| 1. |
- Beecham, Ashley H, et al.
(författare)
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Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis.
- 2013
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:11, s. 1353-60
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Tidskriftsartikel (refereegranskat)abstract
- Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P < 1.0 × 10(-4)). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls. In these 80,094 individuals of European ancestry, we identified 48 new susceptibility variants (P < 5.0 × 10(-8)), 3 of which we found after conditioning on previously identified variants. Thus, there are now 110 established multiple sclerosis risk variants at 103 discrete loci outside of the major histocompatibility complex. With high-resolution Bayesian fine mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals.
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| 2. |
- Andersson, Rolf, 1943-, et al.
(författare)
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Cutaneous manifestations of internal disease
- 2008
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Ingår i: Drug Discovery Today. - : Elsevier. - 1740-6765. ; 5:1, s. e113-e123
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Tidskriftsartikel (refereegranskat)abstract
- The skin mirrors the individual's well being. Visible for both the patient and the attending physician, it can be a source of information for the diagnosis of multi-system diseases and diseases of internal organs. Therapy is usually directed at the primary disease. Pharmaco-therapeutic options for internal diseases are at present not always optimal and specific management of side effects of drugs with vital indication may be necessary. Better understanding of the mechanisms of the cutaneous manifestations may help develop more efficacious, better tolerated therapy and improve the patient's situation.
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| 3. |
- Freedman, Ben, et al.
(författare)
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Screening for Atrial Fibrillation A Report of the AF-SCREEN International Collaboration
- 2017
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Ingår i: Circulation. - : LIPPINCOTT WILLIAMS & WILKINS. - 0009-7322 .- 1524-4539. ; 135:19, s. 1851-
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Tidskriftsartikel (refereegranskat)abstract
- Approximately 10% of ischemic strokes are associated with atrial fibrillation (AF) first diagnosed at the time of stroke. Detecting asymptomatic AF would provide an opportunity to prevent these strokes by instituting appropriate anticoagulation. The AF-SCREEN international collaboration was formed in September 2015 to promote discussion and research about AF screening as a strategy to reduce stroke and death and to provide advocacy for implementation of country-specific AF screening programs. During 2016, 60 expert members of AF-SCREEN, including physicians, nurses, allied health professionals, health economists, and patient advocates, were invited to prepare sections of a draft document. In August 2016, 51 members met in Rome to discuss the draft document and consider the key points arising from it using a Delphi process. These key points emphasize that screen-detected AF found at a single timepoint or by intermittent ECG recordings over 2 weeks is not a benign condition and, with additional stroke factors, carries sufficient risk of stroke to justify consideration of anticoagulation. With regard to the methods of mass screening, handheld ECG devices have the advantage of providing a verifiable ECG trace that guidelines require for AF diagnosis and would therefore be preferred as screening tools. Certain patient groups, such as those with recent embolic stroke of uncertain source (ESUS), require more intensive monitoring for AF. Settings for screening include various venues in both the community and the clinic, but they must be linked to a pathway for appropriate diagnosis and management for screening to be effective. It is recognized that health resources vary widely between countries and health systems, so the setting for AF screening should be both country-and health system-specific. Based on current knowledge, this white paper provides a strong case for AF screening now while recognizing that large randomized outcomes studies would be helpful to strengthen the evidence base.
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| 4. |
- Henricson, Joakim, et al.
(författare)
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Diffuse Reflectance Spectroscopy : Getting the Capillary Refill Test Under Ones Thumb
- 2017
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Ingår i: Journal of Visualized Experiments. - : MyJove Corporation. - 1940-087X. ; :130
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Tidskriftsartikel (refereegranskat)abstract
- The capillary refill test was introduced in 1947 to help estimate circulatory status in critically ill patients. Guidelines commonly state that refill should occur within 2 s after releasing 5 s of firm pressure (e.g., by the physicians finger) in the normal healthy supine patient. A slower refill time indicates poor skin perfusion, which can be caused by conditions including sepsis, blood loss, hypoperfusion, and hypothermia. Since its introduction, the clinical usefulness of the test has been debated. Advocates point out its feasibility and simplicity and claim that it can indicate changes in vascular status earlier than changes in vital signs such as heart rate. Critics, on the other hand, stress that the lack of standardization in how the test is performed and the highly subjective nature of the naked eye assessment, as well as the tests susceptibility to ambient factors, markedly lowers the clinical value. The aim of the present work is to describe in detail the course of the refill event and to suggest potentially more objective and exact endpoint values for the capillary refill test using diffuse polarization spectroscopy.
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| 5. |
- Holmes, Michael V., et al.
(författare)
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Secretory Phospholipase A(2)-IIA and Cardiovascular Disease
- 2013
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Ingår i: Journal of the American College of Cardiology. - : Elsevier. - 0735-1097 .- 1558-3597. ; 62:21, s. 1966-1976
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Tidskriftsartikel (refereegranskat)abstract
- Objectives This study sought to investigate the role of secretory phospholipase A(2) (sPLA(2))-IIA in cardiovascular disease. less thanbrgreater than less thanbrgreater thanBackground Higher circulating levels of sPLA(2)-IIA mass or sPLA(2) enzyme activity have been associated with increased risk of cardiovascular events. However, it is not clear if this association is causal. A recent phase III clinical trial of an sPLA(2) inhibitor (varespladib) was stopped prematurely for lack of efficacy. less thanbrgreater than less thanbrgreater thanMethods We conducted a Mendelian randomization meta-analysis of 19 general population studies (8,021 incident, 7,513 prevalent major vascular events [MVE] in 74,683 individuals) and 10 acute coronary syndrome (ACS) cohorts (2,520 recurrent MVE in 18,355 individuals) using rs11573156, a variant in PLA2G2A encoding the sPLA(2)-IIA isoenzyme, as an instrumental variable. less thanbrgreater than less thanbrgreater thanResults PLA2G2A rs11573156 C allele associated with lower circulating sPLA(2)-IIA mass (38% to 44%) and sPLA(2) enzyme activity (3% to 23%) per C allele. The odds ratio (OR) for MVE per rs11573156 C allele was 1.02 (95% confidence interval [CI]: 0.98 to 1.06) in general populations and 0.96 (95% CI: 0.90 to 1.03) in ACS cohorts. In the general population studies, the OR derived from the genetic instrumental variable analysis for MVE for a 1-log unit lower sPLA(2)-IIA mass was 1.04 (95% CI: 0.96 to 1.13), and differed from the non-genetic observational estimate (OR: 0.69; 95% CI: 0.61 to 0.79). In the ACS cohorts, both the genetic instrumental variable and observational ORs showed a null association with MVE. Instrumental variable analysis failed to show associations between sPLA2 enzyme activity and MVE. less thanbrgreater than less thanbrgreater thanConclusions Reducing sPLA(2)-IIA mass is unlikely to be a useful therapeutic goal for preventing cardiovascular events.
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| 6. |
- Kihlman, Henrik, 1973-, et al.
(författare)
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Low-cost automation for aircraft assembly
- 2004
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Ingår i: SAE Technical Paper Series. - 400 Commonwealth Drive, Warrendale, PA, United States : SAE International. - 0148-7191.
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Konferensbidrag (refereegranskat)abstract
- In this paper solution for low-cost automation of aircraft assembly is presented. The concept of this development is closely related to "Lean Automation", which in this case concerns the use of modern standard equipment such as standard robots, PC-computers and a newlydeveloped spatial sensor system for prec1s1on measurements of positions. The robot is used to perform reconfiguration of tooling modules that arepossible to be configured/reconfigured in six degrees of freedom. A prototype developed as the result of an EU-project called ADFAST* has been evaluated at Linköping University in Sweden. Technical functionality is reported where the robot manages to configure the flexible tooling modules to a total error bellow 50 μm. This paper presents the resu~s on the portion of the project addressing robot, metrology system and tooling.
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| 7. |
- Papachristou, Panagiotis, et al.
(författare)
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Evaluation of an artificial intelligence-based decision support for the detection of cutaneous melanoma in primary care: a prospective real-life clinical trial
- 2024
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Ingår i: BRITISH JOURNAL OF DERMATOLOGY. - : OXFORD UNIV PRESS. - 0007-0963 .- 1365-2133. ; 191:1, s. 125-133
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Tidskriftsartikel (refereegranskat)abstract
- Background Use of artificial intelligence (AI), or machine learning, to assess dermoscopic images of skin lesions to detect melanoma has, in several retrospective studies, shown high levels of diagnostic accuracy on par with - or even outperforming - experienced dermatologists. However, the enthusiasm around these algorithms has not yet been matched by prospective clinical trials performed in authentic clinical settings. In several European countries, including Sweden, the initial clinical assessment of suspected skin cancer is principally conducted in the primary healthcare setting by primary care physicians, with or without access to teledermoscopic support from dermatology clinics.Objectives To determine the diagnostic performance of an AI-based clinical decision support tool for cutaneous melanoma detection, operated by a smartphone application (app), when used prospectively by primary care physicians to assess skin lesions of concern due to some degree of melanoma suspicion.Methods This prospective multicentre clinical trial was conducted at 36 primary care centres in Sweden. Physicians used the smartphone app on skin lesions of concern by photographing them dermoscopically, which resulted in a dichotomous decision support text regarding evidence for melanoma. Regardless of the app outcome, all lesions underwent standard diagnostic procedures (surgical excision or referral to a dermatologist). After investigations were complete, lesion diagnoses were collected from the patients' medical records and compared with the app's outcome and other lesion data.Results In total, 253 lesions of concern in 228 patients were included, of which 21 proved to be melanomas, with 11 thin invasive melanomas and 10 melanomas in situ. The app's accuracy in identifying melanomas was reflected in an area under the receiver operating characteristic (AUROC) curve of 0.960 [95% confidence interval (CI) 0.928-0.980], corresponding to a maximum sensitivity and specificity of 95.2% and 84.5%, respectively. For invasive melanomas alone, the AUROC was 0.988 (95% CI 0.965-0.997), corresponding to a maximum sensitivity and specificity of 100% and 92.6%, respectively.Conclusions The clinical decision support tool evaluated in this investigation showed high diagnostic accuracy when used prospectively in primary care patients, which could add significant clinical value for primary care physicians assessing skin lesions for melanoma. We investigated the diagnostic performance of an AI-based decision support in the form of a mobile app to detect melanoma when used by primary care physicians. The app proved to have high levels of diagnostic accuracy in distinguishing melanomas from other skin lesions. We conclude that it appears to be a potentially valuable diagnostic aid for the primary care physician in the assessment of skin lesions of concern.
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| 8. |
- Rådholm, Karin, et al.
(författare)
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Older age is a strong predictor for poor outcome in intracerebral haemorrhage : the INTERACT2 study
- 2015
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Ingår i: Age and Ageing. - : Oxford University Press. - 0002-0729 .- 1468-2834. ; 44:3, s. 422-427
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE:: Global ageing contributes greatly to the burden of stroke. We investigated the influence of age on the baseline profile and on outcomes in acute intracerebral haemorrhage (ICH) among participants of the INTERACT2 study.METHODS:: INTERACT2 was an international, randomised controlled trial in 2839 patients with spontaneous ICH within 6 h of onset and elevated systolic blood pressure (SBP; 150-220 mmHg) who were allocated to receive intensive (target SBP <140 mmHg within 1 h) or guideline-recommended (target SBP <180 mmHg) blood pressure lowering treatment. Stroke severity was assessed with the National Institutes of Health Stroke Scale. Poor outcome was defined as death or major disability ('dependency', modified Rankin Scale scores 3-6) at 90 days. Health-related quality of life (HRQoL) was assessed with the European Quality of Life-5 Dimensions (EQ-5D) questionnaire. Associations between age and outcomes were analysed in multivariable logistic regression models.RESULTS:: Stroke severity increased in categories of older age (P-trend 0.002). Stroke patients over 75 years old were four times more likely to die or be disabled at 90 days than those <52 years when other confounders were accounted for (odds ratio 4.36, 95% confidence interval 3.12-6.08). Older age was also associated with decreasing HRQoL, across mobility, self-care, usual activities and depression (all P-trend <0.001), and pain or discomfort (P-trend 0.022).CONCLUSION:: In the INTERACT2 cohort, older people had more severe ICH and worse outcomes (death, major disability and HRQoL). These data will help guide clinicians manage older people with haemorrhagic stroke. Clinical Trial Registration: http://www.clinicaltrials.gov (NCT00716079).
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| 9. |
- Sonnenblick, Amir, et al.
(författare)
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Final 10-year results of the Breast International Group 2-98 phase III trial and the role of Ki67 in predicting benefit of adjuvant docetaxel in patients with oestrogen receptor positive breast cancer
- 2015
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Ingår i: European Journal of Cancer. - : Elsevier. - 0959-8049 .- 1879-0852. ; 51:12, s. 1481-1489
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Breast International Group (BIG) 2-98 is a randomised phase III trial that tested the effect of adding docetaxel, either in sequence to or in combination with anthracycline-based adjuvant chemotherapy, in women with node-positive breast cancer (BC). Here, we present the 10-year final trial safety and efficacy analyses. We also report an exploratory analysis on the predictive value of Ki67 for docetaxel efficacy, in the BIG 2-98 and using a pooled analysis of three other randomised trials. Patients and methods: 2887 patients were randomly assigned in a 2 x 2 trial design to one of four treatments. The primary objective was to evaluate the overall efficacy of docetaxel on disease free survival (DFS). Secondary objectives included comparisons of sequential docetaxel versus sequential control arm, safety and overall survival (OS). Ki67 expression was centrally evaluated by immunohistochemistry. Results: After a median follow-up of 10.1 years, the addition of docetaxel did not significantly improve DFS or OS (hazard ratio (HR) = 0.91, 95% confidence interval (CI) = 0.81-1.04; P = 0.16 and HR = 0.88, 95% CI = 0.76-1.03; P = 0.11, respectively). Sequential docetaxel did not improve DFS compared to the sequential control arm (HR = 0.86, 95% CI = 0.721.03; P = 0.10). In oestrogen receptor (ER)-positive tumours with Ki67 greater than= 14%, the addition of docetaxel resulted in 5.4% improvement in 10-year OS (P = 0.03, test for interaction = 0.1). In a multivariate model, there was a trend for improved DFS and OS in ER-positive patients with high Ki67 and treated with docetaxel (HR = 0.79, 95% CI = 0.63-1.01; P = 0.05 and HR = 0.76, 95% CI = 0.57-1.01; P = 0.06, respectively). A pooled analysis of four randomised trials showed a benefit of taxanes in highly proliferative ER-positive disease but not in low proliferating tumours (interaction test P = 0.01). Conclusion: The DFS benefit previously demonstrated with sequential docetaxel is no longer observed at 10 years. However, an exploratory analysis suggested a benefit of docetaxel in patients with highly proliferative ER-positive BC.
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| 10. |
- Speakman, John R., et al.
(författare)
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Total daily energy expenditure has declined over the past three decades due to declining basal expenditure, not reduced activity expenditure
- 2023
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Ingår i: Nature Metabolism. - : NATURE PORTFOLIO. - 2522-5812. ; 5:4, s. 579-588
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Obesity is caused by a prolonged positive energy balance(1,2). Whether reduced energy expenditure stemming from reduced activity levels contributes is debated(3,4). Here we show that in both sexes, total energy expenditure (TEE) adjusted for body composition and age declined since the late 1980s, while adjusted activity energy expenditure increased over time. We use the International Atomic Energy Agency Doubly Labelled Water database on energy expenditure of adults in the United States and Europe (n = 4,799) to explore patterns in total (TEE: n = 4,799), basal (BEE: n = 1,432) and physical activity energy expenditure (n = 1,432) over time. In males, adjusted BEE decreased significantly, but in females this did not reach significance. A larger dataset of basal metabolic rate (equivalent to BEE) measurements of 9,912 adults across 163 studies spanning 100 years replicates the decline in BEE in both sexes. We conclude that increasing obesity in the United States/Europe has probably not been fuelled by reduced physical activity leading to lowered TEE. We identify here a decline in adjusted BEE as a previously unrecognized factor.
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