A dynamic transmission model for predicting trends in Helicobacter pylori and associated diseases in the United States.

To assess the benefits of intervention programs against Helicobacter pylori infection, we estimated the baseline curves of its incidence and prevalence. We developed a mathematical (compartmental) model of the intrinsic dynamics of H. pylori, which represents the natural history of infection and disease progression. Our model divided the population according to age, infection status, and clinical state. Case-patients were followed from birth to death. A proportion of the population acquired H. pylori infection and became ill with gastritis, duodenal ulcer, chronic atrophic gastritis, or gastric cancer. We simulated the change in transmissibility consistent with the incidence of gastric cancer and duodenal ulcer over time, as well as current H. pylori prevalence. In the United States, transmissibility of H. pylori has decreased to values so low that, should this trend continue, the organism will disappear from the population without targeted intervention; this process, however, will take more than a century

Toward cost-effective staffing mixes for Veterans Affairs substance use disorder treatment programs

Background: In fiscal year (FY) 2008, 133,658 patients were provided services within substance use disorders treatment programs (SUDTPs) in the U.S. Department of Veterans Affairs (VA) health care system. To improve the effectiveness and cost-effectiveness of SUDTPs, we analyze the impacts of staffing mix on the benefits and costs of specialty SUD services. This study demonstrates how cost-effective staffing mixes for each type of VA SUDTPs can be defined empirically. Methods: We used a stepwise method to derive prediction functions for benefits and costs based on patients' treatment outcomes at VA SUDTPs nationally from 2001 to 2003, and used them to formulate optimization problems to determine recommended staffing mixes that maximize net benefits per patient for four types of SUDTPs by using the solver function with the Generalized Reduced Gradient algorithm in Microsoft Excel 2010 while conforming to limits of current practice. We conducted sensitivity analyses by varying the baseline severity of addiction problems between lower (2.5 %) and higher (97.5 %) values derived from bootstrapping. Results and conclusions: Compared to the actual staffing mixes in FY01-FY03, the recommended staffing mixes would lower treatment costs while improving patients' outcomes, and improved net benefits are estimated from $1472 to$17,743 per patient. © 2015 Im et al.1

Graphical models for interactive POMDPs: representations and solutions

We develop new graphical representations for the problem of sequential decision making in partially observable multiagent environments, as formalized by interactive partially observable Markov decision processes (I-POMDPs). The graphical models called interactive inf uence diagrams (I-IDs) and their dynamic counterparts, interactive dynamic inf uence diagrams (I-DIDs), seek to explicitly model the structure that is often present in real-world problems by decomposing the situation into chance and decision variables, and the dependencies between the variables. I-DIDs generalize DIDs, which may be viewed as graphical representations of POMDPs, to multiagent settings in the same way that IPOMDPs generalize POMDPs. I-DIDs may be used to compute the policy of an agent given its belief as the agent acts and observes in a setting that is populated by other interacting agents. Using several examples, we show how I-IDs and I-DIDs may be applied and demonstrate their usefulness. We also show how the models may be solved using the standard algorithms that are applicable to DIDs. Solving I-DIDs exactly involves knowing the solutions of possible models of the other agents. The space of models grows exponentially with the number of time steps. We present a method of solving I-DIDs approximately by limiting the number of other agents’ candidate models at each time step to a constant. We do this by clustering models that are likely to be behaviorally equivalent and selecting a representative set from the clusters. We discuss the error bound of the approximation technique and demonstrate its empirical performance

Approaching Proof in the Classroom Through the Logic of Inquiry

The paper analyses a basic gap, highlighted by most of the literature concerning the teaching of proofs, namely, the distance between students' argumentative and proving processes. The analysis is developed from both epistemological and cognitive standpoints: it critiques the Toulmin model of reasoning and introduces a new model, the Logic of Inquiry of Hintikka, more suitable for bridging this gap. An example of didactical activity within Dynamic Geometry Environments is sketched in order to present a concrete illustration of this approach and to show the pedagogical effectiveness of the model

Optimal control as a graphical model inference problem

We reformulate a class of non-linear stochastic optimal control problems introduced by Todorov (2007) as a Kullback-Leibler (KL) minimization problem. As a result, the optimal control computation reduces to an inference computation and approximate inference methods can be applied to efficiently compute approximate optimal controls. We show how this KL control theory contains the path integral control method as a special case. We provide an example of a block stacking task and a multi-agent cooperative game where we demonstrate how approximate inference can be successfully applied to instances that are too complex for exact computation. We discuss the relation of the KL control approach to other inference approaches to control.Comment: 26 pages, 12 Figures; Machine Learning Journal (2012

Analysis of pmpD Expression and PmpD Post-Translational Processing during the Life Cycle of Chlamydia trachomatis Serovars A, D, and L2

BACKGROUND: The polymorphic membrane protein D (PmpD) in Chlamydia is structurally similar to autotransporter proteins described in other bacteria and may be involved in cellular and humoral protective immunity against Chlamydia. The mechanism of PmpD post-translational processing and the role of its protein products in the pathogenesis of chlamydial infection have not been very well elucidated to date. METHODOLOGY/PRINCIPAL FINDINGS: Here we examined the expression and post-translational processing of the protein product of the pmpD gene during the life cycle of C. trachomatis serovars A, D, and L2. Each of these three serovars targets different human organs and tissues and encodes a different pmpD gene nucleotide sequence. Our quantitative real-time reverse transcription polymerase chain reaction results demonstrate that the pmpD gene is up-regulated at 12-24 hours after infection regardless of the Chlamydia serovar. This up-regulation is coincidental with the period of exponential growth and replication of reticulate bodies (RB) of Chlamydia and indicates a probable similarity in function of pmpD in serovars A, D, and L2 of Chlamydia. Using mass spectrometry analysis, we identified the protein products of post-translational processing of PmpD of C. trachomatis serovar L2 and propose a double pathway model for PmpD processing, with one cleavage site between the passenger and autotransporter domains and the other site in the middle of the passenger domain. Notably, when Chlamydia infected culture cells were subjected to low (28 degrees C) temperature, PmpD post-translational processing and secretion was found to be uninhibited in the resulting persistent infection. In addition, confocal microscopy of cells infected with Chlamydia confirms our earlier hypothesis that PmpD is secreted outside Chlamydia and its secretion increases with growth of the chlamydial inclusion. CONCLUSION/SIGNIFICANCE: The results of this current study involving multiple Chlamydia serovars support the general consensus that the pmpD gene is maximally expressed at mid infection and provide new information about PmpD as an autotransporter protein which is post-translationally processed and secreted outside Chlamydia during normal and low temperature induced persistent chlamydial infection

D25V apolipoprotein C-III variant causes dominant hereditary systemic amyloidosis and confers cardiovascular protective lipoprotein profile

Apolipoprotein C-III deficiency provides cardiovascular protection, but apolipoprotein C-III is not known to be associated with human amyloidosis. Here we report a form of amyloidosis characterized by renal insufficiency caused by a new apolipoprotein C-III variant, D25V. Despite their uremic state, the D25V-carriers exhibit low triglyceride (TG) and apolipoprotein C-III levels, and low very-low-density lipoprotein (VLDL)/high high-density lipoprotein (HDL) profile. Amyloid fibrils comprise the D25V-variant only, showing that wild-type apolipoprotein C-III does not contribute to amyloid deposition in vivo. The mutation profoundly impacts helical structure stability of D25V-variant, which is remarkably fibrillogenic under physiological conditions in vitro producing typical amyloid fibrils in its lipid-free form. D25V apolipoprotein C-III is a new human amyloidogenic protein and the first conferring cardioprotection even in the unfavourable context of renal failure, extending the evidence for an important cardiovascular protective role of apolipoprotein C-III deficiency. Thus, fibrate therapy, which reduces hepatic APOC3 transcription, may delay amyloid deposition in affected patients