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Sökning: WFRF:(Loy A)

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  • Feigin, Valery L, et al. (författare)
  • Global, Regional, and Country-Specific Lifetime Risks of Stroke, 1990 and 2016.
  • 2018
  • Ingår i: The New England journal of medicine. - 1533-4406 .- 0028-4793. ; 379:25, s. 2429-2437
  • Tidskriftsartikel (refereegranskat)abstract
    • The lifetime risk of stroke has been calculated in a limited number of selected populations. We sought to estimate the lifetime risk of stroke at the regional, country, and global level using data from a comprehensive study of the prevalence of major diseases.We used the Global Burden of Disease (GBD) Study 2016 estimates of stroke incidence and the competing risks of death from any cause other than stroke to calculate the cumulative lifetime risks of first stroke, ischemic stroke, or hemorrhagic stroke among adults 25 years of age or older. Estimates of the lifetime risks in the years 1990 and 2016 were compared. Countries were categorized into quintiles of the sociodemographic index (SDI) used in the GBD Study, and the risks were compared across quintiles. Comparisons were made with the use of point estimates and uncertainty intervals representing the 2.5th and 97.5th percentiles around the estimate.The estimated global lifetime risk of stroke from the age of 25 years onward was 24.9% (95% uncertainty interval, 23.5 to 26.2); the risk among men was 24.7% (95% uncertainty interval, 23.3 to 26.0), and the risk among women was 25.1% (95% uncertainty interval, 23.7 to 26.5). The risk of ischemic stroke was 18.3%, and the risk of hemorrhagic stroke was 8.2%. In high-SDI, high-middle-SDI, and low-SDI countries, the estimated lifetime risk of stroke was 23.5%, 31.1% (highest risk), and 13.2% (lowest risk), respectively; the 95% uncertainty intervals did not overlap between these categories. The highest estimated lifetime risks of stroke according to GBD region were in East Asia (38.8%), Central Europe (31.7%), and Eastern Europe (31.6%), and the lowest risk was in eastern sub-Saharan Africa (11.8%). The mean global lifetime risk of stroke increased from 22.8% in 1990 to 24.9% in 2016, a relative increase of 8.9% (95% uncertainty interval, 6.2 to 11.5); the competing risk of death from any cause other than stroke was considered in this calculation.In 2016, the global lifetime risk of stroke from the age of 25 years onward was approximately 25% among both men and women. There was geographic variation in the lifetime risk of stroke, with the highest risks in East Asia, Central Europe, and Eastern Europe. (Funded by the Bill and Melinda Gates Foundation.).
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  • Ebersole, Charles R., et al. (författare)
  • Many Labs 5: Testing Pre-Data-Collection Peer Review as an Intervention to Increase Replicability
  • 2020
  • Ingår i: Advances in Methods and Practices in Psychological Science. - : Sage. - 2515-2467 .- 2515-2459. ; 3:3, s. 309-331
  • Tidskriftsartikel (refereegranskat)abstract
    • Replication studies in psychological science sometimes fail to reproduce prior findings. If these studies use methods that are unfaithful to the original study or ineffective in eliciting the phenomenon of interest, then a failure to replicate may be a failure of the protocol rather than a challenge to the original finding. Formal pre-data-collection peer review by experts may address shortcomings and increase replicability rates. We selected 10 replication studies from the Reproducibility Project: Psychology (RP:P; Open Science Collaboration, 2015) for which the original authors had expressed concerns about the replication designs before data collection; only one of these studies had yielded a statistically significant effect (p < .05). Commenters suggested that lack of adherence to expert review and low-powered tests were the reasons that most of these RP:P studies failed to replicate the original effects. We revised the replication protocols and received formal peer review prior to conducting new replication studies. We administered the RP:P and revised protocols in multiple laboratories (median number of laboratories per original study = 6.5, range = 3-9; median total sample = 1,279.5, range = 276-3,512) for high-powered tests of each original finding with both protocols. Overall, following the preregistered analysis plan, we found that the revised protocols produced effect sizes similar to those of the RP:P protocols (Delta r = .002 or .014, depending on analytic approach). The median effect size for the revised protocols (r = .05) was similar to that of the RP:P protocols (r = .04) and the original RP:P replications (r = .11), and smaller than that of the original studies (r = .37). Analysis of the cumulative evidence across the original studies and the corresponding three replication attempts provided very precise estimates of the 10 tested effects and indicated that their effect sizes (median r = .07, range = .00-.15) were 78% smaller, on average, than the original effect sizes (median r = .37, range = .19-.50).
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  • Kraus, Ludwig, 1955-, et al. (författare)
  • Self-exclusion from gambling : A toothless tiger?
  • 2022
  • Ingår i: Frontiers in Psychiatry. - : Frontiers Media SA. - 1664-0640. ; 13
  • Tidskriftsartikel (refereegranskat)abstract
    • While there is evidence for self-exclusion (SE) as an individual-level harm reduction intervention, its effects on reducing harm from gambling at the population level remain unclear. Based on a review of national legal frameworks and SE programs, including their utilization and enforcement in selected high-income societies, the present analysis aims to explore the reach and strengths of SE in the protection of gamblers in these jurisdictions. It places particular emphasis on SE programs' potential to prevent and minimize gambling harm at the population level. The overview examined SE in Finland, Germany, Italy, Massachusetts (USA), Norway, Sweden, and Victoria (Australia). These jurisdictions differ considerably in how gambling is regulated as well as in how SE is implemented and enforced. The reach and extent of enforcement of SE apparently vary with the polity's general policy balance between reducing gambling problems and increasing gambling revenue. But in any case, though SE may benefit individual gamblers and those around them, it does not appear to be capable of significantly reducing gambling harm at the population level. To render SE programs an effective measure that prevents gamblers and those linked to them from financial, social, and psychological harm, utilization needs to be substantially increased by reforming legal regulations and exclusion conditions.
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  • Loy, F., et al. (författare)
  • The antipsychotic amisulpride: ultrastructural evidence of its secretory activity in salivary glands
  • 2014
  • Ingår i: Oral Diseases. - : Wiley. - 1354-523X. ; 20:8, s. 796-802
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectiveAmisulpride is reported to inhibit clozapine-induced sialorrhea. Preclinically, clozapine evokes muscarinic-M1-type-mediated secretion that, however, amisulpride does not reduce. Instead, amisulpride, without causing any overt secretion per se, enhances both nerve- and autonomimetic-evoked salivation by unknown mechanism(s). Hypothesizing that amisulpride prepares the gland for secretion, we looked for ultrastructural events indicating secretory activity in intercellular canaliculi of serous/seromucous cells, that is, density increase in protrusions (reflecting anchored granules) and in microbuds (reflecting recycling membranes and/or vesicle secretion) and decrease in microvilli (reflecting the cytoskeletal re-arrangement related to exocytosis). Material and MethodsRat parotid and submandibular glands were exposed to amisulpride in vivo or in vitro. Glands were processed for transmission electron and scanning electron microscopy and then morphometrically assessed. ResultsCells were packed with secretory granules. The density of protrusions increased in both glands, whereas significant and parallel changes in microvilli and microbuds occurred only in parotid glands, and in vitro. ConclusionsAmisulpride induced ultrastructural signs of secretory activity but to varying extent; in submandibular glands, in contrast to parotid glands, changes were not brought beyond the granular anchoring stage. Amisulpride may provide an overall readiness for secretion that will result in augmented responses to agonists, a phenomenon of potential interest in dry-mouth treatment.
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  • Rochwerger, B., et al. (författare)
  • Reservoir : When one cloud is not enough
  • 2011
  • Ingår i: Computer. - : IEEE Computer Society. - 0018-9162 .- 1558-0814. ; 44:3, s. 44-51
  • Tidskriftsartikel (refereegranskat)abstract
    • As cloud computing becomes more predominant, the problem of scalability has become critical for cloud computing providers. The cloud paradigm is attractive because it offers a dramatic reduction in capital and operation expenses for consumers.
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  • Barnes, N., et al. (författare)
  • Regular polygon detection
  • 2005
  • Ingår i: Proceedings - 10th IEEE International Conference on Computer Vision. - : IEEE Computer Society. - 076952334X - 9780769523347 ; , s. 778-785
  • Konferensbidrag (refereegranskat)abstract
    • This paper describes a new robust regular polygon detector. The regular polygon transform is posed as a mixture of regular polygons in a five dimensional space. Given the edge structure of an image, we derive the a posteriori probability for a mixture of regular polygons, and thus the probability density function for the appearance of a mixture of regular polygons. Likely regular polygons can be isolated quickly by discretising and collapsing the search space into three dimensions. The remaining dimensions may be efficiently recovered subsequently using maximum likelihood at the locations of the most likely polygons in the subspace. This leads to an efficient algorithm. Also the a posteriori formulation facilitates inclusion of additional a priori information leading to real-time application to road sign detection. The use of gradient information also reduces noise compared to existing approaches such as the generalised Hough transform. Results are presented for images with noise to show stability. The detector is also applied to two separate applications: real-time road sign detection for on-line driver assistance; and feature detection, recovering stable features in rectilinear environments.
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  • Chiang, Chern-En, et al. (författare)
  • Alirocumab and Cardiovascular Outcomes in Patients With Previous Myocardial Infarction : Prespecified Subanalysis From ODYSSEY OUTCOMES
  • 2022
  • Ingår i: Canadian Journal of Cardiology. - : Elsevier. - 0828-282X .- 1916-7075. ; 38:10, s. 1542-1549
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: After acute coronary syndrome (ACS), patients with a previous myocardial infarction (MI) may be at particularly high risk for major adverse cardiovascular events (MACE) and death. We studied the effects of the PCSK9 inhibitor alirocumab in patients with recent ACS according to previous history of MI.METHODS: The ODYSSEY OUTCOMES trial compared alirocumab with placebo, beginning 1 to 12 months after ACS with median 2.8-year follow-up. The primary MACE outcome comprised death from coronary heart disease, nonfatal MI, fatal or nonfatal ischemic stroke, and hospitalization for unstable angina. Of 18,924 patients, 3633 (19.2%) had previous MI.RESULTS: Patients with previous MI were older, more likely male, with more cardiovascular risk factors and previous events. With placebo, 4-year risks of MACE and death were higher among those with vs without previous MI (20.5% vs 8.9%, P < 0.001; 7.4% vs 3.4%, P < 0.001, respectively). Alirocumab reduced the risk of events regardless of the presence or absence of a history of MI (MACE, adjusted hazard ratio [aHR] 0.90, 95% confidence interval [CI], 0.78-1.05 vs 0.82, 0.73-0.92; Pinteraction = 0.34; death, aHR 0.84; 95% CI, 0.64-1.08 vs 0.87, 0.72-1.05; Pinteraction = 0.81). Estimated absolute risk reductions with alirocumab were numerically greater with vs without previous MI (MACE, 1.91% vs 1.42%; death, 1.35% vs 0.41%).CONCLUSIONS: A previous history of MI places patients with recent ACS at high risk for recurrent MACE and death. Alirocumab reduced the relative risks of these events consistently in patients with or without previous MI but with numerically greater absolute benefit in the former subgroup. (ODYSSEY OUTCOMES: NCT01663402).
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  • Ekström, Jörgen, 1944, et al. (författare)
  • Parasympathetic vasoactive intestinal peptide (VIP): a likely contributor to clozapine-induced sialorrhoea
  • 2014
  • Ingår i: Oral Diseases. - : Wiley. - 1354-523X. ; 20:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective The parasympathetic transmitter vasoactive intestinal peptide (VIP) increases salivary gland blood flow and evokes protein secretion and, in some species, such as rats, a small fluid secretion. It interacts synergistically with muscarinics for protein and fluid output. Human salivary acini are supplied with VIP-containing nerves. We hypothesise that VIP and clozapine, acting together, evoke a volume of saliva greater than the sum of those induced by each drug given separately. It was further considered whether, in the current test situation, circulatory events influenced the magnitude of the secretory response. Saliva from parotid glands deprived of their autonomic innervation, and saliva and blood from innervated submandibular glands were collected in adrenoceptor antagonist-pretreated pentobarbitone-anaesthetised rats. Initially, the individual and then the combined effects of intravenous doses of VIP and clozapine were established. The submandibular volume response to the combination was 2-3 times higher, while blood pressure and glandular blood flow did not differ from those to VIP alone. The synergism occurred independent of nerves as shown in denervated parotid glands. From the current preclinical data, we speculate that VIP of parasympathetic origin, by its synergistic interaction with clozapine, may contribute to the clozapine (muscarinic M1-receptor)-induced sialorrhoea in schizophrenics.
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  • Fletcher, L., et al. (författare)
  • Correlating driver gaze with the road scene for driver assistance systems
  • 2005
  • Ingår i: Robotics and Autonomous Systems. - : Elsevier BV. - 0921-8890 .- 1872-793X. ; 52:1, s. 71-84
  • Tidskriftsartikel (refereegranskat)abstract
    • A driver assistance system (DAS) should support the driver by monitoring road and vehicle events and presenting relevant and timely information to the driver. It is impossible to know what a driver is thinking, but we can monitor the driver's gaze direction and compare it with the position of information in the driver's viewfield to make inferences. In this way, not only do we monitor the driver's actions, we monitor the driver's observations as well. In this paper we present the automated detection and recognition of road signs, combined with the monitoring of the driver's response. We present a complete system that reads speed signs in real-time, compares the driver's gaze, and provides immediate feedback if it appears the sign has been missed by the driver.
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  • Isola, M., et al. (författare)
  • Dynamics of the melatonin MT1 receptor in the rat parotidgland upon melatonin administration
  • 2016
  • Ingår i: Journal of Physiology and Pharmacology. - 0867-5910. ; 67:1, s. 111-119
  • Tidskriftsartikel (refereegranskat)abstract
    • Our recent ultrastructural study of human parotid glands revealed that the melatonin receptors, MT1 and MT2, are localised in the plasma cell membranes of acinar and ductal cells but also, and intriguingly, predominantly in acinar secretory granules, giving rise to the working hypothesis that secretory granules are a part of a transcytotic transport system for melatonin. To put this hypothesis to the test in rat parotid glands, anaesthetised animals were exposed to a high melatonin dose (3 mg/kg per hour), infused intravenously over two hours and aiming to stimulate a glandular melatonin-receptor-dependent intracellular transport system, if any. Thirty minutes later, the right parotids were removed. Pre-stimulation, left parotid gland tissue was removed to serve as (untreated) controls. Gland tissues were processed for the gold post-embedding technique and for western blot analysis. In untreated glands, on transmission electron microscope images, melatonin receptors displayed a distribution pattern similar to that in human parotids, i.e. here, too, the receptors were principally associated with the acinar secretory granules. In melatonin-treated glands, the number of granules associated with the MT1 receptor was twice that in untreated glands, despite the same total granule number in the two glands. Moreover, the density of gold particles showing MT1-receptor immunoreactivity associated with granules in melatonin-treated glands was 2.5 times that in untreated glands. The number of MT1 receptors associated with the granule membrane was about three times higher in melatonin-treated glands than in untreated glands, while the number of MT1 receptors inside the granules was about twice that in untreated glands. The immunoblotting of membrane-enriched samples showed that the MT1-receptor expression was about three times that of untreated glands. When it came to the MT2 receptor, no changes were observed. Melatonin itself thus exerts dynamic effects on its MT1 receptor, which may reflect an adaptive receptor-linked carrier system for melatonin, delivering - upon gland stimulation - melatonin to the saliva by exocytosis. © 2016, Polish Physiological Society. All right reserved.
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  • Isola, M., et al. (författare)
  • Subcellular distribution of melatonin receptors in human parotid glands
  • 2013
  • Ingår i: Journal of Anatomy. - : Wiley. - 0021-8782. ; 223:5, s. 519-524
  • Tidskriftsartikel (refereegranskat)abstract
    • The hormone melatonin influences oral health through a variety of actions, such as anti-inflammatory, anti-oxidant, immunomodulatory and antitumour. Many of these melatonin functions are mediated by a family of membrane receptors expressed in the oral epithelium and salivary glands. Using immunoblotting and immunohistochemistry, recent studies have shown that the melatonin membrane receptors, MT1 and MT2, are present in rat and human salivary glands. To date, no investigation has dealt with the ultrastructural distribution of the melatonin receptors. This was the aim of the present study, using the immunogold method applied to the human parotid gland. Reactivity to MT1 and, with less intensity, to MT2 appeared in the secretory granules of acinar cells and in the cytoplasmic vesicles of both acinar and ductal cells. Plasma membranes were also stained, albeit slightly. The peculiar intracytoplasmic distribution of these receptors may indicate that there is an uptake/transport system for melatonin from the circulation into the saliva.
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  • Loy, F., et al. (författare)
  • Ultrastructural evidence of a secretory role for melatonin in the human parotid gland
  • 2015
  • Ingår i: Journal of Physiology and Pharmacology. - 0867-5910. ; 66:6, s. 847-853
  • Tidskriftsartikel (refereegranskat)abstract
    • In vivo animal studies show that pentagastrin, cholecystokinin and melatonin cause the secretion and synthesis of salivary proteins. Melatonin occurs in large amounts in the gut and is released into the blood on food intake. In vitro experiments suggest that pentagastrin exerts secretory activity in human salivary glands, as judged by ultrastructural changes, reflecting secretion, and an actual protein output. Currently, it is hypothesised that melatonin induces secretory exocytotic events in the human parotid gland. Human parotid tissues were exposed to a high single concentration of melatonin in vitro, processed for high resolution scanning electron microscopy and then assessed morphometrically with the emphasis on the membrane of the intercellular canaliculi, a site of protein secretion. Compared with controls and in terms of density, the melatonin-exposed parotid tissues displayed increases in protrusions (signalling anchored granules) and microbuds (signalling membrane recycling and/or vesicle secretion) and decreases in microvilli (signalling cytoskeletal re-arrangement related to exocytosis), phenomena abolished or very largely reduced by the melatonin receptor blocker, luzindole. In conclusion, acinar serous cells of parotid tissue displayed in vitro exocytotic activity to melatonin, signalling protein secretion. Whether, under physiological conditions, melatonin influences the secretion of human parotid glands remains to be explored, however.
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  • Schwartz, Gregory G, et al. (författare)
  • Relation of Lipoprotein(a) Levels to Incident Type 2 Diabetes and Modification by Alirocumab Treatment.
  • 2021
  • Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 44:5, s. 1219-1227
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: In observational data, lower levels of lipoprotein(a) have been associated with greater prevalence of type 2 diabetes. Whether pharmacologic lowering of lipoprotein(a) influences incident type 2 diabetes is unknown. We determined the relationship of lipoprotein(a) concentration with incident type 2 diabetes and effects of treatment with alirocumab, a PCSK9 inhibitor.RESEARCH DESIGN AND METHODS: In the ODYSSEY OUTCOMES trial alirocumab was compared with placebo in patients with acute coronary syndrome. Incident diabetes was determined from laboratory, medication, and adverse event data.RESULTS: Among 13,480 patients without diabetes at baseline, 1,324 developed type 2 diabetes over a median 2.7 years. Median baseline lipoprotein(a) was 21.9 mg/dL. With placebo, 10 mg/dL lower baseline lipoprotein(a) was associated with hazard ratio 1.04 (95% CI 1.02-1.06, P < 0.001) for incident type 2 diabetes. Alirocumab reduced lipoprotein(a) by a median 23.2% with greater absolute reductions from higher baseline levels and no overall effect on incident type 2 diabetes (hazard ratio 0.95, 95% CI 0.85-1.05). At low baseline lipoprotein(a) levels, alirocumab tended to reduce incident type 2 diabetes, while at high baseline lipoprotein(a) alirocumab tended to increase incident type 2 diabetes compared with placebo (treatment-baseline lipoprotein(a) interaction P = 0.006). In the alirocumab group, a 10 mg/dL decrease in lipoprotein(a) from baseline was associated with hazard ratio 1.07 (95% CI 1.03-1.12; P = 0.0002) for incident type 2 diabetes.CONCLUSIONS: In patients with acute coronary syndrome, baseline lipoprotein(a) concentration associated inversely with incident type 2 diabetes. Alirocumab had neutral overall effect on incident type 2 diabetes. However, treatment-related reductions in lipoprotein(a), more pronounced from high baseline levels, were associated with increased risk of incident type 2 diabetes. Whether these findings pertain to other therapies that reduce lipoprotein(a) is undetermined.
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