Geographic weighted regression: applicability to epidemiological studies of leprosy

Abstract: INTRODUCTION: Geographic information systems (GIS) enable public health data to be analyzed in terms of geographical variability and the relationship between risk factors and diseases. This study discusses the application of the geographic weighted regression (GWR) model to health data to improve the understanding of spatially varying social and clinical factors that potentially impact leprosy prevalence. METHODS: This ecological study used data from leprosy case records from 1998-2006, aggregated by neighborhood in the Duque de Caxias municipality in the State of Rio de Janeiro, Brazil. In the GWR model, the associations between the log of the leprosy detection rate and social and clinical factors were analyzed. RESULTS: Maps of the estimated coefficients by neighborhood confirmed the heterogeneous spatial relationships between the leprosy detection rates and the predictors. The proportion of households with piped water was associated with higher detection rates, mainly in the northeast of the municipality. Indeterminate forms were strongly associated with higher detections rates in the south, where access to health services was more established. CONCLUSIONS: GWR proved a useful tool for epidemiological analysis of leprosy in a local area, such as Duque de Caxias. Epidemiological analysis using the maps of the GWR model offered the advantage of visualizing the problem in sub-regions and identifying any spatial dependence in the local study area.

Secondary transmission of cryptosporidiosis associated with well water consumption: two case studies

Abstract: Cryptosporidiosis is a very prominent disease in the field of public health, and usually causes diarrhea. We describe two immunocompetent patients who presented with chronic diarrhea that was ultimately found to be caused by continuous exposure to well water contaminated with the microbial cysts (oocysts) of the Cryptosporidium spp parasite. We describe the patients' histories and possible explanations for their prolonged symptoms.

Rehabilitation of renders of old buildings in Portugal: survey, supporting methodology proposal and case studies

The main purpose of the research is to present a proposal for a methodology to support the rehabilitation project of renders of old buildings. To achieve the objective it was considered essential to define the main types of participants and aspects to integrate the proposal. The research methodology consists in an inquiry presented to several professional participants in rehabilitation, a market study of materials and products available in Portugal, the design of a methodology proposal and its application to a case study. The inquiry sample totals 24 answers from the targeted professionals. A sequence of relevant supporting procedures consists in the proposal, which aims to provide a supporting methodology to decide and project in this context and also to be tested with its application to the building. This proposal was applied to an old building with load-bearing stone masonry walls and air-lime based renders. It was concluded that the assessment of the building and external renderings’ condition, its diagnosis and of the supporting walls, the definition of intervention, the specification of materials to be used and performance requirements to comply, and also plans for conservation and periodic maintenance, are crucial. From the inquiry, compatibility between materials and complementary roles and points of view of different types of participants in rehabilitation must be highlighted. A proposal for a methodology to support the project could provide useful guidance particularly for architects and construction engineers, and improve the understanding of direct participants on site, therefore contributing for the correct implementation of the intervention.

Princípios de terapêutica antibiótica na doença crítica

RESUMO: A infeção é frequente durante a doença crítica, quer como causa da doença crítica quer como complicação da sua evolução. Paradoxalmente, os avanços da medicina moderna aumentaram eles próprios o risco de infeção, ao permitir a sobrevida até idades avançadas, ao criar um novo grupo de doentes imunodeprimidos, nomeadamente doentes tratados com fármacos que interferem com as suas defesas naturais (corticóides, citostáticos), ao aumentar o tempo de vida de hospedeiros com comorbilidades debilitantes. Os antibióticos são um dos elos essenciais no tratamento da infeção. Contudo o seu uso também promove a seleção e crescimento de bactérias resistentes. Para além disso as doses convencionais de antibióticos foram selecionadas numa altura em que a resistência era um fenómeno raro e podem não ser atualmente as mais adequadas. Existe hoje muita evidência acumulada que os doentes críticos sofrem alterações da sua farmacocinética (PK) que podem facilitar a ocorrência de falência terapêutica ou de toxicidade tanto por sub como por sobredosagem de antibióticos. Essas alterações são complexas e difíceis de estudar. Finalmente, também a farmacodinâmica (PD) dos antibióticos pode estar alterada nesta população, podendo haver necessidade de ajustar os alvos terapêuticos de forma individual. O objetivo deste trabalho foi investigar a relação entre a terapêutica antibiótica, as suas características PK e PD, a carga bacteriana e o prognóstico dos doentes críticos. O plano de investigação incluiu: 1. Dados da epidemiologia portuguesa de doentes críticos com infeção; 2. Avaliação da relação entre a carga bacteriana, o tempo até ao início do tratamento antibiótico e o prognóstico dos doentes críticos; 3. Avaliação da evolução da PK durante o tratamento da infeção; 4. Um estudo multicêntrico para avaliação da eficácia da terapêutica com um β- lactâmico doseado de acordo com a relação PK/PD. Na introdução é descrita a importância dos antibióticos, a sua origem e o problema crescente das resistências bacterianas relacionadas com o seu emprego e abuso. É salientada a importância de racionalizar a posologia, de acordo com os conceitos de PK e de PD. No Capítulo 1 são apresentados dados de epidemiologia portuguesa de infeção em doentes críticos, sobretudo retirados de dois estudos prospetivos, observacionais, os quais incluíram mais de 50% da capacidade de internamento em cuidados intensivos existente em Portugal. No Capítulo 2 são descritos os conceitos de PK e as suas alterações nos doentes críticos. De seguida são revistos os conceitos de PD de antibióticos e a sua aplicação a esta população, em particular durante as infeções graves (Capítulo 3). Nos capítulos seguintes são aprofundadas estas alterações da PK nos doentes críticos e as suas causas, de forma a destacar a importância da monitorização da concentração dos antibióticos. São apresentados os dados duma revisão sistemática de PK de antibóticos nesta população (Capítulo 4), pormenorizadas as alterações da PD que comprometem a eficácia da terapêutica antibiótica, facilitam o desenvolvimento de resistências e podem levar a falência terapêutica (Capítulo 5). Consequentemente a compreensão global destas alterações, da sua relevância clínica e a revisão da evidência disponível facilitou o desenvolvimento do próprio plano global de investigação (Capítulos 6 e 7). No Capítulo 6.1 são descritos os antibióticos tempo-dependente e a importância de aumentar o seu tempo de perfusão. Foi desenhado um estudo multicêntrico para comparar a eficácia e segurança da perfusão contínua da piperacilina tazobactam (um antibiótico β-lactâmico associado a um inibidor de β-lactamases) com a mesma dose do antibiótico, administrado em dose convencional, intermitente. A importância de dosear corretamente os antibióticos concentração-dependente foi também avaliada num estudo a primeira dose dos aminoglicosídeos (Capítulo 6.2). Outras estratégias para melhorar os resultados assistenciais dos doentes infetados são abordadas no Capítulo 7, em particular a importância da terapêutica antibiótica precoce, a avaliação da carga bacteriana e a compreensão da variação da PK ao longo do tratamento da infeção. Foi desenvolvido um algoritmo de abordagem terapêutica que incluiu estas alterações da PK e da PD nos doentes críticos. Finalmente no Capítulo 8 são descritos mecanismos de desenvolvimento das resistências bacterianas bem como estratégias para a sua abordagem. O Capítulo final (Capítulo 9) aponta um plano para futuras áreas de trabalho. O elemento chave identificado neste trabalho de investigação é o reconhecimento da variabilidade significativa da PK dos antibióticos durante a doença crítica, a qual condiciona a sua posologia. Estas alterações estão relacionadas com a própria gravidade da doença e tendem a diminuir ao longo do seu tratamento. No entanto nem a gravidade da doença nem as características individuais as permitem prever de forma aceitável pelo que a utilização duma posologia universal, independente da situação clínica concreta, pode ser inadequada. As estratégias para melhorar os resultados assistenciais dos doentes críticos infetados devem ser baseadas na individualização da posologia antibiótica de acordo com os princípios da PK e da PD, preferencialmente apoiadas em doseamentos da sua concentração. ------------------------------------ ABSTRACT: Infection commonly occurred during critical illness, either as a cause or complicating the course of the disease. Advances in medicine had paradoxically increase the risk of infection, both by improving survival to older ages and by introducing a new group of immunosuppressed patients, those who are treated with drugs that interfere with their natural defenses (corticosteroids, cytostatics) and those who survived longer with aggressive diseases. Antibiotics are of paramount importance for treating infection. However the use of these drugs also promote the selection and growth of resistant bacteria. Furthermore conventional antibiotic doses were calculated for less severe patients during a time when resistance was rare. Nowadays there is increasing evidence that critically ill patients experiment altered pharmacokinetics (PK) that may lead to therapeutic failure and/or drug toxicity. Equally, such PK alterations are complex and challenging to investigate. Finally pharmacodynamics (PD) may also be different in this population and antibiotic targets may need to be tailored to the individual patient. The aim of this research was to investigate the relationship between antibiotic therapy, its PK and PD, bacterial burden and critically ill patients outcomes. The research plan comprised of: 1. Epidemiological portuguese data of critically ill infected patients; 2. Relationship between burden of bacteria, time until the start of antibiotics and patient outcomes; 3. Evaluation of PK during treatment of infection; 4. A multicentre study evaluating PK guided β-lactam therapy. The introductory chapter outlines the importance of antibiotics, its origins, the problem of increasing bacteria resistance, related to its use and overuse and the importance of rational drug dosing using PK and PD concepts. In Chapter 1 portuguese epidemiological data of infections in critically ill patients is presented, mostly coming from two prospective observational studies, encompassing more than 50% of critically ill beds available in Portugal. Chapter 2 describes the concepts of PK and the changes occurring in critically ill patients. This is followed by a review of the concepts of PD of antibiotics and its application to this population, especially during severe infections (Chapter 3). In the following chapter these changes in antibiotics PK in critical illness are and its causes are detailed, to outline the importance of therapeutic drug monitoring. Data on a systematic review of antibiotics PK in those patients is provided (Chapter 4). The following chapter (Chapter 5) elucidates important changes in PD, that compromises antibiotic therapy, facilitate the occurrence of resistance and may lead to therapeutic failure. Thus, an understanding of the clinical problem and available evidence facilitated the development of a comprehensive research plan (Chapter 6 and Chapter 7). Chapter 6.1 describes time-dependent antibiotics and the importance of extending its perfusion time. A multicenter study was designed to compare the continuous infusion of piperacillin tazobactam (a β-lactam antibiotic) with the same daily dose, prescribed in a conventional, intermittent dose. The importance of correct dosing of antibiotics was also assessed through a study addressing aminoglycoside (a concentration-dependent antibiotic) therapy (Chapter 6.2), focusing on its first dose. Strategies to improve severe infected patients outcomes were addressed in Chapter 7, namely the importance of early antibiotic therapy, assessing the burden of bacteria and understanding changes in antibiotic concentration during the course of infection. An algorithm to include all the described changes in both PK and PD of critically ill patients was developed. Finally in Chapter 8 mechanisms of the increasing resistance of bacteria are described and strategies to address that problem are proposed. The closing chapter (Chapter 9) lays a roadmap for future work. The key finding of this research is the significant variability of the antibiotics PK during critical illness, which makes dosing a challenging issue. These changes are related to the severity of the infection itself and improve through the course of the disease. However neither disease severity nor individual characteristics are useful to predict PK changes. Therefore, the use of a universal dose approach, regardless of the individual patient, may not be the best approach. Strategies to improve patients’ outcomes should be based on tailoring antibiotics to the individual patient, according to PK and PD principles, preferentially supported by therapeutic drug monitoring.

Local Rainfall Variability - A Potential Bias for Bioecological Studies in the Central Amazon

Rainfall data registered betwe en 1910 and 1979 at Manaus confirm the existence of a dry season between June and November (monthly rainfall: 42-162mm) and a rainy season from December until May (monthly rainfall: 211-300mm). Annual precipitation amounted to 2105mm with about 75% of the rainfall recorded during the rainy season. Rainfall data collected over 12 months at eigth stations in the vicinity of and at Manaus are compared. Annual precipitation was lower in Inundation Regions (1150-2150mm) compared with Dryland Regions (2400-2550mm). Considerable differences are found in rainfall patterns (intensity, frequency and time of rainfall). This is also truefor neighbouring stations, even if data of a 11-year record period are compared. Thus, it is highly recommended that preciptation data for bioecological studies be collected at the study site.

Studies on the eucalyptus leaf disease complex in Portugal

Native from south eastern Australia, Eucalyptus globulus is the main species in eucalypts plantations in Portugal. The most serious foliar disease in eucalypt plantations is linked to Mycosphaerella senso lato, which affects young trees in the juvenile phase foliage causing leaf necrosis. This disease results in reduced growth rate of the host and lower wood volume, thus causing significant productivity losses. The most common name for this disease was Mycosphaerella Leaf Disease that became inappropriate when most of the pathogens on eucalypts were re-distributed into several genera. The term "Eucalyptus Leaf Disease Complex" is now more appropriate. The overall aim of this thesis was to investigate the Eucalyptus Leaf Disease Complex in Portugal, focusing on species diversity, taxonomy and the role played by each species in the disease complex on Eucalyptus globulus. Literature on the Eucalyptus Leaf Disease Complex was reviewed and the species were distributed into several genera. A survey based on symptomatic leaves collected from several Eucalyptus globulus plantations and characterized by morphological and molecular tools provided an overview of species incidence and of the most frequent species in the disease complex. The present work reveals additional species of Mycosphaerella senso lato associated with eucalypt plantations in Portugal. Thus, five new records of Teratosphaeria and phylogenetically related species were added to the Iberian Peninsula, namely, Neodevriesia hilliana, for the first time on Myrtaceae; Quasiteratosphaeria mexicana, Teratosphaericola pseudoafricana, Teratosphaeria pluritubularis and Teratosphaeria lusitanica, a new species. Furthermore, new anamorphic structures were found and two new combinations were made. Regarding other genera, some species were observed for the first time, such as Cladosporium cladosporioides, Fusicladium eucalypti, Mycosphaerella madeirae, in the mainland. In addition to leave diseases, Teratosphaeria gauchensis was found causing a severe stem and trunk canker on Eucalyptus globulus. The aggressiveness of several species was compared to evaluate each species individually in the complex, permitting to distinguish different behaviours, from primary to secondary pathogens. Cladosporium cladosporioides, M. communis and M. lateralis, appeared to be more aggressive than Teratosphaeria nubilosa. In fact, contrary to the prevailing views on this disease complex, Teratosphaeria nubilosa is not the only species responsible for the disease, which clearly involves a complex of species acting together.

Fractional pennes' bioheat equation: theoretical and numerical studies

In this work we provide a new mathematical model for the Pennes’ bioheat equation, assuming a fractional time derivative of single order. Alternative versions of the bioheat equation are studied and discussed, to take into account the temperature-dependent variability in the tissue perfusion, and both finite and infinite speed of heat propagation. The proposed bioheat model is solved numerically using an implicit finite difference scheme that we prove to be convergent and stable. The numerical method proposed can be applied to general reaction diffusion equations, with a variable diffusion coefficient. The results obtained with the single order fractional model, are compared with the original models that use classical derivatives.

In vitro studies of the anthelmintic activity of Picrolemma sprucei Hook. f. (Simaroubaceae)

1300 ppm (1.3 g / L), water and ethanol extracts prepared from stems or roots of Picrolemma sprucei Hook. f. were lethal (85-90 % mortality) in vitro to Haemonchus contortus (Barber Pole Worm) larvae, a gastrointestinal nematode parasite found in domestic and wild ruminants. Neosergeolide and isobrucein B were isolated in 0.0083 and 0.0070 % yield from dry, ground P. sprucei stems (0.89 kg). Neosergeolide, isobrucein B and the anthelmintic drug standard levamisole all caused comparable mortality rates (68-77 %) in vitro to H. contortus at similar concentrations (81-86 ppm). The anthelmintic activity of P. sprucei infusions (teas), alcohol extracts, and neosergeolide and isobrucein B, has therefore been demonstrated for the first time.

Epidemiological studies of Mansonella ozzardi (Nematoda, Onchocercidae) in indigenous communities of Pauini municipality, Amazonas, Brazil

The Mansonella ozzardi has a widespread distribution among the indigenous and riverine communities of Amazonas, Brazil. We estimated the prevalence of Mansonella ozzardi in indigenous communities of the Pauini municipality, Amazonas state, Brazil and the rate of parasitic infection in vectors. We collected thick blood smears from individuals from six Apurinã indigenous communities along the Purus River and its tributaries. Collections of simuliids were made and dissected, and the larval instars of M. ozzardi identified. The overall prevalence of M. ozzardi was 28.40%, with the highest incidence among males and agricultural workers. Among age groups, children 2-9 years of age had the lowest incidence, while individuals older than 58 exhibited the highest rates of infection. We found infected simuliids in three communities, with Parasitic Infection Rates (PIR) of 0.34-6.58%. The prevalence of M. ozzardi among the Apurinã people is high, possibly related to the diary activities of the riparian people, where a high abundance of the vectors exists.

(Un)suitability of the use of pH buffers in biological, biochemical and environmental studies and their interaction with metal ions - a review

The use of buffers to maintain the pH within a desired range is a very common practice in chemical, biochemical and biological studies. Among them, zwitterionic N-substituted aminosulfonic acids, usually known as Good's buffers, although widely used, can complex metals and interact with biological systems. The present work reviews, discusses and updates the metal complexation characteristics of thirty one commercially available buffers. In addition, their impact on biological systems is also presented. The influences of these buffers on the results obtained in biological, biochemical and environmental studies, with special focus on their interaction with metal ions, are highlighted and critically reviewed. Using chemical speciation simulations, based on the current knowledge of the metal-buffer stability constants, a proposal of the most adequate buffer to employ for a given metal ion is presented.

Ferroelectric phase transitions studies in 0.5Ba(Zr0.2Ti0.8) O3-0.5(Ba0.7Ca0.3)TiO3 ceramics

The ferroelectric phase transitions in 0.5Ba(Zr0.2Ti0.8)O3-0.5(Ba0.7Ca0.3)TiO3 (BCZT 50/50) ceramics,fabricatedbyasolidstatereaction,werestudiedbyusing X-Ray diffraction, Raman spectroscopy, and measuring electric polarization, dielectric permittivity and pyroelectric current. Xraydiffraction(XRD)confirmsthecoexistenceoftetragonal(T) andrhombohedral(R)phasesatroomtemperature.Thetemperature dependence of the Raman modes frequency reveals the existenceoftwophasetransitionscorrespondingtotherhombohedral – tetragonal, and tetragonal - cubic close to 30 and 100 °C, respectively. The temperature dependence of electric polarization,pyroelectriccurrent,anddielectricpermittivityfurther supports theferroelectric (tetragonal) toparaelectric (cubic) phasetransition.Moreover,thedielectricpermittivityrevealsthe diffuseness of the phase transition and is attributed to the compositional fluctuations of different polar micro-regions.

Mangrove vegetation in Amazonia: a review of studies from the coast of Pará and Maranhão States, north Brazil

The present study is a compilation of the literature about vegetation of mangrove forest of the north coast of Brazil. It synthesizes the knowledge about this important ecosystem and lists the currently available literature. The study focuses on the coast of Pará and Maranhão states, which are covered by a continuous belt of mangroves. The mangrove flora comprises six mangrove tree species and several associated species. Mangrove tree height and stem diameter vary as a function of abiotic local stand parameters. Seasonal variation in rainfall and salinity affect the species' phenology and litter fall. Local population use products derived from mangrove plants for different purposes (e.g. fuel; medicinal; rural construction). The increase in the coastal population has given rise to conflicts, which impact on mangrove forest.

Photolabile protection for amino acids: studies on the release from novel benzoquinolone cages

The synthesis of a novel fused nitrogen heterocycle, benzoquinolone, for evaluation as a photocleavable protecting group is described for the first time, by coupling to model amino acids (alanine, phenylalanine and glutamic acid). Conversion of the phenylalanine ester conjugate to the thionated derivative was accomplished by reaction with Lawesson’s reagent. Photocleavage studies of the carbonyl and thiocarbonyl benzoquinolone conjugates in various solvents and at different wavelengths (300, 350 and 419 nm) showed that the most interesting result was obtained at 419 nm for the thioconjugate, revealing that the presence of the thiocarbonyl group clearly improved the photolysis rates, giving practicable irradiations times for the release of the amino acids (less than 1 minute).