A Rat Model of Diabetic Wound Infection for the Evaluation of Topical Antimicrobial Therapies

Diabetes mellitus is an epidemic multisystemic chronic disease that frequently is complicated by complex wound infections. Innovative topical antimicrobial therapy agents are potentially useful for multimodal treatment of these infections. However, an appropriately standardized in vivo model is currently not available to facilitate the screening of these emerging products and their effect on wound healing. To develop such a model, we analyzed, tested, and modified published models of wound healing. We optimized various aspects of the model, including animal species, diabetes induction method, hair removal technique, splint and dressing methods, the control of unintentional bacterial infection, sampling methods for the evaluation of bacterial burden, and aspects of the microscopic and macroscopic assessment of wound healing, all while taking into consideration animal welfare and the '3Rs' principle. We thus developed a new wound infection model in rats that is optimized for testing topical antimicrobial therapy agents. This model accurately reproduces the pathophysiology of infected diabetic wound healing and includes the current standard treatment (that is, debridement). The numerous benefits of this model include the ready availability of necessary materials, simple techniques, high reproducibility, and practicality for experiments with large sample sizes. Furthermore, given its similarities to infected-wound healing and treatment in humans, our new model can serve as a valid alternative for applied research.

Effects of treatment, awareness and condom use in a coinfection model for HIV and HCV in MSM

We develop a new a coinfection model for hepatitis C virus (HCV) and the human immunodeficiency virus (HIV). We consider treatment for both diseases, screening, unawareness and awareness of HIV infection, and the use of condoms. We study the local stability of the disease-free equilibria for the full model and for the two submodels (HCV only and HIV only submodels). We sketch bifurcation diagrams for different parameters, such as the probabilities that a contact will result in a HIV or an HCV infection. We present numerical simulations of the full model where the HIV, HCV and double endemic equilibria can be observed. We also show numerically the qualitative changes of the dynamical behavior of the full model for variation of relevant parameters. We extrapolate the results from the model for actual measures that could be implemented in order to reduce the number of infected individuals.

Biological implications of the phenotypic plasticity in the Schistosoma mansoni - Nectomys squamipes model

The water-rat Nectomys squamipes is mostly important non-human host in schistosomiasis mansoni transmission in Brazil, due to its susceptibility, high abundance and water-contact pattern. During experimental infection of N. squamipes with Schistosoma mansoni, adult worms show phenotypic plasticity. This finding led us to investigate whether biological behavior is also affected. This was assessed comparing the biological characteristics of four S. mansoni strains: BE (State of Belém do Pará), CE (State of Pernambuco), CMO (State of Rio Grande do Norte) and SJ (State of São Paulo) using laboratory-bred N. squamipes. The infection was monitored by determination of the pre-patent period, fecal egg output, egg viability, intestinal egg count and, infectivity rate. No biological modification was observed in these parameters. Overall results highlight that N. squamipes was susceptible to several S. mansoni strains, suggesting that it might contribute to the maintenance of schistosomiasis mansoni in Brazil.

The ABC model for telework in Portugal

The principal aim of this paper is to develop a simple and objective model which can classify an systematise telework, and provide a standard for Portugal. This model defines special concepts of telework and allows the division of the activity in this area, making its application easier. The model was constructed on the basis of four perspectives which it has to cover: the economic and social, of the employers, of the teleworkers and the suppliers of goods and services.

A simplified four-branch model for the analytical study of the out-of-plane performance of regular stone URM walls

During the last years, several studies have been made aiming to assess the out-of-plane seismic response of unreinforced stone masonry structures. This fact led to the development of a wide variety of models and approaches, ranging from simple kinematic based analytical models up to complex numerical simulations. Nevertheless, for the sake of simplicity, the out-of-plane seismic response of a masonry wall pier may be obtained by means of a simple single-degree-of-freedom system while still providing good results. In fact, despite the assumptions associated with such a simple formulation, it is also true that the epistemic uncertainty inherent with the selection of appropriate input parameters in more complex models may render them truly ineffective. In this framework, this paper focuses on the study of the out-of-plane bending of unreinforced stone masonry walls (cantilevers) by proposing a simplified analytical approach based on the construction of a linearized four-branch model, which is used to characterize the linear and nonlinear response of such structural elements through an overturning moment-rotation relationship. The formulation of the four-branch model is presented and described in detail and the meaningful parameters used for its construction are obtained from a set of experimental laboratory tests performed on six full-scale unreinforced regular sacco stone masonry specimens. Moreover, a parametric analysis aiming to evaluate the effect of these parameters’ variation on the final configuration of the model is presented and critically discussed. Finally, the results obtained from the application of the developed four-branch model on real unreinforced regular sacco stone masonry walls are thoroughly analysed and the main conclusions obtained from its application are summarized.

Projecto de estruturas de uma passagem superior em madeira

Este projecto visa um estudo de uma solução para uma ponte pedonal de Madeira Lamelada Colada (MLC) entre o Hospital Pedro Hispano e o Norte-Shopping, localizada na Senhor da Hora. Inicialmente foram analisadas diversas variantes, com vários tipos de sistemas, sendo adoptada uma ponte formada por dois arcos, que se aproximam à medida que se afastam dos encontros unidos por contraventamentos em cruz. O tabuleiro encontra-se suspenso por tirantes e apoiados dos dois lados nos encontros. Foi realizado uma pequena introdução histórica da utilização da madeira enquanto material de construção, a sua fabricação e os vários tipos de pontes pedonais em MLC. O uso da madeira em estruturas fez com que a abordagem do Eurocódigo 5 (EC5) tivesse uma maior importância. A estrutura é modelada no programa de cálculo “DLUBAL ” através de um modelo de barras tridimensional de modo a efectuar uma análise estática e dinâmica global, recorrendo-se para tal a normas e princípios gerais de verificação de segurança dos regulamentos Europeus, nomeadamente os Eurocódigos das várias especialidades. Apresentam-se em anexo vários desenhos da ponte, desenhos das peças de ligação, o mapa de trabalhos e quantidades, ideias preliminares, dimensionamento e a escolha dos ligadores e por fim os diagramas de esforços dos elementos aos Estados-limite Último.

Crowdsourcing innovation intermediaries functions

Open innovation is a hot topic in innovation management. Its basic premise is open up the innovation process. The innovation process, in general sense, may be seen as the process of designing, developing and commercializing a novel product or service to improve the value added of a company. The development of Web 2.0 tools facilitates this kind of contributions, opening space to the emergence of crowdsourcing innovation initiatives. Crowdsourcing is a form of outsourcing not directed to other companies but to the crowd by means of an open call mostly through an Internet platform. Innovation intermediaries, in general sense, are organizations that work to enable innovation, that just act as brokers or agents between two or more parties. Usually, they are also engaged in other activities like inter-organizational networking and technology development and related activities. A crowdsourcing innovation intermediary is an organization that mediates the communication and relationship between the seekers – companies that aspire to solve some problem or to take advantage of any business opportunity – with a crowd that is prone to give ideas based on their knowledge, experience and wisdom. This paper identifies and analyses the functions to be performed by an intermediary of crowdsourcing innovation through grounded theory analyses from literature. The resulting model is presented and explained. The resulting model summarizes eight main functions that can be performed by a crowdsourcing process, namely, diagnoses, mediation, linking knowledge, community, evaluation, project management, intellectual property governance and marketing and support. These functions are associated with a learning cycle process which covers all the crowdsourcing activities that can be realized by the broker.

A Quantitative Model for Decomposing & Assessing the Value for the Customer

The research presented in this paper proposes a novel quantitative model for decomposing and assessing the Value for the Customer. The proposed approach builds on the different dimensions of the Value Network analysis proposed by Verna Allee having as background the concept of Value for the Customer proposed by Woodall. In this context, the Value for the Customer is modelled as a relationship established between the exchanged deliverables and a combination of tangible and intangible assets projected into their endogenous or exogenous dimensions. The Value Network Analysis of the deliverables exchange enables an in-depth understanding of this frontier and the implicit modelling of co-creation scenarios. The proposed Conceptual Model for Decomposing Value for the Customer combines several concepts: from the marketing area we have the concept of Value for the Customer; from the area of intellectual capital the concept of Value Network Analysis; from the collaborative networks area we have the perspective of the enterprise life cycle and the endogenous and exogenous perspectives; at last, the proposed model is supported by a mathematical formal description that stems from the area of Multi-Criteria Decision Making. The whole concept is illustrated in the context of a case study of an enterprise in the footwear industry (Pontechem). The merits of this approach seem evident from the contact with Pontechem as it provides a structured approach for the enterprises to assess the adequacy of their value proposition to the client/customer needs and how these relate to their endogenous and/or exogenous tangible or intangible assets. The proposed model, as a tool, may therefore be a useful instrument in supporting the commercialisation of new products and/or services.

Relação entre qualidade da quditoria e manipulação de resultados

A presente dissertação tem como objetivo analisar se existe relação entre a manipulação de resultados e a qualidade da auditoria, baseado no estudo do comportamento de determinados “accruals” nas empresas portuguesas não cotadas. Nos diversos estudos existentes sobre o tema “Relação da Qualidade da Auditoria e Manipulação de Resultados”, surgem abordados muitos aspetos, nomeadamente no que respeita às motivações, às formas de manipulação e métodos de deteção que se verifica no campo da auditoria e, este trabalho, pretende abordar se o processo da auditoria é, ou não, eficaz na deteção destas práticas efetuadas pelos gestores, pois isso influencia a confiança naqueles que utilizam a informação financeira. Desta forma, o trabalho pretende basear-se nestas abordagens e complementar visões e conclusões. Neste âmbito, surgem perspetivas e informações que alertam para comportamentos de risco, assim como a sua origem, ou seja, as motivações que provocam esta prática, tanto por parte dos gestores como dos administradores. É nesta perspetiva que este trabalho se enquadra, numa sociedade contemporânea que continuadamente dá exemplos reais e concretos destas práticas. Um ponto é comum, que é o facto de a manipulação dos resultados surgir principalmente pelo motivo dos interesses e motivações por parte dos gestores em conseguirem benefícios. Na tese são abordados os incentivos que levam à manipulação no contexto português, que parecem estar relacionados com o contexto económico e fiscal, onde é desenvolvida a atividade dos agentes económicos. Outra abordagem importante no trabalho é a referência às principais metodologias de detenção da manipulação de resultados, nomeadamente os modelos baseados nos accruals e na distribuição de resultados. O modelo empírico deste estudo consiste numa regressão linear múltipla, com o objetivo de explicar a relação, entre a variável accruals discricionários e as variáveis Big4, a dimensão da empresa, o endividamento, o volume de negócios e a rendibilidade. Para complementar este estudo a análise empírica incidiu sobre 4723 empresas portuguesas não cotadas, a amostra usada foi baseada na base de dados SABI, para um período de análise entre 2011 a 2013. Os resultados encontrados sugerem que existe relação entre a qualidade da auditoria e a manipulação dos resultados concluindo que as empresas auditadas pelas Big4 apresentam accruals discricionários inferiores às restantes empresas.

A Communication Intervention for Training Southern European Oncologists to Recognize Psychosocial Morbidity in Cancer. I - Development of the Model and Preliminary Results on Physicians' Satisfaction

BACKGROUND: The detection of psychosocial distress is a significant communication problem in Southern Europe and other countries. Work in this area is hampered by a lack of data. Because not much is known about training aimed at improving the recognition of psychosocial disorders in cancer patients, we developed a basic course model for medical oncology professionals. METHODS: A specific educational and experiential model (12 hours divided into 2 modules) involving formal teaching (ie, journal articles, large-group presentations), practice in small groups (ie, small-group exercises and role playing), and discussion in large groups was developed with the aim of improving the ability of oncologists to detect emotional disturbances in cancer patients (ie, depression, anxiety, and adjustment disorders). RESULTS: A total of 30 oncologists from 3 Southern European countries (Italy, Portugal, and Spain) participated in the workshop. The training course was well accepted by most participants who expressed general satisfaction and a positive subjective perception of the utility of the course for clinical practice. Of the total participants, 28 physicians (93.3%) thought that had they been exposed to this material sooner, they would have incorporated the techniques received in the workshop into their practices; 2 participants stated they would likely have done so. Half of the doctors (n = 15) believed that their clinical communication techniques were improved by participating in the workshop, and the remaining half thought that their abilities to communicate with cancer patients had improved. CONCLUSIONS: This model is a feasible approach for oncologists and is easily applicable to various oncology settings. Further studies will demonstrate the effectiveness of this method for improving oncologists skills in recognizing emotional disorders in their patients with cancer.

Preliminary study towards a novel experimental model to study localized cutaneous leishmaniasis caused bY Leishmania (Leishmania) mexicana

There is not an experimental model of localized cutaneous leishmaniasis (LCL) caused by Leishmania (Leishmania) mexicana. The aim of the present study was to characterize the clinical and histological features of Peromyscus yucatanicus experimentally infected with L. (L.) mexicana. A total of 54 P. yucatanicus (groups of 18) were inoculated with 1x10(6) promastigotes of L. (L.) mexicana in the base of the tail. They were euthanized at three and six months post experimental infection. The control group was inoculated with RPMI-1640. The predominant clinical sign observed was a single ulcerated lesion in 27.77% (5/18) and in 11.11% (2/18) P. yucatanicus at three and six months respectively. The histological pattern described as chronic granulomatous inflammation with or without necrosis was found in 7/7 (100%) biopsies of euthanized P. yucatanicus at three (n = 5) and six (n = 2) months, respectively. These results resembled clinical and histological features caused by L. (L.) mexicana in humans, and support the possibility to employ P. yucatanicus as a novel experimental model to study LCL caused by this parasite.

Modeling in-Hospital Patient Survival During the First 28 Days After Intensive Care Unit Admission: a Prognostic Model for Clinical Trials in General Critically Ill Patients

OBJECTIVE: The objective of the study was to develop a model for estimating patient 28-day in-hospital mortality using 2 different statistical approaches. DESIGN: The study was designed to develop an outcome prediction model for 28-day in-hospital mortality using (a) logistic regression with random effects and (b) a multilevel Cox proportional hazards model. SETTING: The study involved 305 intensive care units (ICUs) from the basic Simplified Acute Physiology Score (SAPS) 3 cohort. PATIENTS AND PARTICIPANTS: Patients (n = 17138) were from the SAPS 3 database with follow-up data pertaining to the first 28 days in hospital after ICU admission. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: The database was divided randomly into 5 roughly equal-sized parts (at the ICU level). It was thus possible to run the model-building procedure 5 times, each time taking four fifths of the sample as a development set and the remaining fifth as the validation set. At 28 days after ICU admission, 19.98% of the patients were still in the hospital. Because of the different sampling space and outcome variables, both models presented a better fit in this sample than did the SAPS 3 admission score calibrated to vital status at hospital discharge, both on the general population and in major subgroups. CONCLUSIONS: Both statistical methods can be used to model the 28-day in-hospital mortality better than the SAPS 3 admission model. However, because the logistic regression approach is specifically designed to forecast 28-day mortality, and given the high uncertainty associated with the assumption of the proportionality of risks in the Cox model, the logistic regression approach proved to be superior.

DISTINCT CELLULAR MIGRATION INDUCED BY Leishmania infantum chagasi AND SALIVA FROM Lutzomyia longipalpis IN A HEMORRHAGIC POOL MODEL

Recruitment of a specific cell population after Leishmania infection can influence the outcome of the disease. Cellular migration in response to Leishmania or vector saliva has been reported in air pouch model, however, cellular migration induced by Leishmania associated with host's blood and vector saliva in this model has not been described. Herein we investigated cellular migration into air pouch of hamster after stimulation with combination of L. chagasi and host's blood and Lutzomyia longipalpis saliva. Migration induced by saliva was 3-fold more than those induced by L. chagasi alone. Additionally, L. chagasi associated with blood and saliva induced significantly even more leukocytes into air pouch than Leishmania alone. L. chagasi recruited a diverse cell population; however, most of these cells seem to have not migrated to the inflammatory exudate, remaining in the pouch lining tissue. These results indicate that L. chagasi can reduce leukocyte accumulation to the initial site of infection, and when associated with vector saliva in the presence of blood components, increase the influx of more neutrophils than macrophages, suggesting that the parasite has developed a strategy to minimize the initial inflammatory response, allowing an unlimited progression within the host. This work reinforces the importance of studies on the salivary components of sand fly vectors of leishmaniasis in the transmission process and the establishment of the infection.

DOSE RESPONSE EFFECT OF Paracoccidioides brasiliensis IN AN EXPERIMENTAL MODEL OF ARTHRITIS

Paracoccidioidomycosis (PCM) is caused by the dimorphic fungus Paracoccidioides brasiliensis (Pb) and corresponds to prevalent systemic mycosis in Latin America. The aim of the present work was to evaluate the dose response effect of the fungal yeast phase for the standardization of an experimental model of septic arthritis. The experiments were performed with groups of 14 rats that received doses of 103, 104 or 105 P. brasiliensis (Pb18) cells. The fungi were injected in 50 µL of phosphate-buffered saline (PBS) directly into the knee joints of the animals. The following parameters were analyzed in this work: the formation of swelling in knees infused with yeast cells and the radiological and anatomopathological alterations, besides antibody titer by ELISA. After 15 days of infection, signs of inflammation were evident. At 45 days, some features of damage and necrosis were observed in the articular cartilage. The systemic dissemination of the fungus was observed in 11% of the inoculated animals, and it was concluded that the experimental model is able to mimic articular PCM in humans and that the dose of 105 yeast cells can be used as standard in this model.

A crop-land allocation model: A case study in La Rioja, Spain

Dissertation submitted in partial fulfillment of the requirements for the Degree of Master of Science in Geospatial Technologies.