| 1. |
- Sumaila, U. Rashid, et al.
(författare)
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WTO must ban harmful fisheries subsidies
- 2021
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 374:6567, s. 544-544
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 2. |
- Nguyen, Thanh N, et al.
(författare)
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Global Impact of the COVID-19 Pandemic on Stroke Volumes and Cerebrovascular Events: A 1-Year Follow-up.
- 2023
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Ingår i: Neurology. - 1526-632X. ; 100:4
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Tidskriftsartikel (refereegranskat)abstract
- Declines in stroke admission, IV thrombolysis (IVT), and mechanical thrombectomy volumes were reported during the first wave of the COVID-19 pandemic. There is a paucity of data on the longer-term effect of the pandemic on stroke volumes over the course of a year and through the second wave of the pandemic. We sought to measure the effect of the COVID-19 pandemic on the volumes of stroke admissions, intracranial hemorrhage (ICH), IVT, and mechanical thrombectomy over a 1-year period at the onset of the pandemic (March 1, 2020, to February 28, 2021) compared with the immediately preceding year (March 1, 2019, to February 29, 2020).We conducted a longitudinal retrospective study across 6 continents, 56 countries, and 275 stroke centers. We collected volume data for COVID-19 admissions and 4 stroke metrics: ischemic stroke admissions, ICH admissions, IVT treatments, and mechanical thrombectomy procedures. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases.There were 148,895 stroke admissions in the 1 year immediately before compared with 138,453 admissions during the 1-year pandemic, representing a 7% decline (95% CI [95% CI 7.1-6.9]; p < 0.0001). ICH volumes declined from 29,585 to 28,156 (4.8% [5.1-4.6]; p < 0.0001) and IVT volume from 24,584 to 23,077 (6.1% [6.4-5.8]; p < 0.0001). Larger declines were observed at high-volume compared with low-volume centers (all p < 0.0001). There was no significant change in mechanical thrombectomy volumes (0.7% [0.6-0.9]; p = 0.49). Stroke was diagnosed in 1.3% [1.31-1.38] of 406,792 COVID-19 hospitalizations. SARS-CoV-2 infection was present in 2.9% ([2.82-2.97], 5,656/195,539) of all stroke hospitalizations.There was a global decline and shift to lower-volume centers of stroke admission volumes, ICH volumes, and IVT volumes during the 1st year of the COVID-19 pandemic compared with the prior year. Mechanical thrombectomy volumes were preserved. These results suggest preservation in the stroke care of higher severity of disease through the first pandemic year.This study is registered under NCT04934020.
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| 3. |
- Nicolas, Aude, et al.
(författare)
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Genome-wide Analyses Identify KIF5A as a Novel ALS Gene
- 2018
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Ingår i: Neuron. - : Cell Press. - 0896-6273 .- 1097-4199. ; 97:6, s. 1268-1283.e6
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Tidskriftsartikel (refereegranskat)abstract
- To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.
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| 4. |
- Ernest, C. Steven, II, et al.
(författare)
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Methodological Comparison of In Vitro Binding Parameter Estimation : Sequential vs. Simultaneous Non-linear Regression
- 2010
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Ingår i: Pharmaceutical research. - : Springer Science and Business Media LLC. - 0724-8741 .- 1573-904X. ; 27:5, s. 866-877
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Tidskriftsartikel (refereegranskat)abstract
- Analysis of simulated data was compared using sequential (NLR) and simultaneous non-linear regression (SNLR) to evaluate precision and accuracy of ligand binding parameter estimation. Commonly encountered experimental error, specifically residual error of binding measurements (RE), experiment-to-experiment variability (BEV) and non-specific binding (B-NS), were examined for impact of parameter estimation using both methods. Data from equilibrium, dissociation, association and non-specific binding experiments were fit simultaneously (SNLR) using NONMEM VI compared to the common practice of analyzing data from each experiment separately and assigning these as exact values (NLR) for estimation of the subsequent parameters. The greatest contributing factor to bias and variability in parameter estimation was RE of the measured concentrations of ligand bound; however, SNLR provided more accurate and less bias estimates. Subtraction of B-NS from total ligand binding data provided poor estimation of specific ligand binding parameters using both NLR and SNLR. Additional methods examined demonstrated that the use of SNLR provided better estimation of specific binding parameters, whereas there was considerable bias using NLR. NLR cannot account for BEV, whereas SNLR can provide approximate estimates of BEV. SNLR provided superior resolution of parameter estimation in both precision and accuracy compared to NLR.
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| 5. |
- Ernest, C. Steven, et al.
(författare)
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Population pharmacokinetics and pharmacodynamics of prasugrel and clopidogrel in aspirin-treated patients with stable coronary artery disease
- 2008
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Ingår i: Journal of Pharmacokinetics and Pharmacodynamics. - : Springer Science and Business Media LLC. - 1567-567X .- 1573-8744. ; 35:6, s. 593-618
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the current analysis was to characterize the population PK of prasugrel and clopidogrel metabolites, the resulting PD response, and identification of covariates for key PK/PD parameters. Aspirin-treated subjects with coronary artery disease were randomized to double-blind treatment with clopidogrel 600 mg loading dose (LD) followed by daily 75 mg maintenance dose (MD) or prasugrel 60 mg LD and daily 10 mg MD for 28 days. Plasma concentrations of prasugrel active metabolite (Pras-AM) and prasugrel's inactive thiolactone metabolite (Pras-thiolactone) were simultaneously fit to a multicompartmental model; a similar model adequately described clopidogrel's active metabolite (Clop-AM) PK. By linking to the PK model through the active metabolite concentrations, the PK/PD model characterized the irreversible inhibition of platelet aggregation through a sigmoidal Emax model. Although dose, sex, and weight were identified as significant covariates in the prasugrel PK model, only the effect of body weight produced significant changes in Pras-AM exposure. Generally, these factors resulted in only minor changes in Pras-AM exposures such that, overall, the change in the resulting maximal platelet aggregation (MPA) was predicted to be < or =10% points on average. The clopidogrel PK model included dose as a covariate indicating that a significantly less-than-proportional increase in Clop-AM exposure is expected over the dose range of 75-600 mg, thus, the model-predicted PD response is lower than might be anticipated given an 8-fold difference in dose and lower than that typically achieved following prasugrel 60 mg LD. The greater PD response with prasugrel compared with clopidogrel was accounted for by greater conversion of dose to active metabolite.
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| 6. |
- Ernest II, Charles Steven, et al.
(författare)
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Simultaneous optimal experimental design for in vitro binding parameter estimation
- 2013
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Ingår i: Journal of Pharmacokinetics and Pharmacodynamics. - : Springer Science+Business Media B.V.. - 1567-567X .- 1573-8744. ; 40:5, s. 573-585
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Tidskriftsartikel (refereegranskat)abstract
- Simultaneous optimization of in vitro ligand binding studies using an optimal design software package that can incorporate multiple design variables through non-linear mixed effect models and provide a general optimized design regardless of the binding site capacity and relative binding rates for a two binding system. Experimental design optimization was employed with D- and ED-optimality using PopED 2.8 including commonly encountered factors during experimentation (residual error, between experiment variability and non-specific binding) for in vitro ligand binding experiments: association, dissociation, equilibrium and non-specific binding experiments. Moreover, a method for optimizing several design parameters (ligand concentrations, measurement times and total number of samples) was examined. With changes in relative binding site density and relative binding rates, different measurement times and ligand concentrations were needed to provide precise estimation of binding parameters. However, using optimized design variables, significant reductions in number of samples provided as good or better precision of the parameter estimates compared to the original extensive sampling design. Employing ED-optimality led to a general experimental design regardless of the relative binding site density and relative binding rates. Precision of the parameter estimates were as good as the extensive sampling design for most parameters and better for the poorly estimated parameters. Optimized designs for in vitro ligand binding studies provided robust parameter estimation while allowing more efficient and cost effective experimentation by reducing the measurement times and separate ligand concentrations required and in some cases, the total number of samples.
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| 7. |
- Jensen, Karin B, et al.
(författare)
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Anxiety and depressive symptoms in fibromyalgia are related to poor perception of health but not to pain sensitivity or cerebral processing of pain.
- 2010
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 62:11, s. 3488-95
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Mood disturbance is common among patients with fibromyalgia (FM), but the influence of psychological symptoms on pain processing in this disorder is unknown. We undertook the present study to investigate the differential effect of depressive symptoms, anxiety, and catastrophizing on 1) pain symptoms and subjective ratings of general health status and 2) sensitivity to pain and cerebral processing of pressure pain.METHODS: Eighty-three women (mean ± SD age 43.8 ± 8.1 years) who fulfilled the American College of Rheumatology 1990 criteria for the classification of FM participated in the study. Patients rated pain intensity (100-mm visual analog scale [VAS]), severity of FM (Fibromyalgia Impact Questionnaire), general health status (Short Form 36), depressive symptoms (Beck Depression Inventory), anxiety (State-Trait Anxiety Inventory), and catastrophizing (Coping Strategies Questionnaire). Experimental pain in the thumb was induced using a computer-controlled pressure stimulator. Event-related functional magnetic resonance imaging was performed during administration of painful stimuli representing 50 mm on a pain VAS, as well as nonpainful pressures.RESULTS: A correlation analysis including all self-ratings showed that depressive symptoms, anxiety, and catastrophizing scores were correlated with one another (P < 0.001), but did not correlate with ratings of clinical pain or with sensitivity to pressure pain. However, the subjective rating of general health was correlated with depressive symptoms and anxiety (P < 0.001). Analyses of imaging results using self-rated psychological measures as covariates showed that brain activity during experimental pain was not modulated by depressive symptoms, anxiety, or catastrophizing.CONCLUSION: Negative mood in FM patients can lead to a poor perception of one's physical health (and vice versa) but does not influence performance on assessments of clinical and experimental pain. Our data provide evidence that 2 partially segregated mechanisms are involved in the neural processing of experimental pain and negative affect.
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| 8. |
- Jensen, Karin B, et al.
(författare)
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Evidence of dysfunctional pain inhibition in Fibromyalgia reflected in rACC during provoked pain.
- 2009
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Ingår i: Pain. - : Ovid Technologies (Wolters Kluwer Health). - 0304-3959 .- 1872-6623. ; 144:1-2, s. 95-100
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Tidskriftsartikel (refereegranskat)abstract
- Over the years, many have viewed Fibromyalgia syndrome (FMS) as a so-called "functional disorder" and patients have experienced a concomitant lack of interest and legitimacy from the medical profession. The symptoms have not been explained by peripheral mechanisms alone nor by specific central nervous system mechanisms. In this study, we objectively evaluated the cerebral response to individually calibrated pain provocations of a pain-free body region (thumbnail). The study comprised 16 female FMS patients and 16 individually age-matched controls. Brain activity was measured using functional magnetic resonance imaging (fMRI) during individually calibrated painful pressures representing 50 mm on a visual analogue scale (VAS) ranging from 0 to 100 mm. Patients exhibited higher sensitivity to pain provocation than controls as they required less pressure to evoke equal pain magnitudes (U(A)=48, p<.002). Despite lower pressures applied in patients at VAS 50 mm, the fMRI-analysis revealed no difference in activity in brain regions relating to attention and affect or regions with sensory projections from the stimulated body area. However, in the primary link in the descending pain regulating system (the rostral anterior cingulate cortex) the patients failed to respond to pain provocation. The attenuated response to pain in this brain region is the first demonstration of a specific brain region where the impairment of pain inhibition in FMS patients is expressed. These results validate previous reports of dysfunctional endogenous pain inhibition in FMS and advance the understanding of the central pathophysiologic mechanisms, providing a new direction for the development of successful treatments in FMS.
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| 9. |
- Jensen, Karin B, et al.
(författare)
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Overlapping structural and functional brain changes in patients with long-term exposure to fibromyalgia pain.
- 2013
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 65:12, s. 3293-303
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: There is vast evidence to support the presence of brain aberrations in patients with fibromyalgia (FM), and it is possible that central plasticity is critical for the transition from acute to chronic pain. The aim of the present study was to investigate the relationship between brain structure and function in patients with FM.METHODS: Functional connectivity of the brain during application of intermittent pressure-pain stimuli and measures of brain structure were compared between 26 patients with FM and 13 age- and sex-matched healthy controls. Magnetic resonance imaging (MRI) was performed to obtain high-resolution anatomic images and functional MRI scans of the brain, which were used for measurements of pain-evoked brain activity.RESULTS: FM patients displayed a distinct overlap between decreased cortical thickness, decreased brain volumes, and decreased functional regional coherence in the rostral anterior cingulate cortex. The morphometric changes were more pronounced with longer exposure to FM pain. In addition, there was evidence of an association between structural and functional changes in the mesolimbic areas of the brain and the severity of comorbid depression symptoms in FM patients.CONCLUSION: The combined integration of structural and functional measures allowed for a unique characterization of the impact of FM pain on the brain. These data may lead to the identification of early structural and functional brain alterations in response to pain, which could be used to develop markers for predicting the development of FM and other pain disorders.
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| 10. |
- Jensen, Karin B, et al.
(författare)
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Patients with fibromyalgia display less functional connectivity in the brain's pain inhibitory network.
- 2012
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Ingår i: Molecular Pain. - : SAGE Publications. - 1744-8069. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: There is evidence for augmented processing of pain and impaired endogenous pain inhibition in Fibromyalgia syndrome (FM). In order to fully understand the mechanisms involved in FM pathology, there is a need for closer investigation of endogenous pain modulation. In the present study, we compared the functional connectivity of the descending pain inhibitory network in age-matched FM patients and healthy controls (HC).We performed functional magnetic resonance imaging (fMRI) in 42 subjects; 14 healthy and 28 age-matched FM patients (2 patients per HC), during randomly presented, subjectively calibrated pressure pain stimuli. A seed-based functional connectivity analysis of brain activity was performed. The seed coordinates were based on the findings from our previous study, comparing the fMRI signal during calibrated pressure pain in FM and HC: the rostral anterior cingulate cortex (rACC) and thalamus.RESULTS: FM patients required significantly less pressure (kPa) to reach calibrated pain at 50 mm on a 0-100 visual analogue scale (p < .001, two-tailed). During fMRI scanning, the rACC displayed significantly higher connectivity to the amygdala, hippocampus, and brainstem in healthy controls, compared to FM patients. There were no regions where FM patients showed higher rACC connectivity. Thalamus showed significantly higher connectivity to the orbitofrontal cortex in healthy controls but no regions showed higher thalamic connectivity in FM patients.CONCLUSION: Patients with FM displayed less connectivity within the brain's pain inhibitory network during calibrated pressure pain, compared to healthy controls. The present study provides brain-imaging evidence on how brain regions involved in homeostatic control of pain are less connected in FM patients. It is possible that the dysfunction of the descending pain modulatory network plays an important role in maintenance of FM pain and our results may translate into clinical implications by using the functional connectivity of the pain modulatory network as an objective measure of pain dysregulation.
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