EC Agricultural Prices. Price Indices and absolute prices-Quarterly Statistics 1-1993

We propose MAD-GAN, an intuitive generalization to the Generative Adversarial Networks (GANs) and its conditional variants to address the well known problem of mode collapse. First, MAD-GAN is a multi-agent GAN architecture incorporating multiple generators and one discriminator. Second, to enforce that different generators capture diverse high probability modes, the discriminator of MAD-GAN is designed such that along with finding the real and fake samples, it is also required to identify the generator that generated the given fake sample. Intuitively, to succeed in this task, the discriminator must learn to push different generators towards different identifiable modes. We perform extensive experiments on synthetic and real datasets and compare MAD-GAN with different variants of GAN. We show high quality diverse sample generations for challenging tasks such as image-to-image translation and face generation. In addition, we also show that MAD-GAN is able to disentangle different modalities when trained using highly challenging diverse-class dataset (e.g. dataset with images of forests, icebergs, and bedrooms). In the end, we show its efficacy on the unsupervised feature representation task

Mass Drug Administration and beyond: how can we strengthen health systems to deliver complex interventions to eliminate neglected tropical diseases?

Achieving the 2020 goals for Neglected Tropical Diseases (NTDs) requires scale-up of Mass Drug Administration (MDA) which will require long-term commitment of national and global financing partners, strengthening national capacity and, at the community level, systems to monitor and evaluate activities and impact. For some settings and diseases, MDA is not appropriate and alternative interventions are required. Operational research is necessary to identify how existing MDA networks can deliver this more complex range of interventions equitably. The final stages of the different global programmes to eliminate NTDs require eliminating foci of transmission which are likely to persist in complex and remote rural settings. Operational research is required to identify how current tools and practices might be adapted to locate and eliminate these hard-to-reach foci. Chronic disabilities caused by NTDs will persist after transmission of pathogens ceases. Development and delivery of sustainable services to reduce the NTD-related disability is an urgent public health priority. LSTM and its partners are world leaders in developing and delivering interventions to control vector-borne NTDs and malaria, particularly in hard-to-reach settings in Africa. Our experience, partnerships and research capacity allows us to serve as a hub for developing, supporting, monitoring and evaluating global programmes to eliminate NTDs

Expression of polycomb protein BMI-1 1 maintains the plasticity of basal 2 bronchial epithelial cells

The airway epithelium is altered in respiratory disease and is thought to contribute to disease aetiology. A caveat to disease research is that the technique of isolation of bronchial epithelial cells from patients is invasive and cells have a limited lifespan. The aim of the current study was to extensively characterise the plasticity of primary human bronchial epithelial cells that have been engineered to delay cell senescence including the ability of these cells to differentiate. Cells were engineered to express BMI-1 or hTERT using viral vector systems. Cells were characterised at passage (p) early (p5), mid (p10) and late (p15) stage for; BMI-1, p16 and CK14 protein expression, viability and the ability to differentiate at air-liquid interface (ALI), using a range of techniques including immunohistochemistry (IHC), immunofluorescence (IF), transepithelial electrical resistance (TEER), Scanning Electron Microscopy (SEM), (MUC5AC and beta tubulin (BTUB) staining). BMI-1 expressing cells maintained elevated levels of the BMI-1 protein and the epithelial marker CK14 and showed a suppression of p16. BMI-1 expressing cells had a viability advantage, differentiated at ALI and had a normal karyotype. In contrast hTERT expressing cells had a reduced viability, showed limited differentiation and had an abnormal karyotype. We therefore provide extensive characterisation of the plasticity of BMI-1 expression cells in the context of the ALI model. These cells retain properties of wild-type cells and may be useful to characterise respiratory disease mechanisms in vitro over sustained periods

An analysis of convex relaxations for MAP estimation of discrete MRFs

The problem of obtaining the maximum a posteriori estimate of a general discrete Markov random field (i.e., a Markov random field defined using a discrete set of labels) is known to be NP-hard. However, due to its central importance in many applications, several approximation algorithms have been proposed in the literature. In this paper, we present an analysis of three such algorithms based on convex relaxations: (i) LP-S: the linear programming (LP) relaxation proposed by Schlesinger (1976) for a special case and independently in Chekuri et al. (2001), Koster et al. (1998), and Wainwright et al. (2005) for the general case; (ii) QP-RL: the quadratic programming (QP) relaxation of Ravikumar and Lafferty (2006); and (iii) SOCP-MS: the second order cone programming (SOCP) relaxation first proposed by Muramatsu and Suzuki (2003) for two label problems and later extended by Kumar et al. (2006) for a general label set. We show that the SOCP-MS and the QP-RL relaxations are equivalent. Furthermore, we prove that despite the flexibility in the form of the constraints/objective function offered by QP and SOCP, the LP-S relaxation strictly dominates (i.e., provides a better approximation than) QP-RL and SOCP-MS. We generalize these results by defining a large class of SOCP (and equivalent QP) relaxations which is dominated by the LP-S relaxation. Based on these results we propose some novel SOCP relaxations which define constraints using random variables that form cycles or cliques in the graphical model representation of the random field. Using some examples we show that the new SOCP relaxations strictly dominate the previous approaches

Polymeric microspheres as protein transduction reagents

Discovering the function of an unknown protein, particularly one with neither structural nor functional correlates, is a daunting task. Interaction analyses determine binding partners, whereas DNA transfection, either transient or stable, leads to intracellular expression, though not necessarily at physiologically relevant levels. In theory, direct intracellular protein delivery (protein transduction) provides a conceptually simpler alternative, but in practice the approach is problematic. Domains such as HIV TAT protein are valuable, but their effectiveness is protein specific. Similarly, the delivery of intact proteins via endocytic pathways (e.g. using liposomes) is problematic for functional analysis because of the potential for protein degradation in the endosomes/lysosomes. Consequently, recent reports that microspheres can deliver bio-cargoes into cells via a non-endocytic, energy-independent pathway offer an exciting and promising alternative for in vitro delivery of functional protein. In order for such promise to be fully exploited, microspheres are required that (i) are stably linked to proteins, (ii) can deliver those proteins with good efficiency, (iii) release functional protein once inside the cells, and (iv) permit concomitant tracking. Herein, we report the application of microspheres to successfully address all of these criteria simultaneously, for the first time. After cellular uptake, protein release was autocatalyzed by the reducing cytoplasmic environment. Outside of cells, the covalent microsphere-protein linkage was stable for ≥90 h at 37°C. Using conservative methods of estimation, 74.3% ± 5.6% of cells were shown to take up these microspheres after 24 h of incubation, with the whole process of delivery and intracellular protein release occurring within 36 h. Intended for in vitro functional protein research, this approach will enable study of the consequences of protein delivery at physiologically relevant levels, without recourse to nucleic acids, and offers a useful alternative to commercial protein transfection reagents such as Chariot™. We also provide clear immunostaining evidence to resolve residual controversy surrounding FACS-based assessment of microsphere uptake

People, Patches, and Parasites: The Case of Trypanosomiasis in Zimbabwe

Understanding the socio-ecology of disease requires careful attention to the role of patches within disease landscapes. Such patches, and the interfaces between different socio-epidemiological systems, we argue, have important implications for disease control.We conducted an interdisciplinary study over three years to investigate the spatial dynamics of human and animal trypanosomiasis in the Zambezi valley, Zimbabwe. We used a habitat niche model to identify changes in suitable habitat for tsetse fly vectors over time, and this is related to local villagers’ understandings of where flies are found. Fly trapping and blood DNA analysis of livestock highlighted the patchy distribution of both flies and trypanosome parasites. Through livelihoods analysis we explored who makes use of what areas of the landscape and when, identifying the social groups most at risk. We conclude with a discussion of the practical implications, including the need for an integrated ‘One Health’ approach involving targeted approaches to both vector control and surveillance

Tsetse control and Gambian sleeping sickness ; implications for control strategy

Background Gambian sleeping sickness (human African trypanosomiasis, HAT) outbreaks are brought under control by case detection and treatment although it is recognised that this typically only reaches about 75% of the population. Vector control is capable of completely interrupting HAT transmission but is not used because it is considered too expensive and difficult to organise in resource-poor settings. We conducted a full scale field trial of a refined vector control technology to determine its utility in control of Gambian HAT. Methods and Findings The major vector of Gambian HAT is the tsetse fly Glossina fuscipes which lives in the humid zone immediately adjacent to water bodies. From a series of preliminary trials we determined the number of tiny targets required to reduce G. fuscipes populations by more than 90%. Using these data for model calibration we predicted we needed a target density of 20 per linear km of river in riverine savannah to achieve >90% tsetse control. We then carried out a full scale, 500 km(2) field trial covering two HAT foci in Northern Uganda to determine the efficacy of tiny targets (overall target density 5.7/km(2)). In 12 months, tsetse populations declined by more than 90%. As a guide we used a published HAT transmission model and calculated that a 72% reduction in tsetse population is required to stop transmission in those settings. Interpretation The Ugandan census suggests population density in the HAT foci is approximately 500 per km2. The estimated cost for a single round of active case detection (excluding treatment), covering 80% of the population, is US$433,333 (WHO figures). One year of vector control organised within the country, which can completely stop HAT transmission, would cost US$42,700. The case for adding this method of vector control to case detection and treatment is strong. We outline how such a component could be organised

Using molecular data for epidemiological inference: assessing the prevalence of Trypanosoma brucei rhodesiense in Tsetse in Serengeti, Tanzania

Background: Measuring the prevalence of transmissible Trypanosoma brucei rhodesiense in tsetse populations is essential for understanding transmission dynamics, assessing human disease risk and monitoring spatio-temporal trends and the impact of control interventions. Although an important epidemiological variable, identifying flies which carry transmissible infections is difficult, with challenges including low prevalence, presence of other trypanosome species in the same fly, and concurrent detection of immature non-transmissible infections. Diagnostic tests to measure the prevalence of T. b. rhodesiense in tsetse are applied and interpreted inconsistently, and discrepancies between studies suggest this value is not consistently estimated even to within an order of magnitude. Methodology/Principal Findings: Three approaches were used to estimate the prevalence of transmissible Trypanosoma brucei s.l. and T. b. rhodesiense in Glossina swynnertoni and G. pallidipes in Serengeti National Park, Tanzania: (i) dissection/microscopy; (ii) PCR on infected tsetse midguts; and (iii) inference from a mathematical model. Using dissection/microscopy the prevalence of transmissible T. brucei s.l. was 0% (95% CI 0–0.085) for G. swynnertoni and 0% (0–0.18) G. pallidipes; using PCR the prevalence of transmissible T. b. rhodesiense was 0.010% (0–0.054) and 0.0089% (0–0.059) respectively, and by model inference 0.0064% and 0.00085% respectively. Conclusions/Significance: The zero prevalence result by dissection/microscopy (likely really greater than zero given the results of other approaches) is not unusual by this technique, often ascribed to poor sensitivity. The application of additional techniques confirmed the very low prevalence of T. brucei suggesting the zero prevalence result was attributable to insufficient sample size (despite examination of 6000 tsetse). Given the prohibitively high sample sizes required to obtain meaningful results by dissection/microscopy, PCR-based approaches offer the current best option for assessing trypanosome prevalence in tsetse but inconsistencies in relating PCR results to transmissibility highlight the need for a consensus approach to generate meaningful and comparable data