Influence of constraining and confinement in the molecular mobility of low molecular weight materials

Dissertation presented to obtain a Ph.D. Degree in Chemical Physics

Evaluating the combination of relaxation and argumentation in ontology matching negotiation

No decorrer dos últimos anos, os agentes (inteligentes) de software foram empregues como um método para colmatar as dificuldades associadas com a gestão, partilha e reutilização de um crescente volume de informação, enquanto as ontologias foram utilizadas para modelar essa mesma informação num formato semanticamente explícito e rico. À medida que a popularidade da Web Semântica aumenta e cada vez informação é partilhada sob a forma de ontologias, o problema de integração desta informação amplifica-se. Em semelhante contexto, não é expectável que dois agentes que pretendam cooperar utilizem a mesma ontologia para descrever a sua conceptualização do mundo. Inclusive pode revelar-se necessário que agentes interajam sem terem conhecimento prévio das ontologias utilizadas pelos restantes, sendo necessário que as conciliem em tempo de execução num processo comummente designado por Mapeamento de Ontologias [1]. O processo de mapeamento de ontologias é normalmente oferecido como um serviço aos agentes de negócio, podendo ser requisitado sempre que seja necessário produzir um alinhamento. No entanto, tendo em conta que cada agente tem as suas próprias necessidades e objetivos, assim como a própria natureza subjetiva das ontologias que utilizam, é possível que tenham diferentes interesses relativamente ao processo de alinhamento e que, inclusive, recorram aos serviços de mapeamento que considerem mais convenientes [1]. Diferentes matchers podem produzir resultados distintos e até mesmo contraditórios, criando-se assim conflitos entre os agentes. É necessário que se proceda então a uma tentativa de resolução dos conflitos existentes através de um processo de negociação, de tal forma que os agentes possam chegar a um consenso relativamente às correspondências que devem ser utilizadas na tradução de mensagens a trocar. A resolução de conflitos é considerada uma métrica de grande importância no que diz respeito ao processo de negociação [2]: considera-se que existe uma maior confiança associada a um alinhamento quanto menor o número de conflitos por resolver no processo de negociação que o gerou. Desta forma, um alinhamento com um número elevado de conflitos por resolver apresenta uma confiança menor que o mesmo alinhamento associado a um número elevado de conflitos resolvidos. O processo de negociação para que dois ou mais agentes gerem e concordem com um alinhamento é denominado de Negociação de Mapeamentos de Ontologias. À data existem duas abordagens propostas na literatura: (i) baseadas em Argumentação (e.g. [3] [4]) e (ii) baseadas em Relaxamento [5] [6]. Cada uma das propostas expostas apresenta um número de vantagens e limitações. Foram propostas várias formas de combinação das duas técnicas [2], com o objetivo de beneficiar das vantagens oferecidas e colmatar as suas limitações. No entanto, à data, não são conhecidas experiências documentadas que possam provar tal afirmação e, como tal, não é possível atestar que tais combinações tragam, de facto, o benefício que pretendem. O trabalho aqui apresentado pretende providenciar tais experiências e verificar se a afirmação de melhorias em relação aos resultados das técnicas individuais se mantém. Com o objetivo de permitir a combinação e de colmatar as falhas identificadas, foi proposta uma nova abordagem baseada em Relaxamento, que é posteriormente combinada com as abordagens baseadas em Argumentação. Os seus resultados, juntamente com os da combinação, são aqui apresentados e discutidos, sendo possível identificar diferenças nos resultados gerados por combinações diferentes e possíveis contextos de utilização.

Efficacy of oxamniquine, praziquantel and a combination of both drugs in schistosomiasis mansoni in Brazil

A randomized clinical trial was carried out to compare the efficacy of a low-dosage combination of oxamniquine (7.5 mg/kg) plus praziquantel (20 mg/kg) against either agent, oxamniquine (15 mg/kg) or praziquantel (40 mg/kg) alone, in the treatment of schistosomiasis mansoni in the Brazilian north-east. The drugs were randomly administered per os to 91 patients. Six and twelve months after treatment 89% of those admitted to the trial were reexamined by Kato-Katz method (ten slides) and MIF technique (one gram of stool) The achieved cure rates, as defined by absence of S. mansoni eggs in the faeces of individual patients at all points during the parasitological follow-up, were 81.8%, 81.2% and 67.6% for praziquantel, oxamniquine and the combination respectively. The reduction of eggs excretion in non cured patients six months after therapy ranged from 93.8-96.8% with praziquantel, 32.5-97% with oxamniquine and 76.9-99.5% with the combination. It is concluded that, at the used dosages, the three therapeutical regimens give similar and satisfactory results in the treatment of uncomplicated S. mansoni infection in Brazil.

Herb-drug interactions among commonly used psychoactive substances by healthcare students

The concurrent use of herbs and/or nutritional supplements with psychoactive effect and prescription medications is common among college students. College students are a particularly vulnerable population, for they are under less social/familiar surveillance and seek greater independence, as well as under greater intellectual effort, stress, anxiety and depression, which predispose them to a higher consumption of psychoactive substances. Herbs, vitamins, and other dietary supplements may influence the effects of prescription and nonprescription drugs leading to adverse consequences, by increasing the potential for interactions. However, documented interactions between herbal medicinal products and prescribed drugs are rare. Objective: determine the prevalence of concomitant use of psychoactive substances among healthcare students in the Lisbon School of Health Technology, Portugal, in order to assess the risk of potential herb-drug interactions.

Drug susceptibility of Plasmodium falciparum in the western Amazon region, state of Acre, Brazil

Field studies in the western Amazon region (state of Acre, Brazil) indicate that the 4-aminoquinolines, as well as the combined regimen with sulfadoxine-pyrimethamine, can no longer be recomended for the treatment and prophylaxis of P. falciparum infections in this region. Quinine remains an effective drug when used correctly. However, compliance problems arise due to the often occurring side-effects during a ten day regimen. Prospects of overcoming these constraints by combining a short course of quinine with other drugs are limited, because of the lack of suitable partner compounds. For this reason quinine/clindamycin appears to be a more practical therapy of P. falciparum malaria. In vitro data from this study suggest that mefloquine is another effective alternative for the treatment of falciparum malaria in this Amazon region.

Evolution of Drug Resistance: Insight on TEM -Lactamases Structure and Activity and Beta-Lactam Antibiotics

Extended-spectrum β-lactamases (ESBLs) prevalence was studied in the north of Portugal, among 193 clinical isolates belonging to citizens in a district in the boundaries between this country and Spain from a total of 7529 clinical strains. In the present study we recovered some members of Enterobacteriaceae family, producing ESBL enzymes, including Escherichia coli (67.9%), Klebsiella pneumoniae (30.6%), Klebsiella oxytoca (0.5%), Enterobacter aerogenes (0.5%), and Citrobacter freundii (0.5%). β-lactamases genes blaTEM, blaSHV, and blaCTX-M were screened by polymerase chain reaction (PCR) and sequencing approaches. TEM enzymes were among the most prevalent types (40.9%) followed by CTX-M (37.3%) and SHV (23.3%). Among our sample of 193 ESBL-producing strains 99.0% were resistant to the fourth-generation cephalosporin cefepime. Of the 193 isolates 81.3% presented transferable plasmids harboring genes. Clonal studies were performed by PCR for the enterobacterial repetitive intragenic consensus (ERIC) sequences. This study reports a high diversity of genetic patterns. Ten clusters were found for E. coli isolates and five clusters for K. pneumoniae strains by means of ERIC analysis. In conclusion, in this country, the most prevalent type is still the TEM-type, but CTX-M is growing rapidly.

Robot visual localization through local feature fusion: an evaluation of multiple classifiers combination approaches

In the last decade, local image features have been widely used in robot visual localization. In order to assess image similarity, a strategy exploiting these features compares raw descriptors extracted from the current image with those in the models of places. This paper addresses the ensuing step in this process, where a combining function must be used to aggregate results and assign each place a score. Casting the problem in the multiple classifier systems framework, in this paper we compare several candidate combiners with respect to their performance in the visual localization task. For this evaluation, we selected the most popular methods in the class of non-trained combiners, namely the sum rule and product rule. A deeper insight into the potential of these combiners is provided through a discriminativity analysis involving the algebraic rules and two extensions of these methods: the threshold, as well as the weighted modifications. In addition, a voting method, previously used in robot visual localization, is assessed. Furthermore, we address the process of constructing a model of the environment by describing how the model granularity impacts upon performance. All combiners are tested on a visual localization task, carried out on a public dataset. It is experimentally demonstrated that the sum rule extensions globally achieve the best performance, confirming the general agreement on the robustness of this rule in other classification problems. The voting method, whilst competitive with the product rule in its standard form, is shown to be outperformed by its modified versions.

Nonlinear dynamics of the patient’s response to drug effect during general anesthesia

In today’s healthcare paradigm, optimal sedation during anesthesia plays an important role both in patient welfare and in the socio-economic context. For the closed-loop control of general anesthesia, two drugs have proven to have stable, rapid onset times: propofol and remifentanil. These drugs are related to their effect in the bispectral index, a measure of EEG signal. In this paper wavelet time–frequency analysis is used to extract useful information from the clinical signals, since they are time-varying and mark important changes in patient’s response to drug dose. Model based predictive control algorithms are employed to regulate the depth of sedation by manipulating these two drugs. The results of identification from real data and the simulation of the closed loop control performance suggest that the proposed approach can bring an improvement of 9% in overall robustness and may be suitable for clinical practice.

Drug resistance of M. Tuberculosis isolated from patients with HIV infection seen at an AIDS Reference Center in São Paulo, Brazil

M. tuberculosis-positive cultures were obtained from 228 patients seen in our service and drug sensitivity assays were carried out from January 1992 to December 1994. A survey of the medical records of these patients showed resistance to one or more drugs in 47 (20.6%), 25 of whom (10.9%), who reported previous treatment, were considered to have acquired resistance. Among the antecedents investigated, only previous treatment and alcoholism were the factors independently associated with the occurrence of resistance. The survival of patients with resistant strains was lower than that of patients attacked by non-resistant M. tuberculosis. We conclude that in the present series M. tuberculosis resistance to tuberculostatic agents was predominantly of the acquired type.

Etiological drug treatment of human infection by Trypanosoma cruzi

Forty-nine American Trypanosomiasis (Chagas' disease) patients, with xenodiagnosis proven parasitemia were treated by the authors. Forty-one of these patients were given benznidazole, at dosages ranging from 5mg/kg/day to 8mg/kg/day, during a pre-established period of 60 days. In this group, 17 patients had an undetermined form of the disease, whereas 22 had cardiologic disease and 4 had digestive disease (two patients had a mixed form of the disease). Side effects were frequent, and led to the discontinuation of treatment in 17 patients. The follow-up period ranged from 1 to 20 years (mean follow-up period of 6 yrs. 7 mo). 26 (63.4%) of the patients became parasitemia-negative. The other eight patients were treated with nifurtimox, during 120 days, following a variable dose regime of 5mg/kg/day (initial dose) to 17 mg/kg/day (final dose). Six of them had severe side effects, and only one patient remained parasitemia-negative throughout the observation period (ranging from 1 to 18 years). Benznidazole proved to be better tolerated and more effective in the management of parasitemia when compared to nifurtimox, although more effective and less toxic drugs are still desirable.

Evolution of Drug Resistance: Insight on TEM β-Lactamases Structure and Activity and β-Lactam Antibiotics

Since the discovery of the first penicillin bacterial resistance to β-lactam antibiotics has spread and evolved promoting new resistances to pathogens. The most common mechanism of resistance is the production of β-lactamases that have spread thorough nature and evolve to complex phenotypes like CMT type enzymes. New antibiotics have been introduced in clinical practice, and therefore it becomes necessary a concise summary about their molecular targets, specific use and other properties. β-lactamases are still a major medical concern and they have been extensively studied and described in the scientific literature. Several authors agree that Glu166 should be the general base and Ser70 should perform the nucleophilic attack to the carbon of the carbonyl group of the β-lactam ring. Nevertheless there still is controversy on their catalytic mechanism. TEMs evolve at incredible pace presenting more complex phenotypes due to their tolerance to mutations. These mutations lead to an increasing need of novel, stronger and more specific and stable antibiotics. The present review summarizes key structural, molecular and functional aspects of ESBL, IRT and CMT TEM β-lactamases properties and up to date diagrams of the TEM variants with defined phenotype. The activity and structural characteristics of several available TEMs in the NCBI-PDB are presented, as well as the relation of the various mutated residues and their specific properties and some previously proposed catalytic mechanisms.

The role of molecular imaging in modern drug development

Drug development represents a highly complex, inefficient and costly process. Over the past decade, the widespread use of nuclear imaging, owing to its functional and molecular nature, has proven to be a determinant in improving the efficiency in selecting the candidate drugs that should either be abandoned or moved forward into clinical trials. This helps not only with the development of safer and effective drugs but also with the shortening of time-to-market. The modern concept and future trends concerning molecular imaging will assumedly be hybrid or multimodality imaging, including combinations between high sensitivity and functional (molecular) modalities with high spatial resolution and morphological techniques.

A 3-YEAR FOLLOW-UP OF A BRAZILIAN AIDS PATIENT WITH PROTRACTED DIARRHEA CAUSED BY Enterocytozoon bieneusi

Enterocytozoon bieneusi is the most prevalent microsporidian parasite that causes gastrointestinal infection in persons with AIDS. Microsporidia are increasingly recognized as important opportunistic pathogens all over the world but in Brazil only few cases have been reported due either to the non awareness of the clinical presentation of the disease or to difficulties in the laboratory diagnosis. We report a 3-year follow-up of a Brazilian HIV-positive patient in whom microsporidial spores were detected in stools and were identified as E. bieneusi using electron microscopy and PCR. The patient presented with chronic diarrhea, CD4 T-lymphocytes count below 100/mm3 and microsporidial spores were consistently detected in stools. Albendazole was given to the patient in several occasions with transient relief of the diarrhea, which reappeared as soon as the drug was discontinued. Nevertheless, a diarrhea-free period with weight gain up to 18 Kg occurred when a combination of nucleoside and protease inhibitors was initiated as part of the antiviral treatment.