148 research outputs found

    High order structure preserving explicit methods for solving linear-quadratic optimal control problems

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    [EN] We consider the numerical integration of linear-quadratic optimal control problems. This problem requires the solution of a boundary value problem: a non-autonomous matrix Riccati differential equation (RDE) with final conditions coupled with the state vector equation with initial conditions. The RDE has positive definite matrix solution and to numerically preserve this qualitative property we propose first to integrate this equation backward in time with a sufficiently accurate scheme. Then, this problem turns into an initial value problem, and we analyse splitting and Magnus integrators for the forward time integration which preserve the positive definite matrix solutions for the RDE. Duplicating the time as two new coordinates and using appropriate splitting methods, high order methods preserving the desired property can be obtained. The schemes make sequential computations and do not require the storrage of intermediate results, so the storage requirements are minimal. The proposed methods are also adapted for solving linear-quadratic N-player differential games. The performance of the splitting methods can be considerably improved if the system is a perturbation of an exactly solvable problem and the system is properly split. Some numerical examples illustrate the performance of the proposed methods.The author wishes to thank the University of California San Diego for its hospitality where part of this work was done. He also acknowledges the support of the Ministerio de Ciencia e Innovacion (Spain) under the coordinated project MTM2010-18246-C03. The author also acknowledges the suggestions by the referees to improve the presentation of this work.Blanes Zamora, S. (2015). High order structure preserving explicit methods for solving linear-quadratic optimal control problems. 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    Adaptive Significance of the Formation of Multi-Species Fish Spawning Aggregations near Submerged Capes

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    BACKGROUND: Many fishes are known to spawn at distinct geomorphological features such as submerged capes or "promontories," and the widespread use of these sites for spawning must imply some evolutionary advantage. Spawning at these capes is thought to result in rapid offshore transport of eggs, thereby reducing predation levels and facilitating dispersal to areas of suitable habitat. METHODOLOGY/PRINCIPAL FINDINGS: To test this "off-reef transport" hypothesis, we use a hydrodynamic model and explore the effects of topography on currents at submerged capes where spawning occurs and at similar capes where spawning does not occur, along the Mesoamerican Barrier Reef. All capes modeled in this study produced eddy-shedding regimes, but specific eddy attributes differed between spawning and non-spawning sites. Eddies at spawning sites were significantly stronger than those at non-spawning sites, and upwelling and fronts were the products of the eddy formation process. Frontal zones, present particularly at the edges of eddies near the shelf, may serve to retain larvae and nutrients. Spawning site eddies were also more predictable in terms of diameter and longevity. Passive particles released at spawning and control sites were dispersed from the release site at similar rates, but particles from spawning sites were more highly aggregated in their distributions than those from control sites, and remained closer to shore at all times. CONCLUSIONS/SIGNIFICANCE: Our findings contradict previous hypotheses that cape spawning leads to high egg dispersion due to offshore transport, and that they are attractive for spawning due to high, variable currents. Rather, we show that current regimes at spawning sites are more predictable, concentrate the eggs, and keep larvae closer to shore. These attributes would confer evolutionary advantages by maintaining relatively similar recruitment patterns year after year

    A three-country comparison of psychotropic medication prevalence in youth

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    <p>Abstract</p> <p>Background</p> <p>The study aims to compare cross-national prevalence of psychotropic medication use in youth.</p> <p>Methods</p> <p>A population-based analysis of psychotropic medication use based on administrative claims data for the year 2000 was undertaken for insured enrollees from 3 countries in relation to age group (0–4, 5–9, 10–14, and 15–19), gender, drug subclass pattern and concomitant use. The data include insured youth aged 0–19 in the year 2000 from the Netherlands (n = 110,944), Germany (n = 356,520) and the United States (n = 127,157).</p> <p>Results</p> <p>The annual prevalence of any psychotropic medication in youth was significantly greater in the US (6.7%) than in the Netherlands (2.9%) and in Germany (2.0%). Antidepressant and stimulant prevalence were 3 or more times greater in the US than in the Netherlands and Germany, while antipsychotic prevalence was 1.5–2.2 times greater. The atypical antipsychotic subclass represented only 5% of antipsychotic use in Germany, but 48% in the Netherlands and 66% in the US. The less commonly used drugs e.g. alpha agonists, lithium and antiparkinsonian agents generally followed the ranking of US>Dutch>German youth with very rare (less than 0.05%) use in Dutch and German youth. Though rarely used, anxiolytics were twice as common in Dutch as in US and German youth. Prescription hypnotics were half as common as anxiolytics in Dutch and US youth and were very uncommon in German youth. Concomitant drug use applied to 19.2% of US youth which was more than double the Dutch use and three times that of German youth.</p> <p>Conclusion</p> <p>Prominent differences in psychotropic medication treatment patterns exist between youth in the US and Western Europe and within Western Europe. Differences in policies regarding direct to consumer drug advertising, government regulatory restrictions, reimbursement policies, diagnostic classification systems, and cultural beliefs regarding the role of medication for emotional and behavioral treatment are likely to account for these differences.</p

    Національно-демократичні об'єднання та політичні партії в Україні кінця XIX - початку XX століття

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    Deep brain stimulation (DBS) has become increasingly important for the treatment and relief of neurological disorders such as Parkinson's disease, tremor, dystonia and psychiatric illness. As DBS implantations and any other stereotactic and functional surgical procedure require accurate, precise and safe targeting of the brain structure, the technical aids for preoperative planning, intervention and postoperative follow-up have become increasingly important. The aim of this paper was to give and overview, from a biomedical engineering perspective, of a typical implantation procedure and current supporting techniques. Furthermore, emerging technical aids not yet clinically established are presented. This includes the state-of-the-art of neuroimaging and navigation, patient-specific simulation of DBS electric field, optical methods for intracerebral guidance, movement pattern analysis, intraoperative data visualisation and trends related to new stimulation devices. As DBS surgery already today is an important technology intensive domain, an "intuitive visualisation" interface for improving management of these data in relation to surgery is suggested

    Genetics of photoreceptor degeneration and regeneration in zebrafish

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    Zebrafish are unique in that they provide a useful model system for studying two critically important problems in retinal neurobiology, the mechanisms responsible for triggering photoreceptor cell death and the innate stem cell–mediated regenerative response elicited by this death. In this review we highlight recent seminal findings in these two fields. We first focus on zebrafish as a model for studying photoreceptor degeneration. We summarize the genes currently known to cause photoreceptor degeneration, and we describe the phenotype of a few zebrafish mutants in detail, highlighting the usefulness of this model for studying this process. In the second section, we discuss the several different experimental paradigms that are available to study regeneration in the teleost retina. A model outlining the sequence of gene expression starting from the dedifferentiation of Müller glia to the formation of rod and cone precursors is presented

    Anxiety Disorders in Children and Adolescents with Autistic Spectrum Disorders: A Meta-Analysis

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    There is considerable evidence that children and adolescents with autistic spectrum disorders (ASD) are at increased risk of anxiety and anxiety disorders. However, it is less clear which of the specific DSM-IV anxiety disorders occur most in this population. The present study used meta-analytic techniques to help clarify this issue. A systematic review of the literature identified 31 studies involving 2,121 young people (aged <18 years) with ASD, and where the presence of anxiety disorder was assessed using standardized questionnaires or diagnostic interviews. Across studies, 39.6% of young people with ASD had at least one comorbid DSM-IV anxiety disorder, the most frequent being specific phobia (29.8%) followed by OCD (17.4%) and social anxiety disorder (16.6%). Associations were found between the specific anxiety disorders and ASD subtype, age, IQ, and assessment method (questionnaire versus interview). Implications for the identification and treatment of anxiety in young people with ASD are discussed

    Exome Chip Meta-analysis Fine Maps Causal Variants and Elucidates the Genetic Architecture of Rare Coding Variants in Smoking and Alcohol Use

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    BACKGROUND: Smoking and alcohol use have been associated with common genetic variants in multiple loci. Rare variants within these loci hold promise in the identification of biological mechanisms in substance use. Exome arrays and genotype imputation can now efficiently genotype rare nonsynonymous and loss of function variants. Such variants are expected to have deleterious functional consequences and to contribute to disease risk. METHODS: We analyzed similar to 250,000 rare variants from 16 independent studies genotyped with exome arrays and augmented this dataset with imputed data from the UK Biobank. Associations were tested for five phenotypes: cigarettes per day, pack-years, smoking initiation, age of smoking initiation, and alcoholic drinks per week. We conducted stratified heritability analyses, single-variant tests, and gene-based burden tests of nonsynonymous/loss-of-function coding variants. We performed a novel fine-mapping analysis to winnow the number of putative causal variants within associated loci. RESULTS: Meta-analytic sample sizes ranged from 152,348 to 433,216, depending on the phenotype. Rare coding variation explained 1.1% to 2.2% of phenotypic variance, reflecting 11% to 18% of the total single nucleotide polymorphism heritability of these phenotypes. We identified 171 genome-wide associated loci across all phenotypes. Fine mapping identified putative causal variants with double base-pair resolution at 24 of these loci, and between three and 10 variants for 65 loci. Twenty loci contained rare coding variants in the 95% credible intervals. CONCLUSIONS: Rare coding variation significantly contributes to the heritability of smoking and alcohol use. Fine-mapping genome-wide association study loci identifies specific variants contributing to the biological etiology of substance use behavior.Peer reviewe

    Increased Skeletal Muscle 11βHSD1 mRNA Is Associated with Lower Muscle Strength in Ageing

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    Background: Sarcopenia, the loss of muscle mass and function with age, is associated with increased morbidity and mortality. Current understanding of the underlying mechanisms is limited. Glucocorticoids (GC) in excess cause muscle weakness and atrophy. We hypothesized that GC may contribute to sarcopenia through elevated circulating levels or increased glucocorticoid receptor (GR) signaling by increased expression of either GR or the GC-amplifying enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11βHSD1) in muscle. Methods: There were 82 participants; group 1 comprised 33 older men (mean age 70.2years, SD 4.4) and 19 younger men (22.2years, 1.7) and group 2 comprised 16 older men (79.1years, 3.4) and 14 older women (80.1years, 3.7). We measured muscle strength, mid-thigh cross-sectional area, fasting morning plasma cortisol, quadriceps muscle GR and 11βHSD1 mRNA, and urinary glucocorticoid metabolites. Data were analysed using multiple linear regression adjusting for age, gender and body size. Results: Muscle strength and size were not associated with plasma cortisol, total urinary glucocorticoids or the ratio of urinary 5β-tetrahydrocortisol +5α-tetrahydrocortisol to tetrahydrocortisone (an index of systemic 11βHSD activity). Muscle strength was associated with 11βHSD1 mRNA levels (β -0.35, p = 0.04), but GR mRNA levels were not significantly associated with muscle strength or size. Conclusion: Although circulating levels of GC are not associated with muscle strength or size in either gender, increased cortisol generation within muscle by 11βHSD1 may contribute to loss of muscle strength with age, a key component of sarcopenia. Inhibition of 11βHSD1 may have therapeutic potential in sarcopenia

    A Large-Scale Multi-ancestry Genome-wide Study Accounting for Smoking Behavior Identifies Multiple Significant Loci for Blood Pressure

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    Genome-wide association analysis advanced understanding of blood pressure (BP), a major risk factor for vascular conditions such as coronary heart disease and stroke. Accounting for smoking behavior may help identify BP loci and extend our knowledge of its genetic architecture. We performed genome-wide association meta-analyses of systolic and diastolic BP incorporating gene-smoking interactions in 610,091 individuals. Stage 1 analysis examined similar to 18.8 million SNPs and small insertion/deletion variants in 129,913 individuals from four ancestries (European, African, Asian, and Hispanic) with follow-up analysis of promising variants in 480,178 additional individuals from five ancestries. We identified 15 loci that were genome-wide significant (p <5 x 10(-8)) in stage 1 and formally replicated in stage 2. A combined stage 1 and 2 meta-analysis identified 66 additional genome-wide significant loci (13, 35, and 18 loci in European, African, and trans-ancestry, respectively). A total of 56 known BP loci were also identified by our results (p <5 x 10(-8)). Of the newly identified loci, ten showed significant interaction with smoking status, but none of them were replicated in stage 2. Several loci were identified in African ancestry, highlighting the importance of genetic studies in diverse populations. The identified loci show strong evidence for regulatory features and support shared pathophysiology with cardiometabolic and addiction traits. They also highlight a role in BP regulation for biological candidates such as modulators of vascular structure and function (CDKN1B, BCAR1-CFDP1, PXDN, EEA1), ciliopathies (SDCCAG8, RPGRIP1L), telomere maintenance (TNKS, PINX1, AKTIP), and central dopaminergic signaling MSRA, EBF2).Peer reviewe

    From Sea to Sea: Canada's Three Oceans of Biodiversity

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    Evaluating and understanding biodiversity in marine ecosystems are both necessary and challenging for conservation. This paper compiles and summarizes current knowledge of the diversity of marine taxa in Canada's three oceans while recognizing that this compilation is incomplete and will change in the future. That Canada has the longest coastline in the world and incorporates distinctly different biogeographic provinces and ecoregions (e.g., temperate through ice-covered areas) constrains this analysis. The taxonomic groups presented here include microbes, phytoplankton, macroalgae, zooplankton, benthic infauna, fishes, and marine mammals. The minimum number of species or taxa compiled here is 15,988 for the three Canadian oceans. However, this number clearly underestimates in several ways the total number of taxa present. First, there are significant gaps in the published literature. Second, the diversity of many habitats has not been compiled for all taxonomic groups (e.g., intertidal rocky shores, deep sea), and data compilations are based on short-term, directed research programs or longer-term monitoring activities with limited spatial resolution. Third, the biodiversity of large organisms is well known, but this is not true of smaller organisms. Finally, the greatest constraint on this summary is the willingness and capacity of those who collected the data to make it available to those interested in biodiversity meta-analyses. Confirmation of identities and intercomparison of studies are also constrained by the disturbing rate of decline in the number of taxonomists and systematists specializing on marine taxa in Canada. This decline is mostly the result of retirements of current specialists and to a lack of training and employment opportunities for new ones. Considering the difficulties encountered in compiling an overview of biogeographic data and the diversity of species or taxa in Canada's three oceans, this synthesis is intended to serve as a biodiversity baseline for a new program on marine biodiversity, the Canadian Healthy Ocean Network. A major effort needs to be undertaken to establish a complete baseline of Canadian marine biodiversity of all taxonomic groups, especially if we are to understand and conserve this part of Canada's natural heritage
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