| 1. |
- Dunn, R. J. H., et al.
(författare)
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GLOBAL CLIMATE : State of the Climate in 2020
- 2021
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Ingår i: Bulletin of the American Meteorological Society. - : American Meteorological Society. - 0003-0007 .- 1520-0477. ; 102:8
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Tidskriftsartikel (refereegranskat)
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| 2. |
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| 3. |
- Ades, M., et al.
(författare)
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Global Climate : in State of the climate in 2019
- 2020
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Ingår i: Bulletin of The American Meteorological Society - (BAMS). - : American Meteorological Society. - 0003-0007 .- 1520-0477. ; 101:8, s. S17-S127
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Tidskriftsartikel (refereegranskat)
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| 4. |
- Ades, M., et al.
(författare)
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GLOBAL CLIMATE
- 2020
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Ingår i: BULLETIN OF THE AMERICAN METEOROLOGICAL SOCIETY. - 0003-0007 .- 1520-0477. ; 101:8
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Tidskriftsartikel (refereegranskat)
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| 5. |
- van Bragt, JJMH, et al.
(författare)
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Characteristics and treatment regimens across ERS SHARP severe asthma registries
- 2020
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Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 55:1
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Tidskriftsartikel (refereegranskat)abstract
- Little is known about the characteristics and treatments of patients with severe asthma across Europe, but both are likely to vary. This is the first study in the European Respiratory Society Severe Heterogeneous Asthma Research collaboration, Patient-centred (SHARP) Clinical Research Collaboration and it is designed to explore these variations. Therefore, we aimed to compare characteristics of patients in European severe asthma registries and treatments before starting biologicals.This was a cross-sectional retrospective analysis of aggregated data from 11 national severe asthma registries that joined SHARP with established patient databases.Analysis of data from 3236 patients showed many differences in characteristics and lifestyle factors. Current smokers ranged from 0% (Poland and Sweden) to 9.5% (Belgium), mean body mass index ranged from 26.2 (Italy) to 30.6 kg·m−2 (the UK) and the largest difference in mean pre-bronchodilator forced expiratory volume in 1 s % predicted was 20.9% (the Netherlands versus Hungary). Before starting biologicals patients were treated differently between countries: mean inhaled corticosteroid dose ranged from 700 to 1335 µg·day−1 between those from Slovenia versus Poland when starting anti-interleukin (IL)-5 antibody and from 772 to 1344 µg·day−1 in those starting anti-IgE (Slovenia versus Spain). Maintenance oral corticosteroid use ranged from 21.0% (Belgium) to 63.0% (Sweden) and from 9.1% (Denmark) to 56.1% (the UK) in patients starting anti-IL-5 and anti-IgE, respectively.The severe asthmatic population in Europe is heterogeneous and differs in both clinical characteristics and treatment, often appearing not to comply with the current European Respiratory Society/American Thoracic Society guidelines definition of severe asthma. Treatment regimens before starting biologicals were different from inclusion criteria in clinical trials and varied between countries.
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| 6. |
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| 7. |
- Bethlehem, RAI, et al.
(författare)
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Brain charts for the human lifespan
- 2022
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 604:7906, s. 525-
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Tidskriftsartikel (refereegranskat)abstract
- Over the past few decades, neuroimaging has become a ubiquitous tool in basic research and clinical studies of the human brain. However, no reference standards currently exist to quantify individual differences in neuroimaging metrics over time, in contrast to growth charts for anthropometric traits such as height and weight1. Here we assemble an interactive open resource to benchmark brain morphology derived from any current or future sample of MRI data (http://www.brainchart.io/). With the goal of basing these reference charts on the largest and most inclusive dataset available, acknowledging limitations due to known biases of MRI studies relative to the diversity of the global population, we aggregated 123,984 MRI scans, across more than 100 primary studies, from 101,457 human participants between 115 days post-conception to 100 years of age. MRI metrics were quantified by centile scores, relative to non-linear trajectories2 of brain structural changes, and rates of change, over the lifespan. Brain charts identified previously unreported neurodevelopmental milestones3, showed high stability of individuals across longitudinal assessments, and demonstrated robustness to technical and methodological differences between primary studies. Centile scores showed increased heritability compared with non-centiled MRI phenotypes, and provided a standardized measure of atypical brain structure that revealed patterns of neuroanatomical variation across neurological and psychiatric disorders. In summary, brain charts are an essential step towards robust quantification of individual variation benchmarked to normative trajectories in multiple, commonly used neuroimaging phenotypes.
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| 8. |
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| 9. |
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| 10. |
- Khatri, B., et al.
(författare)
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Genome-wide association study identifies Sjogren's risk loci with functional implications in immune and glandular cells
- 2022
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Sjogren's disease is a complex autoimmune disease with twelve established susceptibility loci. This genome-wide association study (GWAS) identifies ten novel genome-wide significant (GWS) regions in Sjogren's cases of European ancestry: CD247, NAB1, PTTG1-MIR146A, PRDM1-ATG5, TNFAIP3, XKR6, MAPT-CRHR1, RPTOR-CHMP6-BAIAP6, TYK2, SYNGR1. Polygenic risk scores yield predictability (AUROC = 0.71) and relative risk of 12.08. Interrogation of bioinformatics databases refine the associations, define local regulatory networks of GWS SNPs from the 95% credible set, and expand the implicated gene list to >40. Many GWS SNPs are eQTLs for genes within topologically associated domains in immune cells and/or eQTLs in the main target tissue, salivary glands. The genetic architecture underlying Sjogren's syndrome is not fully understood. Here, the authors perform a genome-wide association study to identify 10 new genetic risk regions, implicating genes involved in immune and salivary gland function.
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| 11. |
- Azevedo, Flavio, et al.
(författare)
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Social and moral psychology of COVID-19 across 69 countries
- 2023
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Ingår i: Scientific Data. - : NATURE PORTFOLIO. - 2052-4463. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- The COVID-19 pandemic has affected all domains of human life, including the economic and social fabric of societies. One of the central strategies for managing public health throughout the pandemic has been through persuasive messaging and collective behaviour change. To help scholars better understand the social and moral psychology behind public health behaviour, we present a dataset comprising of 51,404 individuals from 69 countries. This dataset was collected for the International Collaboration on Social & Moral Psychology of COVID-19 project (ICSMP COVID-19). This social science survey invited participants around the world to complete a series of moral and psychological measures and public health attitudes about COVID-19 during an early phase of the COVID-19 pandemic (between April and June 2020). The survey included seven broad categories of questions: COVID-19 beliefs and compliance behaviours; identity and social attitudes; ideology; health and well-being; moral beliefs and motivation; personality traits; and demographic variables. We report both raw and cleaned data, along with all survey materials, data visualisations, and psychometric evaluations of key variables.
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| 12. |
- Van Bavel, Jay J., et al.
(författare)
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National identity predicts public health support during a global pandemic
- 2022
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Ingår i: Nature Communications. - : Nature Portfolio. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Understanding collective behaviour is an important aspect of managing the pandemic response. Here the authors show in a large global study that participants that reported identifying more strongly with their nation reported greater engagement in public health behaviours and support for public health policies in the context of the pandemic. Changing collective behaviour and supporting non-pharmaceutical interventions is an important component in mitigating virus transmission during a pandemic. In a large international collaboration (Study 1, N = 49,968 across 67 countries), we investigated self-reported factors associated with public health behaviours (e.g., spatial distancing and stricter hygiene) and endorsed public policy interventions (e.g., closing bars and restaurants) during the early stage of the COVID-19 pandemic (April-May 2020). Respondents who reported identifying more strongly with their nation consistently reported greater engagement in public health behaviours and support for public health policies. Results were similar for representative and non-representative national samples. Study 2 (N = 42 countries) conceptually replicated the central finding using aggregate indices of national identity (obtained using the World Values Survey) and a measure of actual behaviour change during the pandemic (obtained from Google mobility reports). Higher levels of national identification prior to the pandemic predicted lower mobility during the early stage of the pandemic (r = -0.40). We discuss the potential implications of links between national identity, leadership, and public health for managing COVID-19 and future pandemics.
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| 13. |
- Grigoroglou, C., et al.
(författare)
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Effectiveness of collaborative care in reducing suicidal ideation: An individual participant data meta-analysis
- 2021
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Ingår i: General Hospital Psychiatry. - : Elsevier BV. - 0163-8343. ; 71, s. 27-35
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Tidskriftsartikel (refereegranskat)abstract
- To assess whether CC is more effective at reducing suicidal ideation in people with depression compared with usual care, and whether study and patient factors moderate treatment effects. Method: We searched Medline, Embase, PubMed, PsycINFO, CINAHL, CENTRAL from inception to March 2020 for Randomised Controlled Trials (RCTs) that compared the effectiveness of CC with usual care in depressed adults, and reported changes in suicidal ideation at 4 to 6 months post-randomisation. Mixed-effects models accounted for clustering of participants within trials and heterogeneity across trials. This study is registered with PROSPERO, CRD42020201747. Results: We extracted data from 28 RCTs (11,165 patients) of 83 eligible studies. We observed a small significant clinical improvement of CC on suicidal ideation, compared with usual care (SMD, 0.11 [95%CI, 0.15 to 0.08]; I-2, 0.47% [95%CI 0.04% to 4.90%]). CC interventions with a recognised psychological treatment were associated with small reductions in suicidal ideation (SMD, 0.15 [95%CI -0.19 to 0.11]). CC was more effective for reducing suicidal ideation among patients aged over 65 years (SMD, 0.18 [95%CI -0.25 to 0.11]). Conclusion: Primary care based CC with an embedded psychological intervention is the most effective CC framework for reducing suicidal ideation and older patients may benefit the most.
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| 14. |
- Guisado-Clavero, M., et al.
(författare)
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The role of primary health care in long-term care facilities during the COVID-19 pandemic in 30 European countries: a retrospective descriptive study (Eurodata study)
- 2023
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Ingår i: Primary Health Care Research and Development. - 1463-4236. ; 24
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Tidskriftsartikel (refereegranskat)abstract
- Background and aim:Primary health care (PHC) supported long-term care facilities (LTCFs) in attending COVID-19 patients. The aim of this study is to describe the role of PHC in LTCFs in Europe during the early phase of the pandemic.Methods:Retrospective descriptive study from 30 European countries using data from September 2020 collected with an ad hoc semi-structured questionnaire. Related variables are SARS-CoV-2 testing, contact tracing, follow-up, additional testing, and patient care.Results:Twenty-six out of the 30 European countries had PHC involvement in LTCFs during the COVID-19 pandemic. PHC participated in initial medical care in 22 countries, while, in 15, PHC was responsible for SARS-CoV-2 test along with other institutions. Supervision of individuals in isolation was carried out mostly by LTCF staff, but physical examination or symptom's follow-up was performed mainly by PHC.Conclusion:PHC has participated in COVID-19 pandemic assistance in LTCFs in coordination with LTCF staff, public health officers, and hospitals.
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| 15. |
- Ares-Blanco, S., et al.
(författare)
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Clinical pathway of COVID-19 patients in primary health care in 30 European countries: Eurodata study
- 2023
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Ingår i: European Journal of General Practice. - : Informa UK Limited. - 1381-4788 .- 1751-1402. ; 29:2
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundMost COVID-19 patients were treated in primary health care (PHC) in Europe.ObjectivesTo demonstrate the scope of PHC workflow during the COVID-19 pandemic emphasising similarities and differences of patient's clinical pathways in Europe.MethodsDescriptive, cross-sectional study with data acquired through a semi-structured questionnaire in PHC in 30 European countries, created ad hoc and agreed upon among all researchers who participated in the study. GPs from each country answered the approved questionnaire. Main variable: PHC COVID-19 acute clinical pathway. All variables were collected from each country as of September 2020.ResultsCOVID-19 clinics in PHC facilities were organised in 8/30. Case detection and testing were performed in PHC in 27/30 countries. RT-PCR and lateral flow tests were performed in PHC in 23/30, free of charge with a medical prescription. Contact tracing was performed mainly by public health authorities. Mandatory isolation ranged from 5 to 14 days. Sick leave certification was given exclusively by GPs in 21/30 countries. Patient hotels or other resources to isolate patients were available in 12/30. Follow-up to monitor the symptoms and/or new complementary tests was made mainly by phone call (27/30). Chest X-ray and phlebotomy were performed in PHC in 18/30 and 23/30 countries, respectively. Oxygen and low-molecular-weight heparin were available in PHC (21/30).ConclusionIn Europe PHC participated in many steps to diagnose, treat and monitor COVID-19 patients. Differences among countries might be addressed at European level for the management of future pandemics.
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| 16. |
- Conley, R. B., et al.
(författare)
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Secondary Fracture Prevention: Consensus Clinical Recommendations from a Multistakeholder Coalition
- 2020
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 35:1, s. 36-52
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Tidskriftsartikel (refereegranskat)abstract
- Osteoporosis-related fractures are undertreated, due in part to misinformation about recommended approaches to patient care and discrepancies among treatment guidelines. To help bridge this gap and improve patient outcomes, the American Society for Bone and Mineral Research assembled a multistakeholder coalition to develop clinical recommendations for the optimal prevention of secondary fracture among people aged 65 years and older with a hip or vertebral fracture. The coalition developed 13 recommendations (7 primary and 6 secondary) strongly supported by the empirical literature. The coalition recommends increased communication with patients regarding fracture risk, mortality and morbidity outcomes, and fracture risk reduction. Risk assessment (including fall history) should occur at regular intervals with referral to physical and/or occupational therapy as appropriate. Oral, intravenous, and subcutaneous pharmacotherapies are efficacious and can reduce risk of future fracture. Patients need education, however, about the benefits and risks of both treatment and not receiving treatment. Oral bisphosphonates alendronate and risedronate are first-line options and are generally well tolerated; otherwise, intravenous zoledronic acid and subcutaneous denosumab can be considered. Anabolic agents are expensive but may be beneficial for selected patients at high risk. Optimal duration of pharmacotherapy is unknown but because the risk for second fractures is highest in the early post-fracture period, prompt treatment is recommended. Adequate dietary or supplemental vitamin D and calcium intake should be assured. Individuals being treated for osteoporosis should be reevaluated for fracture risk routinely, including via patient education about osteoporosis and fractures and monitoring for adverse treatment effects. Patients should be strongly encouraged to avoid tobacco, consume alcohol in moderation at most, and engage in regular exercise and fall prevention strategies. Finally, referral to endocrinologists or other osteoporosis specialists may be warranted for individuals who experience repeated fracture or bone loss and those with complicating comorbidities (eg, hyperparathyroidism, chronic kidney disease). (c) 2019 American Society for Bone and Mineral Research.
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| 17. |
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| 18. |
- Rahnev, D, et al.
(författare)
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The Confidence Database
- 2020
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Ingår i: Nature human behaviour. - : Springer Science and Business Media LLC. - 2397-3374. ; 4:3, s. 317-325
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Tidskriftsartikel (refereegranskat)
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| 19. |
- Ammirati, Enrico, et al.
(författare)
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Acute Myocarditis Associated With Desmosomal Gene Variants
- 2022
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Ingår i: JACC. Heart failure. - : ELSEVIER SCI LTD. - 2213-1779 .- 2213-1787. ; 10:10, s. 714-727
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND The risk of adverse cardiovascular events in patients with acute myocarditis (AM) and desmosomal gene variants (DGV) remains unknown.OBJECTIVES The purpose of this study was to ascertain the risk of death, ventricular arrhythmias, recurrent myocarditis, and heart failure (main endpoint) in patients with AM and pathogenic or likely pathogenetic DGV.METHODS In a retrospective international study from 23 hospitals, 97 patients were included: 36 with AM and DGV (DGV[+]), 25 with AM and negative gene testing (DGV[-]), and 36 with AM without genetics testing. All patients had troponin elevation plus findings consistent with AM on histology or at cardiac magnetic resonance (CMR). In 86 patients, CMR changes in function and structure were re-assessed at follow-up.RESULTS In the DGV(+) AM group (88.9% DSP variants), median age was 24 years, 91.7% presented with chest pain, and median left ventricular ejection fraction (LVEF) was 56% on CMR (P = NS vs the other 2 groups). Kaplan-Meier curves demonstrated a higher risk of the main endpoint in DGV(+) AM compared with DGV(-) and without genetics testing patients (62.3% vs 17.5% vs 5.3% at 5 years, respectively; P < 0.0001), driven by myocarditis recurrence and ventricular arrhythmias. At follow-up CMR, a higher number of late gadolinium enhanced segments was found in DGV(+) AM. CONCLUSIONS Patients with AM and evidence of DGV have a higher incidence of adverse cardiovascular events compared with patients with AM without DGV. Further prospective studies are needed to ascertain if genetic testing might improve risk stratification of patients with AM who are considered at low risk. (J Am Coll Cardiol HF 2022;10:714-727) (c) 2022 by the American College of Cardiology Foundation.
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| 20. |
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| 21. |
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| 22. |
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| 23. |
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| 24. |
- Vermeulen, Bram D., et al.
(författare)
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Early diagnosis is associated with improved clinical outcomes in benign esophageal perforation : an individual patient data meta-analysis
- 2021
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Ingår i: Surgical Endoscopy. - : Springer Science and Business Media LLC. - 0930-2794 .- 1432-2218. ; 35:7, s. 3492-3505
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Tidskriftsartikel (refereegranskat)abstract
- Background: Time of diagnosis (TOD) of benign esophageal perforation is regarded as an important risk factor for clinical outcome, although convincing evidence is lacking. The aim of this study is to assess whether time between onset of perforation and diagnosis is associated with clinical outcome in patients with iatrogenic esophageal perforation (IEP) and Boerhaave’s syndrome (BS). Methods: We searched MEDLINE, Embase and Cochrane library through June 2018 to identify studies. Authors were invited to share individual patient data and a meta-analysis was performed (PROSPERO: CRD42018093473). Patients were subdivided in early (≤ 24 h) and late (> 24 h) TOD and compared with mixed effects multivariable analysis while adjusting age, gender, location of perforation, initial treatment and center. Primary outcome was overall mortality. Secondary outcomes were length of hospital stay, re-interventions and ICU admission. Results: Our meta-analysis included IPD of 25 studies including 576 patients with IEP and 384 with BS. In IEP, early TOD was not associated with overall mortality (8% vs. 13%, OR 2.1, 95% CI 0.8–5.1), but was associated with a 23% decrease in ICU admissions (46% vs. 69%, OR 3.0, 95% CI 1.2–7.2), a 22% decrease in re-interventions (23% vs. 45%, OR 2.8, 95% CI 1.2–6.7) and a 36% decrease in length of hospital stay (14 vs. 22 days, p < 0.001), compared with late TOD. In BS, no associations between TOD and outcomes were found. When combining IEP and BS, early TOD was associated with a 6% decrease in overall mortality (10% vs. 16%, OR 2.1, 95% CI 1.1–3.9), a 19% decrease in re-interventions (26% vs. 45%, OR 1.9, 95% CI 1.1–3.2) and a 35% decrease in mean length of hospital stay (16 vs. 22 days, p = 0.001), compared with late TOD. Conclusions: This individual patient data meta-analysis confirms the general opinion that an early (≤ 24 h) compared to a late diagnosis (> 24 h) in benign esophageal perforations, particularly in IEP, is associated with improved clinical outcome.
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| 25. |
- Adler, Eric D., et al.
(författare)
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Improving risk prediction in heart failure using machine learning
- 2020
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Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 22:1, s. 139-147
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Tidskriftsartikel (refereegranskat)abstract
- Background: Predicting mortality is important in patients with heart failure (HF). However, current strategies for predicting risk are only modestly successful, likely because they are derived from statistical analysis methods that fail to capture prognostic information in large data sets containing multi-dimensional interactions. Methods and results: We used a machine learning algorithm to capture correlations between patient characteristics and mortality. A model was built by training a boosted decision tree algorithm to relate a subset of the patient data with a very high or very low mortality risk in a cohort of 5822 hospitalized and ambulatory patients with HF. From this model we derived a risk score that accurately discriminated between low and high-risk of death by identifying eight variables (diastolic blood pressure, creatinine, blood urea nitrogen, haemoglobin, white blood cell count, platelets, albumin, and red blood cell distribution width). This risk score had an area under the curve (AUC) of 0.88 and was predictive across the full spectrum of risk. External validation in two separate HF populations gave AUCs of 0.84 and 0.81, which were superior to those obtained with two available risk scores in these same populations. Conclusions: Using machine learning and readily available variables, we generated and validated a mortality risk score in patients with HF that was more accurate than other risk scores to which it was compared. These results support the use of this machine learning approach for the evaluation of patients with HF and in other settings where predicting risk has been challenging.
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| 26. |
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| 27. |
- Braumann, S, et al.
(författare)
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Nitro-Oleic Acid (NO2-OA) Improves Systolic Function in Dilated Cardiomyopathy by Attenuating Myocardial Fibrosis
- 2021
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Ingår i: International journal of molecular sciences. - : MDPI AG. - 1422-0067. ; 22:16
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Tidskriftsartikel (refereegranskat)abstract
- Nitro-oleic acid (NO2-OA), a nitric oxide (NO)- and nitrite (NO2−)-derived electrophilic fatty acid metabolite, displays anti-inflammatory and anti-fibrotic signaling actions and therapeutic benefit in murine models of ischemia-reperfusion, atrial fibrillation, and pulmonary hypertension. Muscle LIM protein-deficient mice (Mlp−/−) develop dilated cardiomyopathy (DCM), characterized by impaired left ventricular function and increased ventricular fibrosis at the age of 8 weeks. This study investigated the effects of NO2-OA on cardiac function in Mlp−/− mice both in vivo and in vitro. Mlp−/− mice were treated with NO2-OA or vehicle for 4 weeks via subcutaneous osmotic minipumps. Wildtype (WT) littermates treated with vehicle served as controls. Mlp−/− mice exhibited enhanced TGFβ signalling, fibrosis and severely reduced left ventricular systolic function. NO2-OA treatment attenuated interstitial myocardial fibrosis and substantially improved left ventricular systolic function in Mlp−/− mice. In vitro studies of TGFβ-stimulated primary cardiac fibroblasts further revealed that the anti-fibrotic effects of NO2-OA rely on its capability to attenuate fibroblast to myofibroblast transdifferentiation by inhibiting phosphorylation of TGFβ downstream targets. In conclusion, we demonstrate a substantial therapeutic benefit of NO2-OA in a murine model of DCM, mediated by interfering with endogenously activated TGFβ signaling.
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| 28. |
- de Flores, Robin, et al.
(författare)
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Characterization of hippocampal subfields using ex vivo MRI and histology data : Lessons for in vivo segmentation
- 2020
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Ingår i: Hippocampus. - : Wiley. - 1050-9631 .- 1098-1063. ; 30:6, s. 545-564
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Tidskriftsartikel (refereegranskat)abstract
- Hippocampal subfield segmentation on in vivo MRI is of great interest for cognition, aging, and disease research. Extant subfield segmentation protocols have been based on neuroanatomical references, but these references often give limited information on anatomical variability. Moreover, there is generally a mismatch between the orientation of the histological sections and the often anisotropic coronal sections on in vivo MRI. To address these issues, we provide a detailed description of hippocampal anatomy using a postmortem dataset containing nine specimens of subjects with and without dementia, which underwent a 9.4 T MRI and histological processing. Postmortem MRI matched the typical orientation of in vivo images and segmentations were generated in MRI space, based on the registered annotated histological sections. We focus on the following topics: the order of appearance of subfields, the location of subfields relative to macroanatomical features, the location of subfields in the uncus and tail and the composition of the dark band, a hypointense layer visible in T2-weighted MRI. Our main findings are that: (a) there is a consistent order of appearance of subfields in the hippocampal head, (b) the composition of subfields is not consistent in the anterior uncus, but more consistent in the posterior uncus, (c) the dark band consists only of the CA-stratum lacunosum moleculare, not the strata moleculare of the dentate gyrus, (d) the subiculum/CA1 border is located at the middle of the width of the hippocampus in the body in coronal plane, but moves in a medial direction from anterior to posterior, and (e) the variable location and composition of subfields in the hippocampal tail can be brought back to a body-like appearance when reslicing the MRI scan following the curvature of the tail. Our findings and this publicly available dataset will hopefully improve anatomical accuracy of future hippocampal subfield segmentation protocols.
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| 29. |
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| 30. |
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| 31. |
- Gudmundsson, Jón E., et al.
(författare)
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The Simons Observatory : modeling optical systematics in the Large Aperture Telescope
- 2021
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Ingår i: Applied Optics. - 1559-128X .- 2155-3165. ; 60:4, s. 823-837
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Tidskriftsartikel (refereegranskat)abstract
- We present geometrical and physical optics simulation results for the Simons Observatory Large Aperture Telescope. This work was developed as part of the general design process for the telescope, allowing us to evaluate the impact of various design choices on performance metrics and potential systematic effects. The primary goal of the simulations was to evaluate the final design of the reflectors and the cold optics that are now being built. We describe nonsequential ray tracing used to inform the design of the cold optics, including absorbers internal to each optics tube. We discuss ray tracing simulations of the telescope structure that allow us to determine geometries that minimize detector loading and mitigate spurious near-field effects that have not been resolved by the internal baffling. We also describe physical optics simulations, performed over a range of frequencies and field locations, that produce estimates of monochromatic far-field beam patterns, which in turn are used to gauge general optical performance. Finally, we describe simulations that shed light on beam sidelobes from panel gap diffraction.
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| 33. |
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| 35. |
- Mastenbroek, Sophie E., et al.
(författare)
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Disease progression modelling reveals heterogeneity in trajectories of Lewy-type α-synuclein pathology
- 2024
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Ingår i: Nature Communications. - 2041-1723. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Lewy body (LB) diseases, characterized by the aggregation of misfolded α-synuclein proteins, exhibit notable clinical heterogeneity. This may be due to variations in accumulation patterns of LB neuropathology. Here we apply a data-driven disease progression model to regional neuropathological LB density scores from 814 brain donors with Lewy pathology. We describe three inferred trajectories of LB pathology that are characterized by differing clinicopathological presentation and longitudinal antemortem clinical progression. Most donors (81.9%) show earliest pathology in the olfactory bulb, followed by accumulation in either limbic (60.8%) or brainstem (21.1%) regions. The remaining donors (18.1%) initially exhibit abnormalities in brainstem regions. Early limbic pathology is associated with Alzheimer’s disease-associated characteristics while early brainstem pathology is associated with progressive motor impairment and substantial LB pathology outside of the brain. Our data provides evidence for heterogeneity in the temporal spread of LB pathology, possibly explaining some of the clinical disparities observed in Lewy body disease.
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| 36. |
- van Amerongen, Suzan, et al.
(författare)
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Inflammatory biomarkers for neurobehavioral dysregulation in former American football players: findings from the DIAGNOSE CTE Research Project
- 2024
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Ingår i: JOURNAL OF NEUROINFLAMMATION. - 1742-2094. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Traumatic encephalopathy syndrome (TES) is defined as the clinical manifestation of the neuropathological entity chronic traumatic encephalopathy (CTE). A core feature of TES is neurobehavioral dysregulation (NBD), a neuropsychiatric syndrome in repetitive head impact (RHI)-exposed individuals, characterized by a poor regulation of emotions/behavior. To discover biological correlates for NBD, we investigated the association between biomarkers of inflammation (interleukin (IL)-1 beta, IL-6, IL-8, IL-10, C-reactive protein (CRP), tumor necrosis factor (TNF)-alpha) in cerebrospinal fluid (CSF) and NBD symptoms in former American football players and unexposed individuals. Methods Our cohort consisted of former American football players, with (n = 104) or without (n = 76) NBD diagnosis, as well as asymptomatic unexposed individuals (n = 55) from the DIAGNOSE CTE Research Project. Specific measures for NBD were derived (i.e., explosivity, emotional dyscontrol, impulsivity, affective lability, and a total NBD score) from a factor analysis of multiple self-report neuropsychiatric measures. Analyses of covariance tested differences in biomarker concentrations between the three groups. Within former football players, multivariable linear regression models assessed relationships among log-transformed inflammatory biomarkers, proxies for RHI exposure (total years of football, cumulative head impact index), and NBD factor scores, adjusted for relevant confounding variables. Sensitivity analyses tested (1) differences in age subgroups (< 60, >= 60 years); (2) whether associations could be identified with plasma inflammatory biomarkers; (3) associations between neurodegeneration and NBD, using plasma neurofilament light (NfL) chain protein; and (4) associations between biomarkers and cognitive performance to explore broader clinical symptoms related to TES. Results CSF IL-6 was higher in former American football players with NBD diagnosis compared to players without NBD. Furthermore, elevated levels of CSF IL-6 were significantly associated with higher emotional dyscontrol, affective lability, impulsivity, and total NBD scores. In older football players, plasma NfL was associated with higher emotional dyscontrol and impulsivity, but also with worse executive function and processing speed. Proxies for RHI exposure were not significantly associated with biomarker concentrations. Conclusion Specific NBD symptoms in former American football players may result from multiple factors, including neuroinflammation and neurodegeneration. Future studies need to unravel the exact link between NBD and RHI exposure, including the role of other pathophysiological pathways.
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| 37. |
- Adler, Alexandre, et al.
(författare)
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Modelling ground pickup for microwave telescopes
- 2022
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Ingår i: Proceedings of SPIE, the International Society for Optical Engineering. - : SPIE. - 0277-786X .- 1996-756X. ; 12190
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Tidskriftsartikel (refereegranskat)abstract
- Microwave telescopes require an ever-increasing control of experimental systematics in their quest to measure the Cosmic Microwave Background (CMB) to exquisite levels of precision. One important systematic for ground and balloon-borne experiments is ground pickup, where beam sidelobes detect the thermal emission of the much warmer ground while the main beam is scanning the sky. This generates scan-synchronous noise in experiment timestreams, which is difficult to filter out without also deleting some of the signal from the sky. Therefore, efficient modelling of pickup can help guide the design of experiments and of analysis pipelines. In this work, we present an extension to the BEAMCONV algorithm that enables us to generate time-ordered data (TOD) from beam-convolved sky and ground maps simultaneously. We simulate ground pickup for both a ground-based experiment and a telescope attached to a stratospheric balloon. Ground templates for the balloon experiment are obtained by re-projecting satellite maps of the Earth's microwave emission.
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| 38. |
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| 39. |
- Beal, Jacob, et al.
(författare)
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Robust estimation of bacterial cell count from optical density
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 40. |
- Butler, Annie A., et al.
(författare)
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Upper Limb Function but Not Proprioception is Impaired in Essential Tremor: A Between-Groups Study and Causal Mediation Analysis
- 2023
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Ingår i: TREMOR AND OTHER HYPERKINETIC MOVEMENTS. - : UBIQUITY PRESS LTD. - 2160-8288. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background: Essential tremor (ET) is characterized by abnormal oscillatory muscle activity and cerebellar involvement, factors that can lead to proprioceptive deficits, especially in active tasks. The present study aimed to quantify the severity of proprioceptive deficits in people with ET and estimate how these contribute to functional impairments.Methods: Upper limb sensory, proprioceptive and motor function was assessed in individualswith ET (n = 20) and healthy individuals (n = 22). To measure proprioceptive ability, participants discriminated the width of grasped objects and the weight of objects lifted with the wrist extensors. Causal mediation analysis was used to estimate the extent that impairments in upper limb function in ET was mediated by proprioceptive ability.Results: Participants with ET had impaired upper limb function in all outcomes, and had greater postural and kinetic tremor. There were no differences between groups in proprioceptive discrimination of width (between-group mean difference [95% CI]: 0.32 mm [-0.23 to 0.87 mm]) or weight (-1.12 g [-7.31 to 5.07 g]). Causal mediation analysis showed the effect of ET on upper limb function was not mediated by proprioceptive ability.Conclusions: Upper limb function but not proprioception was impaired in ET. The effect of ET on motor function was not mediated by proprioception. These results indicate that the central nervous system of people with ET is able to accommodate mild to moderate tremor in active proprioceptive tasks that rely primarily on afferent signals from muscle spindles.
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| 41. |
- Chesmore, Grace E., et al.
(författare)
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Simons Observatory : characterizing the Large Aperture Telescope Receiver with radio holography
- 2022
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Ingår i: Applied Optics. - 1559-128X .- 2155-3165. ; 61:34, s. 10309-10319
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Tidskriftsartikel (refereegranskat)abstract
- We present near-field radio holography measurements of the Simons Observatory Large Aperture Telescope Receiver optics. These measurements demonstrate that radio holography of complex millimeter-wave optical systems comprising cryogenic lenses, filters, and feed horns can provide detailed characterization of wave propagation before deployment. We used the measured amplitude and phase, at 4 K, of the receiver near-field beam pattern to predict two key performance parameters: 1) the amount of scattered light that will spill past the telescope to 300 K and 2) the beam pattern expected from the receiver when fielded on the telescope. These cryogenic measurements informed the removal of a filter, which led to improved optical efficiency and reduced sidelobes at the exit of the receiver. Holography measurements of this system suggest that the spilled power past the telescope mirrors will be less than 1%, and the main beam with its near sidelobes are consistent with the nominal telescope design. This is the first time such parameters have been confirmed in the lab prior to deployment of a new receiver. This approach is broadly applicable to millimeter and submillimeter instruments.
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| 42. |
- Chesmore, Grace E., et al.
(författare)
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Simons Observatory HoloSim-ML : machine learning applied to the efficient analysis of radio holography measurements of complex optical systems
- 2021
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Ingår i: Applied Optics. - 1559-128X .- 2155-3165. ; 60:29, s. 9029-9035
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Tidskriftsartikel (refereegranskat)abstract
- Near-field radio holography is a common method for measuring and aligning mirror surfaces for millimeter and sub-millimeter telescopes. In instruments with more than a single mirror, degeneracies arise in the holography measurement, requiring multiple measurements and new fitting methods. We present HoloSim-ML, a Python code for beam simulation and analysis of radio holography data from complex optical systems. This code uses machine learning to efficiently determine the position of hundreds of mirror adjusters on multiple mirrors with few micrometer accuracy. We apply this approach to the example of the Simons Observatory 6 m telescope.
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| 43. |
- Conley, Robert B., et al.
(författare)
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Secondary Fracture Prevention : Consensus Clinical Recommendations from a Multistakeholder Coalition
- 2020
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Ingår i: Journal of Orthopaedic Trauma. - 0890-5339. ; 34:4, s. 125-141
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Tidskriftsartikel (refereegranskat)abstract
- Osteoporosis-related fractures are undertreated, due in part to misinformation about recommended approaches to patient care and discrepancies among treatment guidelines. To help bridge this gap and improve patient outcomes, the American Society for Bone and Mineral Research assembled a multistakeholder coalition to develop clinical recommendations for the optimal prevention of secondary fractureamong people aged 65 years and older with a hip or vertebral fracture. The coalition developed 13 recommendations (7 primary and 6 secondary) strongly supported by the empirical literature. The coalition recommends increased communication with patients regarding fracture risk, mortality and morbidity outcomes, and fracture risk reduction. Risk assessment (including fall history) should occur at regular intervals with referral to physical and/or occupational therapy as appropriate. Oral, intravenous, andsubcutaneous pharmacotherapies are efficaciousandcanreduce risk of future fracture.Patientsneededucation,however, about thebenefitsandrisks of both treatment and not receiving treatment. Oral bisphosphonates alendronate and risedronate are first-line options and are generally well tolerated; otherwise, intravenous zoledronic acid and subcutaneous denosumab can be considered. Anabolic agents are expensive butmay be beneficial for selected patients at high risk.Optimal duration of pharmacotherapy is unknown but because the risk for second fractures is highest in the earlypost-fractureperiod,prompt treatment is recommended.Adequate dietary or supplemental vitaminDand calciumintake shouldbe assured. Individuals beingtreatedfor osteoporosis shouldbe reevaluated for fracture risk routinely, includingvia patienteducationabout osteoporosisandfracturesandmonitoringfor adverse treatment effects.Patients shouldbestronglyencouraged to avoid tobacco, consume alcohol inmoderation atmost, and engage in regular exercise and fall prevention strategies. Finally, referral to endocrinologists or other osteoporosis specialists may be warranted for individuals who experience repeated fracture or bone loss and those with complicating comorbidities (eg, hyperparathyroidism, chronic kidney disease).
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| 44. |
- Conley, Robert B., et al.
(författare)
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Secondary Fracture Prevention : Consensus Clinical Recommendations from a Multistakeholder Coalition
- 2020
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Ingår i: Orthopaedic Nursing. - 0744-6020. ; 39:3, s. 145-161
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Tidskriftsartikel (refereegranskat)abstract
- Osteoporosis-related fractures are undertreated, due in part to misinformation about recommended approaches to patient care and discrepancies among treatment guidelines. To help bridge this gap and improve patient outcomes, the American Society for Bone and Mineral Research assembled a multistakeholder coalition to develop clinical recommendations for the optimal prevention of secondary fracture among people aged 65 years and older with a hip or vertebral fracture. The coalition developed 13 recommendations (7 primary and 6 secondary) strongly supported by the empirical literature. The coalition recommends increased communication with patients regarding fracture risk, mortality and morbidity outcomes, and fracture risk reduction. Risk assessment (including fall history) should occur at regular intervals with referral to physical and/or occupational therapy as appropriate. Oral, intravenous, and subcutaneous pharmacotherapies are efficacious and can reduce risk offuture fracture. Patients need education, however, about the benefits and risks of both treatment and not receiving treatment. Oral bisphosphonates alendronate and risedronate are first-line options and are generally well tolerated; otherwise, intravenous zoledronic acid and subcutaneous denosumab can be considered. Anabolic agents are expensive but may be beneficial for selected patients at high risk. Optimal duration of pharmacotherapy is unknown but because the riskfor second fractures is highest in the early post-fracture period, prompt treatment is recommended. Adequate dietary or supplemental vitamin D and calcium intake should be assured. Individuals being treated for osteoporosis should be reevaluated for fracture risk routinely, including via patient education about osteoporosis and fractures and monitoring foradverse treatment effects. Patients should be strongly encouraged to avoid tobacco, consume alcohol in moderation at most, and engage in regular exercise and fall prevention strategies. Finally, referral to endocrinologists or other osteoporosis specialists may be warranted for individuals who experience repeated fracture or bone loss and those with complicating comorbidities (eg, hyperparathyroidism, chronic kidney disease). (c) 2019 American Society for Bone and Mineral Research.
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| 45. |
- Hasebe, T., et al.
(författare)
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Sensitivity Modeling for LiteBIRD
- 2023
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Ingår i: Journal of Low Temperature Physics. - : Springer Science and Business Media LLC. - 0022-2291 .- 1573-7357. ; 211:5-6, s. 384-397
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Tidskriftsartikel (refereegranskat)abstract
- LiteBIRD is a future satellite mission designed to observe the polarization of the cosmic microwave background radiation in order to probe the inflationary universe. LiteBIRD is set to observe the sky using three telescopes with transition-edge sensor bolometers. In this work we estimated the LiteBIRD instrumental sensitivity using its current design. We estimated the detector noise due to the optical loadings using physical optics and ray-tracing simulations. The noise terms associated with thermal carrier and readout noise were modeled in the detector noise calculation. We calculated the observational sensitivities over fifteen bands designed for the LiteBIRD telescopes using assumed observation time efficiency.
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| 46. |
- Hege, Inga, et al.
(författare)
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Developing a European longitudinal and interprofessional curriculum for clinical reasoning
- 2023
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Ingår i: Diagnosis. - : Walter de Gruyter GmbH. - 2194-8011 .- 2194-802X.
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Tidskriftsartikel (refereegranskat)abstract
- Clinical reasoning is a complex and crucial ability health professions students need to acquire during their education. Despite its importance, explicit clinical reasoning teaching is not yet implemented in most health professions educational programs. Therefore, we carried out an international and interprofessional project to plan and develop a clinical reasoning curriculum with a train-the-trainer course to support educators in teaching this curriculum to students. We developed a framework and curricular blueprint. Then we created 25 student and 7 train-the-trainer learning units and we piloted 11 of these learning units at our institutions. Learners and faculty reported high satisfaction and they also provided helpful suggestions for improvements. One of the main challenges we faced was the heterogeneous understanding of clinical reasoning within and across professions. However, we learned from each other while discussing these different views and perspectives on clinical reasoning and were able to come to a shared understanding as the basis for developing the curriculum. Our curriculum fills an important gap in the availability of explicit clinical reasoning educational materials both for students and faculty and is unique with having specialists from different countries, schools, and professions. Faculty time and time for teaching clinical reasoning in existing curricula remain important barriers for implementation of clinical reasoning teaching.
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| 47. |
- Hubmayr, J., et al.
(författare)
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Optical Characterization of OMT-Coupled TES Bolometers for LiteBIRD
- 2022
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Ingår i: Journal of Low Temperature Physics. - : Springer Science and Business Media LLC. - 0022-2291 .- 1573-7357. ; 209:3-4, s. 396-408
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Tidskriftsartikel (refereegranskat)abstract
- Feedhorn- and orthomode transducer- (OMT) coupled transition edge sensor (TES) bolometers have been designed and micro-fabricated to meet the optical specifications of the LiteBIRD high frequency telescope (HFT) focal plane. We discuss the design and optical characterization of two LiteBIRD HFT detector types: dual-polarization, dual-frequency-band pixels with 195/280 GHz and 235/337 GHz band centers. Results show well-matched passbands between orthogonal polarization channels and frequency centers within 3% of the design values. The optical efficiency of each frequency channel is conservatively reported to be within the range 0.64-0.72, determined from the response to a cryogenic, temperature-controlled thermal source. These values are in good agreement with expectations and either exceed or are within 10% of the values used in the LiteBIRD sensitivity forecast. Lastly, we report a measurement of loss in Nb/SiN x/Nb microstrip at 100 mK and over the frequency range 200-350 GHz, which is comparable to values previously reported in the literature.
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| 48. |
- Kirkeby, Agnete, et al.
(författare)
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Preclinical quality, safety, and efficacy of a human embryonic stem cell-derived product for the treatment of Parkinson's disease, STEM-PD
- 2023
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Ingår i: Cell Stem Cell. - 1934-5909. ; 30:10, s. 1299-1314
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Tidskriftsartikel (refereegranskat)abstract
- Cell replacement therapies for Parkinson's disease (PD) based on transplantation of pluripotent stem cell-derived dopaminergic neurons are now entering clinical trials. Here, we present quality, safety, and efficacy data supporting the first-in-human STEM-PD phase I/IIa clinical trial along with the trial design. The STEM-PD product was manufactured under GMP and quality tested in vitro and in vivo to meet regulatory requirements. Importantly, no adverse effects were observed upon testing of the product in a 39-week rat GLP safety study for toxicity, tumorigenicity, and biodistribution, and a non-GLP efficacy study confirmed that the transplanted cells mediated full functional recovery in a pre-clinical rat model of PD. We further observed highly comparable efficacy results between two different GMP batches, verifying that the product can be serially manufactured. A fully in vivo-tested batch of STEM-PD is now being used in a clinical trial of 8 patients with moderate PD, initiated in 2022.
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| 49. |
- Ly, Monica T, et al.
(författare)
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Association of Vascular Risk Factors and CSF and Imaging Biomarkers With White Matter Hyperintensities in Former American Football Players.
- 2024
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Ingår i: Neurology. - 1526-632X. ; 102:2
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Tidskriftsartikel (refereegranskat)abstract
- Recent data link exposure to repetitive head impacts (RHIs) from American football with increased white matter hyperintensity (WMH) burden. WMH might have unique characteristics in the context of RHI beyond vascular risk and normal aging processes. We evaluated biological correlates of WMH in former American football players, including markers of amyloid, tau, inflammation, axonal injury, neurodegeneration, and vascular health.Participants underwent clinical interviews, MRI, and lumbar puncture as part of the Diagnostics, Imaging, and Genetics Network for the Objective Study and Evaluation of Chronic Traumatic Encephalopathy Research Project. Structural equation modeling tested direct and indirect effects between log-transformed total fluid-attenuated inversion recovery (FLAIR) lesion volumes (TLV) and the revised Framingham stroke risk profile (rFSRP), MRI-derived global metrics of cortical thickness and fractional anisotropy (FA), and CSF levels of amyloid β1-42, p-tau181, soluble triggering receptor expressed on myeloid cells 2 (sTREM2), and neurofilament light. Covariates included age, race, education, body mass index, APOE ε4 carrier status, and evaluation site. Models were performed separately for former football players and a control group of asymptomatic men unexposed to RHI.In 180 former football players (mean age = 57.2, 36% Black), higher log(TLV) had direct associations with the following: higher rFSRP score (B = 0.26, 95% CI 0.07-0.40), higher p-tau181 (B = 0.17, 95% CI 0.01-0.43), lower FA (B = -0.28, 95% CI -0.42 to -0.13), and reduced cortical thickness (B = -0.25, 95% CI -0.45 to -0.08). In 60 asymptomatic unexposed men (mean age = 59.3, 40% Black), there were no direct effects on log(TLV) (rFSRP: B = -0.03, 95% CI -0.48 to 0.57; p-tau181: B = -0.30, 95% CI -1.14 to 0.37; FA: B = -0.07, 95% CI -0.48 to 0.42; or cortical thickness: B = -0.28, 95% CI -0.64 to 0.10). The former football players showed stronger associations between log(TLV) and rFSRP (1,069% difference in estimates), p-tau181 (158%), and FA (287%) than the unexposed men.Risk factors and biological correlates of WMH differed between former American football players and asymptomatic unexposed men. In addition to vascular health, p-tau181 and diffusion tensor imaging indices of white matter integrity showed stronger associations with WMH in the former football players. FLAIR WMH may have specific risk factors and pathologic underpinnings in RHI-exposed individuals.
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| 50. |
- Möller, Steffen, et al.
(författare)
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Healthspan pathway maps in C. elegans and humans highlight transcription, proliferation/biosynthesis and lipids
- 2020
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Ingår i: Aging. - : Impact Journals LLC. - 1945-4589. ; 12:13, s. 12534-12581
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Forskningsöversikt (refereegranskat)abstract
- The molecular basis of aging and of aging-associated diseases is being unraveled at an increasing pace. An extended healthspan, and not merely an extension of lifespan, has become the aim of medical practice. Here, we define health based on the absence of diseases and dysfunctions. Based on an extensive review of the literature, in particular for humans and C. elegans, we compile a list of features of health and of the genes associated with them. These genes may or may not be associated with survival/lifespan. In turn, survival/lifespan genes that are not known to be directly associated with health are not considered. Clusters of these genes based on molecular interaction data give rise to maps of healthspan pathways for humans and for C. elegans. Overlaying healthspan-related gene expression data onto the healthspan pathway maps, we observe the downregulation of (pro-inflammatory) Notch signaling in humans and of proliferation in C. elegans. We identify transcription, proliferation/biosynthesis and lipids as a common theme on the annotation level, and proliferation-related kinases on the gene/protein level. Our literature-based data corpus, including visualization, should be seen as a pilot investigation of the molecular underpinnings of health in two different species.
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