| 1. |
- Thomas, HS, et al.
(författare)
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- 2019
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swepub:Mat__t
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| 2. |
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| 3. |
- Ratajczak-Tretel, B., et al.
(författare)
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Atrial fibrillation in cryptogenic stroke and TIA patients in the nordic atrial fibrillation and stroke The Nordic Atrial Fibrillation and Stroke (NOR-FIB) Study : Main results
- 2023
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Ingår i: European Stroke Journal. - : SAGE Publications. - 2396-9873 .- 2396-9881. ; 8:1, s. 148-156
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Secondary stroke prevention depends on proper identification of the underlying etiology and initiation of optimal treatment after the index event. The aim of the NOR-FIB study was to detect and quantify underlying atrial fibrillation (AF) in patients with cryptogenic stroke (CS) or transient ischaemic attack (TIA) using insertable cardiac monitor (ICM), to optimise secondary prevention, and to test the feasibility of ICM usage for stroke physicians. Patients and methods: Prospective observational international multicenter real-life study of CS and TIA patients monitored for 12 months with ICM (Reveal LINQ) for AF detection. Results: ICM insertion was performed in 91.5% by stroke physicians, within median 9 days after index event. Paroxysmal AF was diagnosed in 74 out of 259 patients (28.6%), detected early after ICM insertion (mean 48 ± 52 days) in 86.5% of patients. AF patients were older (72.6 vs 62.2; p < 0.001), had higher pre-stroke CHA₂DS₂-VASc score (median 3 vs 2; p < 0.001) and admission NIHSS (median 2 vs 1; p = 0.001); and more often hypertension (p = 0.045) and dyslipidaemia (p = 0.005) than non-AF patients. The arrhythmia was recurrent in 91.9% and asymptomatic in 93.2%. At 12-month follow-up anticoagulants usage was 97.3%. Discussion and conclusions: ICM was an effective tool for diagnosing underlying AF, capturing AF in 29% of the CS and TIA patients. AF was asymptomatic in most cases and would mainly have gone undiagnosed without ICM. The insertion and use of ICM was feasible for stroke physicians in stroke units.
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| 4. |
- Ratajczak-Tretel, B, et al.
(författare)
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Prediction of underlying atrial fibrillation in patients with a cryptogenic stroke : results from the NOR-FIB Study
- 2023
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Ingår i: Journal of Neurology. - 1432-1459. ; 270:8, s. 4049-4059
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Atrial fibrillation (AF) detection and treatment are key elements to reduce recurrence risk in cryptogenic stroke (CS) with underlying arrhythmia. The purpose of the present study was to assess the predictors of AF in CS and the utility of existing AF-predicting scores in The Nordic Atrial Fibrillation and Stroke (NOR-FIB) Study.METHOD: The NOR-FIB study was an international prospective observational multicenter study designed to detect and quantify AF in CS and cryptogenic transient ischaemic attack (TIA) patients monitored by the insertable cardiac monitor (ICM), and to identify AF-predicting biomarkers. The utility of the following AF-predicting scores was tested: AS5F, Brown ESUS-AF, CHA 2DS 2-VASc, CHASE-LESS, HATCH, HAVOC, STAF and SURF. RESULTS: In univariate analyses increasing age, hypertension, left ventricle hypertrophy, dyslipidaemia, antiarrhythmic drugs usage, valvular heart disease, and neuroimaging findings of stroke due to intracranial vessel occlusions and previous ischemic lesions were associated with a higher likelihood of detected AF. In multivariate analysis, age was the only independent predictor of AF. All the AF-predicting scores showed significantly higher score levels for AF than non-AF patients. The STAF and the SURF scores provided the highest sensitivity and negative predictive values, while the AS5F and SURF reached an area under the receiver operating curve (AUC) > 0.7.CONCLUSION: Clinical risk scores may guide a personalized evaluation approach in CS patients. Increasing awareness of the usage of available AF-predicting scores may optimize the arrhythmia detection pathway in stroke units.
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| 5. |
- Ratajczak-Tretel, B, et al.
(författare)
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Underlying causes of cryptogenic stroke and TIA in the nordic atrial fibrillation and stroke (NOR-FIB) study : the importance of comprehensive clinical evaluation
- 2023
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Ingår i: BMC Neurology. - : Springer Science and Business Media LLC. - 1471-2377. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cryptogenic stroke is a heterogeneous condition, with a wide spectrum of possible underlying causes for which the optimal secondary prevention may differ substantially. Attempting a correct etiological diagnosis to reduce the stroke recurrence should be the fundamental goal of modern stroke management.METHODS: Prospective observational international multicenter study of cryptogenic stroke and cryptogenic transient ischemic attack (TIA) patients clinically monitored for 12 months to assign the underlying etiology. For atrial fibrillation (AF) detection continuous cardiac rhythm monitoring with insertable cardiac monitor (Reveal LINQ, Medtronic) was performed. The 12-month follow-up data for 250 of 259 initially included NOR-FIB patients were available for analysis.RESULTS: After 12 months follow-up probable stroke causes were revealed in 43% patients, while 57% still remained cryptogenic. AF and atrial flutter was most prevalent (29%). In 14% patients other possible causes were revealed (small vessel disease, large-artery atherosclerosis, hypercoagulable states, other cardioembolism). Patients remaining cryptogenic were younger (p < 0.001), had lower CHA 2DS 2-VASc score (p < 0.001) on admission, and lower NIHSS score (p = 0.031) and mRS (p = 0.016) at discharge. Smoking was more prevalent in patients that were still cryptogenic (p = 0.014), while dyslipidaemia was less prevalent (p = 0.044). Stroke recurrence rate was higher in the cryptogenic group compared to the group where the etiology was revealed, 7.7% vs. 2.8%, (p = 0.091). CONCLUSION: Cryptogenic stroke often indicates the inability to identify the cause in the acute phase and should be considered as a working diagnosis until efforts of diagnostic work up succeed in identifying a specific underlying etiology. Timeframe of 6-12-month follow-up may be considered as optimal.TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02937077, EudraCT 2018-002298-23.
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| 6. |
- Smedsrud, P. H., et al.
(författare)
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Kvasir-Capsule, a video capsule endoscopy dataset
- 2021
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Ingår i: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Artificial intelligence (AI) is predicted to have profound effects on the future of video capsule endoscopy (VCE) technology. The potential lies in improving anomaly detection while reducing manual labour. Existing work demonstrates the promising benefits of AI-based computer-assisted diagnosis systems for VCE. They also show great potential for improvements to achieve even better results. Also, medical data is often sparse and unavailable to the research community, and qualified medical personnel rarely have time for the tedious labelling work. We present Kvasir-Capsule, a large VCE dataset collected from examinations at a Norwegian Hospital. Kvasir-Capsule consists of 117 videos which can be used to extract a total of 4,741,504 image frames. We have labelled and medically verified 47,238 frames with a bounding box around findings from 14 different classes. In addition to these labelled images, there are 4,694,266 unlabelled frames included in the dataset. The Kvasir-Capsule dataset can play a valuable role in developing better algorithms in order to reach true potential of VCE technology.
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| 7. |
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| 8. |
- Seiffge, D. J., et al.
(författare)
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Recanalization Therapies in Acute Ischemic Stroke Patients Impact of Prior Treatment With Novel Oral Anticoagulants on Bleeding Complications and Outcome A Pilot Study
- 2015
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Ingår i: Circulation. - : Ovid Technologies (Wolters Kluwer Health). - 0009-7322 .- 1524-4539. ; 132:13, s. 1261-1269
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Tidskriftsartikel (refereegranskat)abstract
- Background-We explored the safety of intravenous thrombolysis (IVT) or intra-arterial treatment (IAT) in patients with ischemic stroke on non-vitamin K antagonist oral anticoagulants (NOACs, last intake <48 hours) in comparison with patients (1) taking vitamin K antagonists (VKAs) or (2) without previous anticoagulation (no-OAC). Methods and Results-This is a multicenter cohort pilot study. Primary outcome measures were (1) occurrence of intracranial hemorrhage (ICH) in 3 categories: any ICH (ICH any), symptomatic ICH according to the criteria of the European Cooperative Acute Stroke Study II (ECASS-II) (sICH ECASS-II) and the National Institute of Neurological Disorders and Stroke (NINDS) thrombolysis trial (sICH NINDS); and (2) death (at 3 months). Cohorts were compared by using propensity score matching. Our NOAC cohort comprised 78 patients treated with IVT/IAT and the comparison groups of 441 VKA patients and 8938 no-OAC patients. The median time from last NOAC intake to IVT/IAT was 13 hours (interquartile range, 8-22 hours). In VKA patients, median pre-IVT/IAT international normalized ratio was 1.3 (interquartile range, 1.1-1.6). ICH any was observed in 18.4% NOAC patients versus 26.8% in VKA patients and 17.4% in no-OAC patients. sICH ECASS-II and sICH NINDS occurred in 2.6%/3.9% NOAC patients, in comparison with 6.5%/9.3% of VKA patients and 5.0%/7.2% of no-OAC patients, respectively. At 3 months, 23.0% of NOAC patients in comparison with 26.9% of VKA patients and 13.9% of no-OAC patients had died. Propensity score matching revealed no statistically significant differences. Conclusions-IVT/IAT in selected patients with ischemic stroke under NOAC treatment has a safety profile similar to both IVT/IAT in patients on subtherapeutic VKA treatment or in those without previous anticoagulation. However, further prospective studies are needed, including the impact of specific coagulation tests.
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| 9. |
- Howe, LJ, et al.
(författare)
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Within-sibship genome-wide association analyses decrease bias in estimates of direct genetic effects
- 2022
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 54:65, s. 581-
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Tidskriftsartikel (refereegranskat)abstract
- Estimates from genome-wide association studies (GWAS) of unrelated individuals capture effects of inherited variation (direct effects), demography (population stratification, assortative mating) and relatives (indirect genetic effects). Family-based GWAS designs can control for demographic and indirect genetic effects, but large-scale family datasets have been lacking. We combined data from 178,086 siblings from 19 cohorts to generate population (between-family) and within-sibship (within-family) GWAS estimates for 25 phenotypes. Within-sibship GWAS estimates were smaller than population estimates for height, educational attainment, age at first birth, number of children, cognitive ability, depressive symptoms and smoking. Some differences were observed in downstream SNP heritability, genetic correlations and Mendelian randomization analyses. For example, the within-sibship genetic correlation between educational attainment and body mass index attenuated towards zero. In contrast, analyses of most molecular phenotypes (for example, low-density lipoprotein-cholesterol) were generally consistent. We also found within-sibship evidence of polygenic adaptation on taller height. Here, we illustrate the importance of family-based GWAS data for phenotypes influenced by demographic and indirect genetic effects.
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| 10. |
- Beiske, A G, et al.
(författare)
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Health-related quality of life in secondary progressive multiple sclerosis.
- 2007
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Ingår i: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1352-4585 .- 1477-0970. ; 13:3, s. 386-92
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Tidskriftsartikel (refereegranskat)abstract
- Common disability scales in multiple sclerosis (MS) are often weighted towards physical disability. Non-motor symptoms such as depression, fatigue and pain substantially influence wellbeing in MS. Health-related quality of life (HRQoL) measures the broader impact of MS and might indicate less obvious disease burdens. We analysed HRQoL, using the Nottingham Health Profile Part I (NHP-I), among 345 secondary progressive MS (SPMS) patients participating in a randomized trial of interferon-beta1a (IFN-beta1a), 22 mug subcutaneously weekly, or matching placebo. The results did not reveal any beneficial effect of IFN-beta1a in any outcome measure. NHP-I sub- and sum scores were compared for 217 population controls and correlated with demographic and clinical disease variables. SPMS patients had lower NHP-I sum and all subscores than the controls. Patients experiencing disease progression reported worse NHP-I sum scores. Increased fatigue, Expanded Disability Status Scale (EDSS) and Arm Index scores were independently associated with reduction in several NHP-I subscores. SPMS patients had significantly lower HRQoL than controls and physical disability (EDSS and Arm Index), disease progression and fatigue strongly influenced this. MS.
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| 11. |
- Beiske, A. G., et al.
(författare)
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Health-related quality of life in secondary progressive multiple sclerosis
- 2007
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Ingår i: Multiple Sclerosis Journal. - : SAGE Publications. - 1477-0970 .- 1352-4585. ; 13:3, s. 386-392
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Tidskriftsartikel (refereegranskat)abstract
- Common disability scales in multiple sclerosis (MS) are often weighted towards physical disability. Non-motor symptoms such as depression, fatigue and pain substantially influence wellbeing in MS. Health-related quality of life (HRQoL) measures the broader impact of MS and might indicate less obvious disease burdens. We analysed HRQoL, using the Nottingham Health Profile Part I (NHP-I), among 345 secondary progressive MS (SPMS) patients participating in a randomized trial of interferon-beta 1a (IFN-beta 1a), 22 mu g subcutaneously weekly, or matching placebo. The results did not reveal any beneficial effect of IFN-beta 1a in any outcome measure. NHP-I sub- and sum scores were compared for 217 population controls and correlated with demographic and clinical disease variables. SPMS patients had lower NHP-I sum and all subscores than the controls. Patients experiencing disease progression reported worse NHP-I sum scores. Increased fatigue, Expanded Disability Status Scale (EDSS) and Arm Index scores were independently associated with reduction in several NHP-I subscores. SPMS patients had significantly lower HRQoL than controls and physical disability (EDSS and Arm Index), disease progression and fatigue strongly influenced this. MS influenced subdimensions such as pain, sleep and emotional reactions. Increased focus on optimizing symptomatic treatment and psychosocial patient care could improve patients' HRQoL.
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| 12. |
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| 15. |
- Liu, Jimmy Z, et al.
(författare)
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Dense genotyping of immune-related disease regions identifies nine new risk loci for primary sclerosing cholangitis.
- 2013
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:6, s. 670-5
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Tidskriftsartikel (refereegranskat)abstract
- Primary sclerosing cholangitis (PSC) is a severe liver disease of unknown etiology leading to fibrotic destruction of the bile ducts and ultimately to the need for liver transplantation. We compared 3,789 PSC cases of European ancestry to 25,079 population controls across 130,422 SNPs genotyped using the Immunochip. We identified 12 genome-wide significant associations outside the human leukocyte antigen (HLA) complex, 9 of which were new, increasing the number of known PSC risk loci to 16. Despite comorbidity with inflammatory bowel disease (IBD) in 72% of the cases, 6 of the 12 loci showed significantly stronger association with PSC than with IBD, suggesting overlapping yet distinct genetic architectures for these two diseases. We incorporated association statistics from 7 diseases clinically occurring with PSC in the analysis and found suggestive evidence for 33 additional pleiotropic PSC risk loci. Together with network analyses, these findings add to the genetic risk map of PSC and expand on the relationship between PSC and other immune-mediated diseases.
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| 16. |
- Maas, R. R., et al.
(författare)
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Progressive deafness–dystonia due to SERAC1 mutations: A study of 67 cases
- 2017
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Ingår i: Annals of Neurology. - : Wiley. - 0364-5134 .- 1531-8249. ; 82:6, s. 1004-1015
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Tidskriftsartikel (refereegranskat)abstract
- Objective: 3-Methylglutaconic aciduria, dystonia–deafness, hepatopathy, encephalopathy, Leigh-like syndrome (MEGDHEL) syndrome is caused by biallelic variants in SERAC1. Methods: This multicenter study addressed the course of disease for each organ system. Metabolic, neuroradiological, and genetic findings are reported. Results: Sixty-seven individuals (39 previously unreported) from 59 families were included (age range = 5 days–33.4 years, median age = 9 years). A total of 41 different SERAC1 variants were identified, including 20 that have not been reported before. With the exception of 2 families with a milder phenotype, all affected individuals showed a strikingly homogeneous phenotype and time course. Severe, reversible neonatal liver dysfunction and hypoglycemia were seen in >40% of all cases. Starting at a median age of 6 months, muscular hypotonia (91%) was seen, followed by progressive spasticity (82%, median onset = 15 months) and dystonia (82%, 18 months). The majority of affected individuals never learned to walk (68%). Seventy-nine percent suffered hearing loss, 58% never learned to speak, and nearly all had significant intellectual disability (88%). Magnetic resonance imaging features were accordingly homogenous, with bilateral basal ganglia involvement (98%); the characteristic “putaminal eye” was seen in 53%. The urinary marker 3-methylglutaconic aciduria was present in virtually all patients (98%). Supportive treatment focused on spasticity and drooling, and was effective in the individuals treated; hearing aids or cochlear implants did not improve communication skills. Interpretation: MEGDHEL syndrome is a progressive deafness–dystonia syndrome with frequent and reversible neonatal liver involvement and a strikingly homogenous course of disease. Ann Neurol 2017;82:1004–1015. © 2017 American Neurological Association
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| 21. |
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| 22. |
- Gray, Linsay, et al.
(författare)
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International differences in self-reported health measures in 33 major metropolitan areas in Europe
- 2012
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Ingår i: European Journal of Public Health. - : Oxford University Press (OUP). - 1101-1262 .- 1464-360X. ; 22:1, s. 40-47
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The increasing concentration of populations into large conurbations in recent decades has not been matched by international health assessments, which remain largely focused at the country level. We aimed to demonstrate the use of routine survey data to compare the health of large metropolitan centres across Europe and determine the extent to which differences are due to socio-economic factors.METHODS:Multilevel modelling of health survey data on 126 853 individuals from 33 metropolitan areas in the UK, Republic of Ireland, Sweden, Norway, Finland, Spain, Belgium and Germany compared general health, longstanding illness, acute sickness, psychological distress and obesity with the average for all areas, accounting for education and social class.RESULTS:We found some areas (Greater Glasgow; Greater Manchester, Cheshire and Merseyside; Northumberland, Tyne and Wear and South Yorkshire) had significantly higher levels of poor health. Other areas (West Flanders and Antwerp) had better than average health. Differences in individual socio-economic circumstances did not explain findings. With a few exceptions, acute sickness levels did not vary.CONCLUSION:Health tended to be worse in metropolitan areas in the north and west of the UK and the central belt and south east of Germany, and more favourable in Sweden and north west Belgium, even accounting for socio-economic composition of local populations. This study demonstrated that combining national health survey data covering different areas is viable but not without technical difficulties. Future comparisons between European regions should be made using standardized sampling, recruitment and data collection protocols, allowing proper monitoring of health inequalities.
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| 23. |
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| 24. |
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| 25. |
- Nakling, AE, et al.
(författare)
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Cognitive Deficits in Chronic Stroke Patients: Neuropsychological Assessment, Depression, and Self-Reports
- 2017
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Ingår i: Dementia and geriatric cognitive disorders extra. - : S. Karger AG. - 1664-5464. ; 7:2, s. 283-296
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> Following stroke, clinicians are challenged to detect and untangle symptoms of cognitive dysfunction and mood disorders. Additionally, they need to evaluate the informative value of self-reports to identify patients in need of further attendance. <b><i>Aims:</i></b> To examine the association between neuropsychological measures, symptoms of depression, and self-reported cognitive function. <b><i>Methods:</i></b> One-hundred and five chronic stroke patients underwent assessment covering 6 cognitive domains and answered the Hospital Anxiety and Depression Scale and the Memory and Thinking Scale from the Stroke Impact Scale 1 year after stroke. Age and gender difference in cognitive impairment were examined; linear regression was used to predict depression scores. Sensitivity and specificity analyses were used to validate self-reported functioning against performance on cognitive tests. <b><i>Results:</i></b> Cognitive impairment was observed in 60% of the patients in at least 1 cognitive domain. Cognitive performance was associated with symptoms of depression as well as with self-reported cognitive function. The final analyses revealed low sensitivity and specificity for the Memory and Thinking subscale from the Stroke Impact Scale. <b><i>Conclusion:</i></b> Cognitive impairment occurs frequently even in patients in a chronic phase after stroke and predicts symptoms of depression. Using the Stroke Impact Scale, clinicians should be aware of low sensitivity of self-reported cognitive function.
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| 26. |
- Weismuller, T. J., et al.
(författare)
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Patient Age, Sex, and Inflammatory Bowel Disease Phenotype Associate With Course of Primary Sclerosing Cholangitis
- 2017
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Ingår i: Gastroenterology. - : Elsevier BV. - 0016-5085 .- 1528-0012. ; 152:8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: Primary sclerosing cholangitis (PSC) is an orphan hepatobiliary disorder associated with inflammatory bowel disease (IBD). We aimed to estimate the risk of disease progression based on distinct clinical phenotypes in a large international cohort of patients with PSC. METHODS: We performed a retrospective outcome analysis of patients diagnosed with PSC from 1980 through 2010 at 37 centers in Europe, North America, and Australia. For each patient, we collected data on sex, clinician-reported age at and date of PSC and IBD diagnoses, phenotypes of IBD and PSC, and date and indication of IBD-related surgeries. The primary and secondary endpoints were liver transplantation or death (LTD) and hepatopancreatobiliary malignancy, respectively. Cox proportional hazards models were applied to determine the effects of individual covariates on rates of clinical events, with time-to-event analysis ascertained through Kaplan-Meier estimates. RESULTS: Of the 7121 patients in the cohort, 2616 met the primary endpoint (median time to event of 14.5 years) and 721 developed hepatopancreatobiliary malignancy. The most common malignancy was cholangiocarcinoma (n = 594); patients of advanced age at diagnosis had an increased incidence compared with younger patients (incidence rate: 1.2 per 100 patient-years for patients younger than 20 years old, 6.0 per 100 patient-years for patients 21-30 years old, 9.0 per 100 patient-years for patients 31-40 years old, 14.0 per 100 patient-years for patients 4150 years old, 15.2 per 100 patient-years for patients 51-60 years old, and 21.0 per 100 patient-years for patients older than 60 years). Of all patients with PSC studied, 65.5% were men, 89.8% had classical or large-duct disease, and 70.0% developed IBD at some point. Assessing the development of IBD as a time-dependent covariate, Crohn's disease and no IBD (both vs ulcerative colitis) were associated with a lower risk of LTD (unadjusted hazard ratio [HR], 0.62; P <.001 and HR, 0.90; P =.03, respectively) and malignancy (HR, 0.68; P =.008 and HR, 0.77; P =.004, respectively). Small-duct PSC was associated with a lower risk of LTD or malignancy compared with classic PSC (HR, 0.30 and HR, 0.15, respectively; both P <.001). Female sex was also associated with a lower risk of LTD or malignancy (HR, 0.88; P =.002 and HR, 0.68; P <.001, respectively). In multivariable analyses assessing the primary endpoint, small-duct PSC characterized a low-risk phenotype in both sexes (adjusted HR for men, 0.23; P <.001 and adjusted HR for women, 0.48; P =.003). Conversely, patients with ulcerative colitis had an increased risk of liver disease progression compared with patients with Crohn's disease (HR, 1.56; P <.001) or no IBD (HR, 1.15; P =.002). CONCLUSIONS: In an analysis of data from individual patients with PSC worldwide, we found significant variation in clinical course associated with age at diagnosis, sex, and ductal and IBD subtypes. The survival estimates provided might be used to estimate risk levels for patients with PSC and select patients for clinical trials.
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| 27. |
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| 28. |
- Ade, Peter, et al.
(författare)
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The Simons Observatory : science goals and forecasts
- 2019
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Ingår i: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :2
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Tidskriftsartikel (refereegranskat)abstract
- The Simons Observatory (SO) is a new cosmic microwave background experiment being built on Cerro Toco in Chile, due to begin observations in the early 2020s. We describe the scientific goals of the experiment, motivate the design, and forecast its performance. SO will measure the temperature and polarization anisotropy of the cosmic microwave background in six frequency bands centered at: 27, 39, 93, 145, 225 and 280 GHz. The initial con figuration of SO will have three small-aperture 0.5-m telescopes and one large-aperture 6-m telescope, with a total of 60,000 cryogenic bolometers. Our key science goals are to characterize the primordial perturbations, measure the number of relativistic species and the mass of neutrinos, test for deviations from a cosmological constant, improve our understanding of galaxy evolution, and constrain the duration of reionization. The small aperture telescopes will target the largest angular scales observable from Chile, mapping approximate to 10% of the sky to a white noise level of 2 mu K-arcmin in combined 93 and 145 GHz bands, to measure the primordial tensor-to-scalar ratio, r, at a target level of sigma(r) = 0.003. The large aperture telescope will map approximate to 40% of the sky at arcminute angular resolution to an expected white noise level of 6 mu K-arcmin in combined 93 and 145 GHz bands, overlapping with the majority of the Large Synoptic Survey Telescope sky region and partially with the Dark Energy Spectroscopic Instrument. With up to an order of magnitude lower polarization noise than maps from the Planck satellite, the high-resolution sky maps will constrain cosmological parameters derived from the damping tail, gravitational lensing of the microwave background, the primordial bispectrum, and the thermal and kinematic Sunyaev-Zel'dovich effects, and will aid in delensing the large-angle polarization signal to measure the tensor-to-scalar ratio. The survey will also provide a legacy catalog of 16,000 galaxy clusters and more than 20,000 extragalactic sources.
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| 29. |
- Dachlythra, Nadia, 1993-, et al.
(författare)
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The Simons Observatory : Beam Characterization for the Small Aperture Telescopes
- 2024
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 961:1
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Tidskriftsartikel (refereegranskat)abstract
- We use time-domain simulations of Jupiter observations to test and develop a beam reconstruction pipeline for the Simons Observatory Small Aperture Telescopes. The method relies on a mapmaker that estimates and subtracts correlated atmospheric noise and a beam fitting code designed to compensate for the bias caused by the mapmaker. We test our reconstruction performance for four different frequency bands against various algorithmic parameters, atmospheric conditions, and input beams. We additionally show the reconstruction quality as a function of the number of available observations and investigate how different calibration strategies affect the beam uncertainty. For all of the cases considered, we find good agreement between the fitted results and the input beam model within an ∼1.5% error for a multipole range ℓ = 30–700 and an ∼0.5% error for a multipole range ℓ = 50–200. We conclude by using a harmonic-domain component separation algorithm to verify that the beam reconstruction errors and biases observed in our analysis do not significantly bias the Simons Observatory r-measurement
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| 30. |
- Erdinc, Direnis, et al.
(författare)
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The disease-causing mutation p.F907I reveals a novel pathogenic mechanism for POL?-related diseases
- 2023
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Ingår i: Biochimica Et Biophysica Acta-Molecular Basis of Disease. - 0925-4439 .- 1879-260X. ; 1869:7
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Tidskriftsartikel (refereegranskat)abstract
- Mutations in the catalytic domain of mitochondrial DNA polymerase ? (POL?) cause a broad spectrum of clinical conditions. POL? mutations impair mitochondrial DNA replication, thereby causing deletions and/or depletion of mitochondrial DNA, which in turn impair biogenesis of the oxidative phosphorylation system. We here identify a patient with a homozygous p.F907I mutation in POL?, manifesting a severe clinical phenotype with develop-mental arrest and rapid loss of skills from 18 months of age. Magnetic resonance imaging of the brain revealed extensive white matter abnormalities, Southern blot of muscle mtDNA demonstrated depletion of mtDNA and the patient deceased at 23 months of age. Interestingly, the p.F907I mutation does not affect POL? activity on single-stranded DNA or its proofreading activity. Instead, the mutation affects unwinding of parental double-stranded DNA at the replication fork, impairing the ability of the POL? to support leading-strand DNA synthesis with the TWINKLE helicase. Our results thus reveal a novel pathogenic mechanism for POL?-related diseases.
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| 34. |
- Gramstad, A, et al.
(författare)
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Cognitive profile of elderly patients with mild stroke
- 2011
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Ingår i: Dementia and geriatric cognitive disorders extra. - : S. Karger AG. - 1664-5464. ; 1:1, s. 409-17
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Tidskriftsartikel (refereegranskat)abstract
- <i>Background:</i> A pattern characterizing cognitive deficits in mild stroke could help in differential diagnosis and rehabilitation planning. <i>Methods:</i> Fifty patients with mild stroke (modified Rankin scale ≤2 at discharge) aged >60 years were given the Mini Mental State Examination (MMSE), the Hopkins Verbal Learning Test-Revised (HVLT-R) and the Stroop test. <i>Results:</i> On HVLT-R, significant impairments were found in learning and recall, but not in delayed recall. The Stroop test revealed significant impairments in reading speed, but not in color-word interference. Using the MMSE, significant deficits were only found in the youngest age group.<i> Conclusion:</i> Elderly patients with mild stroke show deficits in verbal learning/recall and in reading speed, but not in the MMSE, delayed recall or color-word interference. The deficits are consistent with a mild-to-moderate brain dysfunction, with relative sparing of medial brain structures.
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| 35. |
- Hietbrink, Falco, et al.
(författare)
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What trauma patients need : the European dilemma
- 2022
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Ingår i: European Journal of Trauma and Emergency Surgery. - : Springer. - 1863-9933 .- 1863-9941.
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Tidskriftsartikel (refereegranskat)abstract
- There is a need for implementation and maturation of an inclusive trauma system in every country in Europe, with patient centered care by dedicated surgeons. This process should be initiated by physicians and medical societies, based on the best available evidence, and supported and subsequently funded by the government and healthcare authorities. A systematic approach to organizing all aspects of trauma will result in health gain in terms of quality of care provided, higher survival rates, better functional outcomes and quality of life. In addition, it will provide reliable data for both research, quality improvement and prevention programs. Severely injured patients need surgeons with broad technical and non-technical competencies to provide holistic, inclusive and compassionate care. Here we describe the philosophy of the surgical approach and define the necessary skills for trauma, both surgical and other, to improve outcome of severely injured patients. As surgery is an essential part of trauma care, surgeons play an important role for the optimal treatment of trauma patients throughout and after their hospital stay, including the intensive care unit (ICU). However, in most European countries, it might not be obvious to either the general public, patients or even the physicians that the surgeon must assume this responsibility in the ICU to optimize outcomes. The aim of this paper is to define key elements in terms of trauma systems, trauma-specific surgical skills and active critical care involvement, to organize and optimize trauma care in Europe.
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| 36. |
- Hikmat, O., et al.
(författare)
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Expanding the phenotypic spectrum of BCS1L-related mitochondrial disease
- 2021
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Ingår i: Annals of Clinical and Translational Neurology. - : Wiley. - 2328-9503. ; 8:11, s. 2155-2165
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To delineate the full phenotypic spectrum of BCS1L-related disease, provide better understanding of the genotype-phenotype correlations and identify reliable prognostic disease markers. Methods: We performed a retrospective multinational cohort study of previously unpublished patients followed in 15 centres from 10 countries. Patients with confirmed biallelic pathogenic BCS1L variants were considered eligible. Clinical, laboratory, neuroimaging and genetic data were analysed. Patients were stratified into different groups based on the age of disease onset, whether homozygous or compound heterozygous for the c.232A>G (p.Ser78Gly) variant, and those with other pathogenic BCS1L variants. Results: Thirty-three patients were included. We found that growth failure, lactic acidosis, tubulopathy, hepatopathy and early death were more frequent in those with disease onset within the first month of life. In those with onset after 1 month, neurological features including movement disorders and seizures were more frequent. Novel phenotypes, particularly involving movement disorder, were identified in this group. The presence of the c.232A>G (p.Ser78Gly) variant was associated with significantly worse survival and exclusively found in those with disease onset within the first month of life, whilst other pathogenic BCS1L variants were more frequent in those with later symptom onset. Interpretation: The phenotypic spectrum of BCS1L-related disease comprises a continuum of clinical features rather than a set of separate syndromic clinical identities. Age of onset defines BCS1L-related disease clinically and early presentation is associated with poor prognosis. Genotype correlates with phenotype in the presence of the c.232A>G (p.Ser78Gly) variant.
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| 39. |
- Klein, Richard J.T., et al.
(författare)
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Portfolio screening to support the mainstreaming of adaptation to climate change into development assistance
- 2007
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Ingår i: Climate change. - : Springer Science and Business Media LLC. - 0165-0009 .- 1573-1480. ; 84:1, s. 23-44
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Tidskriftsartikel (refereegranskat)abstract
- The need to mainstream adaptation to climate change into development planning and ongoing sectoral decision-making is increasingly recognised, and several bilateral and multilateral development agencies are starting to take an interest. Over the past years at least six development agencies have screened their project portfolios, generally with two goals in mind: (1) to ascertain the extent to which existing development projects already consider climate risks or address vulnerability to climate variability and change, and (2) to identify opportunities for incorporating climate change explicitly into future projects. As each portfolio screening was conducted independently, the broader lessons emerging from the screenings have not been systematically analysed. In this paper we assess the screening activities to date, focusing on both the results and the methods applied. Based on this assessment we identify opportunities for development agencies to expand their current focus on the links between climate and development. Most agencies already consider climate change as a real but uncertain threat to future development, but they have given less thought to how different development patterns might affect vulnerability to climate change. The screenings undertaken have shown the need to take a comprehensive approach to adaptation and its integration into development planning and sectoral decision-making, and a number of policy initiatives have been taken to promote such integration. We provide some initial guidance as to how portfolio screening can be carried out in a way that would allow agencies to assess systematically the relevance of climate change to their ongoing and planned development projects.
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| 40. |
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| 45. |
- Næss, Sigrid, et al.
(författare)
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Refinement of the MHC risk map in a scandinavian primary sclerosing cholangitis population
- 2014
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:12
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within the major histocompatibility complex (MHC) represent the strongest genetic susceptibility factors for primary sclerosing cholangitis (PSC). Identifying the causal variants within this genetic complex represents a major challenge due to strong linkage disequilibrium and an overall high physical density of candidate variants. We aimed to refine the MHC association in a geographically restricted PSC patient panel.
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| 46. |
- Schult, A. L., et al.
(författare)
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Colonoscopy quality improvement after initial training: A cross-sectional study of intensive short-term training
- 2023
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Ingår i: Endoscopy International Open. - : Georg Thieme Verlag KG. - 2364-3722 .- 2196-9736. ; 11:01
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Tidskriftsartikel (refereegranskat)abstract
- Background and study aims High-quality is crucial for the effectiveness of colonoscopy and can be achieved by high-quality training and verified with assessment of key performance indicators (KPIs) for colonoscopy such as cecum intubation rate (CIR), adenoma detection rate (ADR) and adequate polyp resection. Typically, trainees achieve adequate CIR after 275 procedures, but little is known about learning curves for KPIs after initial training.Methods This cross-sectional study includes work-up colonoscopies after a positive screening test with fecal occult blood testing (FIT) or sigmoidoscopy, performed by either trainees after 300 training colonoscopies or by consultants. Outcome measures were KPIs. We assessed inter-endoscopist variation in trainees and learning curves for trainees as a group. We also compared KPIs for trainees and consultants as a group.Results Data from 6,655 colonoscopies performed by 21 trainees and 921 colonoscopies performed by 17 consultants were included. Most trainees achieved target standards for main KPIs. With time, trainees shortened cecum intubation time and withdrawal time without decreasing their ADR, reduced the proportion of painful colonoscopies, and increased the adequate polyp resection rate (all P < 0.01). Compared to consultants, trainees had higher CIR (97.7 % vs. 96.3 %, P = 0.02), ADR after positive FIT (57.6 % vs. 50.3 %, P < 0.01), and proximal ADR after sigmoidoscopy screening (41.1 % vs. 29.8 %; P < 0.01), higher adequate polyp resection rate (94.9 % vs. 93.1 %, P = 0.01) and fewer serious adverse events (0.65 % vs. 1.41 %, P = 0.02).Conclusions Trainees performed high-quality colonoscopies and achieved international target standards. Several KPIs continuously improved after initial training. Trainees outperformed consultants on several KPIs.
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| 47. |
- Siibak, Triinu, et al.
(författare)
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A multi-systemic mitochondrial disorder due to a dominant p.Y955H disease variant in DNA polymerase gamma
- 2017
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 26:13, s. 2515-2525
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Tidskriftsartikel (refereegranskat)abstract
- Mutations in the mitochondrial DNA polymerase, POLG, are associated with a variety of clinical presentations, ranging from early onset fatal brain disease in Alpers syndrome to chronic progressive external ophthalmoplegia. The majority of mutations are linked with disturbances of mitochondrial DNA (mtDNA) integrity and maintenance. On a molecular level, depending on their location within the enzyme, mutations either lead to mtDNA depletion or the accumulation of multiple mtDNA deletions, and in some cases these molecular changes can be correlated to the clinical presentation. We identified a patient with a dominant p.Y955H mutation in POLG, presenting with a severe, early-onset multi-systemic mitochondrial disease with bilateral sensorineural hearing loss, cataract, myopathy, and liver failure. Using a combination of disease models of Drosophila melanogaster and in vitro biochemistry analysis, we compare the molecular consequences of the p.Y955H mutation to the well-documented p.Y955C mutation. We demonstrate that both mutations affect mtDNA replication and display a dominant negative effect, with the p.Y955H allele resulting in a more severe polymerase dysfunction.
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| 48. |
- Stranneheim, Henrik, et al.
(författare)
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Rapid pulsed whole genome sequencing for comprehensive acute diagnostics of inborn errors of metabolism
- 2014
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Ingår i: BMC Genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 15, s. 1090-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Massively parallel DNA sequencing (MPS) has the potential to revolutionize diagnostics, in particular for monogenic disorders. Inborn errors of metabolism (IEM) constitute a large group of monogenic disorders with highly variable clinical presentation, often with acute, nonspecific initial symptoms. In many cases irreversible damage can be reduced by initiation of specific treatment, provided that a correct molecular diagnosis can be rapidly obtained. MPS thus has the potential to significantly improve both diagnostics and outcome for affected patients in this highly specialized area of medicine. Results: We have developed a conceptually novel approach for acute MPS, by analysing pulsed whole genome sequence data in real time, using automated analysis combined with data reduction and parallelization. We applied this novel methodology to an in-house developed customized work flow enabling clinical-grade analysis of all IEM with a known genetic basis, represented by a database containing 474 disease genes which is continuously updated. As proof-of-concept, two patients were retrospectively analysed in whom diagnostics had previously been performed by conventional methods. The correct disease-causing mutations were identified and presented to the clinical team after 15 and 18 hours from start of sequencing, respectively. With this information available, correct treatment would have been possible significantly sooner, likely improving outcome. Conclusions: We have adapted MPS to fit into the dynamic, multidisciplinary work-flow of acute metabolic medicine. As the extent of irreversible damage in patients with IEM often correlates with timing and accuracy of management in early, critical disease stages, our novel methodology is predicted to improve patient outcome. All procedures have been designed such that they can be implemented in any technical setting and to any genetic disease area. The strategy conforms to international guidelines for clinical MPS, as only validated disease genes are investigated and as clinical specialists take responsibility for translation of results. As follow-up in patients without any known IEM, filters can be lifted and the full genome investigated, after genetic counselling and informed consent.
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| 49. |
- Sörensen, Lene, et al.
(författare)
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Expanded Screening of One Million Swedish Babies with R4S and CLIR for Post-Analytical Evaluation of Data.
- 2020
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Ingår i: International journal of neonatal screening. - : MDPI AG. - 2409-515X. ; 6:2
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Tidskriftsartikel (refereegranskat)abstract
- Sweden has one neonatal screening laboratory, receiving 115 to 120 thousand samples per year. Among the one million babies screened by tandem mass spectrometry from November 2010 until July 2019, a total of 665 babies were recalled and 311 verified as having one of the diseases screened for with this methodology, giving a positive predictive value (PPV) of 47% and an incidence of 1:3200. The PPV was high (41%) already in the first year after start of screening, thanks to the availability of the collaborative project Region 4 Stork database. The PPV is presently 58%. This improvement was achieved by the implementation of second-tier analyses in the screening for methylmalonic aciduria, propionic aciduria, isovaleric aciduria, and homocystinuria, and the employment of various post analytical tools of the Region 4 Stork, and its successor the collaborative laboratory integrated reports.
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| 50. |
- Torkildsen, J. V., et al.
(författare)
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App-Based Morphological Training Produces Lasting Effects on Word Knowledge in Primary School Children: A Randomized Controlled Trial
- 2022
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Ingår i: Journal of Educational Psychology. - : American Psychological Association (APA). - 0022-0663 .- 1939-2176. ; 114:4, s. 833-854
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Tidskriftsartikel (refereegranskat)abstract
- Morphemes, the smallest meaning-bearing units of language, recur in many words. Therefore, morphological knowledge can facilitate the comprehension of novel words. This study tested the effectiveness of a morphological training program on children's learning and retention of exposed words and morphologically related unexposed words compared with an active control condition. Norwegian second graders (N = 717) unselected for ability were individually randomized to either a morphological (n = 366) or a mathematical training program (n = 351). Both programs lasted for 8 weeks and were delivered as self-contained apps in a classroom setting. The morphological training built on the principle that frequency of target elements together with variation of nontarget elements can support implicit learning. Treatment-blind examiners assessed participants' meaning-based knowledge (word comprehension and definitions) and code-based knowledge (word reading fluency and spelling) at pretraining, immediately post training, and at follow-up 6 months later. An intention-to-treat analysis showed lasting effects of the morphological training on meaning-based knowledge of exposed words (posttest: d = .37; follow-up: d = .31) and unexposed words containing trained morphemes (posttest: d = .27; follow-up: d = .27) and code-based knowledge of exposed words (posttest: d = .22; follow-up: d = .13). For code-based knowledge of unexposed words, there were significant training effects at the posttest (d = .12) but not follow-up (d = .05). There were no significant effects on a far-transfer measure of general vocabulary. These results demonstrate that a brief morphological training program can produce lasting and educationally meaningful gains in students' word knowledge. Educational Impact and Implications Statement Words can consist of several meaningful parts, or morphemes, such as -ist in guitarist and re- in reuse. Understanding common morphemes helps children infer the meanings of new words. In this study, we tested the effects of working with an educational application (app) focusing on morphemes. Children completed app exercises such as sorting words or pictures according to their meaning, combining morphemes to build words, or identifying the correct word or morpheme to fit a sentence or picture context. We found that the app was effective in improving Norwegian second graders' ability to explain, understand, read, and spell words, including words which were not shown in the app, but which contained trained morphemes. The brief low-cost training produced long-term effects with a minimal burden on teachers.
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