Modelling uncertain adaptive decisions: Application to KwaZulu-Natal sugarcane growers

A dynamic Bayesian decision network was developed to model the pre- harvest burning decision-making processes of sugarcane growers in a KwaZulu-Natal sugarcane supply chain and extends previous work by Price et al. (2018). This model was created using an iterative development approach. This paper recounts the development and validation process of the third version of the model. The model was vali- dated using Pitchforth and Mengersen (2013)’s framework for validating expert elicited Bayesian networks. During this process, growers and cane supply members assessed the model in a focus group by executing the model, and reviewing the results of a pre- run scenario. The participants were generally positive about how the model represented their decision-making processes. However, they identified some issues that could be addressed in the next iteration. Dynamic Bayesian decision networks offer a promising approach to modelling adaptive decisions in uncertain conditions. This model can be used to simulate the cognitive mechanism for a grower agent in a simulation of a sugarcane supply chain

A system for pose analysis and selection in virtual reality environments

Depth cameras provide a natural and intuitive user interaction mechanism in virtual reality environments by using hand gestures as the primary user input. However, building robust VR systems that use depth cameras are challenging. Gesture recognition accuracy is affected by occlusion, variation in hand orientation and misclassification of similar hand gestures. This research explores the limits of the Leap Motion depth camera for static hand pose recognition in virtual reality applications. We propose a system for analysing static hand poses and for systematically identifying a pose set that can achieve a near-perfect recognition accuracy. The system consists of a hand pose taxonomy, a pose notation, a machine learning classifier and an algorithm to identify a reliable pose set that can achieve near perfect accuracy levels. We used this system to construct a benchmark hand pose data set containing 2550 static hand pose instances, and show how the algorithm can be used to systematically derive a set of poses that can produce an accuracy of 99% using a Support Vector Machine classifier

Establishing a health informatics research lab in South Africa

Aim/Purpose: The aim of this project was to explore models for stimulating health informatics innovation and capacity development in South Africa. Background: There is generally a critical lack of health informatics innovation and capacity in South Africa and sub-Saharan Africa. This is despite the wide anticipation that digital health systems will play a fundamental role in strengthening health systems and improving service delivery Methodology: We established a program over four years to train Masters and Doctoral students and conducted research projects across a wide range of biomedical and health informatics technologies at a leading South African university. We also developed a Health Architecture Laboratory Capacity Development and Innovation Ecosystem (HeAL-CDIE) designed to be a long-lasting and potentially reproducible output of the project. Contribution: We were able to demonstrate a successful model for building innovation and capacity in a sustainable way. Key outputs included: (i) a successful partnership model; (ii) a sustainable HeAL-CDIE; (iii) research papers; (iv) a world-class software product and several technology demonstrators ; and (iv) highly trained staff. Findings: Our main findings are that: (i) it is possible to create a local ecosystem for capacity development and innovation that creates value for the partners (a university and a private non-profit company); (ii) the ecosystem is able to create valuable outputs that would be much less likely to have been developed singly by each partner, and; (iii) the ecosystem could serve as a powerful model for adoption in other settings. Recommendations: for Practitioners:Non-profit companies and non-governmental organizations implementing health information systems in South Africa and other low resource settings have an opportunity to partner with local universities for purposes of internal capacity development and assisting with the research, reflection and innovation aspects of their projects and programmes. Recommendation for Researchers: Applied health informatics researchers working in low resource settings could productively partner with local implementing organizations in order to gain a better understanding of the challenges and requirements at field sites and to accelerate the testing and deployment of health information technology solutions. Impact on Society This research demonstrates a model that can deliver valuable software products for public health. Future Research: It would be useful to implement the model in other settings and investigate whether the model is more generally usefu

Building Semantic Causal Models to Predict Treatment Adherence for Tuberculosis Patients in Sub-Saharan Africa

Poor adherence to prescribed treatment is a major factor contributing to tuberculosis patients developing drug resistance and failing treatment. Treatment adherence behaviour is influenced by diverse personal, cultural and socio-economic factors that vary between regions and communities. Decision network models can potentially be used to predict treatment adherence behaviour. However, determining the network structure (identifying the factors and their causal relations) and the conditional probabilities is a challenging task. To resolve the former we developed an ontology supported by current scientific literature to categorise and clarify the similarity and granularity of factors

Local and systemic immunomodulatory mechanisms triggered by Human Papillomavirus transformed cells: a potential role for G-CSF and neutrophils

Cervical cancer is the last stage of a series of molecular and cellular alterations initiated with Human Papillomavirus (HPV) infection. The process involves immune responses and evasion mechanisms, which culminates with tolerance toward tumor antigens. Our objective was to understand local and systemic changes in the interactions between HPV associated cervical lesions and the immune system as lesions progress to cancer. Locally, we observed higher cervical leukocyte infiltrate, reflected by the increase in the frequency of T lymphocytes, neutrophils and M2 macrophages, in cancer patients. We observed a strong negative correlation between the frequency of neutrophils and T cells in precursor and cancer samples, but not cervicitis. In 3D tumor cell cultures, neutrophils inhibited T cell activity, displayed longer viability and longer CD16 expression half-life than neat neutrophil cultures. Systemically, we observed higher plasma G-CSF concentration, higher frequency of immature low density neutrophils, and tolerogenic monocyte derived dendritic cells, MoDCs, also in cancer patients. Interestingly, there was a negative correlation between T cell activation by MoDCs and G-CSF concentration in the plasma. Our results indicate that neutrophils and G-CSF may be part of the immune escape mechanisms triggered by cervical cancer cells, locally and systemically, respectively.Tis study was supported by Sao Paulo Research foundation: grants 2008/57889-1, 2010/20010-4, 2014/19326-6, by the Brazilian National Counsel of Technological and Scientifc Development: grant 573799/2008-3. KLFA and RAMR had PhD fellowships by Sao Paulo Research Foundation, CRSF has a Coordination for the Improvement of Higher Education Personnel PhD fellowship. We thank the Pathology Department of the School of Medicine, coordinated by Prof. Venâncio Avancini Ferreira Alves, Universidade de São Paulo for the slides containing histological samples from the biopsies used in this study. We thank Sandra Alexandre Alves for her technical support.info:eu-repo/semantics/publishedVersio

Salmonella Transiently Reside in Luminal Neutrophils in the Inflamed Gut

Enteric pathogens need to grow efficiently in the gut lumen in order to cause disease and ensure transmission. The interior of the gut forms a complex environment comprising the mucosal surface area and the inner gut lumen with epithelial cell debris and food particles. Recruitment of neutrophils to the intestinal lumen is a hallmark of non-typhoidal Salmonella enterica infections in humans. Here, we analyzed the interaction of gut luminal neutrophils with S. enterica serovar Typhimurium (S. Tm) in a mouse colitis model.Upon S. Tm(wt) infection, neutrophils transmigrate across the mucosa into the intestinal lumen. We detected a majority of pathogens associated with luminal neutrophils 20 hours after infection. Neutrophils are viable and actively engulf S. Tm, as demonstrated by live microscopy. Using S. Tm mutant strains defective in tissue invasion we show that pathogens are mostly taken up in the gut lumen at the epithelial barrier by luminal neutrophils. In these luminal neutrophils, S. Tm induces expression of genes typically required for its intracellular lifestyle such as siderophore production iroBCDE and the Salmonella pathogenicity island 2 encoded type three secretion system (TTSS-2). This shows that S. Tm at least transiently survives and responds to engulfment by gut luminal neutrophils. Gentamicin protection experiments suggest that the life-span of luminal neutrophils is limited and that S. Tm is subsequently released into the gut lumen. This "fast cycling" through the intracellular compartment of gut luminal neutrophils would explain the high fraction of TTSS-2 and iroBCDE expressing intra- and extracellular bacteria in the lumen of the infected gut. In conclusion, live neutrophils recruited during acute S. Tm colitis engulf pathogens in the gut lumen and may thus actively engage in shaping the environment of pathogens and commensals in the inflamed gut

Neuroimaging in anxiety disorders

Neuroimaging studies have gained increasing importance in validating neurobiological network hypotheses for anxiety disorders. Functional imaging procedures and radioligand binding studies in healthy subjects and in patients with anxiety disorders provide growing evidence of the existence of a complex anxiety network, including limbic, brainstem, temporal, and prefrontal cortical regions. Obviously, “normal anxiety” does not equal “pathological anxiety” although many phenomena are evident in healthy subjects, however to a lower extent. Differential effects of distinct brain regions and lateralization phenomena in different anxiety disorders are mentioned. An overview of neuroimaging investigations in anxiety disorders is given after a brief summary of results from healthy volunteers. Concluding implications for future research are made by the authors

Gene therapy for monogenic liver diseases: clinical successes, current challenges and future prospects

Over the last decade, pioneering liver-directed gene therapy trials for haemophilia B have achieved sustained clinical improvement after a single systemic injection of adeno-associated virus (AAV) derived vectors encoding the human factor IX cDNA. These trials demonstrate the potential of AAV technology to provide long-lasting clinical benefit in the treatment of monogenic liver disorders. Indeed, with more than ten ongoing or planned clinical trials for haemophilia A and B and dozens of trials planned for other inherited genetic/metabolic liver diseases, clinical translation is expanding rapidly. Gene therapy is likely to become an option for routine care of a subset of severe inherited genetic/metabolic liver diseases in the relatively near term. In this review, we aim to summarise the milestones in the development of gene therapy, present the different vector tools and their clinical applications for liver-directed gene therapy. AAV-derived vectors are emerging as the leading candidates for clinical translation of gene delivery to the liver. Therefore, we focus on clinical applications of AAV vectors in providing the most recent update on clinical outcomes of completed and ongoing gene therapy trials and comment on the current challenges that the field is facing for large-scale clinical translation. There is clearly an urgent need for more efficient therapies in many severe monogenic liver disorders, which will require careful risk-benefit analysis for each indication, especially in paediatrics

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700