Early indication of decompensated heart failure in patients on home-telemonitoring: a comparison of prediction algorithms based on daily weight and noninvasive transthoracic bio-impedance.

Heart Failure (HF) is a common reason for hospitalization. Admissions might be prevented by early detection of and intervention for decompensation. Conventionally, changes in weight, a possible measure of fluid accumulation, have been used to detect deterioration. Transthoracic impedance may be a more sensitive and accurate measure of fluid accumulation.In this study, we review previously proposed predictive algorithms using body weight and noninvasive transthoracic bio-impedance (NITTI) to predict HF decompensations.We monitored 91 patients with chronic HF for an average of 10 months using a weight scale and a wearable bio-impedance vest. Three algorithms were tested using either simple rule-of-thumb differences (RoT), moving averages (MACD), or cumulative sums (CUSUM).Algorithms using NITTI in the 2 weeks preceding decompensation predicted events (P<.001); however, using weight alone did not. Cross-validation showed that NITTI improved sensitivity of all algorithms tested and that trend algorithms provided the best performance for either measurement (Weight-MACD: 33%, NITTI-CUSUM: 60%) in contrast to the simpler rules-of-thumb (Weight-RoT: 20%, NITTI-RoT: 33%) as proposed in HF guidelines.NITTI measurements decrease before decompensations, and combined with trend algorithms, improve the detection of HF decompensation over current guideline rules; however, many alerts are not associated with clinically overt decompensation

Qualitative Multi-Objective Reachability for Ordered Branching MDPs

We study qualitative multi-objective reachability problems for Ordered Branching Markov Decision Processes (OBMDPs), or equivalently context-free MDPs, building on prior results for single-target reachability on Branching Markov Decision Processes (BMDPs). We provide two separate algorithms for "almost-sure" and "limit-sure" multi-target reachability for OBMDPs. Specifically, given an OBMDP, $\mathcal{A}$, given a starting non-terminal, and given a set of target non-terminals $K$ of size $k = |K|$, our first algorithm decides whether the supremum probability, of generating a tree that contains every target non-terminal in set $K$, is $1$. Our second algorithm decides whether there is a strategy for the player to almost-surely (with probability $1$) generate a tree that contains every target non-terminal in set $K$. The two separate algorithms are needed: we show that indeed, in this context, "almost-sure" $\not=$ "limit-sure" for multi-target reachability, meaning that there are OBMDPs for which the player may not have any strategy to achieve probability exactly $1$ of reaching all targets in set $K$ in the same generated tree, but may have a sequence of strategies that achieve probability arbitrarily close to $1$. Both algorithms run in time $2^{O(k)} \cdot |\mathcal{A}|^{O(1)}$, where $|\mathcal{A}|$ is the total bit encoding length of the given OBMDP, $\mathcal{A}$. Hence they run in polynomial time when $k$ is fixed, and are fixed-parameter tractable with respect to $k$. Moreover, we show that even the qualitative almost-sure (and limit-sure) multi-target reachability decision problem is in general NP-hard, when the size $k$ of the set $K$ of target non-terminals is not fixed.Comment: 47 page

Greatest Fixed Points of Probabilistic Min/Max Polynomial Equations, and Reachability for Branching Markov Decision Processes?

We give polynomial time algorithms for quantitative (and qualitative) reachability analysis for Branching Markov Decision Processes (BMDPs). Specifically, given a BMDP, and given an initial population, where the objective of the controller is to maximize (or minimize) the probability of eventually reaching a population that contains an object of a desired (or undesired) type, we give algorithms for approximating the supremum (infimum) reachability probability, within desired precision epsilon > 0, in time polynomial in the encoding size of the BMDP and in log(1/epsilon). We furthermore give P-time algorithms for computing epsilon-optimal strategies for both maximization and minimization of reachability probabilities. We also give P-time algorithms for all associated qualitative analysis problems, namely: deciding whether the optimal (supremum or infimum) reachability probabilities are 0 or 1. Prior to this paper, approximation of optimal reachability probabilities for BMDPs was not even known to be decidable. Our algorithms exploit the following basic fact: we show that for any BMDP, its maximum (minimum) non-reachability probabilities are given by the greatest fixed point (GFP) solution g* in [0,1]^n of a corresponding monotone max (min) Probabilistic Polynomial System of equations (max/min-PPS), x=P(x), which are the Bellman optimality equations for a BMDP with non-reachability objectives. We show how to compute the GFP of max/min PPSs to desired precision in P-time. We also study more general Branching Simple Stochastic Games (BSSGs) with (non-)reachability objectives. We show that: (1) the value of these games is captured by the GFP of a corresponding max-minPPS; (2) the quantitative problem of approximating the value is in TFNP; and (3) the qualitative problems associated with the value are all solvable in P-time

Origins of lymphatic and distant metastases in human colorectal cancer

The spread of cancer cells from primary tumors to regional lymph nodes is often associated with reduced survival. One prevailing model to explain this association posits that fatal, distant metastases are seeded by lymph node metastases. This view provides a mechanistic basis for the TNM staging system and is the rationale for surgical resection of tumor-draining lymph nodes. Here we examine the evolutionary relationship between primary tumor, lymph node, and distant metastases in human colorectal cancer. Studying 213 archival biopsy samples from 17 patients, we used somatic variants in hypermutable DNA regions to reconstruct high-confidence phylogenetic trees. We found that in 65% of cases, lymphatic and distant metastases arose from independent subclones in the primary tumor, whereas in 35% of cases they shared common subclonal origin. Therefore, two different lineage relationships between lymphatic and distant metastases exist in colorectal cancer

Evolution of cooperation in stochastic games

Social dilemmas occur when incentives for individuals are misaligned with group interests 1-7 . According to the 'tragedy of the commons', these misalignments can lead to overexploitation and collapse of public resources. The resulting behaviours can be analysed with the tools of game theory 8 . The theory of direct reciprocity 9-15 suggests that repeated interactions can alleviate such dilemmas, but previous work has assumed that the public resource remains constant over time. Here we introduce the idea that the public resource is instead changeable and depends on the strategic choices of individuals. An intuitive scenario is that cooperation increases the public resource, whereas defection decreases it. Thus, cooperation allows the possibility of playing a more valuable game with higher payoffs, whereas defection leads to a less valuable game. We analyse this idea using the theory of stochastic games 16-19 and evolutionary game theory. We find that the dependence of the public resource on previous interactions can greatly enhance the propensity for cooperation. For these results, the interaction between reciprocity and payoff feedback is crucial: neither repeated interactions in a constant environment nor single interactions in a changing environment yield similar cooperation rates. Our framework shows which feedbacks between exploitation and environment - either naturally occurring or designed - help to overcome social dilemmas

Climate change and the emergence of vector-borne diseases in Europe: Case study of dengue fever

Background: Dengue fever is the most prevalent mosquito-borne viral disease worldwide. Dengue transmission is critically dependent on climatic factors and there is much concern as to whether climate change would spread the disease to areas currently unaffected. The occurrence of autochthonous infections in Croatia and France in 2010 has raised concerns about a potential re-emergence of dengue in Europe. The objective of this study is to estimate dengue risk in Europe under climate change scenarios. Methods. We used a Generalized Additive Model (GAM) to estimate dengue fever risk as a function of climatic variables (maximum temperature, minimum temperature, precipitation, humidity) and socioeconomic factors (population density, urbanisation, GDP per capita and population size), under contemporary conditions (1985-2007) in Mexico. We then used our model estimates to project dengue incidence under baseline conditions (1961-1990) and three climate change scenarios: short-term 2011-2040, medium-term 2041-2070 and long-term 2071-2100 across Europe. The model was used to calculate average number of yearly dengue cases at a spatial resolution of 10 × 10 km grid covering all land surface of the currently 27 EU member states. To our knowledge, this is the first attempt to model dengue fever risk in Europe in terms of disease occurrence rather than mosquito presence. Results: The results were presented using Geographical Information System (GIS) and allowed identification of areas at high risk. Dengue fever hot spots were clustered around the coastal areas of the Mediterranean and Adriatic seas and the Po Valley in northern Italy. Conclusions: This risk assessment study is likely to be a valuable tool assisting effective and targeted adaptation responses to reduce the likely increased burden of dengue fever in a warmer world

Positive and Negative Regulation of Prostate Stem Cell Antigen Expression by Yin Yang 1 in Prostate Epithelial Cell Lines

Prostate cancer is influenced by epigenetic modification of genes involved in cancer development and progression. Increased expression of Prostate Stem Cell Antigen (PSCA) is correlated with development of malignant human prostate cancer, while studies in mouse models suggest that decreased PSCA levels promote prostate cancer metastasis. These studies suggest that PSCA has context-dependent functions, and could be differentially regulated during tumor progression. In the present study, we identified the multi-functional transcription factor Yin Yang 1 (YY1) as a modulator of PSCA expression in prostate epithelial cell lines. Increased YY1 levels are observed in prostatic intraepithelial neoplasia (PIN) and advanced disease. We show that androgen-mediated up-regulation of PSCA in prostate epithelial cell lines is dependent on YY1. We identified two direct YY1 binding sites within the PSCA promoter, and showed that the upstream site inhibited, while the downstream site, proximal to the androgen-responsive element, stimulated PSCA promoter activity. Thus, changes in PSCA expression levels in prostate cancer may at least partly be affected by cellular levels of YY1. Our results also suggest multiple roles for YY1 in prostate cancer which may contribute to disease progression by modulation of genes such as PSCA

Dead or alive: animal sampling during Ebola hemorrhagic fever outbreaks in humans

There are currently no widely accepted animal surveillance guidelines for human Ebola hemorrhagic fever (EHF) outbreak investigations to identify potential sources of Ebolavirus (EBOV) spillover into humans and other animals. Animal field surveillance during and following an outbreak has several purposes, from helping identify the specific animal source of a human case to guiding control activities by describing the spatial and temporal distribution of wild circulating EBOV, informing public health efforts, and contributing to broader EHF research questions. Since 1976, researchers have sampled over 10,000 individual vertebrates from areas associated with human EHF outbreaks and tested for EBOV or antibodies. Using field surveillance data associated with EHF outbreaks, this review provides guidance on animal sampling for resource-limited outbreak situations, target species, and in some cases which diagnostics should be prioritized to rapidly assess the presence of EBOV in animal reservoirs. In brief, EBOV detection was 32.7% (18/55) for carcasses (animals found dead) and 0.2% (13/5309) for live captured animals. Our review indicates that for the purposes of identifying potential sources of transmission from animals to humans and isolating suspected virus in an animal in outbreak situations, (1) surveillance of free-ranging non-human primate mortality and morbidity should be a priority, (2) any wildlife morbidity or mortality events should be investigated and may hold the most promise for locating virus or viral genome sequences, (3) surveillance of some bat species is worthwhile to isolate and detect evidence of exposure, and (4) morbidity, mortality, and serology studies of domestic animals should prioritize dogs and pigs and include testing for virus and previous exposure

Oviposition Site Selection by the Dengue Vector Aedes aegypti and Its Implications for Dengue Control

Controlling the mosquito Aedes aegypti is of public health importance because, at present, it is the only means to stop dengue virus transmission. Implementing successful mosquito control programs requires understanding what factors regulate population abundance, as well as anticipating how mosquitoes may adapt to control measures. In some species of mosquitoes, females choose egg-laying sites to improve the survival and growth of their offspring, a behavior that ultimately influences population distribution and abundance. In the current study, we tested whether Ae. aegypti actively choose the containers in which they lay their eggs and determined what cues are most relevant to that process. We also explored whether females select containers that provide the most food for their larval progeny. Surprisingly, egg-laying females were most attracted to sites containing other immature Ae. aegypti, rather than to sites containing the most food. We propose that this behavior may contribute to density-dependent competition for food among larvae and play a larger role than previously thought in regulating Ae. aegypti populations. We recommend that accounting for, and even taking advantage of, this natural behavior will lead to more effective strategies for dengue prevention

Quantifying the Spatial Dimension of Dengue Virus Epidemic Spread within a Tropical Urban Environment

Global trends in population growth and human redistribution and movement have reshaped the map of dengue transmission risk, exposing a significant proportion of the world's population to the threat of dengue epidemics. Knowledge on the relative contribution of vector and human movement to the widespread and explosive nature of dengue epidemic spread within an urban environment is limited. By analyzing a very detailed dataset of a dengue epidemic that affected the Australian city of Cairns we performed a comprehensive quantification of the spatio-temporal dimensions of dengue virus epidemic transmission and propagation within a complex urban environment. Space and space-time analysis and models allowed derivation of detailed information on the pattern of introduction and epidemic spread of dengue infection within the urban space. We foresee that some of the results and recommendations derived from our study may also be applicable to many other areas currently affected or potentially subject to dengue epidemics