Introduction of an agent-based multi-scale modular architecture for dynamic knowledge representation of acute inflammation

<p>Abstract</p> <p>Background</p> <p>One of the greatest challenges facing biomedical research is the integration and sharing of vast amounts of information, not only for individual researchers, but also for the community at large. Agent Based Modeling (ABM) can provide a means of addressing this challenge via a unifying translational architecture for dynamic knowledge representation. This paper presents a series of linked ABMs representing multiple levels of biological organization. They are intended to translate the knowledge derived from in vitro models of acute inflammation to clinically relevant phenomenon such as multiple organ failure.</p> <p>Results and Discussion</p> <p>ABM development followed a sequence starting with relatively direct translation from in-vitro derived rules into a cell-as-agent level ABM, leading on to concatenated ABMs into multi-tissue models, eventually resulting in topologically linked aggregate multi-tissue ABMs modeling organ-organ crosstalk. As an underlying design principle organs were considered to be functionally composed of an epithelial surface, which determined organ integrity, and an endothelial/blood interface, representing the reaction surface for the initiation and propagation of inflammation. The development of the epithelial ABM derived from an in-vitro model of gut epithelial permeability is described. Next, the epithelial ABM was concatenated with the endothelial/inflammatory cell ABM to produce an organ model of the gut. This model was validated against in-vivo models of the inflammatory response of the gut to ischemia. Finally, the gut ABM was linked to a similarly constructed pulmonary ABM to simulate the gut-pulmonary axis in the pathogenesis of multiple organ failure. The behavior of this model was validated against in-vivo and clinical observations on the cross-talk between these two organ systems</p> <p>Conclusion</p> <p>A series of ABMs are presented extending from the level of intracellular mechanism to clinically observed behavior in the intensive care setting. The ABMs all utilize cell-level agents that encapsulate specific mechanistic knowledge extracted from in vitro experiments. The execution of the ABMs results in a dynamic representation of the multi-scale conceptual models derived from those experiments. These models represent a qualitative means of integrating basic scientific information on acute inflammation in a multi-scale, modular architecture as a means of conceptual model verification that can potentially be used to concatenate, communicate and advance community-wide knowledge.</p

A Review on the Mechanical Modeling of Composite Manufacturing Processes

© 2016, The Author(s). The increased usage of fiber reinforced polymer composites in load bearing applications requires a detailed understanding of the process induced residual stresses and their effect on the shape distortions. This is utmost necessary in order to have more reliable composite manufacturing since the residual stresses alter the internal stress level of the composite part during the service life and the residual shape distortions may lead to not meeting the desired geometrical tolerances. The occurrence of residual stresses during the manufacturing process inherently contains diverse interactions between the involved physical phenomena mainly related to material flow, heat transfer and polymerization or crystallization. Development of numerical process models is required for virtual design and optimization of the composite manufacturing process which avoids the expensive trial-and-error based approaches. The process models as well as applications focusing on the prediction of residual stresses and shape distortions taking place in composite manufacturing are discussed in this study. The applications on both thermoset and thermoplastic based composites are reviewed in detail

Human malarial disease: a consequence of inflammatory cytokine release

Malaria causes an acute systemic human disease that bears many similarities, both clinically and mechanistically, to those caused by bacteria, rickettsia, and viruses. Over the past few decades, a literature has emerged that argues for most of the pathology seen in all of these infectious diseases being explained by activation of the inflammatory system, with the balance between the pro and anti-inflammatory cytokines being tipped towards the onset of systemic inflammation. Although not often expressed in energy terms, there is, when reduced to biochemical essentials, wide agreement that infection with falciparum malaria is often fatal because mitochondria are unable to generate enough ATP to maintain normal cellular function. Most, however, would contend that this largely occurs because sequestered parasitized red cells prevent sufficient oxygen getting to where it is needed. This review considers the evidence that an equally or more important way ATP deficency arises in malaria, as well as these other infectious diseases, is an inability of mitochondria, through the effects of inflammatory cytokines on their function, to utilise available oxygen. This activity of these cytokines, plus their capacity to control the pathways through which oxygen supply to mitochondria are restricted (particularly through directing sequestration and driving anaemia), combine to make falciparum malaria primarily an inflammatory cytokine-driven disease

The impact of gender norms on condom use among HIV-positive adults in KwaZulu-Natal, South Africa.

Critical to preventing the spread of HIV is promoting condom use among HIV-positive individuals. Previous studies suggest that gender norms (social and cultural constructions of the ways that women and men are expected to behave) may be an important determinant of condom use. However, the relationship has not been evaluated among HIV-positive women and men in South Africa. We examined gender norms and condom use at last sex among 550 partnerships reported by 530 sexually-active HIV-positive women (372) and men (158) who had sought care, but not yet initiated antiretroviral therapy in a high HIV-prevalence rural setting in KwaZulu-Natal, South Africa between January 2009 and March 2011. Participants enrolled in the cohort study completed a baseline questionnaire that detailed their socio-demographic characteristics, socio-economic circumstances, religion, HIV testing history and disclosure of HIV status, stigma, social capital, gender norms and self-efficacy. Gender norms did not statistically differ between women and men (p = 0.18). Overall, condoms were used at last sex in 58% of partnerships. Although participants disclosed their HIV status in 66% of the partnerships, 60% did not have knowledge of their partner's HIV status. In multivariable logistic regression, run separately for each sex, women younger than 26 years with more equitable gender norms were significantly more likely to have used a condom at last sex than those of the same age group with inequitable gender norms (OR = 8.88, 95% CI 2.95-26.75); the association between condom use and gender norms among women aged 26+ years and men of all ages was not statistically significant. Strategies to address gender inequity should be integrated into positive prevention interventions, particularly for younger women, and supported by efforts at a societal level to decrease gender inequality

Avaliação da continuidade de uso do preservativo feminino em usuárias do Sistema Único de Saúde em unidades da região metropolitana de São Paulo, Brasil Evaluation of continuity of use of female condoms among users of the Brazilian National Health System (SUS): longitudinal analysis in units in the metropolitan region of São Paulo, Brazil

O perfil da epidemia da Aids vem exigindo alternativas que, além de prevenir a entrada do HIV, facilitem a negociação de uso com o parceiro e possibilitem dupla proteção - contra as infecções transmitidas sexualmente, inclusive a Aids, e contra a gravidez não desejada - como o preservativo feminino. O objetivo do presente estudo foi verificar se a alta aceitabilidade inicial do preservativo feminino, descrita em outros estudos, é mantida na rotina de atendimento às diferentes populações vulneráveis. Foram monitorados durante 12 meses 16 serviços do Sistema Único de Saúde da Grande São Paulo (7 serviços especializados em atendimento às doenças sexualmente transmissíveis, 6 unidades básicas de saúde e 3 projetos comunitários). Foram incluídas no estudo 2.469 mulheres, das quais 713 em serviços de atenção especializada às DST/Aids, 1.417 em unidades básicas e 339 em projetos comunitários. A análise da continuidade de uso foi realizada por tábua de sobrevida Kaplan-Meier, teste log-rank e modelo de regressão de Cox, com intervalo de confiança de 95% (IC=95%). Observou-se que, ao final do seguimento, estavam em uso contínuo do preservativo feminino 14,4% das mulheres (355). O tempo médio de uso foi de 3,55 meses (IC 95%: 3,37- 3,73). Os resultados evidenciaram que o tipo de serviço de dispensação do insumo e a frequência mensal de relações sexuais interferiram na continuidade de uso de forma estatisticamente significante. O número de mulheres que iniciaram o uso do preservativo feminino nos diferentes tipos de serviços mostrou que há uma demanda para alternativas de prevenção, e que é fundamental a criação de espaços onde elas possam ter acesso adequado a orientações e aos insumos.<br>The new profile of the AIDS epidemic necessarily includes the implementation of alternatives which go beyond HIV prevention, meaning sexual partner negotiation and double protection: against STD (including AIDS) and unplanned pregnancy - the female condom (FC) as a possible alternative. The objective of this study was to assess continuity of the high initial acceptability of FC described in different studies. Vulnerable groups were monitored for 12 months: 16 public services of the São Paulo metropolitan area (7 specialized in STD/AIDS; 6 primary care units and 3 community projects). 2,469 women were enrolled, 713 from STD/AIDS services, 1,417 from primary care units and 339 from community projects. Kaplan-Meier, log-rank and the Cox regression model were used to analyze survival curves, CI=95%. At the end of follow-up, 355 (14.4%) women were using female condom continuously. The mean period of use of all participants was 3.55 months (CI 95%: 3.37- 3.73). Results showed type of service providing the device and frequency of sexual intercourse as factors statistically significant related to continuity of use. The high number of women accepting the use of female condom in different services showed an important demand for the device, the need to provide appropriate access to orientation and of making female condom continuously available