Capturing the time-varying drivers of an epidemic using stochastic dynamical systems

Epidemics are often modelled using non-linear dynamical systems observed through partial and noisy data. In this paper, we consider stochastic extensions in order to capture unknown influences (changing behaviors, public interventions, seasonal effects etc). These models assign diffusion processes to the time-varying parameters, and our inferential procedure is based on a suitably adjusted adaptive particle MCMC algorithm. The performance of the proposed computational methods is validated on simulated data and the adopted model is applied to the 2009 H1N1 pandemic in England. In addition to estimating the effective contact rate trajectories, the methodology is applied in real time to provide evidence in related public health decisions. Diffusion driven SEIR-type models with age structure are also introduced.Comment: 21 pages, 5 figure

Bayesian inference for partially observed stochastic differential equations driven by fractional Brownian motion

We consider continuous-time diffusion models driven by fractional Brownian motion. Observations are assumed to possess a nontrivial likelihood given the latent path. Due to the non-Markovian and high-dimensional nature of the latent path, estimating posterior expectations is computationally challenging. We present a reparameterization framework based on the Davies and Harte method for sampling stationary Gaussian processes and use it to construct a Markov chain Monte Carlo algorithm that allows computationally efficient Bayesian inference. The algorithm is based on a version of hybrid Monte Carlo simulation that delivers increased efficiency when used on the high-dimensional latent variables arising in this context. We specify the methodology on a stochastic volatility model, allowing for memory in the volatility increments through a fractional specification. The method is demonstrated on simulated data and on the S&P 500/VIX time series. In the latter case, the posterior distribution favours values of the Hurst parameter smaller than 1/2 , pointing towards medium-range dependence

A Bayesian approach to estimate changes in condom use from limited human immunodeficiency virus prevalence data.

Evaluation of large-scale intervention programmes against human immunodeficiency virus (HIV) is becoming increasingly important, but impact estimates frequently hinge on knowledge of changes in behaviour such as the frequency of condom use over time, or other self-reported behaviour changes, for which we generally have limited or potentially biased data. We employ a Bayesian inference methodology that incorporates an HIV transmission dynamics model to estimate condom use time trends from HIV prevalence data. Estimation is implemented via particle Markov chain Monte Carlo methods, applied for the first time in this context. The preliminary choice of the formulation for the time varying parameter reflecting the proportion of condom use is critical in the context studied, because of the very limited amount of condom use and HIV data available. We consider various novel formulations to explore the trajectory of condom use over time, based on diffusion-driven trajectories and smooth sigmoid curves. Numerical simulations indicate that informative results can be obtained regarding the amplitude of the increase in condom use during an intervention, with good levels of sensitivity and specificity performance in effectively detecting changes. The application of this method to a real life problem demonstrates how it can help in evaluating HIV interventions based on a small number of prevalence estimates, and it opens the way to similar applications in different contexts

Residential mobility of middle-class and popular sectors: the city of Buenos Aires as an arrival destination

El artículo reflexiona acerca de los patrones de movilidad residencial de individuos y hogares de sectores populares y medios que residen en dos zonas de la Ciudad de Buenos Aires configuradas en torno a patrones disimiles de segregación. La movilidad residencial es un lente privilegiado para evidenciar de qué modo la experiencia de la clase es producida y reproducida en los modos de habitar. Mediante un abordaje cualitativo y biográfico hemos analizado las especificidades que presentan las movilidades residenciales de los diferentes sectores sociales. Se identifican patrones en tres dimensiones de la movilidad residencial: su espacialidad, los arreglos residenciales que los hogares despliegan y las motivaciones que guían sus desplazamientos. Los hallazgos presentados dan cuenta de los efectos que produce la posición en la estructura social sobre la movilidad residencial, así como su interacción con la propia estructuración del espacio.The article reconstructs residential mobility patterns of individuals and households from popular and middle-class sectors residing in two areas of the city of Buenos Aires, configured around dissimilar segregation patterns. Residential mobility is a powerful lens to show how the social class experience is produced and reproduced in modes of dwelling. Through a qualitative and biographical approach, we analyzed the specificities presented by residential mobilities of different social sectors. We identified patterns in the three dimensions of residential mobility: spatiality, the residential arrangements that households employ, and the motivations that guide their movements. The findings show the effects that the position in the social structure has on residential mobility, as well as its interaction with the spatial structure itself.publishedVersionFil: Cosacov, Andrea. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; Argentina.Fil: Cosacov, Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones Biológicas; Argentina.Fil: Di Virgilio, María Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigación Gino Germani; Argentina.Fil: Najman, Mercedes. Universidad de Buenos Aires. Facultad de Ciencias Sociales; Argentina.Fil: Di Virgilio, María Mercedes. Universidad de Buenos Aires. Facultad de Ciencias Sociales; Argentina.Fil: Najman, Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigación Gino Germani; Argentina

Safety of Levetiracetam in paediatrics: a systematic review

Objective To identify adverse events (AEs) associated with Levetiracetam (LEV) in children. Methods Databases EMBASE (1974-February 2015) and Medline (1946-February 2015) were searched for articles in which paediatric patients (≤18 years) received LEV treatment for epilepsy. All studies with reports on safety were included. Studies involving adults, mixed age population (i.e. children and adults) in which the paediatric subpopulation was not sufficiently described, were excluded. A meta-analysis of the RCTs was carried out and association between the commonly reported AEs or treatment discontinuation and the type of regimen (polytherapy or monotherapy) was determined using Chi2 analysis. Results Sixty seven articles involving 3,174 paediatric patients were identified. A total of 1,913 AEs were reported across studies. The most common AEs were behavioural problems and somnolence, which accounted for 10.9% and 8.4% of all AEs in prospective studies. 21 prospective studies involving 1120 children stated the number of children experiencing AEs. 47% of these children experienced AEs. Significantly more children experienced AEs with polytherapy (64%) than monotherapy (22%) (p<0.001). Levetiracetam was discontinued in 4.5% of all children on polytherapy and 0.9% on monotherapy (p<0.001), the majority were due to behavioural problems. Conclusion Behavioural problems and somnolence were the most prevalent adverse events to LEV and the most common causes of treatment discontinuation. Children on polytherapy have a greater risk of adverse events than those receiving monotherapy

Renal malformations associated with mutations of developmental genes: messages from the clinic

Renal tract malformations (RTMs) account for about 40% of children with end-stage renal failure. RTMs can be caused by mutations of genes normally active in the developing kidney and lower renal tract. Moreover, some RTMs occur in the context of multi-organ malformation syndromes. For these reasons, and because genetic testing is becoming more widely available, pediatric nephrologists should work closely with clinical geneticists to make genetic diagnoses in children with RTMs, followed by appropriate family counseling. Here we highlight families with renal cysts and diabetes, renal coloboma and Fraser syndromes, and a child with microdeletion of chromosome 19q who had a rare combination of malformations. Such diagnoses provide families with often long-sought answers to the question “why was our child born with kidney disease”. Precise genetic diagnoses will also help to define cohorts of children with RTMs for long-term clinical outcome studies

Mapping of the Disease Locus and Identification of ADAMTS10 As a Candidate Gene in a Canine Model of Primary Open Angle Glaucoma

Primary open angle glaucoma (POAG) is a leading cause of blindness worldwide, with elevated intraocular pressure as an important risk factor. Increased resistance to outflow of aqueous humor through the trabecular meshwork causes elevated intraocular pressure, but the specific mechanisms are unknown. In this study, we used genome-wide SNP arrays to map the disease gene in a colony of Beagle dogs with inherited POAG to within a single 4 Mb locus on canine chromosome 20. The Beagle POAG locus is syntenic to a previously mapped human quantitative trait locus for intraocular pressure on human chromosome 19. Sequence capture and next-generation sequencing of the entire canine POAG locus revealed a total of 2,692 SNPs segregating with disease. Of the disease-segregating SNPs, 54 were within exons, 8 of which result in amino acid substitutions. The strongest candidate variant causes a glycine to arginine substitution in a highly conserved region of the metalloproteinase ADAMTS10. Western blotting revealed ADAMTS10 protein is preferentially expressed in the trabecular meshwork, supporting an effect of the variant specific to aqueous humor outflow. The Gly661Arg variant in ADAMTS10 found in the POAG Beagles suggests that altered processing of extracellular matrix and/or defects in microfibril structure or function may be involved in raising intraocular pressure, offering specific biochemical targets for future research and treatment strategies

The Biochemistry, Ultrastructure, and Subunit Assembly Mechanism of AMPA Receptors

The AMPA-type ionotropic glutamate receptors (AMPA-Rs) are tetrameric ligand-gated ion channels that play crucial roles in synaptic transmission and plasticity. Our knowledge about the ultrastructure and subunit assembly mechanisms of intact AMPA-Rs was very limited. However, the new studies using single particle EM and X-ray crystallography are revealing important insights. For example, the tetrameric crystal structure of the GluA2cryst construct provided the atomic view of the intact receptor. In addition, the single particle EM structures of the subunit assembly intermediates revealed the conformational requirement for the dimer-to-tetramer transition during the maturation of AMPA-Rs. These new data in the field provide new models and interpretations. In the brain, the native AMPA-R complexes contain auxiliary subunits that influence subunit assembly, gating, and trafficking of the AMPA-Rs. Understanding the mechanisms of the auxiliary subunits will become increasingly important to precisely describe the function of AMPA-Rs in the brain. The AMPA-R proteomics studies continuously reveal a previously unexpected degree of molecular heterogeneity of the complex. Because the AMPA-Rs are important drug targets for treating various neurological and psychiatric diseases, it is likely that these new native complexes will require detailed mechanistic analysis in the future. The current ultrastructural data on the receptors and the receptor-expressing stable cell lines that were developed during the course of these studies are useful resources for high throughput drug screening and further drug designing. Moreover, we are getting closer to understanding the precise mechanisms of AMPA-R-mediated synaptic plasticity