Sample size determination for kernel regression estimation using sequential fixed-width confidence bands

We consider a random design model based on independent and identically distributed pairs of observations (Xi, Yi), where the regression function m(x) is given by m(x) = E(Yi|Xi = x) with one independent variable. In a nonparametric setting the aim is to produce a reasonable approximation to the unknown function m(x) when we have no precise information about the form of the true density, f(x) of X. We describe an estimation procedure of non-parametric regression model at a given point by some appropriately constructed fixed-width (2d) confidence interval with the confidence coefficient of at least 1&minus;. Here, d(&gt; 0) and 2 (0, 1) are two preassigned values. Fixed-width confidence intervals are developed using both Nadaraya-Watson and local linear kernel estimators of nonparametric regression with data-driven bandwidths. The sample size was optimized using the purely and two-stage sequential procedures together with asymptotic properties of the Nadaraya-Watson and local linear estimators. A large scale simulation study was performed to compare their coverage accuracy. The numerical results indicate that the confi dence bands based on the local linear estimator have the better performance than those constructed by using Nadaraya-Watson estimator. However both estimators are shown to have asymptotically correct coverage properties.<br /

Self-Tuning PID controller for autonomous car tracking in urban traffic

In this paper an on line self-tuned PID controller is proposed for the control of a car whose goal is to follow another one, at distances and speeds typical in urban traffic. The bestknown tuning mechanism is perhaps the MIT rule, due to its ease of implementation. However, as it is well known, this method does not guarantee the stability of the system, providing good results only for constant or slowly varying reference signals and in the absence of noise, which are unrealistic conditions. When the reference input varies with an appreciable rate or in presence of noise, eventually it could result in system instability. In this paper an alternative method is proposed that significantly improves the robustness of the system for varying inputs or in the presence of noise, as demonstrated by simulation

Compound heterozygosity of predicted loss-of-function DES variants in a family with recessive desminopathy

Background: Variants in the desmin gene (DES) are associated with desminopathy; a myofibrillar myopathy mainly characterized by muscle weakness, conduction block, and dilated cardiomyopathy. To date, only ~50 disease-associated variants have been described, and the majority of these lead to dominant-negative effects. However, the complete genotypic spectrum of desminopathy is not well established. Case presentation: Next-generation sequencing was performed on 51 cardiac disease genes in a proband with profound skeletal myopathy, dilated cardiomyopathy, and respiratory dysfunction. Our analyses revealed compound heterozygous DES variants, both of which are predicted to lead to a loss-of-function. Consistent with recessive inheritance, each variant was identified in an unaffected parent. Conclusions: This case report serves to broaden the variant spectrum of desminopathies and provides insight into the molecular mechanisms of desminopathy, supporting distinct dominant-negative and loss-of-function etiologies

Prenatal maternal immune activation causes epigenetic differences in adolescent mouse brain

Epigenetic processes such as DNA methylation have been implicated in the pathophysiology of neurodevelopmental disorders including schizophrenia and autism. Epigenetic changes can be induced by environmental exposures such as inflammation. Here we tested the hypothesis that prenatal inflammation, a recognized risk factor for schizophrenia and related neurodevelopmental conditions, alters DNA methylation in key brain regions linked to schizophrenia, namely the dopamine rich striatum and endocrine regulatory centre, the hypothalamus. DNA methylation across highly repetitive elements (long interspersed element 1 (LINE1) and intracisternal A-particles (IAPs)) were used to proxy global DNA methylation. We also investigated the Mecp2 gene because it regulates transcription of LINE1 and has a known association with neurodevelopmental disorders. Brain tissue was harvested from 6 week old offspring of mice exposed to the viral analog PolyI:C or saline on gestation day 9. We used Sequenom EpiTYPER assay to quantitatively analyze differences in DNA methylation at IAPs, LINE1 elements and the promoter region of Mecp2. In the hypothalamus, prenatal exposure to PolyI:C caused significant global DNA hypomethylation (t=2.44, P=0.019, PolyI:C mean 69.67%, saline mean 70.19%), especially in females, and significant hypomethylation of the promoter region of Mecp2, (t=3.32, P=0.002; PolyI:C mean 26.57%, saline mean 34.63%). IAP methylation was unaltered. DNA methylation in the striatum was not significantly altered. This study provides the first experimental evidence that exposure to inflammation during prenatal life is associated with epigenetic changes, including Mecp2 promoter hypomethylation. This suggests that environmental and genetic risk factors associated with neurodevelopmental disorders may act upon similar pathways. This is important because epigenetic changes are potentially modifiable and their investigation may open new avenues for treatment

Explorations in anatomy: the remains from Royal London Hospital

This paper considers the faunal remains from recent excavations at the Royal London Hospital. The remains date to the beginning of the 19th century and offer an insight into the life of the hospital's patients and practices of the attached medical school. Many of the animal remains consist of partially dissected skeletons, including the unique finds of Hermann's tortoise (Testudo hermanni) and Cercopithecus monkey. The hospital diet and developments in comparative anatomy are discussed by integrating the results with documentary research. They show that zooarchaeological study of later post-medieval material can significantly enhance our understanding of the exploitation of animals in this perio

Aromatase inhibitors in post-menopausal endometriosis

Postmenopausal endometriosis is a rare clinical condition. The diagnosis and treatment of an endometriotic lesion in postmenopausal women is complicated. First line treatment choice should be surgical, given that there is a potential risk of malignancy. Medical treatment may be considered as second line or as an alternate first line treatment whenever surgery is contradicted and aims to alter the hormonal pathway leading to endometriosis progress. Different hormonal regimens have been administered to these patients, with conflicting however results. Aromatase inhibitors (AIs) represent one of the most recently used drugs for postmenopausal endometriosis. Clinical data for the use of (AIs) in postmenopausal patients is scarce. Up to date only 5 case reports are available regarding the use of these agents in postmenopausal women. Although definite conclusions may be premature, AIs appear to considerably improve patients' symptoms and reduce endometriotic lesions size. Nonetheless the subsequent induced reduction in estrogen production, leads to certain short-term and long-term adverse effects. Despite the limited available data, AIs appear to represent a new promising method which may improve symptoms and treat these patients, either as first line treatment, when surgery is contraindicated or as a second line for recurrences following surgical treatment. However, careful monitoring of patients' risk profile and further research regarding long-term effects and side-effects of these agents is essential prior implementing them in everyday clinical practice

Using population attributable risk to choose HIV prevention strategies in men who have sex with men

<p>Abstract</p> <p>Background</p> <p>In Australia, HIV is concentrated in men who have sex with men (MSM) and rates have increased steadily over the past ten years. Health promotion strategies should ideally be informed by an understanding of both the prevalence of the factors being modified, as well as the size of the risk that they confer. We undertook an analysis of the potential population impact and cost saving that would likely result from modifying key HIV risk factors among men who have sex with men (MSM) in Sydney, Australia.</p> <p>Methods</p> <p>Proportional hazard analyses were used to examine the association between sexual behaviours in the last six months and sexually transmissible infections on HIV incidence in a cohort of 1426 HIV-negative MSM who were recruited primarily from community-based sources between 2001 and 2004 and followed to mid-2007. We then estimated the proportion of HIV infections that would be prevented if specific factors were no longer present in the population, using a population attributable risk (PAR) method which controls for confounding among factors. We also calculated the average lifetime healthcare costs incurred by the HIV infections associated with specific factors by estimating costs associated with clinical care and treatment following infection and discounting at 3% (1% and 5% sensitivity) to present value.</p> <p>Results</p> <p>Unprotected anal intercourse (UAI) with a known HIV-positive partner was reported by 5% of men, the hazard ratio (HR) was 16.1 (95%CI:6.4-40.5), the PAR was 34% (95%CI:24-44%) and the average lifetime HIV-related healthcare costs attributable to UAI with HIV-positive partners were $AUD102 million (uncertainty range:$93-114 m). UAI with unknown HIV status partners was reported by 25% of men, the HR was 4.4 (95%CI:1.8-11.2), the PAR was 33% (95%CI:26-42%) and the lifetime incurred costs were $AUD99 million. Anal warts prevalence was 4$AUD39 million.</p> <p>Conclusions</p> <p>Our analysis has found that although UAI with an HIV-positive sexual partner is a relatively low-prevalence behaviour (reported by 5% of men), if this behaviour was not present in the population, the number of infections would be reduced by one third. No other single behaviour or sexually transmissible infections contributes to a greater proportion of infections and HIV-related healthcare costs.</p