| 1. |
- Haghighi, Mona, et al.
(författare)
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A Comparison of Rule-based Analysis with Regression Methods in Understanding the Risk Factors for Study Withdrawal in a Pediatric Study
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Regression models are extensively used in many epidemiological studies to understand the linkage between specific outcomes of interest and their risk factors. However, regression models in general examine the average effects of the risk factors and ignore subgroups with different risk profiles. As a result, interventions are often geared towards the average member of the population, without consideration of the special health needs of different subgroups within the population. This paper demonstrates the value of using rule-based analysis methods that can identify subgroups with heterogeneous risk profiles in a population without imposing assumptions on the subgroups or method. The rules define the risk pattern of subsets of individuals by not only considering the interactions between the risk factors but also their ranges. We compared the rule-based analysis results with the results from a logistic regression model in The Environmental Determinants of Diabetes in the Young (TEDDY) study. Both methods detected a similar suite of risk factors, but the rule-based analysis was superior at detecting multiple interactions between the risk factors that characterize the subgroups. A further investigation of the particular characteristics of each subgroup may detect the special health needs of the subgroup and lead to tailored interventions.
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| 2. |
- Rewers, Marian, et al.
(författare)
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The Environmental Determinants of Diabetes in the Young (TEDDY) Study
- 2008
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Ingår i: Annals of the New York Academy of Sciences. - : Wiley. - 0077-8923 .- 1749-6632. ; 1150, s. 1-13
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Tidskriftsartikel (refereegranskat)abstract
- The etiology of type 1 diabetes (T1D) remains unknown, but a growing body of evidence points to infectious agents and/or components of early childhood diet. The National Institutes of Health has established the TEDDY Study consortium of six clinical centers in the United States and Europe and a data coordinating center to identify environmental factors predisposing to, or protective against, islet autoimmunity and T1D. From 2004-2009, TEDDY will screen more than 360,000 newborns from both the general population and families already affected by T1D to identify an estimated 17,804 children with high-risk HLA-DR,DQ genotypes. Of those, 7,801 (788 first-degree relatives and 7,013 newborns with no family history of T1D) will be enrolled in prospective follow-up beginning before the age of 4.5 months. As of May 2008, TEDDY has screened more than 250,000 newborns and enrolled nearly 5,000 infants--approximately 70% of the final cohort. Participants are seen every 3 months up to 4 years of age, with subsequent visits every 6 months until the subject is 15 years of age. Blood samples are collected at each visit for detection of candidate infectious agents and nutritional biomarkers; monthly stool samples are collected for infectious agents. These samples are saved in a central repository. Primary endpoints include (1) appearance of one or more islet autoantibodies (to insulin, GAD65 or IA-2) confirmed at two consecutive visits; (2) development of T1D. By age 15, an estimated 800 children will develop islet autoimmunity and 400 will progress to T1D; 67 and 27 children have already reached these endpoints.
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| 3. |
- Benatar, Michael, et al.
(författare)
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Safety and efficacy of arimoclomol in patients with early amyotrophic lateral sclerosis (ORARIALS-01) : a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial
- 2024
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Ingår i: Lancet Neurology. - : Elsevier. - 1474-4422 .- 1474-4465. ; 23:7, s. 687-699
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Tidskriftsartikel (refereegranskat)abstract
- Background: Amyotrophic lateral sclerosis is a progressive neurodegenerative disorder leading to muscle weakness and respiratory failure. Arimoclomol, a heat-shock protein-70 (HSP70) co-inducer, is neuroprotective in animal models of amyotrophic lateral sclerosis, with multiple mechanisms of action, including clearance of protein aggregates, a pathological hallmark of sporadic and familial amyotrophic lateral sclerosis. We aimed to evaluate the safety and efficacy of arimoclomol in patients with amyotrophic lateral sclerosis.Methods: ORARIALS-01 was a multinational, randomised, double-blind, placebo-controlled, parallel-group trial done at 29 centres in 12 countries in Europe and North America. Patients were eligible if they were aged 18 years or older and met El Escorial criteria for clinically possible, probable, probable laboratory-supported, definite, or familial amyotrophic lateral sclerosis; had an ALS Functional Rating Scale-Revised score of 35 or more; and had slow vital capacity at 70% or more of the value predicted on the basis of the participant's age, height, and sex. Patients were randomly assigned (2:1) in blocks of 6, stratified by use of a stable dose of riluzole or no riluzole use, to receive oral arimoclomol citrate 1200 mg/day (400 mg three times per day) or placebo. The Randomisation sequence was computer generated centrally. Investigators, study personnel, and study participants were masked to treatment allocation. The primary outcome was the Combined Assessment of Function and Survival (CAFS) rank score over 76 weeks of treatment. The primary outcome and safety were analysed in the modified intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT03491462, and is completed.Findings: Between July 31, 2018, and July 17, 2019, 287 patients were screened, 245 of whom were enrolled in the trial and randomly assigned. The modified intention-to-treat population comprised 239 patients (160 in the arimoclomol group and 79 in the placebo group): 151 (63%) were male and 88 (37%) were female; mean age was 57·6 years (SD 10·9). CAFS score over 76 weeks did not differ between groups (mean 0·51 [SD 0·29] in the arimoclomol group vs 0·49 [0·28] in the placebo group; p=0·62). Cliff's delta comparing the two groups was 0·039 (95% CI –0·116 to 0·194). Proportions of participants who died were similar between the treatment groups: 29 (18%) of 160 patients in the arimoclomol group and 18 (23%) of 79 patients in the placebo group. Most deaths were due to disease progression. The most common adverse events were gastrointestinal. Adverse events were more often deemed treatment-related in the arimoclomol group (104 [65%]) than in the placebo group (41 [52%]) and more often led to treatment discontinuation in the arimoclomol group (26 [16%]) than in the placebo group (four [5%]).Interpretation: Arimoclomol did not improve efficacy outcomes compared with placebo. Although available biomarker data are insufficient to preclude future strategies that target the HSP response, safety data suggest that a higher dose of arimoclomol would not have been tolerated.Funding: Orphazyme.
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| 4. |
- Sabater-Lleal, Maria, et al.
(författare)
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Common genetic determinants of lung function, subclinical atherosclerosis and risk of coronary artery disease.
- 2014
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:8
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Tidskriftsartikel (refereegranskat)abstract
- Chronic obstructive pulmonary disease (COPD) independently associates with an increased risk of coronary artery disease (CAD), but it has not been fully investigated whether this co-morbidity involves shared pathophysiological mechanisms. To identify potential common pathways across the two diseases, we tested all recently published single nucleotide polymorphisms (SNPs) associated with human lung function (spirometry) for association with carotid intima-media thickness (cIMT) in 3,378 subjects with multiple CAD risk factors, and for association with CAD in a case-control study of 5,775 CAD cases and 7,265 controls. SNPs rs2865531, located in the CFDP1 gene, and rs9978142, located in the KCNE2 gene, were significantly associated with CAD. In addition, SNP rs9978142 and SNP rs3995090 located in the HTR4 gene, were associated with average and maximal cIMT measures. Genetic risk scores combining the most robustly spirometry-associated SNPs from the literature were modestly associated with CAD, (odds ratio (OR) (95% confidence interval (CI95) = 1.06 (1.03, 1.09); P-value = 1.5×10-4, per allele). In conclusion, our study suggests that some genetic loci implicated in determining human lung function also influence cIMT and susceptibility to CAD. The present results should help elucidate the molecular underpinnings of the co-morbidity observed across COPD and CAD.
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| 5. |
- Almgren, Maria, et al.
(författare)
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Länge leve skolan! En text om utbildning, estetik och skolutveckling
- 2011
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Denna skrift har arbetats fram av en grupp studenter på Lärande och samhälle som fortsättning och utveckling av examinationsuppgift på en terminslång kurs, där de hade att iscensätta ett dokumentärfilmsprojekt på högstadiet. Projektet ägde rum inom ramen för huvudämnet Kultur, medier, estetik (KME) - skapat genom en sammanslagning av estetiska ämnen med medie- och kulturstudier 2001 – som ända från starten har tillskrivit det estetiska en särskild förmåga att vända upp och ner på invanda synsätt och kritiserat skolan för att inte lämna tillräckligt utrymme åt denna radikala potential. Den som är det minsta intresserad av skol- och kulturarbete kan inte undgå att dras in i det nät av glödande engagemang, intrikata spörsmål och brottstycken av teoretiska diskussioner som dessa sju studenter väver. Man kommer mycket nära de problem de brottas med utan att någonsin hitta några definitiva svar. Viljan att göra nytt tillsammans med eleverna och med utgångspunkt i deras horisont är obändig. Men så är det ramarna för arbetet... De sju befinner sig i ett interregnum, i en korseld av krav från lärarutbildarna, lärarna på skolan och eleverna, som påminner dem: "Ni är inte våra lärare. Ni kommer hit några timmar i veckan från någon annanstans". Ingenting visar sig vara enkelt. Varför gläds inte eleverna åt att få göra något som kan få betydelse för dem "på riktigt"? Vad är egentligen skillnaden mellan dokumentär- och fiktionsfilm? Hur bedömer man elevernas prestationer i ett så pass öppet projekt? Finns det över huvud taget rum i dagens skola för en pedagogik som vill vara på en gång passionerad, polyfon, prövande och provokativ? Alla dessa är ord som väl kännetecknar skriftens första del, ett grafiskt kaos av utlagda spår som läsaren kan välja bland att följa. Här får man en "cut-up-bild" av de tankevärldar som studenterna försöker orientera sig mot och inom. Den läsare som finner estetiken för provocerande kan alltid börja med andra delen i stället, som analytiskt redogör för de olika filmprojekten. Del tre, slutligen, diskuterar förutsättningarna för de förhållningssätt som utvecklats inom KME att göra sig gällande inom ramen för den nya läroplanen Lgr 11.
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| 6. |
- Bjursell, Cecilia, 1970-, et al.
(författare)
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Lifelong Learning Through Context Collapse : Higher education Teachers’ Narratives About Online education During The Pandemic
- 2022
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Ingår i: Proceedings of INTED2022 Conference 7th-8th March 2022. - : IATED. - 9788409377589 ; , s. 2632-2641
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Konferensbidrag (refereegranskat)abstract
- The COVID-19 pandemic has elicited a shift from campus classrooms to distance education in higher education worldwide, shaping not only students’ experiences, but also those of teachers, especially those who never have taught online. In addition, the pandemic created a meta-context that has positioned distance education as something different from previous efforts. This study aimed to investigate higher education teachers’ experiences during the transition from classroom to online teaching by using a collective auto-ethnography method based on 13 personal stories from Swedish faculty. For the abductive approach in the analysis, a framework that combines lifelong learning theory with the context collapse concept has been applied. The disjuncture that the pandemic has elicited created a situation in which teachers had to make sense of the fact that their previous experiences did not completely fit the new situation. Context collapse, a term used to describe encounters with many audiences in social media, has been introduced to highlight the clash between professional and private contexts in online educational platforms. Based on lifelong learning theories, we suggest that context collapse should be examined in terms of how it can help improve higher education, as it holds the potential to include the entire person – body and mind – in education.
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| 7. |
- Bonander, Carl, et al.
(författare)
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A regression discontinuity analysis of the social distancing recommendations for older adults in Sweden during COVID-19.
- 2022
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Ingår i: European Journal of Public Health. - : Oxford University Press. - 1101-1262 .- 1464-360X. ; 32:5, s. 799-806
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: This paper investigates the impact of a non-mandatory and age-specific social distancing recommendation on isolation behaviors and disease outcomes in Sweden during the first wave of the COVID-19 pandemic (March to July, 2020). The policy stated that people aged 70 years or older should avoid crowded places and contact with people outside the household.METHODS: We used a regression discontinuity design-in combination with self-reported isolation data from COVID Symptom Study Sweden (n = 96,053; age range: 39-79 years) and national register data (age range: 39-100+ years) on severe COVID-19 disease (hospitalization or death, n = 21,804) and confirmed cases (n = 48,984)-to estimate the effects of the policy.RESULTS: Our primary analyses showed a sharp drop in the weekly number of visits to crowded places (-13%) and severe COVID-19 cases (-16%) at the 70-year-threshold. These results imply that the age-specific recommendations prevented approximately 1,800 to 2,700 severe COVID-19 cases, depending on model specification.CONCLUSION: It seems that the non-mandatory, age-specific recommendations helped control COVID-19 disease during the first wave of the pandemic in Sweden, as opposed to not implementing a social distancing policy aimed at older adults. Our study provides empirical data on how populations may react to non-mandatory, age-specific social distancing policies in the face of a novel virus.SUPPLEMENTARY MATERIAL: Online appendix with figures, tables, extra methods and results.
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| 8. |
- Fu, Michael, 1963, et al.
(författare)
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Optimizing the Management of Heart Failure with Preserved Ejection Fraction in the Elderly by Targeting Comorbidities (OPTIMIZE-HFPEF).
- 2016
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Ingår i: Journal of cardiac failure. - : Elsevier BV. - 1532-8414 .- 1071-9164. ; 22:7, s. 539-544
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Tidskriftsartikel (refereegranskat)abstract
- The pathophysiology of heart failure with preserved ejection fraction (HFPEF) is not fully understood. A recently proposed mechanism for HFPEF is that it is a systemic pro-inflammatory state induced by comorbidities, leading to microvascular endothelial dysfunction and subsequent cardiac remodelling and dysfunction. We hypothesize that targeting comorbidities will improve outcomes in elderly patients with HFPEF. Thus, the aim of this study is to determine whether the combination of systematic screening of patients with HFPEF and optimal management of comorbidities associated with HFPEF improves outcomes.
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| 9. |
- Grundy, Myriam M.L., et al.
(författare)
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INFOGEST inter-laboratory recommendations for assaying gastric and pancreatic lipases activities prior to in vitro digestion studies
- 2021
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Ingår i: Journal of Functional Foods. - : Elsevier BV. - 1756-4646. ; 82
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Tidskriftsartikel (refereegranskat)abstract
- In vitro digestion studies often use animal digestive enzyme extracts as substitutes of human gastric and pancreatic secretions. Pancreatin from porcine origin is thus commonly used to provide relevant pancreatic enzymes such as proteases, amylase and lipase. Rabbit gastric extracts (RGE) have been recently introduced to provide gastric lipase in addition to pepsin. Before preparing simulated gastric and pancreatic extracts with targeted enzyme activities as described in in vitro digestion protocols, it is important to determine the activities of enzyme preparations using validated methods. The purpose of this inter-laboratory study within the INFOGEST network was to test the repeatability and reproducibility of lipase assays using the pH-stat technique for measuring the activities of gastric and pancreatic lipases from various sources. Twenty-one laboratories having different pH-stat devices received the same protocol with identical batches of RGE and two pancreatin sources. Lipase assays were performed using tributyrin as a substrate and three different amounts (50, 100 and 200 µg) of each enzyme preparation. The repeatability results within individual laboratories were satisfactory with coefficients of variation (CVs) ranging from 4 to 8% regardless of the enzyme amount tested. However, the inter-laboratory variability was high (CV > 15%) compared to existing standards for bioanalytical assays. We identified and weighted the contributions to inter-laboratory variability of several parameters associated with the various pH-stat equipment used in this study (e.g. reaction vessel volume and shape, stirring mode and rate, burette volume for the automated delivery of sodium hydroxide). Based on this, we established recommendations for improving the reproducibility of lipase assays using the pH-stat technique. Defining accurate and complete recommendations on how to correctly quantify activity levels of enzyme preparations is a gateway to promising comparison of in vitro data obtained from different laboratories following the same in vitro digestion protocol.
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| 10. |
- Hallengren, Erik, et al.
(författare)
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Fasting levels of growth hormone are associated with carotid intima media thickness but are not affected by fluvastatin treatment
- 2017
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Ingår i: BMC Cardiovascular Disorders. - : Springer Science and Business Media LLC. - 1471-2261. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Growth hormone (GH) has been linked to cardiovascular disease but the exact mechanism of this association is still unclear. We here test if the fasting levels of GH are cross-sectionally associated with carotid intima media thickness (IMT) and whether treatment with fluvastatin affects the fasting level of GH. Methods: We examined the association between GH and IMT in 4425 individuals (aged 46-68 years) included in the baseline examination (1991-1994) of the Malmö Diet and Cancer cardiovascular cohort (MDC-CC). From that cohort we then studied 472 individuals (aged 50-70 years) who also participated (1994-1999) in the β-Blocker Cholesterol-Lowering Asymptomatic Plaque Study (BCAPS), a randomized, double blind, placebo-controlled, single-center clinical trial. Using multivariate linear regression models we related the change in GH-levels at 12 months compared with baseline to treatment with 40 mg fluvastatin once daily. Results: In MDC-CC fasting values of GH exhibited a positive cross-sectional relation to the IMT at the carotid bulb independent of traditional cardiovascular risk factors (p = 0.002). In a gender-stratified analysis the correlation were significant for males (p = 0.005), but not for females (p = 0.09). Treatment with fluvastatin was associated with a minor reduction in the fasting levels of hs-GH in males (p = 0.05) and a minor rise in the same levels among females (p = 0.05). Conclusions: We here demonstrate that higher fasting levels of GH are associated with thicker IMT in the carotid bulb in males. Treatment with fluvastatin for 12 months only had a minor, and probably not clinically relevant, effect on the fasting levels of hs-GH.
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