Clopidogrel: A Pharmacogenomic Perspective on its Use in Coronary Artery Disease

The thienopyridine antiplatelet agent clopidogrel is an effective drug for the prevention of vascular events. However, data has accumulated over time to suggest it is prone to significant interpatient variability. While there are several factors that contribute to this, one of the most important is variability in forming the active metabolite necessary for clopidogrel function. Several enzymes are involved in formation of this metabolite, and two, CYP2C19 and P-glycoprotein, appear to have alleles that both occur frequently in the population and have a clinically significant impact. Patients carrying these alleles can be identified, but it remains to be determined if this information is necessary or sufficient for risk stratification. Furthermore, if patients with high-risk alleles are identified, it is unclear how treatment should be adjusted

The filtering equations revisited

The problem of nonlinear filtering has engendered a surprising number of mathematical techniques for its treatment. A notable example is the change-of--probability-measure method originally introduced by Kallianpur and Striebel to derive the filtering equations and the Bayes-like formula that bears their names. More recent work, however, has generally preferred other methods. In this paper, we reconsider the change-of-measure approach to the derivation of the filtering equations and show that many of the technical conditions present in previous work can be relaxed. The filtering equations are established for general Markov signal processes that can be described by a martingale-problem formulation. Two specific applications are treated

A non-autonomous stochastic discrete time system with uniform disturbances

The main objective of this article is to present Bayesian optimal control over a class of non-autonomous linear stochastic discrete time systems with disturbances belonging to a family of the one parameter uniform distributions. It is proved that the Bayes control for the Pareto priors is the solution of a linear system of algebraic equations. For the case that this linear system is singular, we apply optimization techniques to gain the Bayesian optimal control. These results are extended to generalized linear stochastic systems of difference equations and provide the Bayesian optimal control for the case where the coefficients of these type of systems are non-square matrices. The paper extends the results of the authors developed for system with disturbances belonging to the exponential family

Estimating body composition in adolescent sprint athletes : comparison of different methods in a 3 years longitudinal design

A recommended field method to assess body composition in adolescent sprint athletes is currently lacking. Existing methods developed for non-athletic adolescents were not longitudinally validated and do not take maturation status into account. This longitudinal study compared two field methods, i.e., a Bio Impedance Analysis (BIA) and a skinfold based equation, with underwater densitometry to track body fat percentage relative to years from age at peak height velocity in adolescent sprint athletes. In this study, adolescent sprint athletes (34 girls, 35 boys) were measured every 6 months during 3 years (age at start = 14.8 +/- 1.5yrs in girls and 14.7 +/- 1.9yrs in boys). Body fat percentage was estimated in 3 different ways: 1) using BIA with the TANITA TBF 410; 2) using a skinfold based equation; 3) using underwater densitometry which was considered as the reference method. Height for age since birth was used to estimate age at peak height velocity. Cross-sectional analyses were performed using repeated measures ANOVA and Pearson correlations between measurement methods at each occasion. Data were analyzed longitudinally using a multilevel cross-classified model with the PROC Mixed procedure. In boys, compared to underwater densitometry, the skinfold based formula revealed comparable values for body fatness during the study period whereas BIA showed a different pattern leading to an overestimation of body fatness starting from 4 years after age at peak height velocity. In girls, both the skinfold based formula and BIA overestimated body fatness across the whole range of years from peak height velocity. The skinfold based method appears to give an acceptable estimation of body composition during growth as compared to underwater densitometry in male adolescent sprinters. In girls, caution is warranted when interpreting estimations of body fatness by both BIA and a skinfold based formula since both methods tend to give an overestimation

Effect of time-correlation of input patterns on the convergence of on-line learning

We studied the effects of time correlation of subsequent patterns on the convergence of on-line learning by a feedforward neural network with backpropagation algorithm. By using chaotic time series as sequences of correlated patterns, we found that the unexpected scaling of converging time with learning parameter emerges when time-correlated patterns accelerate learning process.Comment: 8 pages(Revtex), 5 figure

Structural Topic Models for Open-Ended Survey Responses

Collection and especially analysis of open-ended survey responses are relatively rare in the discipline and when conducted are almost exclusively done through human coding. We present an alternative, semiautomated approach, the structural topic model (STM) (Roberts, Stewart, and Airoldi 2013; Roberts et al. 2013), that draws on recent developments in machine learning based analysis of textual data. A crucial contribution of the method is that it incorporates information about the document, such as the author's gender, political affiliation, and treatment assignment (if an experimental study). This article focuses on how the STM is helpful for survey researchers and experimentalists. The STM makes analyzing open-ended responses easier, more revealing, and capable of being used to estimate treatment effects. We illustrate these innovations with analysis of text from surveys and experiments

A comparison of 3D particle, fluid and hybrid simulations for negative streamers

In the high field region at the head of a discharge streamer, the electron energy distribution develops a long tail. In negative streamers, these electrons can run away and contribute to energetic processes such as terrestrial gamma-ray and electron flashes. Moreover, electron density fluctuations can accelerate streamer branching. To track energies and locations of single electrons in relevant regions, we have developed a 3D hybrid model that couples a particle model in the region of high fields and low electron densities with a fluid model in the rest of the domain. Here we validate our 3D hybrid model on a 3D (super-)particle model for negative streamers in overvolted gaps, and we show that it almost reaches the computational efficiency of a 3D fluid model. We also show that the extended fluid model approximates the particle and the hybrid model well until stochastic fluctuations become important, while the classical fluid model underestimates velocities and ionization densities. We compare density fluctuations and the onset of branching between the models, and we compare the front velocities with an analytical approximation

Operative Procedures in the Elderly in Low-Resource Settings: A Review of Médecins Sans Frontières Facilities: Reply

As the demographic transition occurs across developing countries, an increasing number of elderly individuals are affected by disasters and conflicts. This study aimed to evaluate the elderly population that underwent an operative procedure at MSF facilities

Optimal treatment allocations in space and time for on-line control of an emerging infectious disease

A key component in controlling the spread of an epidemic is deciding where, whenand to whom to apply an intervention.We develop a framework for using data to informthese decisionsin realtime.We formalize a treatment allocation strategy as a sequence of functions, oneper treatment period, that map up-to-date information on the spread of an infectious diseaseto a subset of locations where treatment should be allocated. An optimal allocation strategyoptimizes some cumulative outcome, e.g. the number of uninfected locations, the geographicfootprint of the disease or the cost of the epidemic. Estimation of an optimal allocation strategyfor an emerging infectious disease is challenging because spatial proximity induces interferencebetween locations, the number of possible allocations is exponential in the number oflocations, and because disease dynamics and intervention effectiveness are unknown at outbreak.We derive a Bayesian on-line estimator of the optimal allocation strategy that combinessimulation–optimization with Thompson sampling.The estimator proposed performs favourablyin simulation experiments. This work is motivated by and illustrated using data on the spread ofwhite nose syndrome, which is a highly fatal infectious disease devastating bat populations inNorth America