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Sökning: WFRF:(Olsen Lars)

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2.
  • Guintivano, Jerry, et al. (författare)
  • Meta-Analyses of Genome-Wide Association Studies for Postpartum Depression
  • 2023
  • Ingår i: American Journal of Psychiatry. - : American Psychiatric Association Publishing. - 0002-953X .- 1535-7228. ; 180:12, s. 884-895
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Postpartum depression (PPD) is a common subtype of major depressive disorder (MDD) that is more heritable, yet is understudied in psychiatric genetics. The authors conducted meta-analyses of genome-wide association studies (GWASs) to investigate the genetic architecture of PPD.METHOD: Meta-analyses were conducted on 18 cohorts of European ancestry (17,339 PPD cases and 53,426 controls), one cohort of East Asian ancestry (975 cases and 3,780 controls), and one cohort of African ancestry (456 cases and 1,255 controls), totaling 18,770 PPD cases and 58,461 controls. Post-GWAS analyses included 1) single-nucleotide polymorphism (SNP)-based heritability ([Formula: see text]), 2) genetic correlations between PPD and other phenotypes, and 3) enrichment of the PPD GWAS findings in 27 human tissues and 265 cell types from the mouse central and peripheral nervous system.RESULTS: No SNP achieved genome-wide significance in the European or the trans-ancestry meta-analyses. The [Formula: see text] of PPD was 0.14 (SE=0.02). Significant genetic correlations were estimated for PPD with MDD, bipolar disorder, anxiety disorders, posttraumatic stress disorder, insomnia, age at menarche, and polycystic ovary syndrome. Cell-type enrichment analyses implicate inhibitory neurons in the thalamus and cholinergic neurons within septal nuclei of the hypothalamus, a pattern that differs from MDD.CONCLUSIONS: While more samples are needed to reach genome-wide levels of significance, the results presented confirm PPD as a polygenic and heritable phenotype. There is also evidence that despite a high correlation with MDD, PPD may have unique genetic components. Cell enrichment results suggest GABAergic neurons, which converge on a common mechanism with the only medication approved by the U.S. Food and Drug Administration for PPD (brexanolone).
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  • Iversen, Anne Kristine Servais, et al. (författare)
  • A simple clinical assessment is superior to systematic triage in prediction of mortality in the emergency department
  • 2019
  • Ingår i: Emergency Medicine Journal. - : BMJ. - 1472-0213 .- 1472-0205. ; 36:2, s. 66-71
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective To compare the Danish Emergency Process Triage (DEPT) with a quick clinical assessment (Eyeball triage) as predictors of short-term mortality in patients in the emergency department (ED).Methods The investigation was designed as a prospective cohort study conducted at North Zealand University Hospital. All patient visits to the ED from September 2013 to December 2013 except minor injuries were included. DEPT was performed by nurses. Eyeball triage was a quick non-systematic clinical assessment based on patient appearance performed by phlebotomists. Both triage methods categorised patients as green (not urgent), yellow, orange or red (most urgent). Primary analysis assessed the association between triage level and 30-day mortality for each triage method. Secondary analyses investigated the relation between triage level and 48-hour mortality as well as the agreement between DEPT and Eyeball triage.Results A total of 6383 patient visits were included. DEPT was performed for 6290 (98.5%) and Eyeball triage for 6382 (~100%) of the patient visits. Only patients with both triage assessments were included. The hazard ratio (HR) for 48-hour mortality for patients categorised as yellow was 0.9 (95% CI 0.4 to 1.9) for DEPT compared with 4.2 (95% CI 1.2 to 14.6) for Eyeball triage (green is reference). For orange the HR for DEPT was 2.2 (95% CI 1.1 to 4.4) and 17.1 (95% CI 5.1 to 57.1) for Eyeball triage. For red the HR was 30.9 (95% CI 12.3 to 77.4) for DEPT and 128.7 (95% CI 37.9 to 436.8) for Eyeball triage. For 30-day mortality the HR for patients categorised as yellow was 1.7 (95% CI 1.2 to 2.4) for DEPT and 2.4 (95% CI 1.6 to 3.5) for Eyeball triage. For orange the HR was 2.6 (95% CI 1.8 to 3.6) for DEPT and 7.6 (95% CI 5.1 to 11.2) for Eyeball triage, and for red the HR was 19.1 (95% CI 10.4 to 35.2) for DEPT and 27.1 (95% CI 16.9 to 43.5) for Eyeball triage. Agreement between the two systems was poor (kappa 0.05).Conclusion Agreement between formalised triage and clinical assessment is poor. A simple clinical assessment by phlebotomists is superior to a formalised triage system to predict short-term mortality in ED patients.
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4.
  • Jones, Michael P., et al. (författare)
  • Gastrointestinal recall questionnaires compare poorly with prospective patient diaries for gastrointestinal symptoms : data from population and primary health centre samples
  • 2019
  • Ingår i: European Journal of Gastroenterology and Hepathology. - : Lippincott Williams & Wilkins. - 0954-691X .- 1473-5687. ; 31:2, s. 163-169
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Clinical understanding of gastrointestinal symptoms is commonly based on patient reports of symptom experience. For diagnosis and treatment choices to be appropriate, symptom reports need to be accurate. We examined the agreement between questionnaire recall and prospective diary enumeration of symptoms relevant to the irritable bowel syndrome.Patients and methods: Data are reported from a randomly selected general population sample (n=238) and also a primary healthcare centre (PHC) sample (n=503, 10 PHCs). All the patients completed the questionnaires, which included Rome III-qualifying irritable bowel syndrome items and a stool and symptom diary over either 7 or 14 days. Agreement between retrospective questionnaire reports and prospective diaries was evaluated.Results: Concordance between questionnaires and diaries was highest for the simple construct of the occurrence of abdominal pain, although after adjusting for possible chance, agreement was only moderate in the general population sample. More complex constructs, such as pain relieved by defecation, yielded poorer concordance. In general, concordance was stronger among PHC respondents than in the general population sample.Conclusion: Concordance between questionnaires and diaries was generally poor and related to the complexity of the symptom construct and the type of respondent. The information used to classify individuals based on patient self-report may be unreliable, and therefore, more effort is needed to develop data collection instruments.
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  • Lill, Christina M., et al. (författare)
  • The role of TREM2 R47H as a risk factor for Alzheimer's disease, frontotemporal lobar degeneration, amyotrophic lateral sclerosis, and Parkinson's disease
  • 2015
  • Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 11:12, s. 1407-1416
  • Tidskriftsartikel (refereegranskat)abstract
    • A rare variant in TREM2 (p.R47H, rs75932628) was recently reported to increase the risk of Alzheimer's disease (AD) and, subsequently, other neurodegenerative diseases, i.e. frontotemporal lobar degeneration (FTLD), amyotrophic lateral sclerosis (ALS), and Parkinson's disease (PD). Here we comprehensively assessed TREM2 rs75932628 for association with these diseases in a total of 19,940 previously untyped subjects of European descent. These data were combined with those from 28 published data sets by meta-analysis. Furthermore, we tested whether rs75932628 shows association with amyloid beta (Ab42) and total-tau protein levels in the cerebrospinal fluid (CSF) of 828 individuals with AD or mild cognitive impairment. Our data show that rs75932628 is highly significantly associated with the risk of AD across 24,086 AD cases and 148,993 controls of European descent (odds ratio or OR = 2.71, P = 4.67 x 10(-25)). No consistent evidence for association was found between this marker and the risk of FTLD (OR = 2.24, P = .0113 across 2673 cases/9283 controls), PD (OR 5 1.36, P = .0767 across 8311 cases/79,938 controls) and ALS (OR 5 1.41, P = .198 across 5544 cases/7072 controls). Furthermore, carriers of the rs75932628 risk allele showed significantly increased levels of CSF-total-tau (P = .0110) but not Ab42 suggesting that TREM2's role in AD may involve tau dysfunction. (C) 2015 The Alzheimer's Association.
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7.
  • Lindahl, Lise M., et al. (författare)
  • STAT5 induces miR-21 expression in cutaneous T cell lymphoma
  • 2016
  • Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 7:29, s. 45730-45744
  • Tidskriftsartikel (refereegranskat)abstract
    • In cutaneous T cell lymphomas (CTCL), miR-21 is aberrantly expressed in skin and peripheral blood and displays anti-apoptotic properties in malignant T cells. It is, however, unclear exactly which cells express miR-21 and what mechanisms regulate miR-21. Here, we demonstrate miR-21 expression in situ in both malignant and reactive lymphocytes as well as stromal cells. qRT-PCR analysis of 47 patients with mycosis fungoides (MF) and Sezary Syndrome (SS) confirmed an increased miR- 21 expression that correlated with progressive disease. In cultured malignant T cells miR-21 expression was inhibited by Tofacitinib (CP-690550), a clinical-grade JAK3 inhibitor. Chromatin immunoprecipitation (ChIP) analysis showed direct binding of STAT5 to the miR-21 promoter. Cytokine starvation ex vivo triggered a decrease in miR-21 expression, whereas IL-2 induced an increased miR-21 expression in primary SS T cells and cultured cytokine-dependent SS cells (SeAx). siRNA-mediated depletion of STAT5 inhibited constitutive- and IL-2- induced miR-21 expression in cytokine- independent and dependent T cell lines, respectively. IL-15 and IL-2 were more potent than IL-21 in inducing miR-21 expression in the cytokine-dependent T cells. In conclusion, we provide first evidence that miR-21 is expressed in situ in CTCL skin lesions, induced by IL-2 and IL-15 cytokines, and is regulated by STAT5 in malignant T cells. Thus, our data provide novel evidence for a pathological role of IL-2Rg cytokines in promoting expression of the oncogenic miR-21 in CTCL.
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8.
  • Mellin, P., et al. (författare)
  • Bonding EBM-built blocks of 316L steel, using hot isostatic pressing
  • 2017
  • Ingår i: Proceedings Euro PM 2017: International Powder Metallurgy Congress and Exhibition. - : European Powder Metallurgy Association (EPMA).
  • Konferensbidrag (refereegranskat)abstract
    • To enable production of the First Wall Beam in the ITER fusion reactor; we attempt to join EBM-built blocks of 316L, by Hot Isostatic Pressing (HIP). For highly critical components, EBM-built material is usually HIPed anyway to heal defects such as pores and cracks. Using HIP to simultaneously bond several print-jobs together into a larger component saves time and reduces manufacturing complexity. We found by carrying out this research, that fine surface roughness is an important enabler for a complete bond. The raw printed surfaces that are obtained straight from the Arcam machine (Ra = 19.2 μm) do not enable a good bond. Instead, traditional machining, which in this paper reached Ra = 2.0 μm, enabled a good bond. HIP parameters are also important. The best bond in this study was achieved after increasing holding time from 1 h to 2 h.
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  • Mikulskis, Paulius, et al. (författare)
  • Binding affinities in the SAMPL3 trypsin and host-guest blind tests estimated with the MM/PBSA and LIE methods.
  • 2012
  • Ingår i: Journal of Computer-Aided Molecular Design. - : Springer Science and Business Media LLC. - 1573-4951 .- 0920-654X. ; 26:5, s. 527-541
  • Tidskriftsartikel (refereegranskat)abstract
    • We have estimated affinities for the binding of 34 ligands to trypsin and nine guest molecules to three different hosts in the SAMPL3 blind challenge, using the MM/PBSA, MM/GBSA, LIE, continuum LIE, and Glide score methods. For the trypsin challenge, none of the methods were able to accurately predict the experimental results. For the MM/GB(PB)SA and LIE methods, the rankings were essentially random and the mean absolute deviations were much worse than a null hypothesis giving the same affinity to all ligand. Glide scoring gave a Kendall's τ index better than random, but the ranking is still only mediocre, τ = 0.2. However, the range of affinities is small and most of the pairs of ligands have an experimental affinity difference that is not statistically significant. Removing those pairs improves the ranking metric to 0.4-1.0 for all methods except CLIE. Half of the trypsin ligands were non-binders according to the binding assay. The LIE methods could not separate the inactive ligands from the active ones better than a random guess, whereas MM/GBSA and MM/PBSA were slightly better than random (area under the receiver-operating-characteristic curve, AUC = 0.65-0.68), and Glide scoring was even better (AUC = 0.79). For the first host, MM/GBSA and MM/PBSA reproduce the experimental ranking fairly good, with τ = 0.6 and 0.5, respectively, whereas the Glide scoring was considerably worse, with a τ = 0.4, highlighting that the success of the methods is system-dependent.
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10.
  • Rohrmann, Sabine, et al. (författare)
  • Ethanol intake and risk of lung cancer in the European prospective investigation into cancer and nutrition (EPIC)
  • 2006
  • Ingår i: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 164:11, s. 1103-1114
  • Tidskriftsartikel (refereegranskat)abstract
    • Within the European Prospective Investigation into Cancer and Nutrition (EPIC), the authors examined the association of ethanol intake at recruitment (1,119 cases) and mean lifelong ethanol intake (887 cases) with lung cancer. Information on baseline and past alcohol consumption, lifetime tobacco smoking, diet, and the anthropometric characteristics of 478,590 participants was collected between 1992 and 2000. Cox proportional hazards regression was used to calculate multivariate-adjusted hazard ratios and 95% confidence intervals. Overall, neither ethanol intake at recruitment nor mean lifelong ethanol intake was significantly associated with lung cancer. However, moderate intake (5-14.9 g/day) at recruitment (hazard ratio (HR) = 0.76, 95% confidence interval (CI): 0.63, 0.90) and moderate mean lifelong intake (HR = 0.80, 95% CI: 0.66, 0.97) were associated with a lower lung cancer risk in comparison with low consumption (0.1-4.9 g/day). Compared with low intake, a high (>= 60 g/day) mean lifelong ethanol intake tended to be related to a higher risk of lung cancer (HR = 1.29, 95% CI: 0.93, 1.74), but high intake at recruitment was not. Although there was no overall association between ethanol intake and risk of lung cancer, the authors cannot rule out a lower risk for moderate consumption and a possibly increased risk for high lifelong consumption.
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11.
  • Watson, Hunna J., et al. (författare)
  • Common Genetic Variation and Age of Onset of Anorexia Nervosa
  • 2022
  • Ingår i: BIOLOGICAL PSYCHIATRY: GLOBAL OPEN SCIENCE. - : Elsevier BV. - 2667-1743. ; 2:4, s. 368-378
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Genetics and biology may influence the age of onset of anorexia nervosa (AN). The aims of this study were to determine whether common genetic variation contributes to age of onset of AN and to investigate the genetic associations between age of onset of AN and age at menarche.METHODS: A secondary analysis of the Psychiatric Genomics Consortium genome-wide association study (GWAS) of AN was performed, which included 9335 cases and 31,981 screened controls, all from European ancestries. We conducted GWASs of age of onset, early-onset AN (,13 years), and typical-onset AN, and genetic correlation, genetic risk score, and Mendelian randomization analyses.RESULTS: Two loci were genome-wide significant in the typical-onset AN GWAS. Heritability estimates (single nucleotide polymorphism-h2) were 0.01-0.04 for age of onset, 0.16-0.25 for early-onset AN, and 0.17-0.25 for typical-onset AN. Early-and typical-onset AN showed distinct genetic correlation patterns with putative risk factors for AN. Specifically, early-onset AN was significantly genetically correlated with younger age at menarche, and typical-onset AN was significantly negatively genetically correlated with anthropometric traits. Genetic risk scores for age of onset and early-onset AN estimated from independent GWASs significantly predicted age of onset. Mendelian randomization analysis suggested a causal link between younger age at menarche and early -onset AN.CONCLUSIONS: Our results provide evidence consistent with a common variant genetic basis for age of onset and implicate biological pathways regulating menarche and reproduction.
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12.
  • Abelev, Betty, et al. (författare)
  • Measurement of prompt J/psi and beauty hadron production cross sections at mid-rapidity in pp collisions at root s=7 TeV
  • 2012
  • Ingår i: Journal of High Energy Physics. - 1029-8479. ; :11
  • Tidskriftsartikel (refereegranskat)abstract
    • The ALICE experiment at the LHC has studied J/psi production at mid-rapidity in pp collisions at root s = 7 TeV through its electron pair decay on a data sample corresponding to an integrated luminosity L-int = 5.6 nb(-1). The fraction of J/psi from the decay of long-lived beauty hadrons was determined for J/psi candidates with transverse momentum p(t) > 1,3 GeV/c and rapidity vertical bar y vertical bar < 0.9. The cross section for prompt J/psi mesons, i.e. directly produced J/psi and prompt decays of heavier charmonium states such as the psi(2S) and chi(c) resonances, is sigma(prompt J/psi) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 8.3 +/- 0.8(stat.) +/- 1.1 (syst.)(-1.4)(+1.5) (syst. pol.) mu b. The cross section for the production of b-hadrons decaying to J/psi with p(t) > 1.3 GeV/c and vertical bar y vertical bar < 0.9 is a sigma(J/psi <- hB) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 1.46 +/- 0.38 (stat.)(-0.32)(+0.26) (syst.) mu b. The results are compared to QCD model predictions. The shape of the p(t) and y distributions of b-quarks predicted by perturbative QCD model calculations are used to extrapolate the measured cross section to derive the b (b) over bar pair total cross section and d sigma/dy at mid-rapidity.
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13.
  • Ahlm, Clas, 1956-, et al. (författare)
  • Brain abscess caused by methicillin-resistant Staphylococcus aureus
  • 2000
  • Ingår i: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 32:5, s. 562-563
  • Tidskriftsartikel (refereegranskat)abstract
    • A Swedish tourist was admitted to a Cuban hospital due to epileptic seizures caused by brain tumors. Upon return to Sweden and admission to our hospital, methicillin-resistant Staphylococcus aureus (MRSA) was isolated. He was later considered to be free of MRSA but then developed a brain abscess from which MRSA was isolated.
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  • Almroth, Gabriel, 1953-, et al. (författare)
  • Acute glomerulonephritis associated with streptococcus pyogenes with concomitant spread of streptococcus constellatus in four rural families
  • 2005
  • Ingår i: Upsala Journal of Medical Sciences. - 0300-9734 .- 2000-1967. ; 110:3, s. 217-231
  • Tidskriftsartikel (refereegranskat)abstract
    • We studied history, renal histopathology and microbiology of an epidemic of acute glomerulonephritis associated with throat infections and uncommon culture results in four neighbour families. A 40-year-old man (index patient) was referred to a university hospital for dialysis and kidney biopsy due to a suspected acute glomerulonephritis. An acute tonsillitis had preceded the condition. Penicillin treatment had been started four days before the discovery of renal failure. Throat swabs were positive for β-hemolytic streptococci, group C (GCS). GCS were also found in throat cultures from his wife and two of their children. The bacteria were typed as Streptococcus constellatus. A third child had S. constellatus expressing Lancefield antigen group G. A neighbour and two of his children fell ill the following week with renal involvement. Throat swabs from both these children were positive for S. constellatus. His third child had erythema multiforme and S. constellatus in the throat while a fourth child had β-hemolytic streptococci group A, Streptococcus pyogenes. Kidney biopsies on the index patient and his neighbour showed an acute diffuse prolipherative glomerulonephritis compatible with acute post-streptococcal nephritis and microbiological analysis of renal tissue revealed in both cases S. pyogenes and S. constellatus. The families had had much contact and had consumed unpasteurized milk from our index patient's farm. In four of seven persons in two additional neighbouring families S. constellatus was found in throat swabs during the same month while two persons carried Streptococcus anginosus expressing the Lancefield C antigen. In conclusion spread of S. constellatus coincided with the occurrence of four cases of acute glomerulonephritis. The two biopsied patients had both S. pyogenes and S. constellatus present in renal tissue. The epidemic either suggested that the outbreak of glomerulonephritis was due to S. pyogenes but coincided with the transmission and colonization of S. constellatus or that the S. constellatus strains were highly pathogenic or nephritogenic and that this organism can be transmitted in such cases.
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16.
  • Arking, D. E., et al. (författare)
  • Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization
  • 2014
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 46:8, s. 826-836
  • Tidskriftsartikel (refereegranskat)abstract
    • The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼ 8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD. © 2014 Nature America, Inc.
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  • Axelsson Olsson, Diana, et al. (författare)
  • Acanthamoeba-Campylobacter coculture as a novel method for enrichment of Campylobacter species
  • 2007
  • Ingår i: Applied and Environmental Microbiology. - 0099-2240 .- 1098-5336. ; 73:21, s. 6864-6869
  • Tidskriftsartikel (refereegranskat)abstract
    • In this study, we present a novel method to isolate and enrich low concentrations of Campylobacter pathogens. This method, Acanthamoeba-Campylobacter coculture (ACC), is based on the intracellular survival and multiplication of Campylobacter species in the free-living protozoan Acanthamoeba polyphaga. Four of the Campylobacter species relevant to humans and livestock, Campylobacter jejuni, C. coli, C. lari, and C. hyointestinalis, were effectively enriched by the coculture method, with growth rates comparable to those observed in other Campylobacter enrichment media. Studying six strains of C. jejuni isolated from different sources, we found that all of the strains could be enriched from an inoculum of fewer than 10 bacteria. The sensitivity of the ACC method was not negatively affected by the use of Campylobacter-selective antibiotics in the culture medium, but these were effective in suppressing the growth of seven different bacterial species added at a concentration of 10(4) CFU/ml of each species as deliberate contamination. The ACC method has advantages over other enrichment methods as it is not dependent on a microaerobic milieu and does not require the use of blood or other oxygen-quenching agents. Our study found the ACC method to be a promising tool for the enrichment of Campylobacter species, particularly from water samples with low bacterial concentrations.
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19.
  • Bach, Anders, et al. (författare)
  • Design and synthesis of highly potent and plasma-stable dimeric inhibitors of the PSD-95-NMDA receptor interaction
  • 2009
  • Ingår i: Angewandte Chemie International Edition. - : Wiley-VCH. - 1433-7851 .- 1521-3773. ; 48:51, s. 9685-9689
  • Tidskriftsartikel (refereegranskat)abstract
    • On the double: Dimerization of monomeric peptide ligands towards the PDZ domains of the protein PSD-95 (postsynaptic density 95) leads to potent inhibitors of protein-protein interactions with stability in blood plasma. Optimization of the length of the polyethylene glycol linker results in unprecedented affinity for inhibitors of the PDZ1-2 domain.
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20.
  • Backe, Marie Balslev, et al. (författare)
  • Lysine demethylase inhibition protects pancreatic β cells from apoptosis and improves β-cell function
  • 2018
  • Ingår i: Molecular and Cellular Endocrinology. - : Elsevier BV. - 0303-7207. ; 460, s. 47-56
  • Tidskriftsartikel (refereegranskat)abstract
    • Transcriptional changes control β-cell survival in response to inflammatory stress. Posttranslational modifications of histone and non-histone transcriptional regulators activate or repress gene transcription, but the link to cell-fate signaling is unclear. Inhibition of lysine deacetylases (KDACs) protects β cells from cytokine-induced apoptosis and reduces type 1 diabetes incidence in animals. We hypothesized that also lysine demethylases (KDMs) regulate β-cell fate in response to inflammatory stress.Expression of the demethylase Kdm6B was upregulated by proinflammatory cytokines suggesting a possible role in inflammation-induced β-cell destruction. Inhibition of KDM6 demethylases using the selective inhibitor GSK-J4 protected insulin-producing cells and human and mouse islets from cytokine-induced apoptosis by blunting nuclear factor (NF)-κB signaling and endoplasmic reticulum (ER) stress response gene expression. GSK-J4 furthermore increased expression of insulin gene and glucose-stimulated insulin secretion. Expression of genes regulating purinergic and cytokine ligand-receptor interactions was downregulated following GSK-J4 exposure, while expression of genes involved in cell maintenance and survival was upregulated. These data suggest that KDMs are important regulators of inflammation-induced β-cell dysfunction and death.
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21.
  • Bahls, M., et al. (författare)
  • Progression of conventional cardiovascular risk factors and vascular disease risk in individuals: insights from the PROG-IMT consortium
  • 2020
  • Ingår i: European Journal of Preventive Cardiology. - : Oxford University Press (OUP). - 2047-4873 .- 2047-4881. ; 27:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: Averaged measurements, but not the progression based on multiple assessments of carotid intima-media thickness, (cIMT) are predictive of cardiovascular disease (CVD) events in individuals. Whether this is true for conventional risk factors is unclear. Methods and results: An individual participant meta-analysis was used to associate the annualised progression of systolic blood pressure, total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol with future cardiovascular disease risk in 13 prospective cohort studies of the PROG-IMT collaboration (n = 34,072). Follow-up data included information on a combined cardiovascular disease endpoint of myocardial infarction, stroke, or vascular death. In secondary analyses, annualised progression was replaced with average. Log hazard ratios per standard deviation difference were pooled across studies by a random effects meta-analysis. In primary analysis, the annualised progression of total cholesterol was marginally related to a higher cardiovascular disease risk (hazard ratio (HR) 1.04, 95% confidence interval (CI) 1.00 to 1.07). The annualised progression of systolic blood pressure, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol was not associated with future cardiovascular disease risk. In secondary analysis, average systolic blood pressure (HR 1.20 95% CI 1.11 to 1.29) and low-density lipoprotein cholesterol (HR 1.09, 95% CI 1.02 to 1.16) were related to a greater, while high-density lipoprotein cholesterol (HR 0.92, 95% CI 0.88 to 0.97) was related to a lower risk of future cardiovascular disease events. Conclusion: Averaged measurements of systolic blood pressure, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol displayed significant linear relationships with the risk of future cardiovascular disease events. However, there was no clear association between the annualised progression of these conventional risk factors in individuals with the risk of future clinical endpoints. © The European Society of Cardiology 2019.
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22.
  • Ben Nasr, Abdelhakim, et al. (författare)
  • Assembly of human contact phase factors and release of bradykinin at the surface of curli-expressing Escherichia coli
  • 1996
  • Ingår i: Molecular Microbiology. - 1365-2958. ; 20:5, s. 35-927
  • Tidskriftsartikel (refereegranskat)abstract
    • Previous work has demonstrated that most strains of the human pathogen Streptococcus pyogenes bind kininogens through M protein, a fibrous surface protein and virulence determinant. Here we find that strains of several other pathogenic bacterial species, both Gram-positive and Gram-negative, isolated from patients with sepsis, also bind kininogens, especially kininogen (HK). The most pronounced interaction was seen between HK and Escherichia coli. Among clinical isolates of E. coli, the majority of the enterohaemorrhagic, enterotoxigenic, and sepsis strains, but none of the enteroinvasive and enteropathogenic strains, bound HK. Binding of HK to E. coli correlated with the expression of curli, another fibrous bacterial surface protein, and the binding of HK to purified curli was specific, saturable, and of high affinity; Ka = 9 x 10(7) M-1. Other contact phase proteins such as factor XI, factor XII, and prekallikrein bound to curliated E. coli, but not to an isogenic curli-deficient mutant strain, suggesting that contact phase activation may occur at the surface of curliated bacteria. Kininogens are also precursor molecules of the vasoactive kinins. When incubated with human plasma, curli-expressing bacteria absorbed HK. Addition of purified plasma kallikrein to the HK-loaded bacteria resulted in a rapid and efficient release of bradykinin from surface-bound HK. The assembly of contact phase factors at the surface of pathogenic bacteria and the release of the potent proinflammatory and vasoactive peptide bradykinin, should have a major impact on the host-microbe relationship and may contribute to bacterial pathogenicity and virulence.
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23.
  • Blumel, Edda, et al. (författare)
  • Staphylococcal alpha-toxin tilts the balance between malignant and non-malignant CD4+ T cells in cutaneous T-cell lymphoma
  • 2019
  • Ingår i: Oncoimmunology. - : Taylor & Francis. - 2162-4011 .- 2162-402X. ; 8:11
  • Tidskriftsartikel (refereegranskat)abstract
    • Staphylococcus aureus is implicated in disease progression in cutaneous T-cell lymphoma (CTCL). Here, we demonstrate that malignant T cell lines derived from CTCL patients as well as primary malignant CD4+ T cells from Sézary syndrome patients are considerably more resistant to alpha-toxin-induced cell death than their non-malignant counterparts. Thus, in a subset of Sézary syndrome patients the ratio between malignant and non-malignant CD4+ T cells increases significantly following exposure to alpha-toxin. Whereas toxin-induced cell death is ADAM10 dependent in healthy CD4+ T cells, resistance to alpha-toxin in malignant T cells involves both downregulation of ADAM10 as well as other resistance mechanisms. In conclusion, we provide first evidence that Staphylococcus aureus derived alpha-toxin can tilt the balance between malignant and non-malignant CD4+ T cells in CTCL patients. Consequently, alpha-toxin may promote disease progression through positive selection of malignant CD4+ T cells, identifying alpha-toxin as a putative drug target in CTCL.
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24.
  • Brännström, Jonas, et al. (författare)
  • Acceptable noise level with Danish, Swedish, and non-semantic speech materials.
  • 2012
  • Ingår i: International Journal of Audiology. - : Informa UK Limited. - 1708-8186 .- 1499-2027. ; 51, s. 146-156
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Acceptable noise level (ANL) has been established as a method to quantify the acceptance of background noise while listening to speech presented at the most comfortable level. The aim of the present study was to generate Danish, Swedish, and a non-semantic version of the ANL test and investigate normal-hearing Danish and Swedish subjects' performance on these tests. Design: ANL was measured using Danish and Swedish running speech with two different noises: Speech-weighted amplitude-modulated noise, and multitalker speech babble. ANL was also measured using the non-semantic international speech test signal (ISTS) as speech signal together with the speech-weighted amplitude-modulated noise. The latter condition was identical in both populations. Study sample: Forty Danish and 40 Swedish normal-hearing subjects. Results: In both populations ANL results were similar to previously reported results from American studies. Generally, significant differences were seen between test conditions using different types of noise within ears in each population. Significant differences were seen for ANL across populations, also when the non-semantic ISTS was used as speech signal. Conclusions: The present findings indicate that there are extrinsic factors, such as instructions, affecting the ANL results. Summario Objetivo: Se ha establecido el Nivel de Ruido Aceptable (ANL) como un método para cuantifi car la aceptación de ruido de fondo mientras se escucha lenguaje presentado al nivel más confortable. El objetivo de este estudio fue generar las versiones sueca, danesa y una no-semántica de la prueba ANL e investigar el desempeño de sujetos normoyentes daneses y suecos en estas pruebas. Diseño: Se midió el ANL utilizando un discurso continuo en danés y sueco con dos diferentes ruidos: ruido con amplitud modulada en el rango del lenguaje y balbuceo de varios hablantes. También se midió el ANL utilizando la prueba internacional no-semántica de señal de lenguaje (ISTS) como la señal lingüística junto con ruido con amplitud modulada en el rango del lenguaje. Esta última condición fue idéntica en ambas poblaciones. Muestra: Cuarenta sujetos daneses y 40 sujetos suecos normoyentes. Resultados: en ambas poblaciones los resultados de ANL fueron muy similares a los reportado previamente en estudios americanos. Generalmente, se vieron diferencias signifi cativas para el ANL entre poblaciones, también cuando el ISTS no semántico fue utilizado como señal lingüística. Conclusiones: Estos hallazgos indican que hay factores extrínsecos tales como las instrucciones, que afectan los resultados de ANL.
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25.
  • Brännström, Jonas, et al. (författare)
  • Prediction of IOI-HA Scores Using Speech Reception Thresholds and Speech Discrimination Scores in Quiet.
  • 2014
  • Ingår i: Journal of the American Academy of Audiology. - : Georg Thieme Verlag KG. - 2157-3107 .- 1050-0545. ; 25:2, s. 154-163
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Outcome measures can be used to improve the quality of the rehabilitation by identifying and understanding which variables influence the outcome. This information can be used to improve outcomes for clients. In clinical practice, pure-tone audiometry, speech reception thresholds (SRTs), and speech discrimination scores (SDSs) in quiet or in noise are common assessments made prior to hearing aid (HA) fittings. It is not known whether SRT and SDS in quiet relate to HA outcome measured with the International Outcome Inventory for Hearing Aids (IOI-HA). Purpose: The aim of the present study was to investigate the relationship between pure-tone average (PTA), SRT, and SDS in quiet and IOI-HA in both first-time and experienced HA users. Research Design: SRT and SDS were measured in a sample of HA users who also responded to the IOI-HA. Study Sample: Fifty-eight Danish-speaking adult HA users. Data Collection and Analysis: The psychometric properties were evaluated and compared to previous studies using the IOI-HA. The associations and differences between the outcome scores and a number of descriptive variables (age, gender, fitted monaurally/binaurally with HA, first-time/experienced HA users, years of HA use, time since last HA fitting, best ear PTA, best ear SRT, or best ear SDS) were examined. A multiple forward stepwise regression analysis was conducted using scores on the separate IOI-HA items, the global score, and scores on the introspection and interaction subscales as dependent variables to examine whether the descriptive variables could predict these outcome measures. Results: Scores on single IOI-HA items, the global score, and scores on the introspection (items 1, 2, 4, and 7) and interaction (items 3, 5, and 6) subscales closely resemble those previously reported. Multiple regression analysis showed that the best ear SDS predicts about 18-19% of the outcome on items 3 and 5 separately, and about 16% on the interaction subscale (sum of items 3, 5, and 6) Conclusions: The best ears SDS explains some of the variance displayed in the IOI-HA global score and the interaction subscale. The relation between SDS and IOI-HA suggests that a poor unaided SDS might in itself be a limiting factor for the HA rehabilitation efficacy and hence the IOI-HA outcome. The clinician could use this information to align the user's HA expectations to what is within possible reach.
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26.
  • Burisch, Johan, et al. (författare)
  • Occurrence of anaemia in the first year of inflammatory bowel disease in a European population-based inception cohort : An ECCO-EpiCom study
  • 2017
  • Ingår i: Journal of Crohn's & Colitis. - : Oxford University Press. - 1873-9946 .- 1876-4479. ; 11:10, s. 1213-1222
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and aims: Anaemia is an important complication of inflammatory bowel disease (IBD). The aim of this study was to determine the prevalence of anaemia and the practice of anaemia screening during the first year following diagnosis in a European prospective population-based inception cohort.Methods: Newly diagnosed IBD patients were included and followed prospectively for one year in 29 European and 1 Australian centre. Clinical data including demographics, medical therapy, surgery and blood samples were collected. Anaemia was defined according to the World Health Organization.Results: A total of 1,871 patients (CD: 686, 88%; UC: 1,021, 87%; IBDU 164. 81%) were included in the study. The prevalence of anaemia was higher in CD than in UC patients and overall, 49% of CD and 39% of UC patients had at least one instance of anaemia during the first 12 months after diagnosis. UC patients with more extensive disease and those from Eastern European countries, and CD patients with penetrating disease or colonic disease location, had higher risks of anaemia. CD and UC patients in need of none or only mild anti-inflammatory treatment had a lower risk of anaemia. In a significant proportion of patients, anaemia was not assessed until several months after diagnosis, and in almost half of all cases of anaemia a thorough work-up was not performed.Conclusions: Overall, 42% of patients had at least one instance of anaemia during the first year following diagnosis. Most patients were assessed for anaemia regularly; however, a full anaemia work-up was frequently neglected in this community setting.
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27.
  • Buus, Terkild Brink, et al. (författare)
  • Single-cell heterogeneity in Sézary syndrome
  • 2018
  • Ingår i: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 2:16, s. 2115-2126
  • Tidskriftsartikel (refereegranskat)abstract
    • Sezary syndrome (SS) is an aggressive leukemic variant of cutaneous T-cell lymphoma (CTCL) with a median life expectancy of less than 4 years. Although initial treatment responses are often good, the vast majority of patients with SS fail to respond to ongoing therapy. We hypothesize that malignant T cells are highly heterogeneous and harbor subpopulations of SS cells that are both sensitive and resistant to treatment. Here, we investigate the presence of single-cell heterogeneity and resistance to histone deacetylase inhibitors (HDACi) within primary malignant T cells from patients with SS. Using single-cell RNA sequencing and flow cytometry, we find that malignant T cells from all investigated patients with SS display a high degree of single-cell heterogeneity at both the mRNA and protein levels. We show that this heterogeneity divides the malignant cells into distinct subpopulations that can be isolated by their expression of different surface antigens. Finally, we show that treatment with HDACi (suberanilohydroxamic acid and romidepsin) selectively eliminates some subpopulations while leaving other subpopulations largely unaffected. In conclusion, we show that patients with SS display a high degree of single-cell heterogeneity within the malignant T-cell population, and that distinct subpopulations of malignant T cells carry HDACi resistance. Our data point to the importance of understanding the heterogeneous nature of malignant SS cells in each individual patient to design combinational and new therapies to counter drug resistance and treatment failure.
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28.
  • Castell, Alina, et al. (författare)
  • MYCMI-7 : A Small MYC-Binding Compound that Inhibits MYC: MAX Interaction and Tumor Growth in a MYC-Dependent Manner
  • 2022
  • Ingår i: Cancer Research Communications. - : American Association For Cancer Research (AACR). - 2767-9764. ; 2:3, s. 182-201
  • Tidskriftsartikel (refereegranskat)abstract
    • Deregulated expression of MYC family oncogenes occurs frequently in human cancer and is often associated with aggressive disease and poor prognosis. While MYC is a highly warranted target, it has been considered "undruggable," and no specific anti-MYC drugs are available in the clinic. We recently identified molecules named MYCMIs that inhibit the interaction between MYC and its essential partner MAX. Here we show that one of these molecules, MYCMI-7, efficiently and selectively inhibits MYC:MAX and MYCN:MAX interactions in cells, binds directly to recombinant MYC, and reduces MYC-driven transcription. In addition, MYCMI-7 induces degradation of MYC and MYCN proteins. MYCMI-7 potently induces growth arrest/apoptosis in tumor cells in a MYC/MYCN-dependent manner and downregulates the MYC pathway on a global level as determined by RNA sequencing. Sensitivity to MYCMI-7 correlates with MYC expression in a panel of 60 tumor cell lines and MYCMI-7 shows high efficacy toward a collection of patient-derived primary glioblastoma and acute myeloid leukemia (AML) ex vivo cultures. Importantly, a variety of normal cells be- come G1 arrested without signs of apoptosis upon MYCMI-7 treatment. Finally, in mouse tumor models of MYC-driven AML, breast cancer, and MYCN-amplified neuroblastoma, treatment with MYCMI-7 downregu- lates MYC/MYCN, inhibits tumor growth, and prolongs survival through apoptosis with few side effects. In conclusion, MYCMI-7 is a potent and selective MYC inhibitor that is highly relevant for the development into clinically useful drugs for the treatment of MYC-driven cancer.Significance: Our findings demonstrate that the small-molecule MYCMI-7 binds MYC and inhibits interaction between MYC and MAX, thereby ham- pering MYC-driven tumor cell growth in culture and in vivo while sparing normal cells.
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29.
  • Catapano, Filomena, et al. (författare)
  • Swarm Langmuir probes' data quality validation and future improvements
  • 2022
  • Ingår i: Geoscientific Instrumentation, Methods and Data Systems. - : Copernicus Publications. - 2193-0856 .- 2193-0864. ; 11:1, s. 149-162
  • Tidskriftsartikel (refereegranskat)abstract
    • Swarm is the European Space Agency (ESA)'s first Earth observation constellation mission, which was launched in 2013 to study the geomagnetic field and its temporal evolution. Two Langmuir probes aboard each of the three Swarm satellites provide in situ measurements of plasma parameters, which contribute to the study of the ionospheric plasma dynamics. To maintain a high data quality for scientific and technical applications, the Swarm products are continuously monitored and validated via science-oriented diagnostics. This paper presents an overview of the data quality of the Swarm Langmuir probes' measurements. The data quality is assessed by analysing short and long data segments, where the latter are selected to be sufficiently long enough to consider the impact of the solar activity. Langmuir probe data have been validated through comparison with numerical models, other satellite missions, and ground observations. Based on the outcomes from quality control and validation activities conducted by ESA, as well as scientific analysis and feedback provided by the user community, the Swarm products are regularly upgraded. In this paper, we discuss the data quality improvements introduced with the latest baseline, and how the data quality is influenced by the solar cycle. In particular, plasma measurements are more accurate in day-side regions during high solar activity, while electron temperature measurements are more reliable during night side at middle and low latitudes during low solar activity. The main anomalies affecting the Langmuir probe measurements are described, as well as possible improvements in the derived plasma parameters to be implemented in future baselines.
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30.
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31.
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32.
  • Cortes Ruiz, Maria F., et al. (författare)
  • Structure-properties relationships of defined CNF single-networks crosslinked by telechelic PEGs
  • 2024
  • Ingår i: Carbohydrate Polymers. - : Elsevier BV. - 0144-8617 .- 1879-1344. ; 339
  • Tidskriftsartikel (refereegranskat)abstract
    • The high structural anisotropy and colloidal stability of cellulose nanofibrils' enable the creation of self-standing fibrillar hydrogel networks at very low solid contents. Adding methacrylate moieties on the surface of TEMPO oxidized CNFs allows the formation of more robust covalently crosslinked networks by free radical polymerization of acrylic monomers, exploiting the mechanical properties of these networks more efficiently. This technique yields strong and elastic networks but with an undefined network structure. In this work, we use acrylate-capped telechelic polymers derived from the step-growth polymerization of PEG diacrylate and dithiothreitol to crosslink methacrylated TEMPO-oxidized cellulose nanofibrils (MATO CNF). This combination resulted in flexible and strong hydrogels, as observed through rheological studies, compression and tensile loading. The structure and mechanical properties of these hydrogel networks were found to depend on the dimensions of the CNFs and polymer crosslinkers. The structure of the networks and the role of individual components were evaluated with SAXS (Small-Angle X-ray Scattering) and photo-rheology. A thorough understanding of hybrid CNF/polymer networks and how to best exploit the capacity of these networks enable further advancement of cellulose-based materials for applications in packaging, soft robotics, and biomedical engineering.
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33.
  • Cortes Ruiz, Maria F. (författare)
  • Tailoring and Characterization of Polymer-linked Fibrillar Structures
  • 2024
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The development of sustainable and renewable materials is paramount in today’s society. As the most abundant biopolymer on Earth, cellulose from cellulose-rich fibres is an excellent alternative for advanced and innovative material solutions. Nonetheless, competing with the impressive material properties and the low manufacturing costs of fossil-based plastics imposes great challenges. To increase the potential of cellulose fibres in a broader set of applications, the material properties of cellulose need to be tuned depending on the application. An in-depth study of the fibre structure and the application of different tailoring techniques is required to induce tailoring of the physical and chemical properties of the cellulose fibre materials. This thesis focuses on the structure-property relationship of fibrillar hydrogel networks as model structures for the delignified wet-fibre wall. First, a mathematical framework was developed to describe the characteristics of the swelling and mechanical behaviour of anisotropic fibrillar structures, considering the fibril aspect ratio, surface chemistry of the fibrils, and electrolyte concentration in the system. A chemical functionalisation was then introduced to the fibrillar structure, which provided the CNFs with colloidal stability and the ability to participate in free radical polymerisation with monomers and telechelic oligomers. As a result, fibrillar networks were crosslinked with flexible polymer links that provided the network with different mechanical and chemical properties. Additionally, by tailoring the molecular weight of the crosslinks, the ionic strength of the solution, and even the aspect ratio of the fibrils, the mechanical properties of the network were tuned to be either stiffer or more ductile. Finally, an innovative and more sustainable approach was developed to introduce charge and alkene functionality to the fibres. Following the lessons learned from the CNF model investigations, a polymerisation approach was developed in the presence of functionalised fibres. The polymers were grown from the fibre wall, followed by radical crosslinking to create strong Fibre reinforced hydrogel structures. Depending on the application, the method can be easily applied to introduce other types of molecules and functionalities to the fibres and tailor the properties of the fibres to suit a wide range of applications.
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34.
  • Davies, J. I., et al. (författare)
  • Global surgery, obstetric, and anaesthesia indicator definitions and reporting: An Utstein consensus report
  • 2021
  • Ingår i: Plos Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 18:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Indicators to evaluate progress towards timely access to safe surgical, anaesthesia, and obstetric (SAO) care were proposed in 2015 by the Lancet Commission on Global Surgery. These aimed to capture access to surgery, surgical workforce, surgical volume, perioperative mortality rate, and catastrophic and impoverishing financial consequences of surgery. Despite being rapidly taken up by practitioners, data points from which to derive the indicators were not defined, limiting comparability across time or settings. We convened global experts to evaluate and explicitly define-for the first time-the indicators to improve comparability and support achievement of 2030 goals to improve access to safe affordable surgical and anaesthesia care globally. Methods and findings The Utstein process for developing and reporting guidelines through a consensus building process was followed. In-person discussions at a 2-day meeting were followed by an iterative process conducted by email and virtual group meetings until consensus was reached. The meeting was held between June 16 to 18, 2019; discussions continued until August 2020. Participants consisted of experts in surgery, anaesthesia, and obstetric care, data science, and health indicators from high-, middle-, and low-income countries. Considering each of the 6 indicators in turn, we refined overarching descriptions and agreed upon data points needed for construction of each indicator at current time (basic data points), and as each evolves over 2 to 5 (intermediate) and >5 year (full) time frames. We removed one of the original 6 indicators (one of 2 financial risk protection indicators was eliminated) and refined descriptions and defined data points required to construct the 5 remaining indicators: geospatial access, workforce, surgical volume, perioperative mortality, and catastrophic expenditure. A strength of the process was the number of people from global institutes and multilateral agencies involved in the collection and reporting of global health metrics; a limitation was the limited number of participants from low- or middle-income countries-who only made up 21% of the total attendees. Conclusions To track global progress towards timely access to quality SAO care, these indicators-at the basic level-should be implemented universally as soon as possible. Intermediate and full indicator sets should be achieved by all countries over time. Meanwhile, these evolutions can assist in the short term in developing national surgical plans and collecting more detailed data for research studies.
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35.
  • De Frenne, Pieter, et al. (författare)
  • Plant movements and climate warming : intraspecific variation in growth responses to nonlocal soils
  • 2014
  • Ingår i: New Phytologist. - : Wiley. - 0028-646X .- 1469-8137. ; 202:2, s. 431-441
  • Tidskriftsartikel (refereegranskat)abstract
    • Most range shift predictions focus on the dispersal phase of the colonization process. Because moving populations experience increasingly dissimilar nonclimatic environmental conditions as they track climate warming, it is also critical to test how individuals originating from contrasting thermal environments can establish in nonlocal sites. We assess the intraspecific variation in growth responses to nonlocal soils by planting a widespread grass of deciduous forests (Milium effusum) into an experimental common garden using combinations of seeds and soil sampled in 22 sites across its distributional range, and reflecting movement scenarios of up to 1600km. Furthermore, to determine temperature and forest-structural effects, the plants and soils were experimentally warmed and shaded. We found significantly positive effects of the difference between the temperature of the sites of seed and soil collection on growth and seedling emergence rates. Migrant plants might thus encounter increasingly favourable soil conditions while tracking the isotherms towards currently colder' soils. These effects persisted under experimental warming. Rising temperatures and light availability generally enhanced plant performance. Our results suggest that abiotic and biotic soil characteristics can shape climate change-driven plant movements by affecting growth of nonlocal migrants, a mechanism which should be integrated into predictions of future range shifts.
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36.
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37.
  • Docherty, Anna R, et al. (författare)
  • GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors.
  • 2023
  • Ingår i: The American journal of psychiatry. - : American Psychiatric Association Publishing. - 1535-7228 .- 0002-953X. ; 180:10, s. 723-738
  • Tidskriftsartikel (refereegranskat)abstract
    • Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and cross-validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS meta-analysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures.This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses.Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values <5×10-8. These loci were mostly intergenic and implicated DRD2, SLC6A9, FURIN, NLGN1, SOX5, PDE4B, and CACNG2. The multi-ancestry SNP-based heritability estimate of SA was 5.7% on the liability scale (SE=0.003, p=5.7×10-80). Significant brain tissue gene expression and drug set enrichment were observed. There was shared genetic variation of SA with attention deficit hyperactivity disorder, smoking, and risk tolerance after conditioning SA on both major depressive disorder and posttraumatic stress disorder. Genetic causal proportion analyses implicated shared genetic risk for specific health factors.This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical phenotypes. These findings provide insight into genetic factors associated with suicide attempt across ancestry admixture populations, in veteran and civilian populations, and in attempt versus death.
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38.
  • Duffy, J. E., et al. (författare)
  • Biodiversity mediates top-down control in eelgrass ecosystems: a global comparative-experimental approach
  • 2015
  • Ingår i: Ecology Letters. - : Wiley. - 1461-023X .- 1461-0248. ; 18:7, s. 696-705
  • Tidskriftsartikel (refereegranskat)abstract
    • Nutrient pollution and reduced grazing each can stimulate algal blooms as shown by numerous experiments. But because experiments rarely incorporate natural variation in environmental factors and biodiversity, conditions determining the relative strength of bottom-up and top-down forcing remain unresolved. We factorially added nutrients and reduced grazing at 15 sites across the range of the marine foundation species eelgrass (Zostera marina) to quantify how top-down and bottom-up control interact with natural gradients in biodiversity and environmental forcing. Experiments confirmed modest top-down control of algae, whereas fertilisation had no general effect. Unexpectedly, grazer and algal biomass were better predicted by cross-site variation in grazer and eelgrass diversity than by global environmental gradients. Moreover, these large-scale patterns corresponded strikingly with prior small-scale experiments. Our results link global and local evidence that biodiversity and top-down control strongly influence functioning of threatened seagrass ecosystems, and suggest that biodiversity is comparably important to global change stressors.
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39.
  • Eijkelkamp, W. B., et al. (författare)
  • Renal function and risk for cardiovascular events in type 2 diabetic patients with hypertension: the RENAAL and LIFE studies
  • 2007
  • Ingår i: J Hypertens. - 0263-6352. ; 25:4, s. 871-6
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To investigate whether a threshold exists for cardiovascular risk in type 2 diabetic patients with hypertension, the association between renal function and cardiovascular risk was examined across the entire physiological range of serum creatinine. DESIGN AND METHODS: The RENAAL and LIFE studies enrolled 1513 and 1195 patients with type 2 diabetes and hypertension, respectively. The relationship between baseline serum creatinine and the risk for a composite outcome of myocardial infarction, stroke or cardiovascular death was examined using Cox regression models. To adjust for heterogeneity between studies and treatment groups, these factors were included as strata when applicable. The analyses were conducted with adjustment for age, gender, smoking, alcohol use, blood pressure, heart rate, total and high-density lipoprotein (HDL) cholesterol, hemoglobin, albuminuria and prior cardiovascular disease. RESULTS: The hazard ratios across the baseline serum creatinine categories < 0.9 mg/dl, 0.9-1.2 mg/dl, 1.2-1.6 mg/dl, 1.6-2.8 mg/dl and >or= 2.8 mg/dl were 0.51 (95% confidence interval 0.34, 0.74), 0.74 (0.55, 1.00), 1.00 (reference), 1.24 (0.96, 1.59) and 1.67 (1.17, 2.91), respectively. Baseline serum creatinine (per mg/dl) strongly predicted the composite cardiovascular endpoint in LIFE [2.82(1.74,4.56), P < 0.001], RENAAL [1.41(1.12,1.79), P < 0.001], as well as the combined studies [1.51(1.21,1.87), P < 0.001]. CONCLUSION: A progressively higher risk for the composite cardiovascular endpoint was observed with incremental baseline serum creatinine in type 2 diabetic patients with hypertension, even within the normal range. Thus, there appears to be no serum creatinine threshold level for an increased cardiovascular risk. Baseline serum creatinine was a major independent risk factor for cardiovascular disease (www.ClinicalTrials.gov number NCT00308347).
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40.
  • Elden, Helen, 1959, et al. (författare)
  • Effects of acupuncture and stabilising exercises as adjunct to standard treatment in pregnant women with pelvic girdle pain: randomised single blind controlled trial
  • 2005
  • Ingår i: Bmj. ; 330:7494, s. 761-764
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: To compare the efficacy of standard treatment, standard treatment plus acupuncture, and standard treatment plus stabilising exercises for pelvic girdle pain during pregnancy. DESIGN: Randomised single blind controlled trial. Settings East Hospital, Gothenburg, and 27 maternity care centres in Sweden. PARTICIPANTS: 386 pregnant women with pelvic girdle pain. INTERVENTIONS: Treatment for six weeks with standard treatment (n = 130), standard treatment plus acupuncture (n = 125), or standard treatment plus stabilising exercises (n = 131). MAIN OUTCOME MEASURES: Primary outcome measure was pain (visual analogue scale); secondary outcome measure was assessment of severity of pelvic girdle pain by an independent examiner before and after treatment. RESULTS: After treatment the stabilising exercise group had less pain than the standard group in the morning (median difference = 9, 95% confidence interval 1.7 to 12.8; P = 0.0312) and in the evening (13, 2.7 to 17.5; P = 0.0245). The acupuncture group, in turn, had less pain in the evening than the stabilising exercise group (-14, -18.1 to -3.3; P = 0.0130). Furthermore, the acupuncture group had less pain than the standard treatment group in the morning (12, 5.9 to 17.3; P < 0.001) and in the evening (27, 13.3 to 29.5; P < 0.001). Attenuation of pelvic girdle pain as assessed by the independent examiner was greatest in the acupuncture group. CONCLUSION: Acupuncture and stabilising exercises constitute efficient complements to standard treatment for the management of pelvic girdle pain during pregnancy. Acupuncture was superior to stabilising exercises in this study.
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41.
  • Elden, Helen, 1959, et al. (författare)
  • Effects of acupuncture and stabilising exercises as adjunct to standard treatment in pregnant women with pelvic girdle pain: randomised single blind controlled trial
  • 2004
  • Ingår i: The 5th Interdisciplinary World Congress on Low Back Pain & Pelvic Pain”, 2004, Melbourne.. - 9080255149
  • Konferensbidrag (refereegranskat)abstract
    • OBJECTIVES: To compare the efficacy of standard treatment, standard treatment plus acupuncture, and standard treatment plus stabilising exercises for pelvic girdle pain during pregnancy. DESIGN: Randomised single blind controlled trial. Settings East Hospital, Gothenburg, and 27 maternity care centres in Sweden. PARTICIPANTS: 386 pregnant women with pelvic girdle pain. INTERVENTIONS: Treatment for six weeks with standard treatment (n = 130), standard treatment plus acupuncture (n = 125), or standard treatment plus stabilising exercises (n = 131). MAIN OUTCOME MEASURES: Primary outcome measure was pain (visual analogue scale); secondary outcome measure was assessment of severity of pelvic girdle pain by an independent examiner before and after treatment. RESULTS: After treatment the stabilising exercise group had less pain than the standard group in the morning (median difference = 9, 95% confidence interval 1.7 to 12.8; P = 0.0312) and in the evening (13, 2.7 to 17.5; P = 0.0245). The acupuncture group, in turn, had less pain in the evening than the stabilising exercise group (-14, -18.1 to -3.3; P = 0.0130). Furthermore, the acupuncture group had less pain than the standard treatment group in the morning (12, 5.9 to 17.3; P < 0.001) and in the evening (27, 13.3 to 29.5; P < 0.001). Attenuation of pelvic girdle pain as assessed by the independent examiner was greatest in the acupuncture group. CONCLUSION: Acupuncture and stabilising exercises constitute efficient complements to standard treatment for the management of pelvic girdle pain during pregnancy. Acupuncture was superior to stabilising exercises in this study.
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42.
  • Elden, Helen, 1959, et al. (författare)
  • Regression of pelvic girdle pain after delivery: follow-up of a randomised single blind controlled trial with different treatment modalities
  • 2008
  • Ingår i: Acta obstetricia et gynecologica Scandinavica. - : Wiley. - 1600-0412 .- 0001-6349. ; 87:2, s. 201-8
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: An earlier publication showed that acupuncture and stabilising exercises as an adjunct to standard treatment was effective for pelvic girdle pain during pregnancy, but the post-pregnancy effects of these treatment modalities are unknown. The aim of this follow-up study was to describe regression of pelvic girdle pain after delivery in these women. DESIGN: A randomised, single blind, controlled trial. SETTING: East Hospital and 27 maternity care centres in Göteborg, Sweden. POPULATION: Some 386 pregnant women with pelvic girdle pain. METHODS: Participants were randomly assigned to standard treatment plus acupuncture (n=125), standard treatment plus specific stabilising exercises (n=131) or to standard treatment alone (n=130). MAIN OUTCOME MEASURES: Primary outcome measures: pain intensity (Visual Analogue Scale). Secondary outcome measure: assessment of the severity of pelvic girdle pain by an independent examiner 12 weeks after delivery. RESULTS: Approximately three-quarters of all the women were free of pain 3 weeks after delivery. There were no differences in recovery between the 3 treatment groups. According to the detailed physical examination, pelvic girdle pain had resolved in 99% of the women 12 weeks after delivery. CONCLUSIONS: This study shows that irrespective of treatment modality, regression of pelvic girdle pain occurs in the great majority of women within 12 weeks after delivery.
  •  
43.
  • Elden, Helen, 1959, et al. (författare)
  • Regression of pelvic girdle pain after delivery: follow-up of a randomised single blind controlled trial with different treatment modalities
  • 2007
  • Ingår i: The 6th Interdiciplinary World Congress on Low Back Pain & Pelvic Pain, 2007 Barcelona.. - 9080255114
  • Konferensbidrag (refereegranskat)abstract
    • OBJECTIVE: An earlier publication showed that acupuncture and stabilising exercises as an adjunct to standard treatment was effective for pelvic girdle pain during pregnancy, but the post-pregnancy effects of these treatment modalities are unknown. The aim of this follow-up study was to describe regression of pelvic girdle pain after delivery in these women. DESIGN: A randomised, single blind, controlled trial. SETTING: East Hospital and 27 maternity care centres in Göteborg, Sweden. POPULATION: Some 386 pregnant women with pelvic girdle pain. METHODS: Participants were randomly assigned to standard treatment plus acupuncture (n=125), standard treatment plus specific stabilising exercises (n=131) or to standard treatment alone (n=130). MAIN OUTCOME MEASURES: Primary outcome measures: pain intensity (Visual Analogue Scale). Secondary outcome measure: assessment of the severity of pelvic girdle pain by an independent examiner 12 weeks after delivery. RESULTS: Approximately three-quarters of all the women were free of pain 3 weeks after delivery. There were no differences in recovery between the 3 treatment groups. According to the detailed physical examination, pelvic girdle pain had resolved in 99% of the women 12 weeks after delivery. CONCLUSIONS: This study shows that irrespective of treatment modality, regression of pelvic girdle pain occurs in the great majority of women within 12 weeks after delivery.
  •  
44.
  • Elden, Helen, 1959, et al. (författare)
  • Treatment Modalities for Pelvic Girdle Pain in Pregnant Women
  • 2014
  • Ingår i: Journal of Acupuncture and Meridian Studies. - : Medical Association of Pharmacopuncture Institute. - 2005-2901.
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Abstract Background: Pelvic girdle pain (PGP) affects 30 percent of pregnant women. It severely affects pregnant women’s daily lives and causes high costs for society. Methods: Two randomized controlled trials (RCT) compared the efficacies of (1) standard treatment (S) plus acupuncture (ACU), S þ stabilizing exercises (SE), and S alone (nZ386) and (2) penetrating acupuncture (PACU) and non-penetrating sham acupuncture (NPACU) as an adjunct to S in pregnant women (nZ115) with well-defined PGP. Results: ACU, as well as SE, constituted efficient complements to S for PGP during pregnancy. ACU had no observable severe adverse influences on the pregnancy, the mother, the delivery or the fetus/neonate. Regression of PGP after delivery was excellent. Both PACU and NPACU led to clinically relevant decreases in pain. Compared to the NPACU group, the PACU group had superior ability in 7 of 13 daily activities. Conclusion: ACU and SE as adjuncts to standard treatment are effective for treating PGP during pregnancy. Acupuncture is not accompanied by any severe adverse influences on the pregnant women or the fetus/neonate. Regression of PGP occurs in the great majority of women after delivery. PACU had no additional effect on PGP reduction compared to NPACU, but it improved the ability to perform daily activities, keeping more women in regular work. Keywords: pelvic girdle pain; acupuncture; stabilizing exercises; adverse events; regression
  •  
45.
  • Elden, Helen, 1959, et al. (författare)
  • Treatmentmodalities for pelvic girdle pain during pregnancy
  • 2010
  • Ingår i: NMAC, Nordisk akupunktur kongress , Aug 2010, Åland..
  • Konferensbidrag (refereegranskat)abstract
    • Pelvic girdle pain (PGP) affects about 20% of pregnant women. It causes great suffering for the individual and high costs for society. Persisting PGP have been reported in 10 to 75% three months after pregnancy and some women have also stated that PGP has been the beginning of a chronic condition. Risk factors for PGP are history of low back pain, history of PGP or trauma to the pelvis. Available evidence of research of treatment for the condition is insufficient to recommend any particular treatment modality for PGP. Also, the use of acupuncture for PGP is sparse due to insufficient documentation of adverse effects of this treatment in this specific condition. The main purpose of this thesis was to study efficacy, safety and post pregnancy effects of standard treatment, acupuncture and stabilising exercises given to pregnant women with PGP. Based on this knowledge, our ultimate aim is to increase our knowledge about treatment of PGP. METHODS: Paper I reports on a randomised single-blind trial comparing efficacy of standard treatment plus acupuncture, standard treatment plus stabilising exercises and standard treatment alone in 386 pregnant women with diagnosed PGP. Paper II is a follow up study of the original randomised trial in which adverse effects during pregnancy and delivery, influence on the mother, fetus, pregnancy and the pregnancy outcome are reported. Paper III describes regression of PGP during 12 weeks after pregnancy among these women. Paper IV reports on a double-blind randomised trial in which effects of penetrating acupuncture and non-penetrating sham acupuncture as adjunct to standard treatment are compared in 115 pregnant women with diagnosed PGP. The aim with this study was to investigate if specific treatment effects of penetrating acupuncture go beyond effects of non-specific effects and individual attention. RESULTS: Acupuncture as well as stabilising exercises as adjunct to standard treatment constituted efficient complements to standard treatment for the management of PGP during pregnancy. Acupuncture administered with a stimulation that may be considered strong lead to minor adverse complaints on the mothers but had no observable severe adverse influences on the pregnancy, mother, delivery or the fetus/ neonate. Regression of PGP after delivery was excellent with no differences in recovery between the three treatment groups. Both penetrating acupuncture and non-penetrating sham acupuncture lead to clinically relevant decrease of median pain after treatment but there were no significant difference between groups. Those who had received penetrating acupuncture were in regular work to a higher extent than those women that received non-penetrating sham acupuncture. The penetrating acupuncture group had superior ability in 7 of 13 daily activities (dressing; outdoor walks; climbing stairs, standing bent over a sink; running; heavy work and lifting heavy objects) than the non-penetrating sham acupuncture group. CONCLUSION: We have shown that acupuncture and stabilizing exercises as adjunct to standard treatment are effective for PGP during pregnancy. Even if our study was of insufficient size to exclude negative effects on delivery, perinatal morbidity and mortality as well as on CTG the study result adds support to the view that acupuncture even with stimulation that may be considered as strong is not accompanied by any severe adverse influences on the pregnant women or the fetus/neonate. Even if more studies are required, our data provides the most comprehensive data reported to date. Our data suggest that irrespective of treatment modality, regression of PGP occurs in the great majority of women within 12 weeks after delivery. Penetrating acupuncture had no additional effect on PGP reduction compared to non-penetrating sham acupuncture but it improved the ability to perform daily activities keeping more women in regular work. Thus, the data imply that needle penetration contributes to the previously reported beneficial effects of acupuncture
  •  
46.
  • Elden, Helen, 1959, et al. (författare)
  • Treatmentmodalities for pelvic girdle pain during pregnancy
  • 2009
  • Ingår i: Acupuncture in Medicine. ; 27:4
  • Konferensbidrag (refereegranskat)abstract
    • Pelvic girdle pain (PGP) affects about 20% of pregnant women. It causes great suffering for the individual and high costs for society. Persisting PGP have been reported in 10 to 75% three months after pregnancy and some women have also stated that PGP has been the beginning of a chronic condition. Risk factors for PGP are history of low back pain, history of PGP or trauma to the pelvis. Available evidence of research of treatment for the condition is insufficient to recommend any particular treatment modality for PGP. Also, the use of acupuncture for PGP is sparse due to insufficient documentation of adverse effects of this treatment in this specific condition. The main purpose of this thesis was to study efficacy, safety and post pregnancy effects of standard treatment, acupuncture and stabilising exercises given to pregnant women with PGP. Based on this knowledge, our ultimate aim is to increase our knowledge about treatment of PGP. METHODS: Paper I reports on a randomised single-blind trial comparing efficacy of standard treatment plus acupuncture, standard treatment plus stabilising exercises and standard treatment alone in 386 pregnant women with diagnosed PGP. Paper II is a follow up study of the original randomised trial in which adverse effects during pregnancy and delivery, influence on the mother, fetus, pregnancy and the pregnancy outcome are reported. Paper III describes regression of PGP during 12 weeks after pregnancy among these women. Paper IV reports on a double-blind randomised trial in which effects of penetrating acupuncture and non-penetrating sham acupuncture as adjunct to standard treatment are compared in 115 pregnant women with diagnosed PGP. The aim with this study was to investigate if specific treatment effects of penetrating acupuncture go beyond effects of non-specific effects and individual attention. RESULTS: Acupuncture as well as stabilising exercises as adjunct to standard treatment constituted efficient complements to standard treatment for the management of PGP during pregnancy. Acupuncture administered with a stimulation that may be considered strong lead to minor adverse complaints on the mothers but had no observable severe adverse influences on the pregnancy, mother, delivery or the fetus/ neonate. Regression of PGP after delivery was excellent with no differences in recovery between the three treatment groups. Both penetrating acupuncture and non-penetrating sham acupuncture lead to clinically relevant decrease of median pain after treatment but there were no significant difference between groups. Those who had received penetrating acupuncture were in regular work to a higher extent than those women that received non-penetrating sham acupuncture. The penetrating acupuncture group had superior ability in 7 of 13 daily activities (dressing; outdoor walks; climbing stairs, standing bent over a sink; running; heavy work and lifting heavy objects) than the non-penetrating sham acupuncture group. CONCLUSION: We have shown that acupuncture and stabilizing exercises as adjunct to standard treatment are effective for PGP during pregnancy. Even if our study was of insufficient size to exclude negative effects on delivery, perinatal morbidity and mortality as well as on CTG the study result adds support to the view that acupuncture even with stimulation that may be considered as strong is not accompanied by any severe adverse influences on the pregnant women or the fetus/neonate. Even if more studies are required, our data provides the most comprehensive data reported to date. Our data suggest that irrespective of treatment modality, regression of PGP occurs in the great majority of women within 12 weeks after delivery. Penetrating acupuncture had no additional effect on PGP reduction compared to non-penetrating sham acupuncture but it improved the ability to perform daily activities keeping more women in regular work. Thus, the data imply that needle penetration contributes to the previously reported beneficial effects of acupuncture
  •  
47.
  • Elden, Helen, 1959, et al. (författare)
  • Treatmentmodalities for pelvic girdle pain during pregnancy.
  • 2008
  • Ingår i: SFOG (Svensk förening för obstetrik och gynekologi), 2008, Luleå..
  • Konferensbidrag (refereegranskat)abstract
    • Pelvic girdle pain (PGP) affects about 20% of pregnant women. It causes great suffering for the individual and high costs for society. Persisting PGP have been reported in 10 to 75% three months after pregnancy and some women have also stated that PGP has been the beginning of a chronic condition. Risk factors for PGP are history of low back pain, history of PGP or trauma to the pelvis. Available evidence of research of treatment for the condition is insufficient to recommend any particular treatment modality for PGP. Also, the use of acupuncture for PGP is sparse due to insufficient documentation of adverse effects of this treatment in this specific condition. The main purpose of this thesis was to study efficacy, safety and post pregnancy effects of standard treatment, acupuncture and stabilising exercises given to pregnant women with PGP. Based on this knowledge, our ultimate aim is to increase our knowledge about treatment of PGP. METHODS: Paper I reports on a randomised single-blind trial comparing efficacy of standard treatment plus acupuncture, standard treatment plus stabilising exercises and standard treatment alone in 386 pregnant women with diagnosed PGP. Paper II is a follow up study of the original randomised trial in which adverse effects during pregnancy and delivery, influence on the mother, fetus, pregnancy and the pregnancy outcome are reported. Paper III describes regression of PGP during 12 weeks after pregnancy among these women. Paper IV reports on a double-blind randomised trial in which effects of penetrating acupuncture and non-penetrating sham acupuncture as adjunct to standard treatment are compared in 115 pregnant women with diagnosed PGP. The aim with this study was to investigate if specific treatment effects of penetrating acupuncture go beyond effects of non-specific effects and individual attention. RESULTS: Acupuncture as well as stabilising exercises as adjunct to standard treatment constituted efficient complements to standard treatment for the management of PGP during pregnancy. Acupuncture administered with a stimulation that may be considered strong lead to minor adverse complaints on the mothers but had no observable severe adverse influences on the pregnancy, mother, delivery or the fetus/ neonate. Regression of PGP after delivery was excellent with no differences in recovery between the three treatment groups. Both penetrating acupuncture and non-penetrating sham acupuncture lead to clinically relevant decrease of median pain after treatment but there were no significant difference between groups. Those who had received penetrating acupuncture were in regular work to a higher extent than those women that received non-penetrating sham acupuncture. The penetrating acupuncture group had superior ability in 7 of 13 daily activities (dressing; outdoor walks; climbing stairs, standing bent over a sink; running; heavy work and lifting heavy objects) than the non-penetrating sham acupuncture group. CONCLUSION: We have shown that acupuncture and stabilizing exercises as adjunct to standard treatment are effective for PGP during pregnancy. Even if our study was of insufficient size to exclude negative effects on delivery, perinatal morbidity and mortality as well as on CTG the study result adds support to the view that acupuncture even with stimulation that may be considered as strong is not accompanied by any severe adverse influences on the pregnant women or the fetus/neonate. Even if more studies are required, our data provides the most comprehensive data reported to date. Our data suggest that irrespective of treatment modality, regression of PGP occurs in the great majority of women within 12 weeks after delivery. Penetrating acupuncture had no additional effect on PGP reduction compared to non-penetrating sham acupuncture but it improved the ability to perform daily activities keeping more women in regular work. Thus, the data imply that needle penetration contributes to the previously reported beneficial effects of acupuncture
  •  
48.
  • Elden, Helen, 1959, et al. (författare)
  • Treatmentmodalities for pelvic girdle pain during pregnancy
  • 2007
  • Ingår i: Riksstämman, 2007, Göteborg.
  • Konferensbidrag (refereegranskat)abstract
    • Pelvic girdle pain (PGP) affects about 20% of pregnant women. It causes great suffering for the individual and high costs for society. Persisting PGP have been reported in 10 to 75% three months after pregnancy and some women have also stated that PGP has been the beginning of a chronic condition. Risk factors for PGP are history of low back pain, history of PGP or trauma to the pelvis. Available evidence of research of treatment for the condition is insufficient to recommend any particular treatment modality for PGP. Also, the use of acupuncture for PGP is sparse due to insufficient documentation of adverse effects of this treatment in this specific condition. The main purpose of this thesis was to study efficacy, safety and post pregnancy effects of standard treatment, acupuncture and stabilising exercises given to pregnant women with PGP. Based on this knowledge, our ultimate aim is to increase our knowledge about treatment of PGP. METHODS: Paper I reports on a randomised single-blind trial comparing efficacy of standard treatment plus acupuncture, standard treatment plus stabilising exercises and standard treatment alone in 386 pregnant women with diagnosed PGP. Paper II is a follow up study of the original randomised trial in which adverse effects during pregnancy and delivery, influence on the mother, fetus, pregnancy and the pregnancy outcome are reported. Paper III describes regression of PGP during 12 weeks after pregnancy among these women. Paper IV reports on a double-blind randomised trial in which effects of penetrating acupuncture and non-penetrating sham acupuncture as adjunct to standard treatment are compared in 115 pregnant women with diagnosed PGP. The aim with this study was to investigate if specific treatment effects of penetrating acupuncture go beyond effects of non-specific effects and individual attention. RESULTS: Acupuncture as well as stabilising exercises as adjunct to standard treatment constituted efficient complements to standard treatment for the management of PGP during pregnancy. Acupuncture administered with a stimulation that may be considered strong lead to minor adverse complaints on the mothers but had no observable severe adverse influences on the pregnancy, mother, delivery or the fetus/ neonate. Regression of PGP after delivery was excellent with no differences in recovery between the three treatment groups. Both penetrating acupuncture and non-penetrating sham acupuncture lead to clinically relevant decrease of median pain after treatment but there were no significant difference between groups. Those who had received penetrating acupuncture were in regular work to a higher extent than those women that received non-penetrating sham acupuncture. The penetrating acupuncture group had superior ability in 7 of 13 daily activities (dressing; outdoor walks; climbing stairs, standing bent over a sink; running; heavy work and lifting heavy objects) than the non-penetrating sham acupuncture group. CONCLUSION: We have shown that acupuncture and stabilizing exercises as adjunct to standard treatment are effective for PGP during pregnancy. Even if our study was of insufficient size to exclude negative effects on delivery, perinatal morbidity and mortality as well as on CTG the study result adds support to the view that acupuncture even with stimulation that may be considered as strong is not accompanied by any severe adverse influences on the pregnant women or the fetus/neonate. Even if more studies are required, our data provides the most comprehensive data reported to date. Our data suggest that irrespective of treatment modality, regression of PGP occurs in the great majority of women within 12 weeks after delivery. Penetrating acupuncture had no additional effect on PGP reduction compared to non-penetrating sham acupuncture but it improved the ability to perform daily activities keeping more women in regular work. Thus, the data imply that needle penetration contributes to the previously reported beneficial effects of acupuncture
  •  
49.
  • Elden, Helen, 1959, et al. (författare)
  • Treatments of pelvic girdle pain in pregnant women: adverse effects of standard treatment, acupuncture and stabilising exercises on the pregnancy, mother, delivery and the fetus/neonate
  • 2008
  • Ingår i: BMC complementary and alternative medicine. - : Springer Science and Business Media LLC. - 1472-6882. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Previous publications indicate that acupuncture is efficient for the treatment of pelvic girdle pain, PGP, in pregnant women. However, the use of acupuncture for PGP is rare due to insufficient documentation of adverse effects of this treatment in this specific condition. The aim of the present work was to assess adverse effects of acupuncture on the pregnancy, mother, delivery and the fetus/neonate in comparison with women that received stabilising exercises as adjunct to standard treatment or standard treatment alone. METHODS: In all, 386 women with PGP entered this controlled, single-blind trial. They were randomly assigned to standard treatment plus acupuncture (n = 125), standard treatment plus specific stabilising exercises (n = 131) or to standard treatment alone (n = 130) for 6 weeks. Acupuncture that may be considered strong was used and treatment was started as early as in the second trimester of pregnancy. Adverse effects were recorded during treatment and throughout the pregnancy. Influence on the fetus was measured with cardiotocography (CTG) before-during and after 43 acupuncture sessions in 43 women. A standardised computerized method to analyze the CTG reading numerically (Oxford 8000, Oxford, England) was used. After treatment, the women rated their overall experience of the treatment and listed adverse events if any in a questionnaire. Data of analgesia and oxytocin augmentation during labour, duration of labour, frequency of preterm birth, operative delivery, Apgar score, cord-blood gas/acid base balance and birth weight were also recorded. RESULTS: There were no serious adverse events after any of the treatments. Minor adverse events were common in the acupuncture group but women rated acupuncture favourably even despite this. The computerized or visually assessed CTG analyses of antenatal recordings in connection with acupuncture were all normal. CONCLUSION: This study shows that acupuncture administered with a stimulation that may be considered strong led to minor adverse complaints from the mothers but had no observable severe adverse influences on the pregnancy, mother, delivery or the fetus/neonate.
  •  
50.
  • Emdal, Kristina B., et al. (författare)
  • Phosphoproteomics of primary AML patient samples reveals rationale for AKT combination therapy and p53 context to overcome selinexor resistance
  • 2022
  • Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 40:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Acute myeloid leukemia (AML) is a heterogeneous disease with variable patient responses to therapy. Selinexor, an inhibitor of nuclear export, has shown promising clinical activity for AML. To identify the molecular context for monotherapy sensitivity as well as rational drug combinations, we profile selinexor signaling responses using phosphoproteomics in primary AML patient samples and cell lines. Functional phosphosite scoring reveals that p53 function is required for selinexor sensitivity consistent with enhanced efficacy of selinexor in combination with the MDM2 inhibitor nutlin-3a. Moreover, combining selinexor with the AKT inhibitor MK-2206 overcomes dysregulated AKT-FOXO3 signaling in resistant cells, resulting in synergistic anti-proliferative effects. Using high-throughput spatial proteomics to profile subcellular compartments, we measure global proteome and phospho-proteome dynamics, providing direct evidence of nuclear translocation of FOXO3 upon combination treatment. Our data demonstrate the potential of phosphoproteomics and functional phosphorylation site scoring to successfully pinpoint key targetable signaling hubs for rational drug combinations.
  •  
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