Multi-criteria dynamic decision under uncertainty: A stochastic viability analysis and an application to sustainable fishery management

Managing natural resources in a sustainable way is a hard task, due to uncertainties, dynamics and conflicting objectives (ecological, social, and economical). We propose a stochastic viability approach to address such problems. We consider a discrete-time control dynamical model with uncertainties, representing a bioeconomic system. The sustainability of this system is described by a set of constraints, defined in practice by indicators - namely, state, control and uncertainty functions - together with thresholds. This approach aims at identifying decision rules such that a set of constraints, representing various objectives, is respected with maximal probability. Under appropriate monotonicity properties of dynamics and constraints, having economic and biological content, we characterize an optimal feedback. The connection is made between this approach and the so-called Management Strategy Evaluation for fisheries. A numerical application to sustainable management of Bay of Biscay nephrops-hakes mixed fishery is given.     

Urban transmission of Chagas disease in Cochabamba, Bolivia

Chagas disease is a major public health problem in Bolivia. In the city of Cochabamba, 58% of the population lives in peripheral urban districts ("popular zones") where the infection prevalence is extremely high. From 1995 to 1999, we studied the demographics of Chagas infections in children from five to 13 years old (n = 2218) from the South zone (SZ) and North zone (NZ) districts, which differ in social, environmental, and agricultural conditions. Information gathered from these districts demonstrates qualitative and quantitative evidence for the active transmission of Trypanosoma cruzi in urban Cochabamba. Seropositivity was high in both zones (25% in SZ and 19% in NZ). We observed a high risk of infection in children from five to nine years old in SZ, but in NZ, a higher risk occurred in children aged 10-13, with odds ratio for infection three times higher in NZ than in SZ. This difference was not due to triatomine density, since more than 1,000 Triatoma infestans were captured in both zones, but was possibly secondary to the vector infection rate (79% in SZ and 37% in NZ). Electrocardiogram abnormalities were found to be prevalent in children and pre-adolescents (SZ = 40%, NZ = 17%), indicating that under continuous exposure to infection and re-infection, a severe form of the disease may develop early in life. This work demonstrates that T. cruzi infection should also be considered an urban health problem and is not restricted to the rural areas and small villages of Bolivia.     

Multi-criteria decision analysis to select metrics for design and monitoring of sustainable ecosystem restorations

The selection of metrics for ecosystem restoration programs is critical for improving the quality and utility of design and monitoring programs, informing adaptive management actions, and characterizing project success. The metrics selection process, that in practice is left to the subjective judgment of stakeholders, is often complex and should simultaneously take into account monitoring data, environmental models, socio-economic considerations, and stakeholder interests. With limited funding, it is often very difficult to balance the importance of multiple metrics, often competing, intended to measure different environmental, social, and economic aspects of the system. To help restoration planners and practitioners develop the most useful and informative design and monitoring programs, we propose the use of multi-criteria decision analysis (MCDA) methods, broadly defined, to select optimal ecosystem restoration metric sets. In this paper, we apply and compare two MCDA methods, multi-attribute utility theory (MAUT), and probabilistic multi-criteria acceptability analysis (ProMAA), for a hypothetical river restoration case study involving multiple stakeholders with competing interests. Overall, the MCDA results in a systematic, quantitative, and transparent evaluation and comparison of potential metrics that provides planners and practitioners with a clear basis for selecting the optimal set of metrics to evaluate restoration alternatives and to inform restoration design and monitoring. In our case study, the two MCDA methods provide comparable results in terms of selected metrics. However, because ProMAA can consider probability distributions for weights and utility values of metrics for each criterion, it is most likely the best option for projects with highly uncertain data and significant stakeholder involvement. Despite the increase in complexity in the metrics selection process, MCDA improves upon the current, commonly-used ad-hoc decision practice based on consultations with stakeholders by applying and presenting quantitative aggregation of data and judgment, thereby increasing the effectiveness of environmental design and monitoring and the transparency of decision making in restoration projects.     

A model for Chagas disease with controlled spraying

Chagas disease is a vector-borne parasitic disease that infects mammals, including humans, through much of Latin America. This work presents a mathematical model for the dynamics of domestic transmission in the form of four coupled nonlinear differential equations. The four equations model the number of domiciliary vectors, the number of infected domiciliary vectors, the number of infected humans, and the number of infected domestic animals. The main interest of this work lies in its study of the effects of insecticide spraying and of the recovery of vector populations with cessation of spraying. A novel aspect in the model is that yearly spraying, which is currently used to prevent transmission, is taken into account. The model's predictions for a representative village are discussed. In particular, the model predicts that if pesticide use is discontinued, the vector population and the disease can return to their pre-spraying levels in approximately 5–8 years.     

A mathematical model for Chagas disease with infection-age-dependent infectivity

In this paper we develop a mathematical model for Chagas disease with infection-age-dependent infectivity. The effects of vector and blood transfusion transmission are considered, and the infected population is structured by the infection age (the time elapsed from infection). The authors identify the basic reproduction ratio R0 and show that the disease can invade into the susceptible population and unique endemic steady state exists if R0 > 1, whereas the disease dies out if R0 is small enough. We show that depending on parameters, backward bifurcation of endemic steady state can occur, so even if R0 < 1, there could exist endemic steady states. We also discuss local and global stability of steady states.     

Doctors' attitudes to risk in difficult clinical decisions: application of decision analysis in hepatobiliary disease.

Twelve doctors with special training in hepatology independently reviewed two to five cases each from a group of seven cases of complicated hepatobiliary problems. A doctor''s willingness to take risks to improve his patients'' health was quantified by a wagering technique based on the probability of achieving a successful intervention. These probabilities were then used to calculate "utilities," which represented the average opinion of the doctors about the relative worth of each of six predefined states of health. The results showed that, in the context of risky decisions for severely ill patients, a year of life was considered by the doctors to be worth 44% of a full recovery; being mobile for that year increased this value to 57%. Survival for up to five years with restricted mobility was considered to be worth 70% of a full recovery and the ability to work during that period increased this value to 85%. It is concluded that in clinical decision making the uncertainty and preferences implicit in a course of action can be quantified and thus made explicit.     

A foliar disease model for use in wheat disease management decision support systems

A model of winter wheat foliar disease is described, parameterised and tested for Septoria tritici (leaf blotch), Puccinia striiformis (yellow rust), Erysiphe graminis (powdery mildew) and Puccinia triticina (brown rust). The model estimates disease‐induced green area loss, and can be coupled with a wheat canopy model, in order to estimate remaining light‐intercepting green tissue and hence the capacity for resource capture. The model differs from those reported by other workers in three respects. First, variables (such as weather, host resistance and inoculum pressure) that affect disease risk are integrated in their effect on disease progress. The agronomic and meteorological data called for are restricted to those commonly available to growers by their own observations and from meteorological service networks. Second, field observations during the growing season can be used both to correct current estimates of disease severity and to modify parameters that determine predicted severity. Third, pathogen growth and symptom expression are modelled to allow the effects of fungicides to be accounted for as protectant activity (reducing infections that occur postapplication) and eradicant activity (reducing growth of presymptomatic infections). The model was tested against data from a wide range of sites and varieties and was shown to predict the expected level of disease sufficiently accurately to support fungicide treatment decisions.     

Protective human leucocyte antigen haplotype, HLA-DRB1*01-B*14, against chronic Chagas disease in Bolivia

Background

Chagas disease, caused by the flagellate parasite Trypanosoma cruzi affects 8–10 million people in Latin America. The mechanisms that underlie the development of complications of chronic Chagas disease, characterized primarily by pathology of the heart and digestive system, are not currently understood. To identify possible host genetic factors that may influence the clinical course of Chagas disease, Human Leucocyte Antigen (HLA) regional gene polymorphism was analyzed in patients presenting with differing clinical symptoms.

Methodology

Two hundred and twenty nine chronic Chagas disease patients in Santa Cruz, Bolivia, were examined by serological tests, electrocardiogram (ECG), and Barium enema colon X-ray. 31.4% of the examinees showed ECG alterations, 15.7% megacolon and 58.1% showed neither of them. A further 62 seropositive megacolon patients who had undergone colonectomy due to acute abdomen were recruited. We analyzed their HLA genetic polymorphisms (HLA-A, HLA-B, MICA, MICB, DRB1 and TNF-alpha promoter region) mainly through Sequence based and LABType SSO typing test using LUMINEX Technology.

Principal Findings

The frequencies of HLA-DRB1*01 and HLA-B*14:02 were significantly lower in patients suffering from megacolon as well as in those with ECG alteration and/or megacolon compared with a group of patients with indeterminate symptoms. The DRB1*0102, B*1402 and MICA*011 alleles were in strong Linkage Disequilibrium (LD), and the HLA-DRB1*01-B*14-MICA*011haplotype was associated with resistance against chronic Chagas disease.

Conclusions

This is the first report of HLA haplotype association with resistance to chronic Chagas disease.     

A novel substrate for arrhythmias in Chagas disease

BackgroundChagas disease (CD) is a neglected disease that induces heart failure and arrhythmias in approximately 30% of patients during the chronic phase of the disease. Despite major efforts to understand the cellular pathophysiology of CD there are still relevant open questions to be addressed. In the present investigation we aimed to evaluate the contribution of the Na⁺/Ca²⁺ exchanger (NCX) in the electrical remodeling of isolated cardiomyocytes from an experimental murine model of chronic CD.Methodology/Principal findingsMale C57BL/6 mice were infected with Colombian strain of Trypanosoma cruzi. Experiments were conducted in isolated left ventricular cardiomyocytes from mice 180–200 days post-infection and with age-matched controls. Whole-cell patch-clamp technique was used to measure cellular excitability and Real-time PCR for parasite detection. In current-clamp experiments, we found that action potential (AP) repolarization was prolonged in cardiomyocytes from chagasic mice paced at 0.2 and 1 Hz. After-depolarizations, both subthreshold and with spontaneous APs events, were more evident in the chronic phase of experimental CD. In voltage-clamp experiments, pause-induced spontaneous activity with the presence of diastolic transient inward current was enhanced in chagasic cardiomyocytes. AP waveform disturbances and diastolic transient inward current were largely attenuated in chagasic cardiomyocytes exposed to Ni²⁺ or SEA0400.Conclusions/SignificanceThe present study is the first to describe NCX as a cellular arrhythmogenic substrate in chagasic cardiomyocytes. Our data suggest that NCX could be relevant to further understanding of arrhythmogenesis in the chronic phase of experimental CD and blocking NCX may be a new therapeutic strategy to treat arrhythmias in this condition.     

Oxidative stress evaluation in patients with chronic Chagas disease

IntroductionChagas disease (CD), caused by protozoan Trypanosoma cruzi (T. cruzi), is a neglected disease that affects millions of people worldwide. The parasite clearance by the immune cells is accomplished by the activation of inflammation and production of reactive oxygen species, including nitric oxide (NO) that can lead to tissue injury and DNA damage. On the other hand, to balance the oxidative environment and decrease free radicals, there is an antioxidant system composed of enzymes and vitamins. The aim was to evaluate oxidative stress parameters in symptomatic and asymptomatic patients with Chagas disease.MethodsParticipants were divided into three groups: indeterminate CD (asymptomatic, n = 8), CD with cardiac/digestive involvement (symptomatic, n = 14), and Control healthy individuals (n = 20). The following parameters were analyzed: DNA damage, NO serum levels, hydrophilic antioxidant capacity (HAC) and vitamin E.ResultsSymptomatic patients showed increased DNA damage and NO levels and lower HAC and vitamin E levels compared to asymptomatic patients and control subjects.ConclusionsIt is possible to conclude that CD patients with clinical symptoms have higher oxidative stress, characterized by increased DNA damage and NO levels, and reduced antioxidant capacity and vitamin E levels.     

Improved Completion Rates and Characterization of Drug Reactions with an Intensive Chagas Disease Treatment Program in Rural Bolivia

Background

Chagas disease treatment is limited by drug availability, adverse side effect profiles of available medications, and poor adherence.

Methods

Adult Chagas disease patients initiating 60-days of benznidazole were randomized to weekly or twice-weekly evaluations of medication adherence and screening for adverse drug events (ADEs). Mid-week evaluations employed phone-based evaluations. Adherence was measured by self-report, pill counts with intentional over-distribution, and Medication Event Monitoring Systems (MEMS). Prospective data were compared to historical controls treated with benznidazole at the same hospital.

Results

162 prospective patients were compared to 172 historical patients. Pill counts correlated well with MEMS data (R = 0.498 for 7-day intervals, R = 0.872 for intervals >7 days). Treatment completion rates were higher among prospective than historical patients (82.1% vs. 65.1%), primarily due to lower abandonment rates. Rates of ADEs were lower among prospective than historical patients (56.8% vs. 66.9%). Twice-weekly evaluations increased identification of mild ADEs, prompting higher suspension rates than weekly evaluations. While twice-weekly evaluations identified ADEs earlier, they did not reduce incidence of moderate or severe ADEs. Many dermatologic ADEs were moderately severe upon presentation (35.6%), were not reduced by use of antihistamines, occurred among adult patients of all ages, and occurred throughout treatment, rather than the first few weeks alone.

Conclusions

Intensive management improved completion and identified more ADEs, but did not reduce moderate or severe ADEs. Risk of dermatologic ADEs cannot be reduced by selecting younger adults or monitoring only during the first few weeks of treatment. Pill counts and phone-based encounters are reliable tools for treatment programming in rural Bolivia.     

A wheat canopy model for use in disease management decision support systems

A model is described which predicts those aspects of wheat canopy development and growth which are influential in determining the development of epidemics of foliar pathogens, the efficacy of foliar applied fungicides and the impact of disease on yield; specifically the emergence, expansion and senescence of upper culm leaves in relation to anthesis date. This focus on upper leaves allowed prediction of leaf emergence dates by reference to anthesis, rather than sowing. This avoided the step changes in flag leaf emergence date with temperature, reported with earlier models, without the additional complexity of a stochastic approach. The model is designed to be coupled to models of foliar disease, where the primary effect on yield is via reduction in green canopy area and hence interception of photosynthetically active radiation. Mechanisms were incorporated to allow observations of crop development during the growing season to update state variables and adjust parameters affecting future predictions. The model was calibrated using experimental data, and validated against independent observations of crop development on four wheat cultivars across seven contrasting sites in the UK. Anthesis date and upper culm leaf emergence were always predicted within one week of their observed dates.     

Rural housing for control of Chagas disease in Venezuela

The home is an important protective element for the health of its inhabitants - but these inhabitants often include not only the householders but also domestic pests and vectors of disease. This is particularly so in Latin America where domestic triatomine bugs thrive in many of the poorer quality rural houses, emerging from their crevices at night to feed and transmit Trypanosoma cruzi in their faeces. At the public health level, there is neither drug nor vaccine suitable for controlling T. cruzi - causative agent of Chagas disease - but transmission can be interrupted by control of the domestic vectors. Traditionally, vector control has involved spraying houses with residual insecticides, but a more long-term solution, with many colateral benefits, is to improve rural housing in such a way that colonization by triatomine bugs is inhibited. Such an approach involves development of low-cost techniques for house construction, and mobilization of rural communities to make use of them. In this, Venezuela has played a leading role, as Roberto Briceno-Leon reports.     

Usability evaluation of a clinical decision support tool for osteoporosis disease management

Background

There is an extensive body of literature on health system quality reporting that has yet to be characterized. Scoping is a novel methodology for systematically assessing the breadth of a body of literature in a particular research area. Our objectives were to showcase the scoping review methodology in the review of health system quality reporting, and to report on the extent of the literature in this area.

Methods

A scoping review was performed based on the York methodology outlined by Arksey and O'Malley from the University of York, United Kingdom. We searched 14 peer reviewed and grey literature databases limiting the search to English language and non-English language articles with English abstracts published between 1980 and June 2006 with an update to November 2008. We also searched specific websites, reference lists, and key journals for relevant material and solicited input from key stakeholders. Inclusion/exclusion criteria were applied to select relevant material and qualitative information was charted from the selected literature.

Results

A total of 10,102 articles were identified from searching the literature databases, 821 were deemed relevant to our scoping review. An additional 401 were identified from updates, website searching, references lists, key journals, and stakeholder suggestions for a total of 1,222 included articles. These were categorized and catalogued according to the inclusion criteria, and further subcategories were identified through the charting process. Topic areas represented by this review included the effectiveness of health system report cards (n = 194 articles), methodological issues in their development (n = 815 articles), stakeholder views on report cards (n = 144 articles), and ethical considerations around their development (n = 69 articles).

Conclusions

The scoping review methodology has permitted us to characterize and catalogue the extensive body of literature pertaining to health system report cards. The resulting literature repository that our review has created can be of use to researchers and health system stakeholders interested in the topic of health system quality measurement and reporting.     

Thyroid carcinoma; an approach to management of the disease

The substance isolated from the anterior pituitary and responsible for the induction of thyroid hyperplasia in the tadpole (TSH) is not invariably found in increased amounts in the blood of patients with exophthalmos. The blood concentration of this substance is inversely related to the level of thyroid activity. Thyroid extract, pituitary irradiation and adrenocorticotropic hormone have not been shown conclusively to alter the course of exophthalmos.     

Microscale to manufacturing scale-up of cell-free cytokine production--a new approach for shortening protein production development timelines

Engineering robust protein production and purification of correctly folded biotherapeutic proteins in cell-based systems is often challenging due to the requirements for maintaining complex cellular networks for cell viability and the need to develop associated downstream processes that reproducibly yield biopharmaceutical products with high product quality. Here, we present an alternative Escherichia coli-based open cell-free synthesis (OCFS) system that is optimized for predictable high-yield protein synthesis and folding at any scale with straightforward downstream purification processes. We describe how the linear scalability of OCFS allows rapid process optimization of parameters affecting extract activation, gene sequence optimization, and redox folding conditions for disulfide bond formation at microliter scales. Efficient and predictable high-level protein production can then be achieved using batch processes in standard bioreactors. We show how a fully bioactive protein produced by OCFS from optimized frozen extract can be purified directly using a streamlined purification process that yields a biologically active cytokine, human granulocyte-macrophage colony-stimulating factor, produced at titers of 700 mg/L in 10 h. These results represent a milestone for in vitro protein synthesis, with potential for the cGMP production of disulfide-bonded biotherapeutic proteins.     

A new approach for the joint analysis of multiple ChIP-seq libraries with application to histone modification

Most approaches for analyzing ChIP-Seq data are focused on inferring exact protein binding sites from a single library. However, frequently multiple ChIP-Seq libraries derived from differing cell lines or tissue types from the same individual may be available. In such a situation, a separate analysis for each tissue or cell line may be inefficient. Here, we describe a novel method to analyze such data that intelligently uses the joint information from multiple related ChIP-Seq libraries. We present our method as a two-stage procedure. First, separate single cell line analysis is performed for each cell line. Here, we use a novel mixture regression approach to infer the subset of genes that are most likely to be involved in protein binding in each cell line. In the second step, we combine the separate single cell line analyses using an Empirical Bayes algorithm that implicitly incorporates inter-cell line correlation. We demonstrate the usefulness of our method using both simulated data, as well as real H3K4me3 and H3K27me3 histone methylation libraries.