| 51. |
- Lindberger, M, et al.
(författare)
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Gabapentin versus vigabatrin as first add-on for patients with partial seizures that failed to respond to monotherapy: a randomized, double-blind, dose titration study. GREAT Study Investigators Group. Gabapentin in Refractory Epilepsy Add-on Treatment.
- 2000
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Ingår i: Epilepsia. - : Wiley. - 0013-9580 .- 1528-1167. ; 41:10, s. 1289-95
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Tidskriftsartikel (refereegranskat)abstract
- Our objective was to compare the efficacy and safety of gabapentin and vigabatrin as first-line add-on treatment in patients with partial epilepsy.This was a multicenter, double-blind, randomized dose titration study. After baseline assessment and randomization, the dose could be increased if seizures persisted and reduced if side effects occurred. Health-related quality of life was assessed at baseline and at the end of the study. By a protocol amendment post hoc, all randomized patients were offered a standardized perimetry examination at the end of the study. Improvement rate was the proportion of patients with a reduction of seizure frequency of at least 50% during an 8-week period without any adverse events causing withdrawal.One hundred two patients were randomized and analyzed on an intent-to-treat basis. The improvement rate was 48% in the gabapentin group and 56% in the vigabatrin group. The improvement rate, when per protocol criteria were fulfilled, was 57% in the gabapentin group and 59% in the vigabatrin group. The proportion of seizure-free patients was 31% in the gabapentin group and 39% in the vigabatrin group. There was no difference in quality-of-life scores between the groups. Perimetry after termination of the study on 64 patients showed abnormal results in 3 of 32 patients in the vigabatrin group.Approximately one third of the patients in both groups became seizure-free. Although no major differences were seen in terms of the improvement rate between the groups, equivalence between the two drugs was not found.
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| 52. |
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| 53. |
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| 54. |
- Lukmanji, S., et al.
(författare)
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Accuracy of an online tool to assess appropriateness for an epilepsy surgery evaluation-A population-based Swedish study
- 2018
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Ingår i: Epilepsy Research. - : Elsevier BV. - 0920-1211. ; 145, s. 140-144
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The Canadian Appropriateness of Epilepsy Surgery (CASES) tool was developed to help physicians identify patients who should be referred for an epilepsy surgery evaluation. The aim of this study was to determine the accuracy of this tool using a population-based cohort registry (the Swedish National Epilepsy Surgery Register) of patients who underwent epilepsy surgery between 1990 and 2012. Methods: Overall, 1044 patients met eligibility criteria for the study and were deemed to be surgical candidates by epilepsy experts. Demographic and epilepsy related characteristics were examined and summarized using descriptive statistics. A CASES appropriateness score was calculated for each of these patients. Chi squared analyses or fisher's exact tests were used to determine if there were any relationships between demographic and epilepsy related characteristics not captured in the tool and appropriateness scores. Results: The mean appropriateness score was 8.6 and 985 (Sensitivity: 94.35%; 95% CI, 92.77%-95.60%) patients were appropriate, 46 (4.41%; 95% CI, 3.31%-5.84%) were uncertain, and 13 (1.25%; 95% CI, 0.72%-2.13%) were inappropriate for an epilepsy surgery evaluation. The mean necessity score, which was only calculated for the 985 appropriate patients, was 8.7. All 13 inappropriate patients had tried less than two antiepileptic drugs (AEDs). In addition, age at onset of epilepsy and age at epilepsy surgery were both significantly associated with appropriateness score. Conclusions: These results demonstrate that the CASES tool is highly sensitive as it designated 94.3% of epilepsy surgery patients as appropriate for an epilepsy surgery evaluation. All of those classified as inappropriate were not drug resistant, as they had not yet tried two AEDs.
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| 55. |
- MALMGREN, A, et al.
(författare)
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OPTIMAL STATE-FEEDBACK CONTROL WITH A PRESCRIBED CONTRACTION PROPERTY
- 1994
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Ingår i: AUTOMATICA. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0005-1098. ; 30:11, s. 1751-1756
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- In this paper, we consider time-varying state feedback control of single-input linear time-invariant discrete-time systems. The approach that we propose is based on a contraction property that was introduced in a previous paper. All time-varying controlle
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| 56. |
- Malmgren, B., et al.
(författare)
-
Tooth agenesis in osteogenesis imperfecta related to mutations in the collagen type I genes
- 2017
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Ingår i: Oral Diseases. - : Wiley. - 1354-523X .- 1601-0825. ; 23:1, s. 42-49
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundOsteogenesis imperfecta (OI) is a heterogeneous group of disorders of connective tissue, mainly caused by mutations in the collagen type I genes (COL1A1 and COL1A2). Tooth agenesis is a common feature of OI. We investigated the association between tooth agenesis and collagen type I mutations in individuals with OI. Subjects and methodsIn this cohort study, 128 unrelated individuals with OI were included. Panoramic radiographs were analyzed regarding dentinogenesis imperfecta (DGI) and congenitally missing teeth. The collagen I genes were sequenced in all individuals, and in 25, multiplex ligation-dependent probe amplification was performed. ResultsMutations in the COL1A1 and COL1A2 genes were found in 104 of 128 individuals. Tooth agenesis was diagnosed in 17% (hypodontia 11%, oligodontia 6%) and was more frequent in those with DGI (P=0.016), and in those with OI type III, 47%, compared to those with OI types I, 12% (P=0.003), and IV, 13% (P=0.017). Seventy-five percent of the individuals with oligodontia (6 missing teeth) had qualitative mutations, but there was no association with OI type, gender, or presence of DGI. ConclusionThe prevalence of tooth agenesis is high (17%) in individuals with OI, and OI caused by a qualitative collagen I mutation is associated with oligodontia.
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| 57. |
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| 58. |
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| 59. |
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| 60. |
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| 61. |
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| 62. |
- Malmgren, K, et al.
(författare)
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Vigabatrin visual toxicity: evolution and dose dependence.
- 2001
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Ingår i: Epilepsia. - 0013-9580. ; 42:5, s. 609-15
-
Tidskriftsartikel (refereegranskat)abstract
- To investigate the prevalence and prognosis of visual field defects (VFDs) in epilepsy patients with and without vigabatrin (VGB) treatment; to investigate the possible relationship between VFDs and cumulative VGB dose, and to characterise the evolution of VFDs.A cohort of 155 presurgical candidates who had undergone full-field Goldmann perimetry (GP) was studied, 99 (64%) of whom had been treated with VGB. All GPs were reevaluated in 1998 by one experienced examiner, blinded to medication. Duration of treatment and total VGB dose were related to perimetric results.Twenty-five (16%) of the 155 patients had VFDs: Nineteen (19%) of the 99 VGB-treated patients, and six (11%) of the 56 patients unexposed to VGB. VGB-treated patients with VFDs had been treated significantly longer than those without VFDs. Cumulative VGB dose could be calculated for 84 patients. The prevalence of VFDs increased significantly with increasing total VGB-dose, from 4% in the 51 patients who had been exposed to
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| 63. |
- Malmgren, L., et al.
(författare)
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Kidney function and its association to imminent, short- and long-term fracture risk—a longitudinal study in older women
- 2020
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Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 31:1, s. 97-107
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Tidskriftsartikel (refereegranskat)abstract
- Summary: Reduced kidney function is associated with an increased fracture risk, although the relationship between an age-related decline and fractures needs further investigation. We followed kidney function and fracture risk for 10 years. A mild-moderate decline in kidney function was associated with fracture, but not in advanced age. Introduction: With age, kidney function declines. Though well known that chronic kidney disease is associated with increased fracture risk, the extent to which the typical age-related decline contributes is unclear. In the OPRA cohort, a longitudinal study of older non-selected women, we investigated the association between kidney function and fracture. Methods: Cystatin C–based kidney function estimates were available at age 75 (n = 981) and 80 (n = 685). Women were categorized by kidney function: normal (CKD stages 1 and 2), mild-moderate (3a), poor (3b-5), and imminent, short- and long-term fracture risk investigated. BMD measurements and kidney function for risk prediction were also evaluated; women were categorized by both reduced kidney function (stages 3–5) and osteoporosis status. Results: In the short term, 2–3 years, mild-moderate kidney dysfunction was associated with the highest risk increase: osteoporotic fractures (2 years HRadj 2.21, 95% CI 1.27–3.87) and also up to 5 years (between 75 and 80 years) (HRadj 1.51, 1.04–2.18). Hip fracture risk was similarly increased. This association was not observed from age 80 nor for women with poorest kidney function. Reduced kidney function was associated with higher risk even without osteoporosis (osteoporotic fracture; HRadj 1.66, 1.08–2.54); risk increased by having both osteoporosis and reduced function (HRadj 2.53, 1.52–4.23). Conclusion: Older women with mild-moderate reduction of kidney function are at increased risk of fractures, but not those with the worst function. Our findings furthermore confirm the value of osteoporosis assessment and it is possible that in this age group, age-related decline of kidney function has limited contribution compared with BMD.
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| 64. |
- Malmgren, L., et al.
(författare)
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Reduced kidney function is associated with BMD, bone loss and markers of mineral homeostasis in older women : a 10-year longitudinal study
- 2017
-
Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 28:12, s. 3463-3473
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Tidskriftsartikel (refereegranskat)abstract
- Summary: Kidney function decreases with age; however, the long-term influence on bone density (BMD) in older women already at risk of osteoporosis is unknown. We followed kidney function and bone loss for 10 years. Declining kidney function was adversely associated with bone loss and mineral homeostasis in old women, though it attenuated with advanced aging. Introduction: Existing studies do not fully address the relationship between kidney function and bone metabolism with advanced aging in Caucasian women. This study describes the association between kidney function, BMD, bone loss and bone metabolism in older women and provides a review of the available literature for context. Methods: We studied participants from the OPRA cohort with follow-up after 5 and 10 years. Using plasma cystatin C (cysC), estimated glomerular function rate (eGFR) was evaluated at age 75 (n = 981), 80 (n = 685) and 85 (n = 365). Women were stratified into “normal” function (CKD stages 1–2), “intermediate” (stage 3a) and “poor” (stages 3b–5), and outcome measures—BMD, bone loss and markers of mineral homeostasis—were compared. Results: Femoral neck (FN) BMD positively associated with kidney function at 75 years old ((Formula presented.) = 0.001, p = 0.028) and 80 years old ((Formula presented.) = 0.001, p = 0.001), although with small effect size. Prevalence of osteoporosis (FN T-score ≤ − 2.5) did not differ with kidney function. Measured at age 75, women with poor kidney function had higher annual percentage bone loss over 5 years compared to those with normal function (2.3%, 95% CI 1.8–2.8 versus 1.3%, 95% CI 1.1–1.5, p = 0.007), although not when measured from age 80 or 85. Additionally, markers of mineral homeostasis (PTH, phosphate, vitamin D, calcium), CRP and osteocalcin differed by kidney function. Conclusions: In old women, kidney function is associated with BMD, bone loss and altered mineral homeostasis; probably, a relationship attenuated in the very elderly.
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| 65. |
- Markhus, R., et al.
(författare)
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EEG in fitness to drive evaluations in people with epilepsy - Considerable variations across Europe
- 2020
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Ingår i: Seizure-European Journal of Epilepsy. - : Elsevier BV. - 1059-1311. ; 79, s. 56-60
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Epilepsy patients consider driving issues to be one of their most serious concerns. Ideally, decisions regarding fitness to drive should be based upon thorough evaluations by specialists in epilepsy care. In 2009, an EU directive was published aiming to harmonize evaluation practices within European countries, but, despite these recommendations, whether all epileptologists use the same criteria is unclear. We therefore conducted this study to investigate routine practices on how epileptologists at European epilepsy centers evaluate fitness to drive. Methods: A questionnaire was sent to 63 contact persons identified through the European Epi-Care and the Epilepsy network. The questionnaire addressed how fitness-to-drive evaluations were conducted, the involvement of different professionals, the use and interpretation of EEG, and opinions on existing regulations and guidelines. Results: The questionnaire was completed by 35 participants (56 % response rate). Results showed considerable variation regarding test routines and the emphasis placed on the occurrence and extent of epileptiform discharges revealed by EEG. 82 % of the responders agreed that there was a need for more research on how to better evaluate fitness-to-drive in people with epilepsy, and 89 % agreed that regulations on fitness to drive evaluations should be internationally coordinated. Conclusion: Our survey showed considerable variations among European epileptologists regarding use of EEG and how findings of EEG pathology should be assessed in fitness-to-drive evaluations. There is a clear need for more research on this issue and international guidelines on how such evaluations should be carried out would be of value.
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| 66. |
- Markoula, S., et al.
(författare)
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A European questionnaire survey on epilepsy monitoring units' current practice for postoperative psychogenic nonepileptic seizures' detection
- 2020
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Ingår i: Epilepsy and Behavior. - : Elsevier BV. - 1525-5050. ; 112
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Tidskriftsartikel (refereegranskat)abstract
- Background: In cases undergoing epilepsy surgery, postoperative psychogenic nonepileptic seizures (PNES) may be underdiagnosed complicating the assessment of postsurgical seizures' outcome and the clinical management. We conducted a survey to investigate the current practices in the European epilepsy monitoring units (EMUs) and the data that EMUs could provide to retrospectively detect cases with postoperative PNES and to assess the feasibility of a subsequent postoperative PNES research project for cases with postoperative PNES. Methods: We developed and distributed a questionnaire survey to 57 EMUs. Questions addressed the number of patients undergoing epilepsy surgery, the performance of systematic preoperative and postoperative psychiatric evaluation, the recording of sexual or other abuse, the follow-up period of patients undergoing epilepsy surgery, the performance of video-electroencephalogram (EEG) and postoperative psychiatric assessment in suspected postoperative cases with PNES, the existence of electronic databases to allow extraction of cases with postoperative PNES, the data that these bases could provide, and EMUs' interest to participate in a retrospective postoperative PNES project. Results: Twenty EMUs completed the questionnaire sheet. The number of patients operated every year/per center is 26.7 (+ 19.1), and systematic preoperative and postoperative psychiatric evaluation is performed in 75% and 50% of the EMUs accordingly. Sexual or other abuse is systematically recorded in one-third of the centers, and the mean follow-up period after epilepsy surgery is 10.5 ± 7.5 years. In suspected postoperative PNES, video-EEG is performed in 85% and psychiatric assessment in 95% of the centers. An electronic database to allow extraction of patients with PNES after epilepsy surgery is used in 75% of the EMUs, and all EMUs that sent the sheet completed expressed their interest to participate in a retrospective postoperative PNES project. Conclusion: Postoperative PNES is an underestimated and not well-studied entity. This is a European survey to assess the type of data that the EMUs surgical cohorts could provide to retrospectively detect postoperative PNES. In cases with suspected PNES, most EMUs perform video-EEG and psychiatric assessment, and most EMUs use an electronic database to allow extraction of patients developing PNES. © 2020 Elsevier Inc.
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| 67. |
- McCrae, Cristopher, et al.
(författare)
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INEXAS: A Phase 2 Randomized Trial of On-demand Inhaled Interferon Beta-1a in Severe Asthmatics
- 2021
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Ingår i: Clinical and Experimental Allergy. - : Wiley. - 0954-7894 .- 1365-2222. ; 51:2, s. 273-283
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Tidskriftsartikel (refereegranskat)abstract
- Background: Upper respiratory tract infections (URTIs) are important triggers for asthma exacerbations. We hypothesized that inhalation of the anti-viral cytokine, interferon (IFN)-β, during URTI, could prevent these exacerbations. Objective: To evaluate the efficacy of on-demand inhaled IFN-β1a (AZD9412) to prevent severe asthma exacerbations following symptomatic URTI. Methods: This was a randomized, double-blind, placebo-controlled trial in which patients with severe asthma (GINA 4-5; n=121) reporting URTI symptoms were randomized to 14days of once-daily nebulized AZD9412 or placebo. The primary endpoint was severe exacerbations during treatment. Secondary endpoints included 6-item asthma control questionnaire (ACQ-6) and lung function. Exploratory biomarkers included IFN-response markers in serum and sputum, blood leucocyte counts and serum inflammatory cytokines. Results: Following a pre-planned interim analysis, the trial was terminated early due to an unexpectedly low exacerbation rate. Asthma worsenings were generally mild and tended to peak at randomization, possibly contributing to the lack of benefit of AZD9412 on other asthma endpoints. Numerically, AZD9412 did not reduce severe exacerbation rate, ACQ-6, asthma symptom scores or reliever medication use. AZD9412 improved lung function (morning peak expiratory flow; mPEF) by 19.7 L/min. Exploratory post hoc analyses indicated a greater mPEF improvement by AZD9412 in patients with high blood eosinophils (>0.3×109/L) at screening and low serum interleukin-18 relative change at pre-treatment baseline. Pharmacodynamic effect of AZD9412 was confirmed using IFN-response markers. Conclusions & Clinical Relevance: Colds did not have the impact on asthma patients that was expected and, due to the low exacerbation rate, the trial was stopped early. On-demand AZD9412 treatment did not numerically reduce the number of exacerbations, but did attenuate URTI-induced worsening of mPEF. Severe asthma patients with high blood eosinophils or low serum interleukin-18 response are potential subgroups for further investigation of inhaled IFN-β1a. @2020 AstraZeneca. International Journal of Cosmetic Science published by John Wiley & Sons
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| 68. |
- Mouthaan, B. E., et al.
(författare)
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Current use of imaging and electromagnetic source localization procedures in epilepsy surgery centers across Europe
- 2016
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Ingår i: Epilepsia. - : Wiley. - 0013-9580. ; 57:5, s. 770-776
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Tidskriftsartikel (refereegranskat)abstract
- Objective: In 2014 the European Union-funded E-PILEPSY project was launched to improve awareness of, and accessibility to, epilepsy surgery across Europe. We aimed to investigate the current use of neuroimaging, electromagnetic source localization, and imaging postprocessing procedures in participating centers. Methods: A survey on the clinical use of imaging, electromagnetic source localization, and postprocessing methods in epilepsy surgery candidates was distributed among the 25 centers of the consortium. A descriptive analysis was performed, and results were compared to existing guidelines and recommendations. Results: Response rate was 96%. Standard epilepsy magnetic resonance imaging (MRI) protocols are acquired at 3 Tesla by 15 centers and at 1.5 Tesla by 9 centers. Three centers perform 3T MRI only if indicated. Twenty-six different MRI sequences were reported. Six centers follow all guideline-recommended MRI sequences with the proposed slice orientation and slice thickness or voxel size. Additional sequences are used by 22 centers. MRI postprocessing methods are used in 16 centers. Interictal positron emission tomography (PET) is available in 22 centers; all using 18F-fluorodeoxyglucose (FDG). Seventeen centers perform PET postprocessing. Single-photon emission computed tomography (SPECT) is used by 19 centers, of which 15 perform postprocessing. Four centers perform neither PET nor SPECT in children. Seven centers apply magnetoencephalography (MEG) source localization, and nine apply electroencephalography (EEG) source localization. Fourteen combinations of inverse methods and volume conduction models are used. Significance: We report a large variation in the presurgical diagnostic workup among epilepsy surgery centers across Europe. This diversity underscores the need for highquality systematic reviews, evidence-based recommendations, and harmonization of available diagnostic presurgical methods.
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| 69. |
- Nyberg, Johan, et al.
(författare)
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Is recent major hurricane activity normal? Reply
- 2008
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 451:7181
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 70. |
- Nyberg, Johan, et al.
(författare)
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Low Atlantic hurricane activity in the 1970s and 1980s compared to the past 270 years
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7145, s. 698-701
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Hurricane activity in the North Atlantic Ocean has increased significantly since 1995 (refs 1, 2). This trend has been attributed to both anthropogenically induced climate change3 and natural variability1, but the primary cause remains uncertain. Changes in the frequency and intensity of hurricanes in the past can provide insights into the factors that influence hurricane activity, but reliable observations of hurricane activity in the North Atlantic only cover the past few decades2. Here we construct a record of the frequency of major Atlantic hurricanes over the past 270 years using proxy records of vertical wind shear and sea surface temperature (the main controls on the formation of major hurricanes in this region1, 3, 4, 5) from corals and a marine sediment core. The record indicates that the average frequency of major hurricanes decreased gradually from the 1760s until the early 1990s, reaching anomalously low values during the 1970s and 1980s. Furthermore, the phase of enhanced hurricane activity since 1995 is not unusual compared to other periods of high hurricane activity in the record and thus appears to represent a recovery to normal hurricane activity, rather than a direct response to increasing sea surface temperature. Comparison of the record with a reconstruction of vertical wind shear indicates that variability in this parameter primarily controlled the frequency of major hurricanes in the Atlantic over the past 270 years, suggesting that changes in the magnitude of vertical wind shear will have a significant influence on future hurricane activity.
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| 71. |
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| 72. |
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| 73. |
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| 74. |
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| 75. |
- Ruiz-Solani, N., et al.
(författare)
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Arabidopsis metacaspase MC1 localizes in stress granules, clears protein aggregates, and delays senescence
- 2023
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Ingår i: Plant Cell. - 1040-4651. ; 35:9, s. 3325-3344
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Tidskriftsartikel (refereegranskat)abstract
- The Arabidopsis metacaspase MC1 is recruited to stress granules upon proteotoxic stress, participates in clearance of pathological protein aggregates, and delays senescence. Stress granules (SGs) are highly conserved cytoplasmic condensates that assemble in response to stress and contribute to maintaining protein homeostasis. These membraneless organelles are dynamic, disassembling once the stress is no longer present. Persistence of SGs due to mutations or chronic stress has been often related to age-dependent protein-misfolding diseases in animals. Here, we find that the metacaspase MC1 is dynamically recruited into SGs upon proteotoxic stress in Arabidopsis (Arabidopsis thaliana). Two predicted disordered regions, the prodomain and the 360 loop, mediate MC1 recruitment to and release from SGs. Importantly, we show that MC1 has the capacity to clear toxic protein aggregates in vivo and in vitro, acting as a disaggregase. Finally, we demonstrate that overexpressing MC1 delays senescence and this phenotype is dependent on the presence of the 360 loop and an intact catalytic domain. Together, our data indicate that MC1 regulates senescence through its recruitment into SGs and this function could potentially be linked to its remarkable protein aggregate-clearing activity.
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| 76. |
- Rydenhag, B., et al.
(författare)
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Long term follow-up after callosotomy
- 2013
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Ingår i: Epilepsia. - 0013-9580 .- 1528-1167. ; 54:S3, s. 180-180
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 77. |
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| 78. |
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| 79. |
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| 80. |
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| 81. |
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| 82. |
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| 83. |
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| 84. |
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| 85. |
- Van den Bulcke, Bo, et al.
(författare)
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Ethical climate and intention to leave among critical care clinicians: an observational study in 68 intensive care units across Europe and the United States.
- 2020
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Ingår i: Intensive care medicine. - 1432-1238. ; 46:1, s. 46-56
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Tidskriftsartikel (refereegranskat)abstract
- Apart from organizational issues, quality of inter-professional collaboration during ethical decision-making may affect the intention to leave one's job. To determine whether ethical climate is associated with the intention to leave after adjustment for country, ICU and clinicians characteristics.Perceptions of the ethical climate among clinicians working in 68 adult ICUs in 12 European countries and the US were measured using a self-assessment questionnaire, together with job characteristics and intent to leave as a sub-analysis of the Dispropricus study. The validated ethical decision-making climate questionnaire included seven factors: not avoiding decision-making at end-of-life (EOL), mutual respect within the interdisciplinary team, open interdisciplinary reflection, ethical awareness, self-reflective physician leadership, active decision-making at end-of-life by physicians, and involvement of nurses in EOL. Hierarchical mixed effect models were used to assess associations between these factors, and the intent to leave in clinicians within ICUs, within the different countries.Of 3610 nurses and 1137 physicians providing ICU bedside care, 63.1% and 62.9% participated, respectively. Of 2992 participating clinicians, 782 (26.1%) had intent to leave, of which 27% nurses, 24% junior and 22.7% senior physicians. After adjustment for country, ICU and clinicians characteristics, mutual respect OR 0.77 (95% CI 0.66- 0.90), open interdisciplinary reflection (OR 0.73 [95% CI 0.62-0.86]) and not avoiding EOL decisions (OR 0.87 [95% CI 0.77-0.98]) were all associated with a lower intent to leave.This is the first large multicenter study showing an independent association between clinicians' intent to leave and the quality of the ethical climate in the ICU. Interventions to reduce intent to leave may be most effective when they focus on improving mutual respect, interdisciplinary reflection and active decision-making at EOL.
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| 86. |
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| 87. |
- Vogt, Viola Lara, et al.
(författare)
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Current standards of neuropsychological assessment in epilepsy surgery centers across Europe.
- 2017
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Ingår i: Epilepsia. - : Wiley. - 1528-1167 .- 0013-9580. ; 58:3, s. 343-355
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Tidskriftsartikel (refereegranskat)abstract
- We explored the current practice with respect to the neuropsychological assessment of surgical epilepsy patients in European epilepsy centers, with the aim of harmonizing and establishing common standards. Twenty-six epilepsy centers and members of "E-PILEPSY" (a European pilot network of reference centers in refractory epilepsy and epilepsy surgery), were asked to report the status of neuropsychological assessment in adults and children via two different surveys. There was a consensus among these centers regarding the role of neuropsychology in the presurgical workup. Strong agreement was found on indications (localization, epileptic dysfunctions, adverse drugs effects, and postoperative monitoring) and the domains to be evaluated (memory, attention, executive functions, language, visuospatial skills, intelligence, depression, anxiety, and quality of life). Although 186 different tests are in use throughout these European centers, a core group of tests reflecting a moderate level of agreement could be discerned. Variability exists with regard to indications, protocols, and paradigms for the assessment of hemispheric language dominance. For the tests in use, little published evidence of clinical validity in epilepsy was provided. Participants in the survey reported a need for improvement concerning the validity of the tests, tools for the assessment of everyday functioning and accelerated forgetting, national norms, and test co-normalization. Based on the present survey, we documented a consensus regarding the indications and principles of neuropsychological testing. Despite the variety of tests in use, the survey indicated that there may be a core set of tests chosen based on experience, as well as on published evidence. By combining these findings with the results of an ongoing systematic literature review, we aim for a battery that can be recommended for the use across epilepsy surgical centers in Europe.
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| 88. |
- Wahby, S., et al.
(författare)
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Validity and reliability of global ratings of satisfaction with epilepsy surgery
- 2022
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Ingår i: Epilepsia. - : Wiley. - 0013-9580 .- 1528-1167. ; 63:4, s. 777-788
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Tidskriftsartikel (refereegranskat)abstract
- Objective: We aimed to assess the reliability and validity of single-item global ratings (GR) of satisfaction with epilepsy surgery. Methods: We recruited 240 patients from four centers in Canada and Sweden who underwent epilepsy surgery ≥1year earlier. Participants completed a validated questionnaire on satisfaction with epilepsy surgery (the ESSQ-19), plus a single-item GR of satisfaction with epilepsy surgery twice, 4–6weeks apart. They also completed validated questionnaires on quality of life, depression, health state utilities, epilepsy severity and disability, medical treatment satisfaction and social desirability. Test-retest reliability of the GR was assessed with the intra-class correlation coefficient (ICC). Construct and criterion validity were examined with polyserial correlations between the GR measure of satisfaction and validated questionnaires and with the ESSQ-19summary score. Non-parametric rank tests evaluated levels of satisfaction, and ROC analysis assessed the ability of GRs to distinguish among clinically different patient groups. Results: Median age and time since surgery were 42years (IQR 32–54) and 5years (IQR 2–8), respectively. The GR demonstrated good to excellent test-retest reliability (ICC=0.76; 95% CI 0.67–0.84) and criterion validity (0.85; 95% CI 0.81–0.89), and moderate correlations in the expected direction with instruments assessing quality of life (0.59; 95% CI 0.51–0.63), health utilities (0.55; 95% CI 0.45–0.65), disability (−0.51; 95% CI −0.41, −0.61), depression (−0.48; 95% CI −0.38, −0.58), and epilepsy severity (−0.48; 95% CI −0.38, −0.58). As expected, correlations were lower for social desirability (0.40; 95% CI 0.28–0.52) and medical treatment satisfaction (0.33; 95% CI 0.21–0.45). The GR distinguished participants who were seizure-free (AUC 0.75; 95% CI 0.67–0.82), depressed (AUC 0.75; 95% CI 0.67–0.83), and self-rated as having more severe epilepsy (AUC 0.78; 95% CI 0.71–0.85) and being more disabled (AUC 0.82; 95% CI 0.74–0.90). Significance: The GR of epilepsy surgery satisfaction showed good measurement properties, distinguished among clinically different patient groups, and appears well-suited for use in clinical practice and research. © 2022 International League Against Epilepsy
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| 89. |
- Wiebe, S., et al.
(författare)
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Development and validation of the Epilepsy Satisfaction Questionnaire: ESSQ-19
- 2020
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Ingår i: Epilepsia. - : Wiley. - 0013-9580 .- 1528-1167. ; 61:12, s. 2729-2738
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Tidskriftsartikel (refereegranskat)abstract
- Objective No validated tools exist to assess satisfaction with epilepsy surgery. We aimed to develop and validate a new measure of patient satisfaction with epilepsy surgery, the 19-item Epilepsy Surgery Satisfaction Questionnaire (ESSQ-19). Methods An initial 31-item measure was developed based on literature review, patient focus groups, thematic analysis, and Delphi panels. The questionnaire was administered twice, 4-6 weeks apart, to 229 adults (>= 18 years old) who underwent epilepsy surgery >= 1 year earlier, at three centers in Canada and one in Sweden. Participants also completed seven validated questionnaires to assess construct validity. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) assessed the factorial structure of the questionnaire. Cronbach alpha and intraclass correlation coefficients (ICCs) assessed the internal consistency and test-retest reliability of the ESSQ-19. Spearman and polyserial correlations assessed construct validity. Results Median age of participants and time since surgery were 42 years (interquartile range [IQR] = 32-54) and 5 years (IQR = 2-8.75), respectively. EFA and CFA yielded 18 items that segregated into four domains (mean score [SD]), namely, seizure control (76.4 [25]), psychosocial functioning (67.3 [26]), surgical complications (84 [22]), and recovery from surgery (73 [24]), one global satisfaction item, and a summary global score (74 [21]). The domain and summary scores demonstrated good to excellent internal reliability (Cronbach range = .84-.95) and test-retest reliability (ICC range = 0.71-0.85). Construct validity was supported by predicted correlations with other instruments. Significance The ESSQ-19 is a new, valid, and reliable measure of patient satisfaction with epilepsy surgery that can be used in clinical and research settings.
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- Wrobel, L., et al.
(författare)
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Compounds activating VCP D1 ATPase enhance both autophagic and proteasomal neurotoxic protein clearance
- 2022
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Enhancing the removal of aggregate-prone toxic proteins is a rational therapeutic strategy for a number of neurodegenerative diseases, especially Huntington's disease and various spinocerebellar ataxias. Ideally, such approaches should preferentially clear the mutant/misfolded species, while having minimal impact on the stability of wild-type/normally-folded proteins. Furthermore, activation of both ubiquitin-proteasome and autophagy-lysosome routes may be advantageous, as this would allow effective clearance of both monomeric and oligomeric species, the latter which are inaccessible to the proteasome. Here we find that compounds that activate the D1 ATPase activity of VCP/p97 fulfill these requirements. Such effects are seen with small molecule VCP activators like SMER28, which activate autophagosome biogenesis by enhancing interactions of PI3K complex components to increase PI(3)P production, and also accelerate VCP-dependent proteasomal clearance of such substrates. Thus, this mode of VCP activation may be a very attractive target for many neurodegenerative diseases. Several neurodegenerative diseases are characterized by the aggregation of cytoplasmic proteins. Here, the authors demonstrate that the small molecule SMER28 activates VCP, which enhances both autophagic and proteasomal clearance of aggregate-prone proteins.
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