Dynamic simulation of human motion

In order to study the mechanisms behind the human motion and its disorders, and to comprehend how do neuromuscular impairments affect the human movements, it is crucial to know the human musculoskeletal system. This knowledge is also essential to effectively model and analyse the musculoskeletal system, and to classify the human movement. With this work we conducted preliminary studies over a musculoskeletal model in motion, and performed a comparative analysis in gait between two models: one with a non-pathological gait and another with a disordered gait

Learning hybrid locomotion skills—Learn to exploit residual actions and modulate model-based gait control

This work has developed a hybrid framework that combines machine learning and control approaches for legged robots to achieve new capabilities of balancing against external perturbations. The framework embeds a kernel which is a model-based, full parametric closed-loop and analytical controller as the gait pattern generator. On top of that, a neural network with symmetric partial data augmentation learns to automatically adjust the parameters for the gait kernel, and also generate compensatory actions for all joints, thus significantly augmenting the stability under unexpected perturbations. Seven Neural Network policies with different configurations were optimized to validate the effectiveness and the combined use of the modulation of the kernel parameters and the compensation for the arms and legs using residual actions. The results validated that modulating kernel parameters alongside the residual actions have improved the stability significantly. Furthermore, The performance of the proposed framework was evaluated across a set of challenging simulated scenarios, and demonstrated considerable improvements compared to the baseline in recovering from large external forces (up to 118%). Besides, regarding measurement noise and model inaccuracies, the robustness of the proposed framework has been assessed through simulations, which demonstrated the robustness in the presence of these uncertainties. Furthermore, the trained policies were validated across a set of unseen scenarios and showed the generalization to dynamic walking

Pathogen- and Host-Directed Antileishmanial Effects Mediated by Polyhexanide (PHMB)

BACKGROUND:Cutaneous leishmaniasis (CL) is a neglected tropical disease caused by protozoan parasites of the genus Leishmania. CL causes enormous suffering in many countries worldwide. There is no licensed vaccine against CL, and the chemotherapy options show limited efficacy and high toxicity. Localization of the parasites inside host cells is a barrier to most standard chemo- and immune-based interventions. Hence, novel drugs, which are safe, effective and readily accessible to third-world countries and/or drug delivery technologies for effective CL treatments are desperately needed. METHODOLOGY/PRINCIPAL FINDINGS:Here we evaluated the antileishmanial properties and delivery potential of polyhexamethylene biguanide (PHMB; polyhexanide), a widely used antimicrobial and wound antiseptic, in the Leishmania model. PHMB showed an inherent antileishmanial activity at submicromolar concentrations. Our data revealed that PHMB kills Leishmania major (L. major) via a dual mechanism involving disruption of membrane integrity and selective chromosome condensation and damage. PHMB's DNA binding and host cell entry properties were further exploited to improve the delivery and immunomodulatory activities of unmethylated cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODN). PHMB spontaneously bound CpG ODN, forming stable nanopolyplexes that enhanced uptake of CpG ODN, potentiated antimicrobial killing and reduced host cell toxicity of PHMB. CONCLUSIONS:Given its low cost and long history of safe topical use, PHMB holds promise as a drug for CL therapy and delivery vehicle for nucleic acid immunomodulators

Transcription of toll-like receptors 2, 3, 4 and 9, FoxP3 and Th17 cytokines in a susceptible experimental model of canine Leishmania infantum infection

Canine leishmaniosis (CanL) due to Leishmania infantum is a chronic zoonotic systemic disease resulting from complex interactions between protozoa and the canine immune system. Toll-like receptors (TLRs) are essential components of the innate immune system and facilitate the early detection of many infections. However, the role of TLRs in CanL remains unknown and information describing TLR transcription during infection is extremely scarce. The aim of this research project was to investigate the impact of L. infantum infection on canine TLR transcription using a susceptible model. The objectives of this study were to evaluate transcription of TLRs 2, 3, 4 and 9 by means of quantitative reverse transcription polymerase chain reaction (qRT-PCR) in skin, spleen, lymph node and liver in the presence or absence of experimental L. infantum infection in Beagle dogs. These findings were compared with clinical and serological data, parasite densities in infected tissues and transcription of IL-17, IL-22 and FoxP3 in different tissues in non-infected dogs (n = 10), and at six months (n = 24) and 15 months (n = 7) post infection. Results revealed significant down regulation of transcription with disease progression in lymph node samples for TLR3, TLR4, TLR9, IL-17, IL-22 and FoxP3. In spleen samples, significant down regulation of transcription was seen in TLR4 and IL-22 when both infected groups were compared with controls. In liver samples, down regulation of transcription was evident with disease progression for IL-22. In the skin, upregulation was seen only for TLR9 and FoxP3 in the early stages of infection. Subtle changes or down regulation in TLR transcription, Th17 cytokines and FoxP3 are indicative of the silent establishment of infection that Leishmania is renowned for. These observations provide new insights about TLR transcription, Th17 cytokines and Foxp3 in the liver, spleen, lymph node and skin in CanL and highlight possible markers of disease susceptibility in this model

Towards general cooperative game playing

Attempts to develop generic approaches to game playing have been around for several years in the field of Artificial Intelligence. However, games that involve explicit cooperation among otherwise competitive players cooperative negotiation games have not been addressed by current approaches. Yet, such games provide a much richer set of features, related with social aspects of interactions, which make them appealing for envisioning real-world applications. This work proposes a generic agent architecture Alpha to tackle cooperative negotiation games, combining elements such as search strategies, negotiation, opponent modeling and trust management. The architecture is then validated in the context of two different games that fall in this category Diplomacy and Werewolves. Alpha agents are tested in several scenarios, against other state-of-the-art agents. Besides highlighting the promising performance of the agents, the role of each architectural component in each game is assessed. (c) Springer International Publishing AG, part of Springer Nature 2018

Global, regional, and national incidence, prevalence, and mortality of HIV, 1980–2017, and forecasts to 2030, for 195 countries and territories: a systematic analysis for the Global Burden of Diseases, Injuries, and Risk Factors Study 2017

Background Understanding the patterns of HIV/AIDS epidemics is crucial to tracking and monitoring the progress of prevention and control efforts in countries. We provide a comprehensive assessment of the levels and trends of HIV/AIDS incidence, prevalence, mortality, and coverage of antiretroviral therapy (ART) for 1980–2017 and forecast these estimates to 2030 for 195 countries and territories. Methods We determined a modelling strategy for each country on the basis of the availability and quality of data. For countries and territories with data from population-based seroprevalence surveys or antenatal care clinics, we estimated prevalence and incidence using an open-source version of the Estimation and Projection Package—a natural history model originally developed by the UNAIDS Reference Group on Estimates, Modelling, and Projections. For countries with cause-specific vital registration data, we corrected data for garbage coding (ie, deaths coded to an intermediate, immediate, or poorly defined cause) and HIV misclassification. We developed a process of cohort incidence bias adjustment to use information on survival and deaths recorded in vital registration to back-calculate HIV incidence. For countries without any representative data on HIV, we produced incidence estimates by pulling information from observed bias in the geographical region. We used a re-coded version of the Spectrum model (a cohort component model that uses rates of disease progression and HIV mortality on and off ART) to produce age-sex-specific incidence, prevalence, and mortality, and treatment coverage results for all countries, and forecast these measures to 2030 using Spectrum with inputs that were extended on the basis of past trends in treatment scale-up and new infections. Findings Global HIV mortality peaked in 2006 with 1·95 million deaths (95% uncertainty interval 1·87–2·04) and has since decreased to 0·95 million deaths (0·91–1·01) in 2017. New cases of HIV globally peaked in 1999 (3·16 million, 2·79–3·67) and since then have gradually decreased to 1·94 million (1·63–2·29) in 2017. These trends, along with ART scale-up, have globally resulted in increased prevalence, with 36·8 million (34·8–39·2) people living with HIV in 2017. Prevalence of HIV was highest in southern sub-Saharan Africa in 2017, and countries in the region had ART coverage ranging from 65·7% in Lesotho to 85·7% in eSwatini. Our forecasts showed that 54 countries will meet the UNAIDS target of 81% ART coverage by 2020 and 12 countries are on track to meet 90% ART coverage by 2030. Forecasted results estimate that few countries will meet the UNAIDS 2020 and 2030 mortality and incidence targets. Interpretation Despite progress in reducing HIV-related mortality over the past decade, slow decreases in incidence, combined with the current context of stagnated funding for related interventions, mean that many countries are not on track to reach the 2020 and 2030 global targets for reduction in incidence and mortality. With a growing population of people living with HIV, it will continue to be a major threat to public health for years to come. The pace of progress needs to be hastened by continuing to expand access to ART and increasing investments in proven HIV prevention initiatives that can be scaled up to have population-level impact

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Gliders2d: Source Code Base for RoboCup 2D Soccer Simulation League

We describe Gliders2d, a base code release for Gliders, a soccer simulation team which won the RoboCup Soccer 2D Simulation League in 2016. We trace six evolutionary steps, each of which is encapsulated in a sequential change of the released code, from v1.1 to v1.6, starting from agent2d-3.1.1 (set as the baseline v1.0). These changes improve performance by adjusting the agents' stamina management, their pressing behaviour and the action-selection mechanism, as well as their positional choice in both attack and defense, and enabling riskier passes. The resultant behaviour, which is sufficiently generic to be applicable to physical robot teams, increases the players' mobility and achieves a better control of the field. The last presented version, Gliders2d-v1.6, approaches the strength of Gliders2013, and outperforms agent2d-3.1.1 by four goals per game on average. The sequential improvements demonstrate how the methodology of human-based evolutionary computation can markedly boost the overall performance with even a small number of controlled steps.Comment: 12 pages, 1 figure, Gliders2d code releas

Influence of Podocyte Injury on the Development of Class IV Lupus Nephritis

Cyntia Camilo Franco Borges Zago,1 Bruna de Freitas Oliveira,1 Giovanna Uehara,1 Ana Laura Carvalho da Silva,1 Laura Penna Rocha,1 Fabiano Bichuette Custódio,2 Liliane Silvano Araújo,1 Crislaine Aparecida da Silva,1 Marlene Antônia Reis,1 Juliana Reis Machado1 1Kidney Research Center-Department of Pathology, Genetics and Evolution, Federal University of Triângulo Mineiro, Uberaba, Minas Gerais, Brazil; 2Department of Clinical Medicine, Federal University of Triângulo Mineiro, Uberaba, Minas Gerais, BrazilCorrespondence: Juliana Reis Machado, Kidney Research Center – Department of Pathology, Genetics and Evolution, Federal University of Triângulo Mineiro, Uberaba, Minas Gerais, Brazil, Tel +55 (34) 3700-6450, Email [email protected]: In the kidneys, Systemic Lupus Erythematosus leads to Lupus Nephritis (LN), a form of glomerulonephritis. There is evidence that patients with LN may present activation of specific pathways for podocyte injury. This injury can occur through different mechanisms such as loss of podocyte adhesion to the glomerular basement membrane, cell death or dedifferentiation. Podocyturia with consequent podocytopenia has been described in some nephropathies such as LN, highlighting the importance of studying podocyte injuries in this condition. Evaluating in situ morphological characteristics of podocytes becomes relevant for a better understanding of the processes involved in their pathogenesis. This study investigated podocytes in different classes of LN in renal biopsies performed by the Kidney Research Center at the Federal University of Triângulo Mineiro.Patients and Methods: Twenty control cases and 29 biopsy cases diagnosed with LN were selected, divided according to the histopathological classes of the disease. Podocyte density was assessed through immunohistochemistry for Wilms tumor 1 protein and the evaluation of foot process effacement was performed by transmission electron microscopy.Results: Podocyte density was lower in the LN and this reduction was observed in all analyzed classes when compared to the control group. More foot process effacement was observed in the LN group, with more effacement in classes I/II and class IV compared to the control group. The class IV group showed more foot process effacement than the class III group and presented higher proteinuria levels compared to the classes I/II group. A strong, positive, and significant correlation was observed between the activity index and foot process effacement in the class IV group.Conclusion: Podocytes play an important role in the development of LN, and possibly, injuries to these cells are more closely related to the inflammatory/diffuse proliferative cellular process developed in class IV LN.Keywords: podocyte density, foot processes effacement, activity index, renal biops