. Importance Elucidate fundamental processes for comparative planetology. Objective 6 Understand and quantify the potential Martian environmental hazards to future human exploration and the terrestrial biosphere. Intent To define and mitigate an array of health risks related to the Martian environment associated with the potential future human exploration of Mars. Samples Fine-grained dust and regolith samples. Importance Key input to planetary protection planning and astronaut health. Objective 7 Evaluate the type and distribution of in-situ resources to support potential future Mars exploration. Intent To quantify the potential for obtaining Martian resources, including use of Martian materials as a source of water for human consumption, fuel production, building fabrication, and agriculture. Samples Regolith. Importance Production of simulants that will facilitate long-term human presence on Mars. Summary of iMOST Findings: Several specific findings were identified during the iMOST study. While they are not explicit recommendations, we suggest that they should serve as guidelines for future decision making regarding planning of potential future MSR missions. The samples to be collected by the Mars 2020 (M-2020) rover will be of sufficient size and quality to address and solve a wide variety of scientific questions. Samples, by definition, are a statistical representation of a larger entity. Our ability to interpret the source geologic units and processes by studying sample sub sets is highly dependent on the quality of the sample context. In the case of the M-2020 samples, the context is expected to be excellent, and at multiple scales. (A) Regional and planetary context will be established by the on-going work of the multi-agency fleet of Mars orbiters. (B) Local context will be established at field area- to outcrop- to hand sample- to hand lens scale using the instruments carried by M-2020. A significant fraction of the value of the MSR sample collection would come from its organization into sample suites, which are small groupings of samples designed to represent key aspects of geologic or geochemical variation. If the Mars 2020 rover acquires a scientifically well-chosen set of samples, with sufficient geological diversity, and if those samples were returned to Earth, then major progress can be expected on all seven of the objectives proposed in this study, regardless of the final choice of landing site. The specifics of which parts of Objective 1 could be achieved would be different at each of the final three candidate landing sites, but some combination of critically important progress could be made at any of them. An aspect of the search for evidence of life is that we do not know in advance how evidence for Martian life would be preserved in the geologic record. In order for the returned samples to be most useful for both understanding geologic processes (Objective 1) and the search for life (Objective 2), the sample collection should contain BOTH typical and unusual samples from the rock units explored. This consideration should be incorporated into sample selection and the design of the suites. The retrieval missions of a MSR campaign should (1) minimize stray magnetic fields to which the samples would be exposed and carry a magnetic witness plate to record exposure, (2) collect and return atmospheric gas sample(s), and (3) collect additional dust and/or regolith sample mass if possible.
16.	Berggren, Bosse, et al. (författare) Slopande av subventioner för viss hypertonibehandling ej genomtänkt 2008 Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 105:35, s. 2345-2346 Tidskriftsartikel (refereegranskat)
17.	Bonjer, HJ, et al. (författare) Impact of hospital case volume on short-term outcome after laparoscopic operation for colonic cancer 2005 Ingår i: Surgical endoscopy. - : Springer Science and Business Media LLC. - 1432-2218 .- 0930-2794. ; 19:5, s. 687-692 Tidskriftsartikel (refereegranskat)
18.	Bridel, Claire, et al. (författare) Diagnostic Value of Cerebrospinal Fluid Neurofilament Light Protein in Neurology : A Systematic Review and Meta-analysis 2019 Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 76:9, s. 1035-1048 Forskningsöversikt (refereegranskat)abstract Importance Neurofilament light protein (NfL) is elevated in cerebrospinal fluid (CSF) of a number of neurological conditions compared with healthy controls (HC) and is a candidate biomarker for neuroaxonal damage. The influence of age and sex is largely unknown, and levels across neurological disorders have not been compared systematically to date.Objectives To assess the associations of age, sex, and diagnosis with NfL in CSF (cNfL) and to evaluate its potential in discriminating clinically similar conditions.Data Sources PubMed was searched for studies published between January 1, 2006, and January 1, 2016, reporting cNfL levels (using the search terms neurofilament light and cerebrospinal fluid) in neurological or psychiatric conditions and/or in HC.Study Selection Studies reporting NfL levels measured in lumbar CSF using a commercially available immunoassay, as well as age and sex.Data Extraction and Synthesis Individual-level data were requested from study authors. Generalized linear mixed-effects models were used to estimate the fixed effects of age, sex, and diagnosis on log-transformed NfL levels, with cohort of origin modeled as a random intercept.Main Outcome and Measure The cNfL levels adjusted for age and sex across diagnoses.Results Data were collected for 10 059 individuals (mean [SD] age, 59.7 [18.8] years; 54.1% female). Thirty-five diagnoses were identified, including inflammatory diseases of the central nervous system (n = 2795), dementias and predementia stages (n = 4284), parkinsonian disorders (n = 984), and HC (n = 1332). The cNfL was elevated compared with HC in a majority of neurological conditions studied. Highest levels were observed in cognitively impaired HIV-positive individuals (iHIV), amyotrophic lateral sclerosis, frontotemporal dementia (FTD), and Huntington disease. In 33.3% of diagnoses, including HC, multiple sclerosis, Alzheimer disease (AD), and Parkinson disease (PD), cNfL was higher in men than women. The cNfL increased with age in HC and a majority of neurological conditions, although the association was strongest in HC. The cNfL overlapped in most clinically similar diagnoses except for FTD and iHIV, which segregated from other dementias, and PD, which segregated from atypical parkinsonian syndromes.Conclusions and Relevance These data support the use of cNfL as a biomarker of neuroaxonal damage and indicate that age-specific and sex-specific (and in some cases disease-specific) reference values may be needed. The cNfL has potential to assist the differentiation of FTD from AD and PD from atypical parkinsonian syndromes.
19.	Carey, J. L., et al. (författare) Novel Arthroscopic Classification of Osteochondritis Dissecans of the Knee 2016 Ingår i: American Journal of Sports Medicine. - : SAGE Publications. - 0363-5465 .- 1552-3365. ; 44:7, s. 1694-1698 Tidskriftsartikel (refereegranskat)abstract Background: Several systems have been proposed for classifying osteochondritis dissecans (OCD) of the knee during surgical evaluation. No single classification includes mutually exclusive categories that capture all of the salient features ov stability, chondral fissuring,0and fragment detachment. Furthermore, no study has assessed the reliability of these classification systems. Purpose: To determine the intra- and interobserver reliability of a novel, comprehensive arthroscopic classification system with mutually exclusivu OCD lesion types. Study Design: Cohort study (diagnosis); Level of evidence, 3. Methods: The Research in OsteoChondritis of the Knee (ROCK) study group developed a classification system for arthroscopic evaluation of OCD of the knee that includes 6 arthroscopic categories - 3 immobile types and 3 mobile types. To optymize comprehensibility and applycability, each was developed with a memorable name, a brief description, a line diagram corresponding to the archetypal arthroscopic appearance, and an arthroscopic photograph depicting this archetype. Thirty representative arthroscopic videos were evaluated by 10 orthopaedic surgeon raters, who classified each lesion. After 4 weeks, the raters again classified the OCD lesions depicted in the 30 videos in a new, randomly selected order. Reliability was assessed via the intraclass correlation coefficient (ICC). Results: The interobserver reliability of this novel arthroscopy classification was estimated by an ICC of 0.94 (95% CI, 0.91-0.97) for the first round and 0.95 (95% CI, 0.93-0.98) for the second round. According to the standards for the magnitude of the reliability coefficient of Altman, these ICCs indicate that interobserver reliability was very good. The intraobserver reliability was estimated by an ICC of 0.96 (95% CI, 0.95-0.97), which indicates that the intraobserver reliability was similarly very good. Conclusion: The ROCK OCD knee arthroscopy classification system demonstrated excellent intra- and interobserver reliability. In light of this reliability, this classification system may be used clinically and to facilitate future research, including multicenter studies for OCD. © American Orthopaedic Society for Sports Medicine.
20.	Chen, Chen, et al. (författare) Long-range ion-water and ion-ion interactions in aqueous solutions 2015 Ingår i: Physical Chemistry, Chemical Physics - PCCP. - : Royal Society of Chemistry (RSC). - 1463-9076 .- 1463-9084. ; 17:13, s. 8427-8430 Tidskriftsartikel (refereegranskat)abstract Using small-angle X-ray scattering (SAXS), we obtained direct experimental evidence on the structure of hydrated polyatomic anions, with hydration effects starkly different from those of cations (J. Chem. Phys., 2011, 134, 064513). We propose that the size and charge density of the naked ions do not sufficiently account for the differences in the SAXS curves. For cations, the ion-ion contribution gives a prominent first-order diffraction peak, whereas for anions, the low-Q enhancement in the SAXS curves indicates density inhomogeneities as a result of ion-water interactions.
21.	Chen, Chen, et al. (författare) Solvation structures of protons and hydroxide ions in water 2013 Ingår i: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 138:15, s. 154506- Tidskriftsartikel (refereegranskat)abstract X-ray Raman spectroscopy (XRS) combined with small-angle x-ray scattering (SAXS) were used to study aqueous solutions of HCl and NaOH. Hydrated structures of H+ and OH- are not simple mirror images of each other. While both ions have been shown to strengthen local hydrogen bonds in the hydration shell as indicated by XRS, SAXS suggests that H+ and OH- have qualitatively different long-range effects. The SAXS structure factor of HCl (aq) closely resembles that of pure water, while NaOH (aq) behaves similar to NaF (aq). We propose that protons only locally enhance hydrogen bonds while hydroxide ions induce tetrahedrality in the overall hydrogen bond network of water.
22.	da Silva, G. M., et al. (författare) The effect of diverticular disease on the colonic J pouch 2004 Ingår i: Colorectal disease. - 1462-8910. ; 6:3, s. 171-5 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE: The aim of this study was to assess the impact of the diverticular disease (DD) on function and on postoperative complications of the colonic J-pouch (CJP) with pouch-anal anastomosis. METHODS: Patients who underwent a CJP between December 1990 and August 2001, were retrospectively reviewed. The presence of DD in the CJP was assessed on pouchogram prior to ileostomy closure. A questionnaire designed to evaluate the degree of continence (total incontinence score (IS): 0 = worst, 20 = best) and pouch evacuation (total evacuation score (ES): 0 = worst, 28 = best) was used for comparison between patients with DD and those without DD (NDD). RESULTS: Sixty-six patients (47 males; 19 females) with a median age of 68 years (range 28-87 years) were included. The median follow-up period was 22 months (range 2-106 months). Twenty-four patients comprised the DD group and 42 were in the NDD group. The two groups were comparable for age, gender and time from ileostomy closure; all patients with postoperative chemoradiation therapy were in the NDD group. The total ES and IS total did not significantly differ between the two groups with a P-value of 0.11 and 0.09 respectively. Furthermore, there was no significant difference in the total incidence of pouch complications between the two groups (3 strictures, 1 leak, 1 fistula in the NDD group vs. 1 pelvic sepsis in the DD group; P = 0.4). CONCLUSIONS: The presence of DD in a CJP does not seem to impact pouch function or the postoperative complication rate.
23.	da Silva, Giovanna M, et al. (författare) The efficacy of a nerve stimulator (CaverMap) to enhance autonomic nerve identification and confirm nerve preservation during total mesorectal excision. 2004 Ingår i: Diseases of the colon and rectum. - : Ovid Technologies (Wolters Kluwer Health). - 0012-3706. ; 47:12, s. 2032-8 Tidskriftsartikel (refereegranskat)abstract PURPOSE: Sexual dysfunction after total mesorectal excision may be caused by injury to the autonomic nerves. During surgery, nerve identification is not always achieved, and, to date, there has been no method to objectively confirm nerve preservation. The aim of this study was to assess the efficacy of a nerve-stimulating device (CaverMap) to assist in the intraoperative identification of the autonomic nerves during total mesorectal excision, and objectively confirm nerve preservation after proctectomy is completed. PATIENTS AND METHODS: Sexually active consecutive male patients undergoing total mesorectal excision were prospectively enrolled in this study. During pelvic dissection, the surgeon attempted to localize the hypogastric and cavernous nerves. CaverMap was used to confirm these findings and to facilitate the identification in cases of uncertainty. At the completion of proctectomy, the nerves were restimulated to ensure preservation. Factors that could affect the surgeon's ability to localize the nerves and CaverMap to confirm this were evaluated. RESULTS: Twenty-nine male patients with a median age of 58 years were enrolled in this study. An attempt to visualize the hypogastric nerves during dissection was made in 26 patients; the surgeon was able to identify the nerves in 19 (73 percent) patients. CaverMap successfully identified the nerves in six of the seven remaining patients, and failed to identify them in only one case. An attempt to localize the cavernous nerves during dissection was made in 13 patients, of which localization was successful in 8 (61.5 percent) patients. CaverMap improved the identification rate in four of the remaining five patients. After proctectomy, CaverMap successfully confirmed the preservation of both hypogastric and cavernous nerves in 27 of 29 (93 percent) patients. A history of previous surgery statistically correlated with failure to identify the hypogastric nerves by the surgeon (P = 0.005). There were no adverse events related to use of the device. CONCLUSION: CaverMap may be a useful tool to facilitate identification of the pelvic autonomic nerves during total mesorectal excision and to objectively confirm nerve preservation.
24.	Feigin, Valery L., et al. (författare) Global, regional, and national burden of neurological disorders, 1990–2016 : a systematic analysis for the Global Burden of Disease Study 2016 2019 Ingår i: Lancet Neurology. - : Elsevier. - 1474-4422 .- 1474-4465. ; 18:5, s. 459-480 Tidskriftsartikel (refereegranskat)abstract Background: Neurological disorders are increasingly recognised as major causes of death and disability worldwide. The aim of this analysis from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 is to provide the most comprehensive and up-to-date estimates of the global, regional, and national burden from neurological disorders.Methods: We estimated prevalence, incidence, deaths, and disability-adjusted life-years (DALYs; the sum of years of life lost [YLLs] and years lived with disability [YLDs]) by age and sex for 15 neurological disorder categories (tetanus, meningitis, encephalitis, stroke, brain and other CNS cancers, traumatic brain injury, spinal cord injury, Alzheimer's disease and other dementias, Parkinson's disease, multiple sclerosis, motor neuron diseases, idiopathic epilepsy, migraine, tension-type headache, and a residual category for other less common neurological disorders) in 195 countries from 1990 to 2016. DisMod-MR 2.1, a Bayesian meta-regression tool, was the main method of estimation of prevalence and incidence, and the Cause of Death Ensemble model (CODEm) was used for mortality estimation. We quantified the contribution of 84 risks and combinations of risk to the disease estimates for the 15 neurological disorder categories using the GBD comparative risk assessment approach.Findings: Globally, in 2016, neurological disorders were the leading cause of DALYs (276 million [95% UI 247–308]) and second leading cause of deaths (9·0 million [8·8–9·4]). The absolute number of deaths and DALYs from all neurological disorders combined increased (deaths by 39% [34–44] and DALYs by 15% [9–21]) whereas their age-standardised rates decreased (deaths by 28% [26–30] and DALYs by 27% [24–31]) between 1990 and 2016. The only neurological disorders that had a decrease in rates and absolute numbers of deaths and DALYs were tetanus, meningitis, and encephalitis. The four largest contributors of neurological DALYs were stroke (42·2% [38·6–46·1]), migraine (16·3% [11·7–20·8]), Alzheimer's and other dementias (10·4% [9·0–12·1]), and meningitis (7·9% [6·6–10·4]). For the combined neurological disorders, age-standardised DALY rates were significantly higher in males than in females (male-to-female ratio 1·12 [1·05–1·20]), but migraine, multiple sclerosis, and tension-type headache were more common and caused more burden in females, with male-to-female ratios of less than 0·7. The 84 risks quantified in GBD explain less than 10% of neurological disorder DALY burdens, except stroke, for which 88·8% (86·5–90·9) of DALYs are attributable to risk factors, and to a lesser extent Alzheimer's disease and other dementias (22·3% [11·8–35·1] of DALYs are risk attributable) and idiopathic epilepsy (14·1% [10·8–17·5] of DALYs are risk attributable).Interpretation: Globally, the burden of neurological disorders, as measured by the absolute number of DALYs, continues to increase. As populations are growing and ageing, and the prevalence of major disabling neurological disorders steeply increases with age, governments will face increasing demand for treatment, rehabilitation, and support services for neurological disorders. The scarcity of established modifiable risks for most of the neurological burden demonstrates that new knowledge is required to develop effective prevention and treatment strategies.Funding: Bill & Melinda Gates Foundation.
25.	Fernström, Anders, et al. (författare) Achievement of recommended treatment targets for bone and mineral metabolism in haemodialysis patients using paricalcitol : An observational study 2011 Ingår i: Scandinavian Journal of Urology and Nephrology. - : Informa UK Limited. - 0036-5599 .- 1651-2065. ; 45:3, s. 196-205 Tidskriftsartikel (refereegranskat)abstract Objective. Secondary hyperparathyroidism (SHPT) is a common problem among patients with chronic kidney disease (CKD) on haemodialysis. This study was conducted to assess the use, effectiveness and safety of intravenous paricalcitol in haemodialysis patients with various degrees of SHPT. Material and methods. This observational, multicentre, prospective study was conducted in 14 Swedish dialysis centres from May 2007 to June 2008 and included 92 haemodialysis patients with a diagnosis of SHPT associated with CKD. The decision to initiate treatment with intravenous paricalcitol was made by the treating physician. No treatment algorithms were provided. Results. Mean patient age was 64 years. Of the 92 patients included, 74 had an intact parathyroid hormone (iPTH) level of > 300 pg/ml at baseline. Median iPTH was 584 pg/ml in patients with a baseline PTH of > 300 pg/ml. During follow-up there was a decrease in iPTH to 323 pg/ml at 6 months (--45%, p < 0.0001). In parallel, there was a small increase in serum calcium, but serum phosphorus and the calcium xx phosphorus product remained unchanged. Conclusions. This study showed that intravenous paricalcitol substantially and safely decreased iPTH in haemodialysis patients with a baseline iPTH above the Kidney Disease Outcomes Quality Initiative recommended target range (150--300 pg/ml) and had minimal impact on serum minerals.
26.	Fernström, Anders, et al. (författare) Hemodiafiltration - för och emot 2013 Ingår i: Vaskulär medicin. - Linköping : Svensk förening för hypertoni, stroke och vaskulär medicin. - 2000-3188. ; 29:3, s. 142-144 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract ESHOL-studien är den första RCT som visat skillnad i mortalitet mellan två dialysmetoder. Studiens resultat styrks av de två post hoc-analyserna från CONTRAST-studien och den turkiska studien som båda visat ökad överlevnad i grupper med hög ultrafiltrerad volym. Resultatet torde innebära ökad användning av högvolyms OL-HDF-behandling vid de dialysenheter som har möjlighet att utföra detta.
27.	Gakidou, E., et al. (författare) Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016 2017 Ingår i: Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 390:10100, s. 1345-1422 Tidskriftsartikel (refereegranskat)abstract Background The Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) provides a comprehensive assessment of risk factor exposure and attributable burden of disease. By providing estimates over a long time series, this study can monitor risk exposure trends critical to health surveillance and inform policy debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2016. This study included 481 risk-outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk (RR) and exposure estimates from 22 717 randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources, according to the GBD 2016 source counting methods. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. Finally, we explored four drivers of trends in attributable burden: population growth, population ageing, trends in risk exposure, and all other factors combined. Findings Since 1990, exposure increased significantly for 30 risks, did not change significantly for four risks, and decreased significantly for 31 risks. Among risks that are leading causes of burden of disease, child growth failure and household air pollution showed the most significant declines, while metabolic risks, such as body-mass index and high fasting plasma glucose, showed significant increases. In 2016, at Level 3 of the hierarchy, the three leading risk factors in terms of attributable DALYs at the global level for men were smoking (124.1 million DALYs [95% UI 111.2 million to 137.0 million]), high systolic blood pressure (122.2 million DALYs [110.3 million to 133.3 million], and low birthweight and short gestation (83.0 million DALYs [78.3 million to 87.7 million]), and for women, were high systolic blood pressure (89.9 million DALYs [80.9 million to 98.2 million]), high body-mass index (64.8 million DALYs [44.4 million to 87.6 million]), and high fasting plasma glucose (63.8 million DALYs [53.2 million to 76.3 million]). In 2016 in 113 countries, the leading risk factor in terms of attributable DALYs was a metabolic risk factor. Smoking remained among the leading five risk factors for DALYs for 109 countries, while low birthweight and short gestation was the leading risk factor for DALYs in 38 countries, particularly in sub-Saharan Africa and South Asia. In terms of important drivers of change in trends of burden attributable to risk factors, between 2006 and 2016 exposure to risks explains an 9.3% (6.9-11.6) decline in deaths and a 10.8% (8.3-13.1) decrease in DALYs at the global level, while population ageing accounts for 14.9% (12.7-17.5) of deaths and 6.2% (3.9-8.7) of DALYs, and population growth for 12.4% (10.1-14.9) of deaths and 12.4% (10.1-14.9) of DALYs. The largest contribution of trends in risk exposure to disease burden is seen between ages 1 year and 4 years, where a decline of 27.3% (24.9-29.7) of the change in DALYs between 2006 and 2016 can be attributed to declines in exposure to risks. Interpretation Increasingly detailed understanding of the trends in risk exposure and the RRs for each risk-outcome pair provide insights into both the magnitude of health loss attributable to risks and how modification of risk exposure has contributed to health trends. Metabolic risks warrant particular policy attention, due to their large contribution to global disease burden, increasing trends, and variable patterns across countries at the same level of development. GBD 2016 findings show that, while it has huge potential to improve health, risk modification has played a relatively small part in the past decade. Copyright (C) The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
28.	Gao, Yang, et al. (författare) Live Cell FRET Imaging Reveals Amyloid beta-Peptide Oligomerization in Hippocampal Neurons 2021 Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 22:9 Tidskriftsartikel (refereegranskat)abstract Amyloid beta-peptide (A beta) oligomerization is believed to contribute to the neuronal dysfunction in Alzheimer disease (AD). Despite decades of research, many details of A beta oligomerization in neurons still need to be revealed. Forster resonance energy transfer (FRET) is a simple but effective way to study molecular interactions. Here, we used a confocal microscope with a sensitive Airyscan detector for FRET detection. By live cell FRET imaging, we detected A beta 42 oligomerization in primary neurons. The neurons were incubated with fluorescently labeled A beta 42 in the cell culture medium for 24 h. A beta 42 were internalized and oligomerized in the lysosomes/late endosomes in a concentration-dependent manner. Both the cellular uptake and intracellular oligomerization of A beta 42 were significantly higher than for A beta 40. These findings provide a better understanding of A beta 42 oligomerization in neurons.
29.	García-Trabanino, Ramón, et al. (författare) Heat stress, dehydration, and kidney function in sugarcane cutters in El Salvador - A cross-shift study of workers at risk of Mesoamerican nephropathy. 2015 Ingår i: Environmental research. - : Elsevier BV. - 1096-0953 .- 0013-9351. ; 142, s. 746-755 Tidskriftsartikel (refereegranskat)abstract An epidemic of progressive kidney failure afflicts sugarcane workers in Central America. Repeated high-intensity work in hot environments is a possible cause. To assess heat stress, dehydration, biomarkers of renal function and their possible associations. A secondary aim was to evaluate the prevalence of pre-shift renal damage and possible causal factors. Sugarcane cutters (N=189, aged 18–49 years, 168 of them male) from three regions in El Salvador were examined before and after shift. Cross-shift changes in markers of dehydration and renal function were examined and associations with temperature, work time, region, and fluid intake were assessed. Pre-shift glomerular filtration rate was estimated (eGFR) from serum creatinine. The mean work-time was 4 (1.4–11) hours. Mean workday temperature was 34–36 °C before noon, and 39–42 °C at noon. The mean liquid intake during work was 0.8 L per hour. There were statistically significant changes across shift. The mean urine specific gravity, urine osmolality and creatinine increased, and urinary pH decreased. Serum creatinine, uric acid and urea nitrogen increased, while chloride and potassium decreased. Pre-shift serum uric acid levels were remarkably high and pre-shift eGFR was reduced (<60 mL/min) in 23 male workers (14%). The high prevalence of reduced eGFR, and the cross-shift changes are consistent with recurrent dehydration from strenuous work in a hot and humid environment as an important causal factor. The pathophysiology may include decreased renal blood flow, high demands on tubular reabsorption, and increased levels of uric acid.
30.	Graham, SE, et al. (författare) The power of genetic diversity in genome-wide association studies of lipids 2021 Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 600:7890, s. 675- Tidskriftsartikel (refereegranskat)
31.	Haytural, Hazal, et al. (författare) Insights into the changes in the proteome of Alzheimer disease elucidated by a meta-analysis 2021 Ingår i: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 8:1 Tidskriftsartikel (refereegranskat)abstract Mass spectrometry (MS)-based proteomics is a powerful tool to explore pathogenic changes of a disease in an unbiased manner and has been used extensively in Alzheimer disease (AD) research. Here, by performing a meta-analysis of high-quality proteomic studies, we address which pathological changes are observed consistently and therefore most likely are of great importance for AD pathogenesis. We retrieved datasets, comprising a total of 21,588 distinct proteins identified across 857 postmortem human samples, from ten studies using labeled or label-free MS approaches. Our meta-analysis findings showed significant alterations of 757 and 1,195 proteins in AD in the labeled and label-free datasets, respectively. Only 33 proteins, some of which were associated with synaptic signaling, had the same directional change across the individual studies. However, despite alterations in individual proteins being different between the labeled and the label-free datasets, several pathways related to synaptic signaling, oxidative phosphorylation, immune response and extracellular matrix were commonly dysregulated in AD. These pathways represent robust changes in the human AD brain and warrant further investigation.
32.	Ho, Kok Sun, et al. (författare) Ileal pouch anal anastomosis for ulcerative colitis is feasible for septuagenarians. 2006 Ingår i: Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland. - : Wiley. - 1462-8910. ; 8:3, s. 235-8 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE: Proctocolectomy and ileal pouch anal anastomosis (IPAA) has become the standard surgery for patients with mucosal ulcerative colitis (MUC). Although there is no absolute age limitation, there are concerns as to its use in elderly patients due to the risks of potential complications and poor function. The aim of this study was to assess the complications and outcome of patients over the age of 70 years with MUC who underwent IPAA. Results in these patients were compared to the results in a group of patients aged less than 70 years who had IPAA. METHODS: After Institutional Review Board approval, a retrospective review of the medical records of patients with MUC who underwent IPAA was undertaken. These patients were divided into four age groups: <30 years of age, 30-49 years, 50-69 years, >or=70 years. RESULTS: From 1989 to 2001, 330 patients underwent IPAA for preoperative clinical and histopathological and postoperative histopathologically confirmed MUC; 17 were aged>or=70 years. The mean hospital stay was 5.8 (SEM 0.7) days in the patients aged<70 years and 6.0 (SEM 0.4) days in the patients aged>or=70 years (P=0.911). Postoperative complications occurred in 39% of patients>or=70 years and in 40% in the <70 years group (P=0.08). Pouch failure occurred in two (11.8%) patients>or=70 years and in 6 (1.9%)<70 (P=0.2). CONCLUSION: IPAA is a safe and feasible option in MUC patients over the age of 70 with functional results similar to results seen in younger patients.
33.	Huang, Congcong, et al. (författare) Increasing correlation length in bulk supercooled H2O, D2O and NaCl solution determined from small angle x-ray scattering 2010 Ingår i: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 133:13, s. 134504- Tidskriftsartikel (refereegranskat)abstract Using small angle x-ray scattering, we find that the correlation length of bulk liq. water shows a steep increase as temp. decreases at subzero temps. (supercooling) and that it can, similar to the thermodn. response functions, be fitted to a power law. This indicates that the anomalous properties of water are attributable to fluctuations between low- and high-d. regions with rapidly growing av. size upon supercooling. The substitution of H2O with D2O, as well as the addn. of NaCl salt, leads to substantial changes of the power law behavior of the correlation length. Our results are consistent with the proposed existence of a liq.-liq. crit. point in the deeply supercooled region but do not exclude a singularity-free model
34.	Huang, C, et al. (författare) Letter: Reply to Soper et al.: Fluctuations in water around a bimodal distribution of local hydrogen-bonded structural motifs 2010 Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 107:12, s. E45-E45 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract n/a
35.	Huang, Ningdong, et al. (författare) Microscopic Probing of the Size Dependence in Hydrophobic Solvation 2012 Ingår i: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 136:7, s. 074507- Tidskriftsartikel (refereegranskat)abstract A dependence on solute size of the hydrophobic effect has been proposed based on theory and simulations, such that small apolar solutes leave the hydrogen (H-) bonding network in water intact or even strengthened, whereas hydration of larger, nanometer-sized apolar solutes breaks hydrogen bonds and creates a liquid-vapor-like interface around the solutes. Here we report the direct experimental microscopic observation of the small-to-large crossover behavior of hydrophobic effects in aqueous solutions of amphiphilic tetraalkyl-ammonium (CnH2n+1)4N + (TAA) cations with increased side chain length by probing the H-bonding network in water through O K-edge x-ray absorption spectroscopy and the solute-solute interaction using small angle x-ray scattering. These results open for unique experimental opportunities to investigate hydrophobic effects for a range of important processes in chemistry and biology.We report small angle x-ray scattering data demonstrating the direct experimental microscopic observation of the small-to-large crossover behavior of hydrophobic effects in hydrophobic solvation. By increasing the side chain length of amphiphilic tetraalkyl-ammonium (CnH2n+1)4N+ (R4N+) cations in aqueous solution we observe diffraction peaks indicating association between cations at a solute size between 4.4 and 5 Å, which show temperature dependence dominated by hydrophobic attraction. Using O K-edge x-ray absorption we show that small solutes affect hydrogen bonding in water similar to a temperature decrease, while large solutes affect water similar to a temperature increase. Molecular dynamics simulations support, and provide further insight into, the origin of the experimental observations.
36.	Huang, Ningdong, et al. (författare) X-ray Raman scattering provides evidence for interfacial acetonitrile-water dipole interactions in aqueous solutions 2011 Ingår i: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 135:16, s. 164509- Tidskriftsartikel (refereegranskat)abstract Aqueous solutions of acetonitrile (MeCN) have been studied with oxygen K-edge x-ray Raman scattering (XRS) which is found to be sensitive to the interaction between water and MeCN. The changes in the XRS spectra can be attributed to water directly interacting with MeCN and are reproduced by density functional theory calculations on small clusters of water and MeCN. The dominant structural arrangement features dipole interaction instead of H-bonds between the two species as revealed by the XRS spectra combined with spectrum calculations. Small-angle x-ray scattering shows the largest heterogeneity for a MeCN to water ratio of 0.4 in agreement with earlier small-angle neutron scattering data.
37.	Jackson, Victoria E, et al. (författare) Meta-analysis of exome array data identifies six novel genetic loci for lung function. 2018 Ingår i: Wellcome open research. - : F1000 Research Ltd. - 2398-502X. ; 3 Tidskriftsartikel (refereegranskat)abstract Background: Over 90 regions of the genome have been associated with lung function to date, many of which have also been implicated in chronic obstructive pulmonary disease. Methods: We carried out meta-analyses of exome array data and three lung function measures: forced expiratory volume in one second (FEV 1), forced vital capacity (FVC) and the ratio of FEV 1 to FVC (FEV 1/FVC). These analyses by the SpiroMeta and CHARGE consortia included 60,749 individuals of European ancestry from 23 studies, and 7,721 individuals of African Ancestry from 5 studies in the discovery stage, with follow-up in up to 111,556 independent individuals. Results: We identified significant (P<2·8x10 -7) associations with six SNPs: a nonsynonymous variant in RPAP1, which is predicted to be damaging, three intronic SNPs ( SEC24C, CASC17 and UQCC1) and two intergenic SNPs near to LY86 and FGF10. Expression quantitative trait loci analyses found evidence for regulation of gene expression at three signals and implicated several genes, including TYRO3 and PLAU. Conclusions: Further interrogation of these loci could provide greater understanding of the determinants of lung function and pulmonary disease.
38.	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.
39.	Klionsky, Daniel J., et al. (författare) Guidelines for the use and interpretation of assays for monitoring autophagy 2012 Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544 Forskningsöversikt (refereegranskat)abstract In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
40.	Kraja, Aldi T., et al. (författare) New Blood Pressure-Associated Loci Identified in Meta-Analyses of 475000 Individuals 2017 Ingår i: Circulation. - : LIPPINCOTT WILLIAMS & WILKINS. - 1942-325X .- 1942-3268. ; 10:5 Tidskriftsartikel (refereegranskat)abstract Background - Genome-wide association studies have recently identified >400 loci that harbor DNA sequence variants that influence blood pressure (BP). Our earlier studies identified and validated 56 single nucleotide variants (SNVs) associated with BP from meta-analyses of exome chip genotype data. An additional 100 variants yielded suggestive evidence of association.Methods and Results - Here, we augment the sample with 140886 European individuals from the UK Biobank, in whom 77 of the 100 suggestive SNVs were available for association analysis with systolic BP or diastolic BP or pulse pressure. We performed 2 meta-analyses, one in individuals of European, South Asian, African, and Hispanic descent (pan-ancestry, approximate to 475000), and the other in the subset of individuals of European descent (approximate to 423000). Twenty-one SNVs were genome-wide significant (P<5x10(-8) ) for BP, of which 4 are new BP loci: rs9678851 (missense, SLC4A1AP), rs7437940 (AFAP1), rs13303 (missense, STAB1), and rs1055144 (7p15.2). In addition, we identified a potentially independent novel BP-associated SNV, rs3416322 (missense, SYNPO2L) at a known locus, uncorrelated with the previously reported SNVs. Two SNVs are associated with expression levels of nearby genes, and SNVs at 3 loci are associated with other traits. One SNV with a minor allele frequency <0.01, (rs3025380 at DBH) was genome-wide significant.Conclusions - We report 4 novel loci associated with BP regulation, and 1 independent variant at an established BP locus. This analysis highlights several candidate genes with variation that alter protein function or gene expression for potential follow-up.
41.	Langer, Sina M., et al. (författare) A three-dimensional perspective of Daphnia’s swimming behavior with and without predator cues 2019 Ingår i: Limnology and Oceanography. - : Wiley. - 1939-5590 .- 0024-3590. ; 64:4, s. 1515-1525 Tidskriftsartikel (refereegranskat)abstract Behavioral adaptations play an important role in predator–prey interactions as they reduce predation risk. Prey organisms have therefore evolved a tremendous variability in behavioral adaptations. In case of small crustaceans of the genus Daphnia, which are common and important herbivores transferring energy from primary producers to higher trophic levels, such as predatory fish, and insects, altered migration patterns, swarming, or adaptive swimming speeds may increase survival rates. However, hitherto it has been difficult to analyze predator-induced behavioral adaptations as the small body size, as well as the low contrast between the transparent animals and their environment, most often impede behavioral movement analysis of individual animals. Therefore, we worked with a newly established technique providing higher contrast. We tagged daphniids with fluorescent nanoparticles and used a three-dimensional movement analysis system. We analyzed behavioral defense strategies of Daphnia clones from three species against different types of predators by measuring their behavior in presence and absence of predator cues. We analyzed swimming speed, depth selection, and motion patterns of Daphnia, as well as swarming behavior. We observed differences in the general swimming behavior in all analyzed aspects and show that daphniids change their behavioral strategies in the presence of predator cues, e.g., decrease their swimming speed as well as their vertical position or increase their nearest neighbor distance. Based on the observed changes in behavioral patterns, we conclude that the swimming behavior of daphniids may play an important role as inducible defense strategy that has the potential to improve prey survival chances.
42.	Lindholm, Lars H, et al. (författare) Darusentan lowers blood pressure significant on top of multi-drug treatment in patients with resistant hypertension 2009 Ingår i: Journal of Hypertension. - 0263-6352 .- 1473-5598. ; 27:Suppl. 4, s. s167-s168 Tidskriftsartikel (refereegranskat)
43.	Lindholm, Lars H, et al. (författare) Darusentan treatment significantly decreases blood pressure and results in better systolic blood pressure control when added to multi-drug therapy in patients with resistant hypertension 2009 Ingår i: Journal of Human Hypertension. - : Springer Science and Business Media LLC. - 0950-9240 .- 1476-5527. ; 23:10, s. 697-697 Tidskriftsartikel (refereegranskat)
44.	Lumbers, R. T., et al. (författare) The genomics of heart failure: design and rationale of the HERMES consortium 2021 Ingår i: Esc Heart Failure. - : Wiley. - 2055-5822. ; 8:6, s. 5531-5541 Tidskriftsartikel (refereegranskat)abstract Aims The HERMES (HEart failure Molecular Epidemiology for Therapeutic targets) consortium aims to identify the genomic and molecular basis of heart failure. Methods and results The consortium currently includes 51 studies from 11 countries, including 68 157 heart failure cases and 949 888 controls, with data on heart failure events and prognosis. All studies collected biological samples and performed genome-wide genotyping of common genetic variants. The enrolment of subjects into participating studies ranged from 1948 to the present day, and the median follow-up following heart failure diagnosis ranged from 2 to 116 months. Forty-nine of 51 individual studies enrolled participants of both sexes; in these studies, participants with heart failure were predominantly male (34-90%). The mean age at diagnosis or ascertainment across all studies ranged from 54 to 84 years. Based on the aggregate sample, we estimated 80% power to genetic variant associations with risk of heart failure with an odds ratio of >1.10 for common variants (allele frequency > 0.05) and >1.20 for low-frequency variants (allele frequency 0.01-0.05) at P < 5 x 10(-8) under an additive genetic model. Conclusions HERMES is a global collaboration aiming to (i) identify the genetic determinants of heart failure; (ii) generate insights into the causal pathways leading to heart failure and enable genetic approaches to target prioritization; and (iii) develop genomic tools for disease stratification and risk prediction.
45.	Lundgren, Jolanta L, et al. (författare) ADAM10 and BACE1 are localized to synaptic vesicles. 2015 Ingår i: Journal of Neurochemistry. - : Wiley. - 1471-4159 .- 0022-3042. ; 135:3, s. 606-615 Tidskriftsartikel (refereegranskat)abstract Synaptic degeneration and accumulation of the neurotoxic amyloid β-peptide (Aβ) in the brain are hallmarks of Alzheimer disease. Aβ is produced by sequential cleavage of its precursor protein, APP, by the β-secretase BACE1 and γ-secretase. However, Aβ generation is precluded if APP is cleaved by the α-secretase ADAM10 instead of BACE1. We have previously shown that Aβ can be produced locally at the synapse. To study the synaptic localization of the APP processing enzymes we used western blotting to demonstrate that, compared to total brain homogenate, ADAM10 and BACE1 were greatly enriched in synaptic vesicles isolated from rat brain using controlled-pore glass chromatography, whereas Presenilin1 was the only enriched component of the γ-secretase complex. Moreover, we detected ADAM10 activity in synaptic vesicles and enrichment of the intermediate APP-C-terminal fractions (APP-CTFs). We confirmed the western blotting findings using in situ proximity ligation assay to demonstrate close proximity of ADAM10 and BACE1 with the synaptic vesicle marker synaptophysin in intact mouse primary hippocampal neurons. In contrast, only sparse co-localization of active γ-secretase and synaptophysin was detected. These results indicate that the first step of APP processing occurs in synaptic vesicles whereas the final step is more likely to take place elsewhere. This article is protected by copyright. All rights reserved.
46.	Menkveld, Albert J., et al. (författare) Nonstandard Errors 2024 Ingår i: JOURNAL OF FINANCE. - : Wiley-Blackwell. - 0022-1082 .- 1540-6261. ; 79:3, s. 2339-2390 Tidskriftsartikel (refereegranskat)abstract In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty-nonstandard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for more reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants.
47.	Naghavi, M., et al. (författare) Global, regional, and national age-sex specific mortality for 264 causes of death, 1980-2016: a systematic analysis for the Global Burden of Disease Study 2016 2017 Ingår i: Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 390:10100, s. 1151-1210 Tidskriftsartikel (refereegranskat)abstract Background Monitoring levels and trends in premature mortality is crucial to understanding how societies can address prominent sources of early death. The Global Burden of Disease 2016 Study (GBD 2016) provides a comprehensive assessment of cause-specific mortality for 264 causes in 195 locations from 1980 to 2016. This assessment includes evaluation of the expected epidemiological transition with changes in development and where local patterns deviate from these trends. Methods We estimated cause-specific deaths and years of life lost (YLLs) by age, sex, geography, and year. YLLs were calculated from the sum of each death multiplied by the standard life expectancy at each age. We used the GBD cause of death database composed of: vital registration (VR) data corrected for under-registration and garbage coding; national and subnational verbal autopsy (VA) studies corrected for garbage coding; and other sources including surveys and surveillance systems for specific causes such as maternal mortality. To facilitate assessment of quality, we reported on the fraction of deaths assigned to GBD Level 1 or Level 2 causes that cannot be underlying causes of death (major garbage codes) by location and year. Based on completeness, garbage coding, cause list detail, and time periods covered, we provided an overall data quality rating for each location with scores ranging from 0 stars (worst) to 5 stars (best). We used robust statistical methods including the Cause of Death Ensemble model (CODEm) to generate estimates for each location, year, age, and sex. We assessed observed and expected levels and trends of cause-specific deaths in relation to the Socio-demographic Index (SDI), a summary indicator derived from measures of average income per capita, educational attainment, and total fertility, with locations grouped into quintiles by SDI. Relative to GBD 2015, we expanded the GBD cause hierarchy by 18 causes of death for GBD 2016. Findings The quality of available data varied by location. Data quality in 25 countries rated in the highest category (5 stars), while 48, 30, 21, and 44 countries were rated at each of the succeeding data quality levels. Vital registration or verbal autopsy data were not available in 27 countries, resulting in the assignment of a zero value for data quality. Deaths from non-communicable diseases (NCDs) represented 72.3% (95% uncertainty interval [UI] 71.2-73.2) of deaths in 2016 with 19.3% (18.5-20.4) of deaths in that year occurring from communicable, maternal, neonatal, and nutritional (CMNN) diseases and a further 8.43% (8.00-8.67) from injuries. Although age-standardised rates of death from NCDs decreased globally between 2006 and 2016, total numbers of these deaths increased; both numbers and age-standardised rates of death from CMNN causes decreased in the decade 2006-16-age-standardised rates of deaths from injuries decreased but total numbers varied little. In 2016, the three leading global causes of death in children under-5 were lower respiratory infections, neonatal preterm birth complications, and neonatal encephalopathy due to birth asphyxia and trauma, combined resulting in 1.80 million deaths (95% UI 1.59 million to 1.89 million). Between 1990 and 2016, a profound shift toward deaths at older ages occurred with a 178% (95% UI 176-181) increase in deaths in ages 90-94 years and a 210% (208-212) increase in deaths older than age 95 years. The ten leading causes by rates of age-standardised YLL significantly decreased from 2006 to 2016 (median annualised rate of change was a decrease of 2.89%); the median annualised rate of change for all other causes was lower (a decrease of 1.59%) during the same interval. Globally, the five leading causes of total YLLs in 2016 were cardiovascular diseases; diarrhoea, lower respiratory infections, and other common infectious diseases; neoplasms; neonatal disorders; and HIV/AIDS and tuberculosis. At a finer level of disaggregation within cause groupings, the ten leading causes of total YLLs in 2016 were ischaemic heart disease, cerebrovascular disease, lower respiratory infections, diarrhoeal diseases, road injuries, malaria, neonatal preterm birth complications, HIV/AIDS, chronic obstructive pulmonary disease, and neonatal encephalopathy due to birth asphyxia and trauma. Ischaemic heart disease was the leading cause of total YLLs in 113 countries for men and 97 countries for women. Comparisons of observed levels of YLLs by countries, relative to the level of YLLs expected on the basis of SDI alone, highlighted distinct regional patterns including the greater than expected level of YLLs from malaria and from HIV/AIDS across sub-Saharan Africa; diabetes mellitus, especially in Oceania; interpersonal violence, notably within Latin America and the Caribbean; and cardiomyopathy and myocarditis, particularly in eastern and central Europe. The level of YLLs from ischaemic heart disease was less than expected in 117 of 195 locations. Other leading causes of YLLs for which YLLs were notably lower than expected included neonatal preterm birth complications in many locations in both south Asia and southeast Asia, and cerebrovascular disease in western Europe. Interpretation The past 37 years have featured declining rates of communicable, maternal, neonatal, and nutritional diseases across all quintiles of SDI, with faster than expected gains for many locations relative to their SDI. A global shift towards deaths at older ages suggests success in reducing many causes of early death. YLLs have increased globally for causes such as diabetes mellitus or some neoplasms, and in some locations for causes such as drug use disorders, and conflict and terrorism. Increasing levels of YLLs might reflect outcomes from conditions that required high levels of care but for which effective treatments remain elusive, potentially increasing costs to health systems. Copyright (C) The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
48.	Nilsson, Peter, et al. (författare) Ambitiösa amerikanska riktlinjer för riskfaktorkontroll vid diabetes. Har man lagt ribban alltför högt? 2003 Ingår i: Läkartidningen. - 0023-7205. ; 100:1-2, s. 26-30 Tidskriftsartikel (refereegranskat)
49.	Norgren, Lars, 1942-, et al. (författare) PACE : randomized, controlled, multicentre, multinational, phase III study of PLX-PAD for critical limb ischaemia in patients unsuitable for revascularization: randomized clinical trial 2024 Ingår i: British Journal of Surgery. - : Oxford University Press. - 0007-1323 .- 1365-2168. ; 111:2 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Revascularization is the primary treatment modality for chronic limb-threatening ischaemia (CLTI), but is not feasible in all patients. PLX-PAD is an off-the-shelf, placental-derived, mesenchymal stromal cell-like cell therapy. This study aimed to evaluate whether PLX-PAD would increase amputation-free survival in people with CLTI who were not candidates for revascularization.METHODS: People with CLTI and minor tissue loss (Rutherford 5) who were unsuitable for revascularization were entered into a randomized, parallel-group, placebo-controlled, multinational, blinded, trial, in which PLX-PAD was compared with placebo (2 : 1 randomization), with 30 intramuscular injections (0.5 ml each) into the index leg on days 0 and 60. Planned follow-up was 12-36 months, and included vital status, amputations, lesion size, pain and quality-of-life assessments, haemodynamic parameters, and adverse events.RESULTS: Of 213 patients enrolled, 143 were randomized to PLX-PAD and 70 to placebo. Demographics and baseline characteristics were balanced. Most patients were Caucasian (96.2%), male (76.1%), and ambulatory (85.9%). Most patients (76.6%) reported at least one adverse event, which were mostly expected events in CLTI, such as skin ulcer or gangrene. The probability of major amputation or death was similar for placebo and PLX-PAD (33 and 28.6% respectively; HR 0.93, 95% c.i. 0.53 to 1.63; P = 0.788). Revascularization and complete wound healing rates were similar in the two groups. A post hoc analysis of a subpopulation of 121 patients with a baseline haemoglobin A1c level below 6.5% showed improved 12-month amputation-free survival (HR 0.46, 0.21 to 0.99; P = 0.048).CONCLUSION: Although there was no evidence that PLX-PAD reduced amputation-free survival in the entire study population, benefit was observed in patients without diabetes mellitus or whose diabetes was well controlled; this requires confirmation in further studies. Trial registration: NCT03006770 (http://www.clinicaltrials.gov); 2015-005532-18 (EudraCT Clinical Trials register - Search for 2015-005532-18).
50.	Ntalla, Ioanna, et al. (författare) Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction 2020 Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1 Tidskriftsartikel (refereegranskat)abstract The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N=293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease. On the electrocardiogram, the PR interval reflects conduction from the atria to ventricles and also serves as risk indicator of cardiovascular morbidity and mortality. Here, the authors perform genome-wide meta-analyses for PR interval in multiple ancestries and identify 141 previously unreported genetic loci.

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