| 1. |
- Frid, P., et al.
(författare)
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Migraine-associated common genetic variants confer greater risk of posterior vs. anterior circulation ischemic stroke☆
- 2022
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Ingår i: Journal of Stroke and Cerebrovascular Diseases. - : Elsevier BV. - 1052-3057. ; 31:8
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To examine potential genetic relationships between migraine and the two distinct phenotypes posterior circulation ischemic stroke (PCiS) and anterior circulation ischemic stroke (ACiS), we generated migraine polygenic risk scores (PRSs) and compared these between PCiS and ACiS, and separately vs. non-stroke control subjects. Methods: Acute ischemic stroke cases were classified as PCiS or ACiS based on lesion location on diffusion-weighted MRI. Exclusion criteria were lesions in both vascular territories or uncertain territory; supratentorial PCiS with ipsilateral fetal posterior cerebral artery; and cases with atrial fibrillation. We generated migraine PRS for three migraine phenotypes (any migraine; migraine without aura; migraine with aura) using publicly available GWAS data and compared mean PRSs separately for PCiS and ACiS vs. non-stroke control subjects, and between each stroke phenotype. Results: Our primary analyses included 464 PCiS and 1079 ACiS patients with genetic European ancestry. Compared to non-stroke control subjects (n=15396), PRSs of any migraine were associated with increased risk of PCiS (p=0.01–0.03) and decreased risk of ACiS (p=0.010–0.039). Migraine without aura PRSs were significantly associated with PCiS (p=0.008–0.028), but not with ACiS. When comparing PCiS vs. ACiS directly, migraine PRSs were higher in PCiS vs. ACiS for any migraine (p=0.001–0.010) and migraine without aura (p=0.032–0.048). Migraine with aura PRS did not show a differential association in our analyses. Conclusions: Our results suggest a stronger genetic overlap between unspecified migraine and migraine without aura with PCiS compared to ACiS. Possible shared mechanisms include dysregulation of cerebral vessel endothelial function.
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| 2. |
- Giese, A. K., et al.
(författare)
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Design and rationale for examining neuroimaging genetics in ischemic stroke The MRI-GENIE study
- 2017
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Ingår i: Neurology-Genetics. - : Ovid Technologies (Wolters Kluwer Health). - 2376-7839. ; 3:5
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To describe the design and rationale for the genetic analysis of acute and chronic cerebrovascular neuroimaging phenotypes detected on clinical MRI in patients with acute ischemic stroke (AIS) within the scope of the MRI-GENetics Interface Exploration (MRI-GENIE) study.& para;& para;Methods: MRI-GENIE capitalizes on the existing infrastructure of the Stroke Genetics Network (SiGN). In total, 12 international SiGN sites contributed MRIs of 3,301 patients with AIS. Detailed clinical phenotyping with the web-based Causative Classification of Stroke (CCS) system and genome-wide genotyping data were available for all participants. Neuroimaging analyses include the manual and automated assessments of established MRI markers. A high-throughput MRI analysis pipeline for the automated assessment of cerebrovascular lesions on clinical scans will be developed in a subset of scans for both acute and chronic lesions, validated against gold standard, and applied to all available scans. The extracted neuroimaging phenotypes will improve characterization of acute and chronic cerebrovascular lesions in ischemic stroke, including CCS subtypes, and their effect on functional outcomes after stroke. Moreover, genetic testing will uncover variants associated with acute and chronic MRI manifestations of cerebrovascular disease.& para;& para;Conclusions: The MRI-GENIE study aims to develop, validate, and distribute the MRI analysis platform for scans acquired as part of clinical care for patients with AIS, which will lead to (1) novel genetic discoveries in ischemic stroke, (2) strategies for personalized stroke risk assessment, and (3) personalized stroke outcome assessment.
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| 3. |
- Drake, Mattias, et al.
(författare)
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Diffusion-Weighted Imaging, MR Angiography, and Baseline Data in a Systematic Multicenter Analysis of 3,301 MRI Scans of Ischemic Stroke Patients-Neuroradiological Review Within the MRI-GENIE Study
- 2020
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Ingår i: Frontiers in Neurology. - : Frontiers Media SA. - 1664-2295. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Background:Magnetic resonance imaging (MRI) serves as a cornerstone in defining stroke phenotype and etiological subtype through examination of ischemic stroke lesion appearance and is therefore an essential tool in linking genetic traits and stroke. Building on baseline MRI examinations from the centralized and structured radiological assessments of ischemic stroke patients in the Stroke Genetics Network, the results of the MRI-Genetics Interface Exploration (MRI-GENIE) study are described in this work. Methods:The MRI-GENIE study included patients with symptoms caused by ischemic stroke (N= 3,301) from 12 international centers. We established and used a structured reporting protocol for all assessments. Two neuroradiologists, using a blinded evaluation protocol, independently reviewed the baseline diffusion-weighted images (DWIs) and magnetic resonance angiography images to determine acute lesion and vascular occlusion characteristics. Results:In this systematic multicenter radiological analysis of clinical MRI from 3,301 acute ischemic stroke patients according to a structured prespecified protocol, we identified that anterior circulation infarcts were most prevalent (67.4%), that infarcts in the middle cerebral artery (MCA) territory were the most common, and that the majority of large artery occlusions 0 to 48 h from ictus were in the MCA territory. Multiple acute lesions in one or several vascular territories were common (11%). Of 2,238 patients with unilateral DWI lesions, 52.6% had left-sided infarct lateralization (P= 0.013 for chi(2)test). Conclusions:This large-scale analysis of a multicenter MRI-based cohort of AIS patients presents a unique imaging framework facilitating the relationship between imaging and genetics for advancing the knowledge of genetic traits linked to ischemic stroke.
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| 4. |
- Frid, Petrea, et al.
(författare)
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Detailed phenotyping of posterior vs. anterior circulation ischemic stroke: a multi-center MRI study
- 2020
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Ingår i: Journal of Neurology. - : Springer Science and Business Media LLC. - 0340-5354 .- 1432-1459. ; 267, s. 649-658
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Tidskriftsartikel (refereegranskat)abstract
- Objective Posterior circulation ischemic stroke (PCiS) constitutes 20-30% of ischemic stroke cases. Detailed information about differences between PCiS and anterior circulation ischemic stroke (ACiS) remains scarce. Such information might guide clinical decision making and prevention strategies. We studied risk factors and ischemic stroke subtypes in PCiS vs. ACiS and lesion location on magnetic resonance imaging (MRI) in PCiS. Methods Out of 3,301 MRIs from 12 sites in the National Institute of Neurological Disorders and Stroke (NINDS) Stroke Genetics Network (SiGN), we included 2,381 cases with acute DWI lesions. The definition of ACiS or PCiS was based on lesion location. We compared the groups using Chi-squared and logistic regression. Results PCiS occurred in 718 (30%) patients and ACiS in 1663 (70%). Diabetes and male sex were more common in PCiS vs. ACiS (diabetes 27% vs. 23%, p < 0.05; male sex 68% vs. 58%, p < 0.001). Both were independently associated with PCiS (diabetes, OR = 1.29; 95% CI 1.04-1.61; male sex, OR = 1.46; 95% CI 1.21-1.78). ACiS more commonly had large artery atherosclerosis (25% vs. 20%, p < 0.01) and cardioembolic mechanisms (17% vs. 11%, p < 0.001) compared to PCiS. Small artery occlusion was more common in PCiS vs. ACiS (20% vs. 14%, p < 0.001). Small artery occlusion accounted for 47% of solitary brainstem infarctions. Conclusion Ischemic stroke subtypes differ between the two phenotypes. Diabetes and male sex have a stronger association with PCiS than ACiS. Definitive MRI-based PCiS diagnosis aids etiological investigation and contributes additional insights into specific risk factors and mechanisms of injury in PCiS.
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| 5. |
- Schirmer, M. D., et al.
(författare)
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White matter hyperintensity quantification in large-scale clinical acute ischemic stroke cohorts - The MRI-GENIE study
- 2019
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Ingår i: Neuroimage-Clinical. - : Elsevier BV. - 2213-1582. ; 23
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Tidskriftsartikel (refereegranskat)abstract
- White matter hyperintensity (WMH) burden is a critically important cerebrovascular phenotype linked to prediction of diagnosis and prognosis of diseases, such as acute ischemic stroke (AIS). However, current approaches to its quantification on clinical MRI often rely on time intensive manual delineation of the disease on T2 fluid attenuated inverse recovery (FLAIR), which hinders high-throughput analyses such as genetic discovery. In this work, we present a fully automated pipeline for quantification of WMH in clinical large-scale studies of AIS. The pipeline incorporates automated brain extraction, intensity normalization and WMH segmentation using spatial priors. We first propose a brain extraction algorithm based on a fully convolutional deep learning architecture, specifically designed for clinical FLAIR images. We demonstrate that our method for brain extraction outperforms two commonly used and publicly available methods on clinical quality images in a set of 144 subject scans across 12 acquisition centers, based on dice coefficient (median 0.95; inter-quartile range 0.94-0.95; p < 0.01) and Pearson correlation of total brain volume (r = 0.90). Subsequently, we apply it to the large-scale clinical multi-site MRI-GENIE study (N = 2783) and identify a decrease in total brain volume of -2.4 cc/year. Additionally, we show that the resulting total brain volumes can successfully be used for quality control of image preprocessing. Finally, we obtain WMH volumes by building on an existing automatic WMH segmentation algorithm that delineates and distinguishes between different cerebrovascular pathologies. The learning method mimics expert knowledge of the spatial distribution of the WMH burden using a convolutional auto-encoder. This enables successful computation of WMH volumes of 2533 clinical AIS patients. We utilize these results to demonstrate the increase of WMH burden with age (0.950 cc/year) and show that single site estimates can be biased by the number of subjects recruited.
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| 6. |
- Wu, O., et al.
(författare)
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Big Data Approaches to Phenotyping Acute Ischemic Stroke Using Automated Lesion Segmentation of Multi-Center Magnetic Resonance Imaging Data
- 2019
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Ingår i: Stroke. - : Ovid Technologies (Wolters Kluwer Health). - 0039-2499 .- 1524-4628. ; 50:7, s. 1734-1741
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose- We evaluated deep learning algorithms' segmentation of acute ischemic lesions on heterogeneous multi-center clinical diffusion-weighted magnetic resonance imaging (MRI) data sets and explored the potential role of this tool for phenotyping acute ischemic stroke. Methods- Ischemic stroke data sets from the MRI-GENIE (MRI-Genetics Interface Exploration) repository consisting of 12 international genetic research centers were retrospectively analyzed using an automated deep learning segmentation algorithm consisting of an ensemble of 3-dimensional convolutional neural networks. Three ensembles were trained using data from the following: (1) 267 patients from an independent single-center cohort, (2) 267 patients from MRI-GENIE, and (3) mixture of (1) and (2). The algorithms' performances were compared against manual outlines from a separate 383 patient subset from MRI-GENIE. Univariable and multivariable logistic regression with respect to demographics, stroke subtypes, and vascular risk factors were performed to identify phenotypes associated with large acute diffusion-weighted MRI volumes and greater stroke severity in 2770 MRI-GENIE patients. Stroke topography was investigated. Results- The ensemble consisting of a mixture of MRI-GENIE and single-center convolutional neural networks performed best. Subset analysis comparing automated and manual lesion volumes in 383 patients found excellent correlation (rho=0.92; P<0.0001). Median (interquartile range) diffusion-weighted MRI lesion volumes from 2770 patients were 3.7 cm(3) (0.9-16.6 cm(3)). Patients with small artery occlusion stroke subtype had smaller lesion volumes (P<0.0001) and different topography compared with other stroke subtypes. Conclusions- Automated accurate clinical diffusion-weighted MRI lesion segmentation using deep learning algorithms trained with multi-center and diverse data is feasible. Both lesion volume and topography can provide insight into stroke subtypes with sufficient sample size from big heterogeneous multi-center clinical imaging phenotype data sets.
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| 7. |
- Blanken, M. A. J. T., et al.
(författare)
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Sex-specifics of ECT outcome
- 2023
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Ingår i: Journal of Affective Disorders. - : ELSEVIER. - 0165-0327 .- 1573-2517. ; 326, s. 243-248
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Electroconvulsive therapy (ECT) is the most effective treatment for patients with severe major depressive disorder (MDD). Given the known sex differences in MDD, improved knowledge may provide more sex-specific recommendations in clinical guidelines and improve outcome. In the present study we examine sex differences in ECT outcome and its predictors. Methods: Clinical data from 20 independent sites participating in the Global ECT-MRI Research Collaboration (GEMRIC) were obtained for analysis, totaling 500 patients with MDD (58.6 % women) with a mean age of 54.8 years. Severity of depression before and after ECT was assessed with validated depression scales. Remission was defined as a HAM-D score of 7 points or below after ECT. Variables associated with remission were selected based on literature (i.e. depression severity at baseline, age, duration of index episode, and presence of psychotic symptoms). Results: Remission rates of ECT were independent of sex, 48.0 % in women and 45.7 % in men (X2(1) = 0.2, p = 0.70). In the logistic regression analyses, a shorter index duration was identified as a sex-specific predictor for ECT outcome in women (X2(1) = 7.05, p = 0.01). The corresponding predictive margins did show overlapping confidence intervals for men and women. Conclusion: The evidence provided by our study suggests that ECT as a biological treatment for MDD is equally effective in women and men. A shorter duration of index episode was an additional sex-specific predictor for remission in women. Future research should establish whether the confidence intervals for the corresponding predictive margins are overlapping, as we find, or not.
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| 8. |
- Bonkhoff, A. K., et al.
(författare)
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Deep profiling of multiple ischemic lesions in a large, multi-center cohort: Frequency, spatial distribution, and associations to clinical characteristics
- 2022
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Ingår i: Frontiers in Neuroscience. - : Frontiers Media SA. - 1662-453X .- 1662-4548. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- Background purposeA substantial number of patients with acute ischemic stroke (AIS) experience multiple acute lesions (MAL). We here aimed to scrutinize MAL in a large radiologically deep-phenotyped cohort. Materials and methodsAnalyses relied upon imaging and clinical data from the international MRI-GENIE study. Imaging data comprised both Fluid-attenuated inversion recovery (FLAIR) for white matter hyperintensity (WMH) burden estimation and diffusion-weighted imaging (DWI) sequences for the assessment of acute stroke lesions. The initial step featured the systematic evaluation of occurrences of MAL within one and several vascular supply territories. Associations between MAL and important imaging and clinical characteristics were subsequently determined. The interaction effect between single and multiple lesion status and lesion volume was estimated by means of Bayesian hierarchical regression modeling for both stroke severity and functional outcome. ResultsWe analyzed 2,466 patients (age = 63.4 +/- 14.8, 39% women), 49.7% of which presented with a single lesion. Another 37.4% experienced MAL in a single vascular territory, while 12.9% featured lesions in multiple vascular territories. Within most territories, MAL occurred as frequently as single lesions (ratio similar to 1:1). Only the brainstem region comprised fewer patients with MAL (ratio 1:4). Patients with MAL presented with a significantly higher lesion volume and acute NIHSS (7.7 vs. 1.7 ml and 4 vs. 3, p(FDR) < 0.001). In contrast, patients with a single lesion were characterized by a significantly higher WMH burden (6.1 vs. 5.3 ml, p(FDR) = 0.048). Functional outcome did not differ significantly between patients with single versus multiple lesions. Bayesian analyses suggested that the association between lesion volume and stroke severity between single and multiple lesions was the same in case of anterior circulation stroke. In case of posterior circulation stroke, lesion volume was linked to a higher NIHSS only among those with MAL. ConclusionMultiple lesions, especially those within one vascular territory, occurred more frequently than previously reported. Overall, multiple lesions were distinctly linked to a higher acute stroke severity, a higher total DWI lesion volume and a lower WMH lesion volume. In posterior circulation stroke, lesion volume was linked to a higher stroke severity in multiple lesions only.
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| 9. |
- Fischer, J., et al.
(författare)
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Prevalence of temporomandibular disorder in children and adolescents with juvenile idiopathic arthritis : a Norwegian cross-sectional multicentre study
- 2020
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Ingår i: BMC Oral Health. - : BioMed Central. - 1472-6831. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Children and adolescents with juvenile idiopathic arthritis (JIA) may suffer pain from temporomandibular disorder (TMD). Still, routines for the assessment of temporomandibular joint (TMJ) pain in health and dental care are lacking. The aims of this study were to examine the prevalence of TMD in children and adolescents with JIA compared to their healthy peers and to investigate potential associations between JIA and TMD. Methods This comparative cross-sectional study is part of a longitudinal multicentre study performed during 2015-2020, including 228 children and adolescents aged 4-16 years with a diagnosis of JIA according to the ILAR criteria. This particular substudy draws on a subset of data from the first study visit, including assessments of TMD as part of a broader oral health examination. Children and adolescents with JIA were matched with healthy controls according to gender, age, and centre site. Five calibrated examiners performed the clinical oral examinations according to a standardised protocol, including shortened versions of the diagnostic criteria for TMD (DC/TMD) and the TMJaw Recommendations for Clinical TMJ Assessment in Patients Diagnosed with JIA. Symptoms were recorded and followed by a clinical examination assessing the masticatory muscles and TMJs. Results In our cohort of 221 participants with JIA and 221 healthy controls, 88 (39.8%) participants with JIA and 25 (11.3%) healthy controls presented with TMD based on symptoms and clinical signs. Painful TMD during the last 30 days was reported in 59 (26.7%) participants with JIA vs. 10 (5.0%) of the healthy controls (p < 0.001). Vertical unassisted jaw movement was lower in participants with JIA than in controls, with means of 46.2 mm vs. 49.0 mm, respectively (p < 0.001). Among participants with JIA, a higher proportion of those using synthetic disease-modifying antirheumatic-drugs and biologic disease-modifying antirheumatic-drugs presented with painful masticatory muscles and TMJs at palpation. Conclusion Symptoms and clinical signs of TMD were seen in approximately half of the JIA patients compared to about one fourth of their healthy peers. Painful palpation to masticatory muscles and decreased vertical unassisted jaw movement were more frequent in participants with JIA than among healthy controls and should be part of both medical and dental routine examinations in patients with JIA.
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| 10. |
- Frid, Anders, et al.
(författare)
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New injection recommendations for patients with diabetes.
- 2010
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Ingår i: Diabetes & Metabolism. - 1878-1780. ; 36 Suppl 1, s. 3-18
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Tidskriftsartikel (refereegranskat)abstract
- AIM: Injections administered by patients are one of the mainstays of diabetes management. Proper injection technique is vital to avoiding intramuscular injections, ensuring appropriate delivery to the subcutaneous tissues and avoiding common complications such as lipohypertrophy. Yet few formal guidelines have been published summarizing all that is known about best practice. We propose new injection guidelines which are thoroughly evidence-based, written and vetted by a large group of international injection experts. METHODS: A systematic literature study was conducted for all peer-reviewed studies and publications which bear on injections in diabetes. An international group of experts met regularly over a two-year period to review this literature and draft the recommendations. These were then presented for review and revision to 127 experts from 27 countries at the TITAN workshop in September, 2009. RESULTS: Of 292 articles reviewed, 157 were found to meet the criteria of relevance to the recommendations. Each recommendation was graded by the weight it should have in daily practice and by its degree of support in the medical literature. The topics covered include The Role of the Professional, Psychological Challenges, Education, Site Care, Storage, Suspension and Priming, Injecting Process, Proper Use of Pens and Syringes, Insulin analogues, Human and Pre-mixed Insulins, GLP-1 analogs, Needle Length, Skin Folds, Lipohypertrophy, Rotation, Bleeding and Bruising, Pregnancy, Safety and Disposal. CONCLUSION: These injecting recommendations provide practical guidance and fill an important gap in diabetes management. If followed, they should help ensure comfortable, effective and largely complication-free injections.
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| 11. |
- Frid, Anders, et al.
(författare)
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The Third Injection Technique Workshop in Athens (TITAN).
- 2010
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Ingår i: Diabetes & Metabolism. - 1878-1780. ; 36 Suppl 1, s. 19-29
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Tidskriftsartikel (refereegranskat)abstract
- The first Injection Technique workshop brought together endocrinologists and injection experts from around the world in Strasbourg in 1997. From its work came groundbreaking recommendations which advanced best practices in areas such as the use of a skin fold when injecting. The second Injection Technique workshop, with an expanded format including nurses and diabetes educators, took place in Barcelona in 2000. The initial stimulus to use shorter injecting needles can be said to date from this meeting. The third Injection Technique workshop was held in Athens in September 2009 and involved 127 experts from across the globe. After a comprehensive review of all publications since 2000 as well as several unpublished studies, the attendees divided into smaller groups to debate and draft new injecting recommendations based on the new data and their collective experience. This paper summarizes all the formal presentations given at this practical consensus workshop.
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| 12. |
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| 13. |
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| 14. |
- Frid, M, et al.
(författare)
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Lower limb lymphedema: Experiences and perceptions of cancer patients in the late palliative stage
- 2006
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Ingår i: Journal of Palliative Care. - : SAGE Publications. - 0825-8597 .- 2369-5293. ; 22:1, s. 5-11
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Tidskriftsartikel (refereegranskat)abstract
- Lower limb lymphedema (LLL) is a common but neglected problem in palliative cancer patients. No studies have focused on these patients' experiences of lymphedema. The aims of this study were to explore patients' experiences regarding LLL and how they manage to deal with this in the late palliative stage. Methods: Thirteen patients with cancer-related LLL were included to satisfy a maximum variation sampling strategy. Interviews were analyzed using a qualitative phenomenographic method. Results: LLL influenced the patients' thoughts about the future. Body image was often strongly influenced. Interactions with other persons were perceived as both positive and negative, and a range of coping strategies were expressed. Conclusion: LLL can exert a considerable influence on the physical experiences and the psychosocial situation of cancer patients in palliative care. Areas in need of increased education, attention, and further research are highlighted.
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| 15. |
- Frid, P. E., et al.
(författare)
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The Posterior Cerebral Artery and its Main Cortical Branches Identified with Noninvasive Transcranial Color-Coded Duplex Sonography
- 2015
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Ingår i: Ultrasound International Open. - : Georg Thieme Verlag KG. - 2509-596X .- 2199-7152. ; 1:2, s. 53-57
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To differentiate PCA segments and cortical branches by means of transcranial color-coded duplex sonography (TCCD) and to measure flow parameters at rest and during visual stimulation. Materials and Methods: 60 healthy subjects with a good acoustic temporal bone window were examined. The main stem of the PCA (P1, P2 and P3) and 4 main cortical branches-the anterior temporal artery (ATA), the occipital temporal artery (OTA), the parietooccipital artery (POA) and the calcarine artery (CA)-were assessed using an axial transtemporal approach. Systolic and diastolic blood flow velocities (BFVs) were recorded at rest and during visual stimulation. Results: Identification of the P1 segment of the PCA was successful in 97.5% (117/120) of cases. The P2 and P3 segments were visualized in all cases. The 4 main cortical branches could be identified to varying degrees: ATA in 88%, OTA in 96%, POA in 69% and CA in 62%. There was an evoked flow response in the P2 main stem and in all cortical branches. The most pronounced increase in diastolic/systolic BFV after visual stimulation test was seen in the CA (42%/35%), followed by P2 (30%/24%), the POA (27%/27%), the OTA (16%/13%) and the ATA (9%/8%). Conclusion: Insonation through the temporal bone window with TCCD confidently allows the assessment of the P1 to P3 segments of the PCA as well as the 2 proximal branches, the ATA and the OTA. An ultrasound-based classification of PCA anatomy and its cortical branches may be used as a noninvasive method for the evaluation of posterior circulation pathology.
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| 16. |
- Giese, Anne Katrin, et al.
(författare)
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Design and rationale for examining neuroimaging genetics in ischemic stroke : The MRI-GENIE study
- 2017
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Ingår i: Neurology: Genetics. - 2376-7839. ; 3:5
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To describe the design and rationale for the genetic analysis of acute and chronic cerebrovascular neuroimaging phenotypes detected on clinical MRI in patients with acute ischemic stroke (AIS) within the scope of the MRI-GENetics Interface Exploration (MRI-GENIE) study. Methods: MRI-GENIE capitalizes on the existing infrastructure of the Stroke Genetics Network (SiGN). In total, 12 international SiGN sites contributedMRIs of 3,301 patients with AIS. Detailed clinical phenotyping with the web-based Causative Classification of Stroke (CCS) system and genome-wide genotyping data were available for all participants. Neuroimaging analyses include themanual and automated assessments of established MRI markers. A high-throughputMRI analysis pipeline for the automated assessment of cerebrovascular lesions on clinical scans will be developed in a subset of scans for both acute and chronic lesions, validated against gold standard, and applied to all available scans. The extracted neuroimaging phenotypes will improve characterization of acute and chronic cerebrovascular lesions in ischemic stroke, including CCS subtypes, and their effect on functional outcomes after stroke. Moreover, genetic testing will uncover variants associated with acute and chronic MRI manifestations of cerebrovascular disease.Conclusions: The MRI-GENIE study aims to develop, validate, and distribute the MRI analysis platform for scans acquired as part of clinical care for patients with AIS, which will lead to (1) novel genetic discoveries in ischemic stroke, (2) strategies for personalized stroke risk assessment, and (3) personalized stroke outcome assessment.
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| 17. |
- Hermanides, J, et al.
(författare)
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Sensor-augmented pump therapy lowers HbA(1c) in suboptimally controlled Type 1 diabetes; a randomized controlled trial.
- 2011
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Ingår i: Diabetic Medicine: A journal of the British Diabetic Association. - : Wiley. - 1464-5491. ; 28, s. 1158-1167
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Tidskriftsartikel (refereegranskat)abstract
- Aims To investigate the efficacy of sensor-augmented pump therapy vs. multiple daily injection therapy in patients with suboptimally controlled Type 1 diabetes. Methods In this investigator-initiated multi-centre trial (the Eurythmics Trial) in eight outpatient centres in Europe, we randomized 83 patients with Type 1 diabetes (40 women) currently treated with multiple daily injections, age 18-65 years and HbA(1c) ≥ 8.2% (≥ 66 mmol/mol) to 26 weeks of treatment with either a sensor-augmented insulin pump (n = 44) (Paradigm(®) REAL-Time) or continued with multiple daily injections (n = 39). Change in HbA(1c) between baseline and 26 weeks, sensor-derived endpoints and patient-reported outcomes were assessed. Results The trial was completed by 43/44 (98%) patients in the sensor-augmented insulin pump group and 35/39 (90%) patients in the multiple daily injections group. Mean HbA(1c) at baseline and at 26 weeks changed from 8.46% (sd 0.95) (69 mmol/mol) to 7.23% (sd 0.65) (56 mmol/mol) in the sensor-augmented insulin pump group and from 8.59% (sd 0.82) (70 mmol/mol) to 8.46% (sd 1.04) (69 mmol/mol) in the multiple daily injections group. Mean difference in change in HbA(1c) after 26 weeks was -1.21% (95% confidence interval -1.52 to -0.90, P < 0.001) in favour of the sensor-augmented insulin pump group. This was achieved without an increase in percentage of time spent in hypoglycaemia: between-group difference 0.0% (95% confidence interval -1.6 to 1.7, P = 0.96). There were four episodes of severe hypoglycaemia in the sensor-augmented insulin pump group and one episode in the multiple daily injections group (P = 0.21). Problem Areas in Diabetes and Diabetes Treatment Satisfaction Questionnaire scores improved in the sensor-augmented insulin pump group. Conclusions Sensor augmented pump therapy effectively lowers HbA(1c) in patients with Type 1 diabetes suboptimally controlled with multiple daily injections.
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| 18. |
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| 19. |
- Kumar, Nitin, et al.
(författare)
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Adaptation of host transmission cycle during Clostridium difficile speciation
- 2019
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:9, s. 1315-1320
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Tidskriftsartikel (refereegranskat)abstract
- Bacterial speciation is a fundamental evolutionary process characterized by diverging genotypic and phenotypic properties. However, the selective forces that affect genetic adaptations and how they relate to the biological changes that underpin the formation of a new bacterial species remain poorly understood. Here, we show that the spore-forming, healthcare-associated enteropathogen Clostridium difficile is actively undergoing speciation. Through large-scale genomic analysis of 906 strains, we demonstrate that the ongoing speciation process is linked to positive selection on core genes in the newly forming species that are involved in sporulation and the metabolism of simple dietary sugars. Functional validation shows that the new C. difficile produces spores that are more resistant and have increased sporulation and host colonization capacity when glucose or fructose is available for metabolism. Thus, we report the formation of an emerging C. difficile species, selected for metabolizing simple dietary sugars and producing high levels of resistant spores, that is adapted for healthcare-mediated transmission.
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| 20. |
- Nyman, Ulf, et al.
(författare)
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Preventing contrast medium-induced acute kidney injury: Side-by-side comparison of Swedish-ESUR guidelines
- 2018
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Ingår i: European Radiology. - : Springer Science and Business Media LLC. - 0938-7994 .- 1432-1084. ; 28:12, s. 5384-5395
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Tidskriftsartikel (refereegranskat)abstract
- A side-by-side comparison of updated guidelines regarding contrast medium-induced acute kidney injury (CI-AKI) from the Swedish Society of Uroradiology (SSUR) and the European Society of Urogenital Radiology (ESUR) is presented. The major discrepancies include a higher glomerular filtration rate (GFR) threshold as a risk factor for CI-AKI and for discontinuation of metformin by SSUR, i.e., < 45 ml/min versus < 30 ml/min/1.73 m(2) by ESUR, when intravenous or intra-arterial contrast media (CM) with second-pass renal exposure is administered. SSUR also continues to recommend consideration of traditional non-renal risk factors such as diabetes and congestive heart failure, while ESUR considers these factors as non-specific for CI-AKI and does not recommend anyconsideration. Contrary to ESUR, SSUR also recommends discontinuation of NSAID and nephrotoxic medication if possible. Insufficient evidence at the present time motivates the more cautionary attitude taken by SSUR. Furthermore, SSUR expresses GFR thresholds in absolute values in ml/min as recommended by the National Kidney Foundation for drugs excreted by glomerular filtration, while ESUR uses the relative GFR normalised to body surface area in ml/min/1.73 m(2). CM dose/GFR ratio thresholds established for coronary angiography/interventions are also applied as recommendations for CM-enhanced CT by SSUR, since SSUR regards coronary procedures as a second-pass renal exposure of CM with no obvious difference in the incidence of AKI compared withIV CM administration. Finally, SSUR recommends reducing the gram-iodine dose/GFR ratio from < 1.0 in patients not at risk to < 0.5 in patients at risk of CI-AKI, while ESUR has no such recommendation.Key Points center dot The more cautionary attitude taken by SSUR compared with that of ESUR is motivated by insufficient evidence regarding risk for contrast medium-induced acute kidney injuries (CI-AKI).center dot SSUR recommends that absolute and not relative GFR should be used when dosing drugs eliminated by the kidneys such as contrast media.center dot According to SSUR the gram-iodine dose/GFR ratio should be < 0.5 in patients at risk of CI-AKI, while ESUR has no such recommendation.
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| 21. |
- Warhuus, Jan P., et al.
(författare)
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Ready or not? : Nascent entrepreneurs' actions and the acquisition of external financing
- 2021
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Ingår i: International Journal of Entrepreneurial Behaviour & Research. - : Emerald Group Publishing Limited. - 1355-2554 .- 1758-6534. ; 27:6, s. 1605-1628
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Tidskriftsartikel (refereegranskat)abstract
- PurposeThis study offers empirical evidence from a nationally representative panel dataset of nascent entrepreneurs (PSED-II) regarding when external financing is acquired and how certain factors affect this timing during the cumulative process of nascent entrepreneurs taking actions toward establishing an operational entity. By assessing the relationship between the external financing event and the cumulative set of actions that nascent entrepreneurs undertake to create new businesses, we improve our understanding of how the timing of acquiring external financing affects organizational survival and growth.Design/methodology/approachWe apply nonparametric and semiparametric survival analysis techniques to a nationally representative panel dataset of nascent entrepreneurs. This ascertains the probability of an external financing event at any given moment in time and a set of startup conditions that we hypothesize will affect this timing. First, we use Kaplan-Meier analysis to explore when external financing occurs during new business creation. We then use discrete-time survival analysis to investigate whether certain startup conditions affect when external financing occurs. Finally, we conduct a test of independence to examine the external financing event relative to other startup activities completed during new business creation.FindingsNascent entrepreneurs tend to acquire external funding relatively late in the new venture startup process - on average, about two-thirds of the way from conceiving of the idea and becoming operational. They tend to take actions that are less resource-demanding early in the startup process to build their organizations to a fundable stage. Net worth tends to speed up the acquisition of external funding as wealthy entrepreneurs tend to ask for funding earlier in the process. Finally, entrepreneurs in capital-intensive industries do not seem to get outside funding before entrepreneurs in other industries.Originality/valueThis study is unique in three ways. First, we investigate the timing of the highly important external financing event. Timing is critical in unpacking and making sense of the very early stages of a new business and in guiding entrepreneurs and students about when to do what. Second, we do so in a subsample of preoperational, nascent, funded entrepreneurs derived from a nationally representative panel dataset of startup attempts. Third, our findings provide a counter-intuitive yet systematic understanding of organizational emergence and very early-stage financing.
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| 22. |
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