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1.
  • Hayes, A., et al. (författare)
  • A European multicentre evaluation of detection and typing methods for human enteroviruses and parechoviruses using RNA transcripts
  • 2020
  • Ingår i: Journal of Medical Virology. - : Wiley. - 0146-6615 .- 1096-9071. ; 92:8, s. 1065-1074
  • Tidskriftsartikel (refereegranskat)abstract
    • Polymerase chain reaction (PCR) detection has become the gold standard for diagnosis and typing of enterovirus (EV) and human parechovirus (HPeV) infections. Its effectiveness depends critically on using the appropriate sample types and high assay sensitivity as viral loads in cerebrospinal fluid samples from meningitis and sepsis clinical presentation can be extremely low. This study evaluated the sensitivity and specificity of currently used commercial and in-house diagnostic and typing assays. Accurately quantified RNA transcript controls were distributed to 27 diagnostic and 12 reference laboratories in 17 European countries for blinded testing. Transcripts represented the four human EV species (EV-A71, echovirus 30, coxsackie A virus 21, and EV-D68), HPeV3, and specificity controls. Reported results from 48 in-house and 15 commercial assays showed 98% detection frequencies of high copy (1000 RNA copies/5 µL) transcripts. In-house assays showed significantly greater detection frequencies of the low copy (10 copies/5 µL) EV and HPeV transcripts (81% and 86%, respectively) compared with commercial assays (56%, 50%; P = 7 × 10−5). EV-specific PCRs showed low cross-reactivity with human rhinovirus C (3 of 42 tests) and infrequent positivity in the negative control (2 of 63 tests). Most or all high copy EV and HPeV controls were successfully typed (88%, 100%) by reference laboratories, but showed reduced effectiveness for low copy controls (41%, 67%). Stabilized RNA transcripts provide an effective, logistically simple and inexpensive reagent for evaluation of diagnostic assay performance. The study provides reassurance of the performance of the many in-house assay formats used across Europe. However, it identified often substantially reduced sensitivities of commercial assays often used as point-of-care tests.
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2.
  • Bosnic-Anticevich, S, et al. (författare)
  • ARIA pharmacy 2018 "Allergic rhinitis care pathways for community pharmacy"
  • 2019
  • Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538 .- 1398-9995. ; 74:7, s. 1219-1236
  • Forskningsöversikt (refereegranskat)abstract
    • Pharmacists are trusted health professionals. Many patients use over-the-counter (OTC) medications and are seen by pharmacists who are the initial point of contact of allergic rhinitis management in most countries. The role of pharmacists in integrated care pathways (ICPs) for allergic diseases is important. This paper builds on existing studies and provides tools intended to help pharmacists provide optimal advice/interventions/strategies to patients with rhinitis. The ARIA-pharmacy ICP includes a diagnostic questionnaire specifically focusing attention on key symptoms and markers of the disease, a systematic Diagnosis Guide (including differential diagnoses) and a simple flowchart with proposed treatment for rhinitis and asthma multimorbidity. Key prompts for referral within the ICP are included. The use of technology is critical to enhance the management of AR. However, the ARIA-pharmacy ICP should be adapted to local health care environments/situations as regional (national) differences exist in pharmacy care.
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3.
  • Wilking, N., et al. (författare)
  • Long-term follow-up of the SBG 9401 study comparing tailored FEC-based therapy versus marrow-supported high-dose therapy
  • 2007
  • Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 18:4, s. 694-700
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The purpose was to investigate adjuvant marrow-supportive high-dose chemotherapy compared with an equitoxicity-tailored comparator arm. Patients and methods: Five hundred and twenty-five women below theage of 60 years with operated high-risk primary breast cancer were randomised to nine cycles of granulocyte colony-stimulating factor supported and individually tailored FEC (5-fluorouracil, epirubicin, cyclophosphamide), (n = 251) or standard FEC followed by marrow-supported high-dose therapy with CTCb (cyclophosphamide, thiotepa, carboplatin) therapy (n = 274), followed by locoregional radiotherapy and tamoxifen for 5 years. Results: There were 104 breast cancer relapses in the tailored FEC group versus 139 in the CTCb group (double triangular method by Whitehead, P = 0.046), with a median follow-up of all included patients of 60.8 months. The event-free survival demonstrated 121 and 150 events in the tailored FEC- and CTCb group, respectively [P = 0.074, hazard ratio (HR) 0.804, 95% confidence interval (CI) 0.633-1.022]. Ten patients in the tailored FEC regimen developed acute myeloid leukaemia (AML)/myelodysplasia (MDS). One hundred deaths occurred in the tailored FEC group and 121 in the CTCb group (P = 0.287, HR 0.866, 95% CI 0.665-1.129). Conclusion: The update of this study shows an improved outcome linked to the tailored FEC treatment in relation to breast cancer relapse, but also an increased incidence of AML/MDS. © 2007 Oxford University Press.
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4.
  • Baratoux, L., et al. (författare)
  • New U–PB baddeleyite ages of mafic dyke swarms of the west African and amazonian cratons : Implication for their configuration in supercontinents through time
  • 2019
  • Ingår i: Springer Geology. - Singapore : Springer Singapore. - 2197-9545 .- 2197-9553. ; , s. 263-314
  • Bokkapitel (refereegranskat)abstract
    • Eight different generations of dolerite dykes crosscutting the Paleoproterozoic basement in West Africa and one in South America were dated using the high precision U–Pb TIMS method on baddeleyite. Some of the individual dykes reach over 300 km in length and they are considered parts of much larger systems of mafic dyke swarms representing the plumbing systems for large igneous provinces (LIPs). The new U–Pb ages obtained for the investigated swarms in the southern West African Craton (WAC) are the following (oldest to youngest): 1791 ± 3 Ma for the N010° Libiri swarm, 1764 ± 4 Ma for the N035° Kédougou swarm, 1575 ± 5 for the N100° Korsimoro swarm, ~1525–1529 Ma for the N130° Essakane swarm, 1521 ± 3 Ma for the N90° Sambarabougou swarm, 915 ± 7 Ma for the N070° Oda swarm, 867 ± 16 Ma for the N355° Manso swarm, 202 ± 5 Ma and 198 ± 16 Ma for the N040° Hounde swarm, and 200 ± 3 Ma for the sills in the Taoudeni basin. The last ones are related to the Central Atlantic Magmatic Province (CAMP) event. The Hounde swarm is oblique to the dominant radiating CAMP swarm and may be linked with the similar-trending elongate Kakoulima intrusion in Guinea. In addition, the N150° Käyser swarm (Amazonian craton, South America) is dated at 1528 ± 2 Ma, providing a robust match with the Essakane swarm in a standard Amazonia-West African craton reconstruction, and resulting in a combined linear swarm >1500 km by >1500 km in extent. The Precambrian LIP barcode ages of c. 1790, 1765–1750, 1575, 1520, 915. 870 Ma for the WAC are compared with the global LIP record to identify possible matches on other crustal blocks, with reconstruction implications. These results contribute to the refinement of the magmatic ‘barcode’ for the West African and Amazonian cratons, representing the first steps towards plausible global paleogeographic reconstructions involving the West African and Amazonian cratons.
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5.
  • Dean, E., et al. (författare)
  • Health Competency Standards in Physical Therapist Practice
  • 2019
  • Ingår i: Physical Therapy. - : NLM (Medline). - 0031-9023 .- 1538-6724. ; 99:9, s. 1242-1254
  • Tidskriftsartikel (refereegranskat)abstract
    • Although the physical therapist profession is the leading established, largely nonpharmacological health profession in the world and is committed to health promotion and noncommunicable disease (NCD) prevention, these have yet to be designated as core physical therapist competencies. Based on findings of 3 Physical Therapy Summits on Global Health, addressing NCDs (heart disease, cancer, hypertension, stroke, diabetes, obesity, and chronic lung disease) has been declared an urgent professional priority. The Third Summit established the status of health competencies in physical therapist practice across the 5 World Confederation for Physical Therapy (WCPT) regions with a view to establish health competency standards, this article's focus. Three general principles related to health-focused practice emerged, along with 3 recommendations for its inclusion. Participants acknowledged that specific competencies are needed to ensure that health promotion and NCD prevention are practiced consistently by physical therapists within and across WCPT regions (ie, effective counseling for smoking cessation, basic nutrition, weight control, and reduced sitting and increased activity/exercise in patients and clients, irrespective of their presenting complaints/diagnoses). Minimum accreditable health competency standards within the profession, including use of the WCPT-supported Health Improvement Card, were recommended for inclusion into practice, entry-to-practice education, and research. Such standards are highly consistent with the mission of the WCPT and the World Health Organization. The physical therapist profession needs to assume a leadership role vis-à-vis eliminating the gap between what we know unequivocally about the causes of and contributors to NCDs and the long-term benefits of effective, sustained, nonpharmacological lifestyle behavior change, which no drug nor many surgical procedures have been reported to match.
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6.
  • Ilander, M, et al. (författare)
  • Increased proportion of mature NK cells is associated with successful imatinib discontinuation in chronic myeloid leukemia.
  • 2017
  • Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 31:5, s. 1108-1116
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent studies suggest that a proportion of chronic myeloid leukemia (CML) patients in deep molecular remission can discontinue the tyrosine kinase inhibitor (TKI) treatment without disease relapse. In this multi-center, prospective clinical trial (EURO-SKI, NCT01596114) we analyzed the function and phenotype of T and NK cells and their relation to successful TKI cessation. Lymphocyte subclasses were measured from 100 imatinib-treated patients at baseline and 1 month after the discontinuation, and functional characterization of NK and T cells was done from 45 patients. The proportion of NK cells was associated with the molecular relapse-free survival as patients with higher than median NK-cell percentage at the time of drug discontinuation had better probability to stay in remission. Similar association was not found with T or B cells or their subsets. In non-relapsing patients the NK-cell phenotype was mature, whereas patients with more naïve CD56(bright) NK cells had decreased relapse-free survival. In addition, the TNF-α/IFN-γ cytokine secretion by NK cells correlated with the successful drug discontinuation. Our results highlight the role of NK cells in sustaining remission and strengthen the status of CML as an immunogenic tumor warranting novel clinical trials with immunomodulating agents.Leukemia advance online publication, 16 December 2016; doi:10.1038/leu.2016.360.
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7.
  • Rogers, C., et al. (författare)
  • Geochemistry and U-Pb geochronology of 1590 and 1550 Ma mafic dyke swarms of western Laurentia : Mantle plume magmatism shared with Australia
  • 2018
  • Ingår i: Lithos. - : Elsevier BV. - 0024-4937. ; 314-315, s. 216-235
  • Tidskriftsartikel (refereegranskat)abstract
    • Three new U–Pb ID-TIMS isotopic ages confirm previous evidence for two geochemically distinct, early Mesoproterozoic pulses of mafic magmatism along the western margin of Laurentia. The first is a U–Pb baddeleyite age of 1590 ± 5 Ma from a dyke swarm in the Tobacco Root Mountains of western Laurentia. It is the first evidence for magmatism of this age in west-central Laurentia. The second is a U–Pb baddeleyite age of 1592.4 ± 2.5 from the Western Channel Diabase, 2000 km to the north in NW Laurentia, which supports two previous U–Pb baddeleyite ages of ca. 1590 Ma for these intrusions. The third is a U–Pb baddeleyite age of 1551 ± 5 Ma, also from the Tobacco Root Mountains, and provides evidence for a distinct younger pulse of mafic magmatism. We propose that the ca. 1590 Ma mafic intrusions in northwestern and west-central Laurentia represent components of a large igneous province (LIP), which we name the “ca. 1590 Ma Mammoth-Western Channel LIP.” This 1590 Ma LIP is geochemically similar to the contemporaneous volcanic rocks in the Gawler Craton and Curnamona Province of Australia. Furthermore, the 1599 Ma Wernecke Breccias near the Western Channel Diabase are geologically similar to the 1590 Ma Olympic Dam Breccias on the South Australian craton. We propose that a mantle plume at ca. 1590 Ma centered between the Laurentian and Southern Australian cratons, located by converging dyke swarms, fed the intrusions on Laurentia plus the Gawler Range Volcanics, the Hiltaba Suite granites and the Ninnerie Supersuite on the South Australian craton. Additionally, magmatic underplating from the plume set up the hydrothermal system responsible for the formation of the Wernecke and Olympic Dam Breccias. The younger 1551 Ma magmatism in the Tobacco Root Mountains, which shows less contamination of a metasomatized subcontinental lithospheric mantle than the older 1590 Ma pulse, may represent an early stage of rifting that pre-dates the ca. 1470 Ma Belt-Purcell Basin extension of western Laurentia. Felsic magmatism, hypothesized to have accompanied the 1590–1550 Ma LIP magmatism, could be a potential source for detrital zircon, thereby reducing the requirement for a non-Laurentian source for detrital zircon ages within the 1610–1490 Ma “North American Magmatic Gap.” Additionally, the 1590 Ma and 1550 Ma ages on western Laurentia dykes provide tighter constraints for previous paleomagnetic studies.
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8.
  • Söderlund, A, et al. (författare)
  • Allergen induced cytokine profiles in type I allergic individuals before and after immunotherapy.
  • 1997
  • Ingår i: Immunology Letters. - 0165-2478 .- 1879-0542. ; 57:1-3, s. 177-81
  • Tidskriftsartikel (refereegranskat)abstract
    • Allergen immunotherapy (IT) involves subcutaneous injections of increasing doses of specific allergen over a period of time. It is recognised as highly effective in the treatment of patients with allergic rhinitis. However, the specific immunological mechanisms by which IT achieves its effect have not been fully elucidated. Recent studies, have shown that the clinical effects following IT of allergic individuals is concomitant with a reduced production of IL-4 by allergen specific CD4+ T-cells. The aim of the present study was to gain better knowledge about the immunological mechanisms by which IT exerts its beneficial effects. For this purpose, peripheral blood mononuclear cells (PBMC) from ten individuals receiving birch allergen or placebo in an IT-study performed in a double-blind manner, were analysed for IL-4, IFN-gamma, IL-5 and IL-10 mRNA expression at the onset of the study and during the pollen season, during treatment. Both spontaneous and in vitro allergen-induced cytokine mRNA expression was analysed using reverse transcriptase-polymerase chain reaction (RT-PCR). Spontaneous expression of IL-4 mRNA could be detected in most of the allergic patients, but not in healthy donors. The IT-treated patients showed a decrease in the spontaneous expression of IL-4 mRNA during the pollen season as compared to at the onset of the study, while in patients receiving placebo the IL-4 mRNA expression increased or remained unchanged. Similar results were obtained after in vitro stimulation with allergen. This was in contrast to the results for IFN-gamma, which was readily detected in both patient groups with no significant differences between the groups at either timepoint. IL-5 was shown to be increased during the pollen season in both groups and thereby presumably not affected by allergen IT. Taken together, these observations suggest that the cytokine profiles in circulating T lymphocytes change as a consequence of allergen IT.
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10.
  • Dolinska, Monika, et al. (författare)
  • Characterization of Bone Marrow Niche in Chronic Myeloid Leukemia Patients Identifies CXCL14 as a New Therapeutic Option
  • 2023
  • Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 142:1, s. 73-89
  • Tidskriftsartikel (refereegranskat)abstract
    • Although tyrosine kinase inhibitors (TKIs) are effective in treating chronic myeloid leukemia (CML), they often fail to eradicate the leukemia-initiating stem cells (LSCs), causing disease persistence and relapse. Evidence indicates that LSC persistence may be because of bone marrow (BM) niche protection; however, little is known about the underlying mechanisms. Herein, we molecularly and functionally characterize BM niches in patients with CML at diagnosis and reveal the altered niche composition and function in these patients. Long-term culture initiating cell assay showed that the mesenchymal stem cells from patients with CML displayed an enhanced supporting capacity for normal and CML BM CD34+CD38- cells. Molecularly, RNA sequencing detected dysregulated cytokine and growth factor expression in the BM cellular niches of patients with CML. Among them, CXCL14 was lost in the BM cellular niches in contrast to its expression in healthy BM. Restoring CXCL14 significantly inhibited CML LSC maintenance and enhanced their response to imatinib in vitro, and CML engraftment in vivo in NSG-SGM3 mice. Importantly, CXCL14 treatment dramatically inhibited CML engraftment in patient-derived xenografted NSG-SGM3 mice, even to a greater degree than imatinib, and this inhibition persisted in patients with suboptimal TKI response. Mechanistically, CXCL14 upregulated inflammatory cytokine signaling but downregulated mTOR signaling and oxidative phosphorylation in CML LSCs. Together, we have discovered a suppressive role of CXCL14 in CML LSC growth. CXCL14 might offer a treatment option targeting CML LSCs.
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11.
  • Grootens, Jennine, et al. (författare)
  • Single-cell analysis reveals the KIT D816V mutation in haematopoietic stem and progenitor cells in systemic mastocytosis
  • 2019
  • Ingår i: EBioMedicine. - : ELSEVIER SCIENCE BV. - 2352-3964. ; 43, s. 150-158
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Systemic mastocytosis (SM) is a haematological disease characterised by organ infiltration by neoplastic mast cells. Almost all SM patients have a mutation in the gene encoding the tyrosine kinase receptor KIT causing a D816V substitution and autoactivation of the receptor. Mast cells and CD34(+) haematopoietic progenitors can carry the mutation: however, in which progenitor cell subset the mutation arises is unknown. We aimed to investigate the distribution of the D816V mutation in single mast cells and single haematopoietic stem and progenitor cells.Methods: Fluorescence-activated single-cell index sorting and KIT D816V mutation assessment were applied to analyse mast cells and >10,000 CD34(+) bone marrow progenitors across 10 haematopoietic progenitor subsets. In vitro assays verified cell-forming potential.Findings: We found that in SM 60-99% of the mast cells harboured the KIT D816V mutation. Despite increased frequencies of mast cells in SM patients compared with control subjects, the haematopoietic progenitor subset frequencies were comparable. Nevertheless, the mutation could be detected throughout the haematopoietic landscape of SM patients, from haematopoietic stem cells to more lineage-primed progenitors. In addition, we demonstrate that Fc epsilon RI+ bone marrow progenitors exhibit mast cell-forming potential, and we describe aberrant CD45RA expression on SM mast cells for the first time.Interpretation: The KIT D816V mutation arises in early haematopoietic stem and progenitor cells and the mutation frequency is approaching 100% in mature mast cells, which express the aberrant marker CD45RA.
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12.
  • Lindstedt, B A, et al. (författare)
  • Use of multilocus variable-number tandem repeat analysis (MLVA) in eight European countries, 2012
  • 2013
  • Ingår i: Eurosurveillance. - : European Centre for Disease Prevention and Control. - 1025-496X .- 1560-7917. ; 18:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Genotyping of important medical or veterinary prokaryotes has become a very important tool during the last decades. Rapid development of fragment-separation and sequencing technologies has made many new genotyping strategies possible. Among these new methods is multilocus variable-number tandem repeat analysis (MLVA). Here we present an update on the use of MLVA in eight European countries (Denmark, France, Germany, Ireland, Italy, the Netherlands, Norway and Sweden). Researchers in Europe have been active in developing and implementing a large array of different assays. MLVA has been used as a typing tool in several contexts, from aiding in resolving outbreaks of foodborne bacteria to typing organisms that may pose a bioterrorist threat, as well as in scientific studies.
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13.
  • Nilsson, Lars-Göran, et al. (författare)
  • Cognitive test battery of CASCADE : Tasks and data.
  • 2005
  • Ingår i: Aging, Neuropsychology and Cognition. - 1382-5585. ; 12:1, s. 32-56
  • Tidskriftsartikel (refereegranskat)abstract
    • This paper presents the cognitive test battery used in the CASCADE Study (Cardiovascular Determinants of Dementia) for examining the consequences of cerebral white matter lesions and atrophy. The test battery includes nine different tasks assessing memory, executive function, and global cognitive function. Three episodic memory tasks were used in combinations to assess the role of attention and speed on encoding. Estimates of short- and long-term memory capacity were also derived from these three memory tasks. Semantic memory production / frontal lobe functions were assessed by means of a word fluency test. The Letter Digit Substitution test and the Stroop test were used to assess speed of processing and attention. Motor speed was measured with the Purdue Pegboard test, and global cognitive function was assessed by the Mini Mental State Examination. Overall performance data for the whole CASCADE sample and for each of eight study centers are presented for each test. Possible reasons for performance differences among study centers are discussed.
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14.
  • Taskinen, M. R., et al. (författare)
  • Adverse effects of fructose on cardiometabolic risk factors and hepatic lipid metabolism in subjects with abdominal obesity
  • 2017
  • Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 282, s. 187-201
  • Tidskriftsartikel (refereegranskat)abstract
    • © 2017 The Association for the Publication of the Journal of Internal Medicine Background: Overconsumption of dietary sugars, fructose in particular, is linked to cardiovascular risk factors such as type 2 diabetes, obesity, dyslipidemia and nonalcoholic fatty liver disease. However, clinical studies have to date not clarified whether these adverse cardiometabolic effects are induced directly by dietary sugars, or whether they are secondary to weight gain. Objectives: To assess the effects of fructose (75 g day −1 ), served with their habitual diet over 12 weeks, on liver fat content and other cardiometabolic risk factors in a large cohort (n = 71) of abdominally obese men. Methods: We analysed changes in body composition, dietary intake, an extensive panel of cardiometabolic risk markers, hepatic de novo lipogenesis (DNL), liver fat content and postprandial lipid responses after a standardized oral fat tolerance test (OFTT). Results: Fructose consumption had modest adverse effects on cardiometabolic risk factors. However, fructose consumption significantly increased liver fat content and hepatic DNL and decreased β-hydroxybutyrate (a measure of β-oxidation). The individual changes in liver fat were highly variable in subjects matched for the same level of weight change. The increase in liver fat content was significantly more pronounced than the weight gain. The increase in DNL correlated positively with triglyceride area under the curve responses after an OFTT. Conclusion: Our data demonstrated adverse effects of moderate fructose consumption for 12 weeks on multiple cardiometabolic risk factors in particular on liver fat content despite only relative low increases in weight and waist circumference. Our study also indicates that there are remarkable individual differences in susceptibility to visceral adiposity/liver fat after real-world daily consumption of fructose-sweetened beverages over 12 weeks.
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15.
  • Abdel-Moneim, Ahmed S., et al. (författare)
  • WSV 2019 : The First Committee Meeting of the World Society for Virology
  • 2020
  • Ingår i: Virologica Sinica. - : Elsevier BV. - 1674-0769 .- 1995-820X. ; 35:2, s. 248-252
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • The World Society for Virology (WSV) was founded and incorporated as a nonprofit organization in the United States in 2017. WSV seeks to strengthen and support both virological research and virologists who conduct research of viruses that affect humans, other animals, plants, and other organisms. One of the objectives of WSV is to connect virologists worldwide and support collaboration. Fulfilling this objective, virologists from fourteen countries in North America, Europe, Africa, Asia, and the Middle East met on 25-27th August 2019 in Stockholm, Sweden at the Karolinska University Hospital for the first Committee Meeting of WSV. This meeting included compelling keynote and honorary speeches and a series of 18 scientific talks were given encompassing a diverse array of subjects within virology. Followed by the scientific session, a business session was held where multiple aspects and next steps of the society were discussed and charted out.
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16.
  • Adiels, Martin, 1976, et al. (författare)
  • Role of apolipoprotein C-III overproduction in diabetic dyslipidaemia
  • 2019
  • Ingår i: Diabetes, obesity and metabolism. - : Wiley. - 1462-8902 .- 1463-1326. ; 21:8, s. 1861-1870
  • Tidskriftsartikel (refereegranskat)abstract
    • - Aims: To investigate how apolipoprotein C-III (apoC-III) metabolism is altered in subjects with type 2 diabetes, whether the perturbed plasma triglyceride concentrations in this condition are determined primarily by the secretion rate or the removal rate of apoC-III, and whether improvement of glycaemic control using the glucagon-like peptide-1 analogue liraglutide for 16 weeks modifies apoC-III dynamics. Materials and Methods: Postprandial apoC-III kinetics were assessed after a bolus injection of [5,5,5- 2 H 3 ]leucine using ultrasensitive mass spectrometry techniques. We compared apoC-III kinetics in two situations: in subjects with type 2 diabetes before and after liraglutide therapy, and in type 2 diabetic subjects with matched body mass index (BMI) non-diabetic subjects. Liver fat content, subcutaneous abdominal and intra-abdominal fat were determined using proton magnetic resonance spectroscopy. Results: Improved glycaemic control by liraglutide therapy for 16 weeks significantly reduced apoC-III secretion rate (561 ± 198 vs. 652 ± 196 mg/d, P = 0.03) and apoC-III levels (10.0 ± 3.8 vs. 11.7 ± 4.3 mg/dL, P = 0.035) in subjects with type 2 diabetes. Change in apoC-III secretion rate was significantly associated with the improvement in indices of glucose control (r = 0.67; P = 0.009) and change in triglyceride area under the curve (r = 0.59; P = 0.025). In line with this, the apoC-III secretion rate was higher in subjects with type 2 diabetes compared with BMI-matched non-diabetic subjects (676 ± 208 vs. 505 ± 174 mg/d, P = 0.042). Conclusions: The results reveal that the secretion rate of apoC-III is associated with elevation of triglyceride-rich lipoproteins in subjects with type 2 diabetes, potentially through the influence of glucose homeostasis on the production of apoC-III. © 2019 John Wiley & Sons Ltd
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17.
  • Andersen, E. S., et al. (författare)
  • Projects and politics : exploring the duality between action and politics in complex projects
  • 2010
  • Ingår i: International Journal of Management and Decision Making. - : InderScience Publishers. - 1462-4621 .- 1741-5187. ; 11:2, s. 121-139
  • Tidskriftsartikel (refereegranskat)abstract
    • Traditional research and literature on project management and organisation theory tend to view project organisations as non-political bodies and purely action-oriented endeavours. In contrast, this paper presents an alternative analysis drawing on the idea of projects as political and emergent processes. Based on in-depth, case-study findings of a complex development and implementation project, we suggest an analytical framework that focuses on the interrelatedness of action and political processes and which explains how project management deals with the two processes simultaneously. We identify and analyse three separate but nested organisational logics applied by the project management team to cope with the dual challenges of politics and action. The general idea is to illustrate the notion of projects as emergent processes involving both politics and action. The three logics are: 1) balancing openness and closure; 2) reformulating tasks to seek solutions; 3) relating to improve action capacity. Our findings add to the literature on the role and practice of project management in complex projects that entail both stakeholder and technological challenges.
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18.
  • Baskici, C., et al. (författare)
  • “Being in the digital box”. Academic staff experiences in online practical teaching : A qualitative study from six universities and countries
  • 2024
  • Ingår i: Heliyon. - : Elsevier. - 2405-8440. ; 10:2
  • Tidskriftsartikel (refereegranskat)abstract
    • The COVID-19 pandemic has caused radical changes in education, as in everything else, bringing many challenges. Despite all the difficulties, the COVID-19 pandemic has enormous opportunities for online teaching and the use of digital technologies. A comprehensive understanding of this period is needed to investigate these opportunities. Thus, this study aims to explore the academic staff's experiences of online teaching and the use of digital technologies in practical skills-based courses in health care education. This study was conducted at six universities from six countries (Türkiye, Sweden, Finland, Portugal, Latvia, Lithuania). Data were collected between June 17, 2021 and November 30, 2021 via a focus group with an in-depth interview technique. 22 focus group interviews were conducted with a total of 117 participants. Colaizzi's method was used to evaluate the data to discover, comprehend, and define the experiences of academic staff. The analysis of the interview data resulted in 6 themes, 25 subthemes and 56 categories that captured participants' experiences regarding online teaching of practical skills and using digital technologies in health care education. The findings of the study provide crucial information that will help online teaching and digital technology for practical skills be successfully integrated.
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20.
  • Christiansson, Lisa, et al. (författare)
  • Increased Level of Myeloid-Derived Suppressor Cells, Programmed Death Receptor Ligand 1/Programmed Death Receptor 1, and Soluble CD25 in Sokal High Risk Chronic Myeloid Leukemia
  • 2013
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:1, s. e55818-
  • Tidskriftsartikel (refereegranskat)abstract
    • Immunotherapy (eg interferon α) in combination with tyrosine kinase inhibitors is currently in clinical trials for treatment of chronic myeloid leukemia (CML). Cancer patients commonly have problems with so called immune escape mechanisms that may hamper immunotherapy. Hence, to study the function of the immune system in CML is of interest. In the present paper we have identified immune escape mechanisms in CML with focus on those that directly hamper T cells since these cells are important to control tumor progression. CML patient samples were investigated for the presence of myeloid-derived suppressor cells (MDSCs), expression of programmed death receptor ligand 1/programmed death receptor 1 (PD-L1/PD-1), arginase 1 and soluble CD25. MDSC levels were increased in samples from Sokal high risk patients (p<0,05) and the cells were present on both CD34 negative and CD34 positive cell populations. Furthermore, expression of the MDSC-associated molecule arginase 1, known to inhibit T cells, was increased in the patients (p = 0,0079). Myeloid cells upregulated PD-L1 (p<0,05) and the receptor PD-1 was present on T cells. However, PD-L1 blockade did not increase T cell proliferation but upregulated IL-2 secretion. Finally, soluble CD25 was increased in high risk patients (p<0,0001). In conclusion T cells in CML patients may be under the control of different immune escape mechanisms that could hamper the use of immunotherapy in these patients. These escape mechanisms should be monitored in trials to understand their importance and how to overcome the immune suppression.
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21.
  • Elming, Sten-åke, et al. (författare)
  • Proterozoic Basic dykes in the Ukrainian Shield: A palaeomagnetic, geochronologic and geochemical study-The accretion of the Ukrainian Shield to Fennoscandia
  • 2010
  • Ingår i: Precambrian Research. - : Elsevier BV. - 0301-9268 .- 1872-7433. ; 178:1-4, s. 119-135
  • Tidskriftsartikel (refereegranskat)abstract
    • A palaeomagnetic, geochronologic and geochemical study of basic dykes in the Ukrainian Shield has been undertaken with the purpose of testing a hypothesis for timing of accretion of the Ukrainian Shield with Fennoscandia. On the basis of geological data it has been suggested that the two shields amalgamated at ca. 1900-1800 Ma. With this study of 11 basic dykes the palaeomagnetic database for the Ukrainian Shield is extended. The palaeomagnetic data indicate three generations of dykes. This is supported by the age data and the difference in geochemical compositions. Ages of two ca. 25 m wide dykes (Susly) in the North-Western Block of the shield have been determined, one for which a positive palaeomagnetic field test is demonstrated. The lower of the two Ar-40/Ar-39 hornblende ages of this dyke, 2061 +/- 20 Ma, is similar to the U-Pb, zircon age of the granitic host rock (ca. 2067 Ma, U-Pb, zircon), which suggests that the dyke intruded shortly after crystallization of the granite. Combined with the magnetization of the baked contact and that of another dyke a new ca 2060 Ma pole is presented (Plat. = 15.7 degrees, Plon. = 182.9 degrees, A(95) = 13.7 degrees). which may be regarded as a VGP. An U-Pb age of 1722 +/- 12 Ma of baddeleyite from the Khmelnik dyke, which yields a well-defined VGP, is similar to the age of nearby anorthosite complexes. A new 1740-1770 Ma key pole for the Ukranian Shield is also presented (Plat. = 26.5 degrees, Plon. = 169.1 degrees, A(95) = 3.9 degrees). On the basis of palaeomagnetic and geochronological data a 2060-1720 Ma apparent polar wander for the Ukrainian Shield is defined. This apparent polar wander is significantly different from that of Fennoscandia during the same time interval and indicates that the two shields were not in their present relative positions at ca. 1770 Ma. A scenario is here proposed where the Ukrainian Shield (and Sarmatia) collided with Fennoscandia at ca. 1900-1800 Ma and after that event, at ca. 1720-1660 Ma, it rotated approximately 43 degrees into its present position. (C) 2010 Elsevier B.V. All rights reserved.
  •  
22.
  • Ernst, R. E., et al. (författare)
  • Identification of the ca. 720 Ma Irkutsk LIP and its plume centre in southern Siberia : The initiation of Laurentia-Siberia separation
  • 2023
  • Ingår i: Precambrian Research. - 0301-9268. ; 394
  • Tidskriftsartikel (refereegranskat)abstract
    • Widespread 720 Ma magmatism has been linked with the break-up of Rodinia and the onset of the Sturtian ‘Snowball Earth’ event. We report a new U-Pb baddeleyite age from the Baikal dyke subswarm in southern Siberia which increases the known extent of the 720 Ma Irkutsk LIP and confirms a previous hypothesis that the Baikal and Sayan subswarms converge at the southern tip of the Irkutsk promontory. Together they define a mantle plume centre with direct links to the 720 Ma Franklin plume centre of northern Laurentia, thus constraining the paleo-reconstruction of southern Siberia and northern Laurentia. It is inferred that this combined 720 Franklin – Irktusk LIP event is associated with the breakup of southern Siberia from northern Laurentia during fragmentation of the Rodinia supercontinent. Expansion of 720 Ma magmatism into Siberia greatly increases the scale of the Franklin-Irktusk LIP.
  •  
23.
  • Ernst, R. E., et al. (författare)
  • Long-lived connection between southern Siberia and northern Laurentia in the Proterozoic
  • 2016
  • Ingår i: Nature Geoscience. - : Springer Science and Business Media LLC. - 1752-0894 .- 1752-0908. ; 9:6, s. 464-469
  • Tidskriftsartikel (refereegranskat)abstract
    • Precambrian supercontinents Nuna-Columbia (1.7 to 1.3 billion years ago) and Rodinia (1.1 to 0.7 billion years ago) have been proposed. However, the arrangements of crustal blocks within these supercontinents are poorly known. Huge, dominantly basaltic magmatic outpourings and intrusions, covering up to millions of square kilometres, termed Large Igneous Provinces, typically accompany (super) continent breakup, or attempted breakup and offer an important tool for reconstructing supercontinents. Here we focus on the Large Igneous Province record for Siberia and Laurentia, whose relative position in Nuna-Columbia and Rodinia reconstructions is highly controversial. We present precise geochronology - nine U-Pb and six Ar-Ar ages - on dolerite dykes and sills, along with existing dates from the literature, that constrain the timing of emplacement of Large Igneous Province magmatism in southern Siberia and northern Laurentia between 1,900 and 720 million years ago. We identify four robust age matches between the continents 1,870, 1,750, 1,350 and 720 million years ago, as well as several additional approximate age correlations that indicate southern Siberia and northern Laurentia were probably near neighbours for this 1.2-billion-year interval. Our reconstructions provide a framework for evaluating the shared geological, tectonic and metallogenic histories of these continental blocks.
  •  
24.
  • Evans, D. A D, et al. (författare)
  • Return to Rodinia? Moderate to high palaeolatitude of the São Francisco/Congo craton at 920 Ma
  • 2015. - 1
  • Ingår i: Geological Society Special Publication. - 0305-8719. ; 424:1, s. 167-190
  • Bokkapitel (refereegranskat)abstract
    • Moderate to high palaeolatitudes recorded in mafic dykes, exposed along the coast of Bahia, Brazil, are partly responsible for some interpretations that the São Francisco/Congo craton was separate from the low-latitude Rodinia supercontinent at about 1050 Ma. We report new palaeomagnetic data that replicate the previous results. However, we obtain substantially younger U-Pb baddeleyite ages from five dykes previously thought to be 1.02-1.01 Ga according to the 40Ar/39Ar method. Specifically, the so-called «A-normal» remanence direction from Salvador is dated at 924.2±3.8 Ma, within error of the age for the «C» remanence direction at 921.5±4.3 Ma. An «A-normal» dyke at Ilh»us is dated at 926.1±4.6 Ma, and two «A-normal» dykes at Olivença have indistinguishable ages with best estimate of emplacement at 918.2±6.7 Ma. We attribute the palaeomagnetic variance of the «A-normal» and «C» directions to lack of averaging of geomagnetic palaeosecular variation in some regions. Our results render previous 40Ar/39Ar ages from the dykes suspect, leaving late Mesoproterozoic palaeolatitudes of the São Francisco/Congo craton unconstrained. The combined «A-normal» palaeomagnetic pole from coastal Bahia places the São Francisco/Congo craton in moderate to high palaeolatitudes at c. 920 Ma, allowing various possible positions of that block within Rodinia.
  •  
25.
  •  
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