163 research outputs found

    Moderate deviations for particle filtering

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    Consider the state space model (X_t,Y_t), where (X_t) is a Markov chain, and (Y_t) are the observations. In order to solve the so-called filtering problem, one has to compute L(X_t|Y_1,...,Y_t), the law of X_t given the observations (Y_1,...,Y_t). The particle filtering method gives an approximation of the law L(X_t|Y_1,...,Y_t) by an empirical measure \frac{1}{n}\sum_1^n\delta_{x_{i,t}}. In this paper we establish the moderate deviation principle for the empirical mean \frac{1}{n}\sum_1^n\psi(x_{i,t}) (centered and properly rescaled) when the number of particles grows to infinity, enhancing the central limit theorem. Several extensions and examples are also studied.Comment: Published at http://dx.doi.org/10.1214/105051604000000657 in the Annals of Applied Probability (http://www.imstat.org/aap/) by the Institute of Mathematical Statistics (http://www.imstat.org

    Evaluation of the spatial and temporal trends of dengue outbreaks in Kolonnawa Urban Council, Western province, Sri Lanka.

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    Dengue which is renowned as world's fastest growing vector borne disease, has become one of the major health issues in Sri Lanka gaining a growing concern due to recent outbreaks throughout the country. Timely implementation of ideal precautionary and control measures is often respected as the prime solution for controlling and reducing potential risks posed by dengue outbreaks. Recent localized trends in spatial and temporal distribution patterns of dengue play a critical role in drafting and implementing management/action plans for effective management of dengue epidemic at regional scale. Thus, a statistic and geo informatics based analysis of the recent trends in dengue distribution was carried out to identify the trends in spatial and temporal distribution patterns of Dengue in Kolonnawa Urban Council (KUC) area (6.9283° N, 79.8950° E). Monthly records of dengue cases in 2013 and 2014 in each Grama Niladari (GN) Division (13) of KUC area were obtained from the Public Health Division of KUC. The collected data from each GN Division were then subjected to a graphical analysis (scatter plot analysis) in MINITAB (version 14.12.0) to identify the temporal patterns in dengue cases. Spatial maps of the recorded dengue case distribution in each GN Division for each month and for the whole study period were prepared using Arc GIS 10.1. The spatial and temporal variation of dengue outbreak distribution within the KUC at GND level were analyzed to identify the recent trends in dengue distribution. Significant temporal variation in dengue outbreak distribution were recognized in all GN Divisions, which is mainly influenced by the rainfall pattern, and Government and community based dengue controlling practices. Sedawatta Meethotamulla, Dahampura, Kolonnawa, Salamulla and Wellampitiya localities indicate relatively high susceptibility to dengue outbreaks while localities such as Wadulla and Gajabapura indicate less susceptibilities. The land use types, management actions taken by the Government and other relevant entities, public awareness and community participation act as the key factors that govern the trends in spatial distribution of dengue outbreaks. Thus the evaluation of the trends in temporal and spatial distribution of dengue outbreaks at the localized level, could be recommended for the government sector and other relevant entities in developing and implementing action plans to control the rise of dengue and also to evaluate the effectiveness of already implemented practices for reducing and controlling dengue outbreaks at regional scale

    Bioaccumulation of heavy metals in the selected commercially important edible fish species gray mullet (Mugil cephalus) from Negombo estuary

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    Consumption of fish contaminated with non essential heavy metals such as Pb, Hg and Cd metals which exceed the required limits pose a risk to human health. Bioaccumulations of heavy metals in fish depend on several factors such as increased levels of industrial pollution and domestic solid waste dumping in the estuary. Based on the pollution inputs into the estuary, it is considered that different localities within the estuary are polluted at different rates.The objectives of this study were to determine the non essential heavy metals concentration in fish tissues and assess the seasonal variations in the ecosystem. For this study, fish tissue samples were collected from nine sampling locations along the North (n =3), South (n=2), West (n=2), and East (n=2) parts of the estuary for a period of one year from January to December 2014. Fish tissue heavy metals levels were analyzed employing standard methods. Results revealed that the average concentrations (mg/kg) varied from Pb 0 to 0.15 ± 0.06, Cd 0.35 ± 0.16 to 1.04 ± 0.28 and Hg 0.0005 ± 0.0004 to 0.05 ± 0.046 mg/kg respectively. The detected levels were below the maximum permissible limits for hazardous substances in fish and fishery products for recommendation of FAO. The detected lead, mercury and cadmium contents in fish tissue were below the standard limits defined for each element < 0.5 mg/kg < 0.05 mg/kg and < 0.05 mg/kg respectively. Significant differences (P < 0.05) were observed for Pb and Hg depending on fish tissues. The levels of Pb and Hg metals in muscle tissue were lower than the standard limit for FAO. The value obtained on Cd 1.04 ± 0.28 mg/kg concentration was much higher than the permissible threshold limit observed in the north, south, east and west regions. The most prominent increases in Pb and Cd metal concentrations in fish tissue were found during the October, November and December study of 2014, which corresponded to peak periods from October, November and December which apparently coincided with the second inter monsoon of the island respectively

    Anti-Hyperglycaemic properties of an ethanolic extract from Costus spicatus (jacq) on Streptozotocin-induced diabetic male albino Wistar rats

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    In this contribution, for the first time an ethanolic extract of Costus spicatus, was screened for evaluating its composition followed by its in vitro antidiabetic activity. Both spectrometric and gas chromatography techniques were employed along with the antidiabetic activity on (STZ)-Streptozotocin-induced male albino Wistar rats. A rich phytochemical content, made up of tannins, saponins, flavonoids, steroids, etc, was attained together with a high amount of ash content (11.3%) and moisture content (1.27%); further, a total of 25 compounds were positively identified by GC-MS analysis. For antidiabetic activity, different treatment period of 0th day, 21th days, 45th days were taken into consideration. Histopathological studies, considering high blood glucose levels, Serum Glutamic oxaloacetic Transaminase (SGOT), Serum Glutamic Pyruvic Transaminase (SGPT), and Alkaline Phosphatase (ALP) levels highlighted no damage in the pancreas tissue cells. Based on the findings of this study, such an insulin plant might be considered a potential source and therapeutic agent for diabetic patients

    Novel ATP13A2 (PARK9) homozygous mutation in a family with marked phenotype variability

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    Mutations in the ATP13A2 (PARK9) and FBXO7 (PARK15) genes are linked to different forms of autosomal recessive juvenile-onset neurodegenerative diseases with overlapping phenotypes, including levodopa-responsive parkinsonism, pyramidal disturbances, cognitive decline, and supranuclear gaze disturbance. However, the associated genotypes and phenotypes are poorly characterized due to the small number of patients described. Here, we report clinical, instrumental, and genetic findings in an Italian family with novel PARK9 and PARK15 mutations. The proband developed a severe progressive phenotype including juvenile-onset parkinsonism, pyramidal disturbances, cognitive decline, and oculomotor abnormalities. On the contrary, his brother only shows mild abnormalities (pyramidal, cognitive, and oculomotor) on the neurological examination at the age of 31 years. These two brothers both carry a novel homozygous PARK9 missense (p.G877R) and a novel heterozygous PARK15 mutation (p.R481C). The PARK9 mutation replaces a crucial residue for the ATPase activity, and is therefore most likely a loss-of-function mutation and disease-causing in homozygous state. The pathogenic significance of the PARK15 single heterozygous mutation remains unclear. In both sibs, DaTSCAN single photon emission computed tomography showed marked nigrostriatal dopaminergic defects, and transcranial magnetic stimulation detected prolonged central motor conduction time. MRI, including T2*-weighted imaging, detected no evidence of brain iron accumulation. This family, the third reported with homozygous PARK9 mutations and the first with mutations in two genes for atypical juvenile parkinsonism, illustrates that PARK9-linked disease might display wide intra-familial clinical variability and milder phenotypes, suggesting the existence of strong, still unknown, modifiers

    Canonical moments and random spectral measures

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    We study some connections between the random moment problem and the random matrix theory. A uniform draw in a space of moments can be lifted into the spectral probability measure of the pair (A,e) where A is a random matrix from a classical ensemble and e is a fixed unit vector. This random measure is a weighted sampling among the eigenvalues of A. We also study the large deviations properties of this random measure when the dimension of the matrix grows. The rate function for these large deviations involves the reversed Kullback information.Comment: 32 pages. Revised version accepted for publication in Journal of Theoretical Probabilit

    Warsaw Breakage Syndrome associated DDX11 helicase resolves G-quadruplex structures to support sister chromatid cohesion

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    Warsaw Breakage Syndrome (WABS) is a rare disorder related to cohesinopathies and Fanconi anemia, caused by bi-allelic mutations in DDX11. Here, we report multiple compound heterozygous WABS cases, each displaying destabilized DDX11 protein and residual DDX11 function at the cellular level. Patient-derived cell lines exhibit sensitivity to topoisomerase and PARP inhibitors, defective sister chromatid cohesion and reduced DNA replication fork speed. Deleting DDX11 in RPE1-TERT cells inhibits proliferation and survival in a TP53-dependent manner and causes chromosome breaks and cohesion defects, independent of the expressed pseudogene DDX12p. Importantly, G-quadruplex (G4) stabilizing compounds induce chromosome breaks and cohesion defects which are strongly aggravated by inactivation of DDX11 but not FANCJ. The DNA helicase domain of DD

    Utility of Post-Mortem Genetic Testing in Cases of Sudden Arrhythmic Death Syndrome.

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    BACKGROUND: Sudden arrhythmic death syndrome (SADS) describes a sudden death with negative autopsy and toxicological analysis. Cardiac genetic disease is a likely etiology. OBJECTIVES: This study investigated the clinical utility and combined yield of post-mortem genetic testing (molecular autopsy) in cases of SADS and comprehensive clinical evaluation of surviving relatives. METHODS: We evaluated 302 expertly validated SADS cases with suitable DNA (median age: 24 years; 65% males) who underwent next-generation sequencing using an extended panel of 77 primary electrical disorder and cardiomyopathy genes. Pathogenic and likely pathogenic variants were classified using American College of Medical Genetics (ACMG) consensus guidelines. The yield of combined molecular autopsy and clinical evaluation in 82 surviving families was evaluated. A gene-level rare variant association analysis was conducted in SADS cases versus controls. RESULTS: A clinically actionable pathogenic or likely pathogenic variant was identified in 40 of 302 cases (13%). The main etiologies established were catecholaminergic polymorphic ventricular tachycardia and long QT syndrome (17 [6%] and 11 [4%], respectively). Gene-based rare variants association analysis showed enrichment of rare predicted deleterious variants in RYR2 (p = 5 × 10(-5)). Combining molecular autopsy with clinical evaluation in surviving families increased diagnostic yield from 26% to 39%. CONCLUSIONS: Molecular autopsy for electrical disorder and cardiomyopathy genes, using ACMG guidelines for variant classification, identified a modest but realistic yield in SADS. Our data highlighted the predominant role of catecholaminergic polymorphic ventricular tachycardia and long QT syndrome, especially the RYR2 gene, as well as the minimal yield from other genes. Furthermore, we showed the enhanced utility of combined clinical and genetic evaluation
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