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A secção UAciência é coordenada pelo Professor Universitário Armindo Rodrigues. […]. Neste trabalho pretendemos compreender o papel do Facebook e do Moodle, como ferramentas de apoio as atividades de aprendizagem fora da sala de aula. Para isso, conduzimos um estudo por inquérito com uma amostra de estudantes das licenciaturas de Informática - Redes e Multimédia e de Psicologia da Universidade dos Açores. Escolhemos estes cursos de licenciatura na expectativa de encontrar diferenças significativas nas formas e na frequência da utilização das ferramentas para as atividades de aprendizagem, tendo em conta as respetivas áreas científicas de formação. […]. info:eu-repo/semantics/publishedVersion

CISTI'2015 - 10ª Conferência Ibérica de Sistemas e Tecnologias de Informação, 17 a 20 de junho de 2015, Águeda, Aveiro, Portugal. Learning management systems and social networks on Web have been tools most used by students in higher education institutions as learning support tools outside of the classroom. In this paper, we present the results from a survey conducted at a Portuguese university to 159 students in Computer Science and Psychology about the purposes and reasons for the use of Moodle and Facebook. We conclude, among other conclusions, that they complement each other: while the first is mostly used for formal communication with teachers, the second is mostly used for informal communication with peers.

One of the most important decisions a retailer can make is where to locate a retail outlet. Because convenience is so important to today's consumers, a retail store can prosper or fail solely based on its location. Recently, a changing retail environment is augmenting the location importance as retail economic groups develop multi-outlet chains of small stores. The methods used in the development and calibration of location models for commercial spaces and sales forecast are multiple, varying from simple analogy forecast models to very complex spatial interactions models, which may incorporate dependence models in a gravitational or logit structure and many exploratory variables. More recent developments incorporating meta-heuristics such as genetic algorithms for the global problem of the multi-outlet chain configuration, or the use of Voronoi diagrams in store trade area delimitation, are also presented. Finally, the Geographical Information Systems' role on the decision support process is equally explored.

Purpose/aim: 3Y-TZP is a biocompatible material that presents appropriated mechanical and tribological properties to be used as metal free prosthesis in dentistry. Processing parameters such as sintering temperature and time affect simultaneously the tribological behavior. The aim of this study was to evaluate the coefficient of friction of 3Y-TZP ceramics sintered at different temperatures and times and to relate this with average grain size and hardness of these materials

Neste trabalho, descreve-se um Sistema de Apoio à Decisão para fornecer indicadores de suporte a decisões de gestão numa organização de poder local, a autarquia de Lagoa - S. Miguel, Açores. É contemplada a modelação, recorrendo à notação UML, a criação de base de dados relacional MySQL, algoritmos de recolha de dados implementados em PHP e modelos de previsão na linguagem R. O sistema disponibiliza aos utilizadores previsões efetuadas por diferentes modelos, para os vários indicadores, aconselhando aqueles com erros mais próximos de zero. Usam-se funções R para alisamento exponencial, decomposição clássica com tendência linear e modelos ARIMA. Da aplicação realizada, com dados para 12 anos, concluiu-se que para a maior parte dos indicadores, o modelo da decomposição clássica é o aconselhado. Mas, para alguns indicadores, verificou-se que as duas medidas de erro usadas não são coerentes, deixando-se ao decisor a escolha final de qual o modelo a utilizar., Revista de Ciências da Computação, v. 10 (2015)

BACKGROUND Previously we reported that cultures of fine-needle aspiration biopsy (FNAB) samples synthesize different cytokine pattern depending on the alloimmune response towards the kidney graft. However, we failed to find a clear picture for growth factors implicated in early T-cell activation (interferon-gamma, interleukin [IL]-4, IL-12), although we observed that interleukin-1 receptor antagonist (IL-1ra) was associated with absence of acute rejection. We have now studied tumor necrosis factor-alpha (TNF-alpha) and its two soluble receptors, sTNFRI and sTNFRII, IL-1beta and soluble IL-1 receptor II (sIL-1RII), and leukemia inhibitory factor (LIF), all potential modulators of T-cell activation. METHODS Sixty-six cadaver kidney transplants (KTX) were divided into four groups: group 1, day 7 after KTX, stable (n=30); group 2, day 7 after KTX, 8+/-4.5 days before acute rejection (n=12); group 3, first day of acute rejection (n=17); and group 4, day 14 after KTX, stable (n=32). Patients from groups 1 and 4 remained rejection-free for the first 6 months. All rejection episodes were confirmed by core renal biopsy. FNAB samples were cultured according to our published methodology, and culture supernatants were collected at 48 hr and analyzed by ELISA for IL-1beta, sIL-1RII, TNF-alpha, sTNFRI, sTNFRII, and LIF. Serum levels for sIL-1RII, sTNFRI, and sTNFRII were also measured. RESULTS FNAB cultures from groups 1 and 4 synthesized significantly lower amounts of sTNFRI and sTNFRII than those from either groups 2 or 3. Both sTNFRI and sTNFRII reached high positive and negative predictive values for acute rejection. IL-1beta and sIL-1RII were synthesized by all groups but without differences. No trace of LIF and TNF-alpha was found. sTNFRII was significantly higher in serum from group 3. CONCLUSIONS Both TNF receptors were positively associated with acute rejection and were good predictors of impending acute rejection. The ratio of sIL-1RII over IL-1 (together with IL-1ra that we previously measured in FNAB cultures) suggests that IL-1 actions may be inhibited with current immunosuppression early after transplantation.

Initially an eleven variable, sixteen assay 215−11 fractional factorial design, was used to determine the key factors in the production of violacein produced by Chromobacterium violaceum, CCT 3496. Subsequently five and three factor central composite designs were executed to determine response surfaces with the aim of optimizing cellular mass and crude violacein production. The 7.5 g l−1 dry cell mass and 0.17 g l−1 crude violacein productions obtained with our initial culture medium were increased to 21 g l−1 and 0.43 g l−1, respectively, for a medium investigated in the three factor design.

A paremiologic (study of proverbs) case is presented as part of a wider project based on data collected among the Azorean population. Given the considerable distance between the Azores islands, the authors present the hypothesis that there are significant differences in the proverbs from each island, thus permitting the identification of the native island of the interviewee based on his or her knowledge of proverbs. In this chapter, a feature selection algorithm that combines Rough Sets and the Logical Analysis of Data (LAD) is presented. The algorithm named LAID (Logical Analysis of Inconsistent Data) deals with noisy data, and the authors believe that an important link was established between the two different schools with similar approaches. The algorithm was applied to a real world dataset based on data collected using thousands of interviews of Azoreans, involving an initial set of twenty-two thousand Portuguese proverbs.

Copyright © 2013 Springer Netherlands. This chapter proposes to estimate the technical efficiency in agricultural grazing systemsgrazing systems (dairy, beef and mixed) in Azores, in the year 2002. This research used 184 agricultural farms of FADN – Farm Accountancy Data Network. DEA, a non-parametric methodology, was used to estimate efficiency by means of DEAP software. The results have shown that the average technical efficiency in the dairy grazing system was 63.2% (CRS) and was higher (71.4%) in VRS, and the scale efficiency was about 89.2%. In beef grazing system, the average technical efficiency (CRS) was 69.4%; VRS and the scale efficiency were 82.9 and 84.2%, espectively. In the mixed grazing system, the average technical efficiency (CRS) was 89%, the VRS was higher (99.24%) and the scale efficiency was 89.8%. The mixed system is the most efficient, and about half (46.7%) of the farms were efficient. In the dairy grazing system and in the beef systems, only 9.8 and 11.1% were efficient farms. The efficiency is generally higher in mixed systems than in dairy and beef systems.

Copyright © 2013 Springer Netherlands. The producers always aspire at increasing the efficiency of their production process. However, they do not always succeed in optimising their production. In the last years, the interest on Data Envelopment Analysis (DEA) as a powerful tool for measuring efficiency has increased. This is due to the large amount of data sets collected to better understand the phenomena under study and, at the same time, to the need of timely and inexpensive information. The "Productivity Analysis with R" (PAR) framework establishes a user-friendly data envelopment analysis environment with special emphasis on variable selection, aggregation, summarisation and interpretation of the results. The starting point is the following R packages: DEA (Diaz-Martinez and Fernandez-Menendez 2008) and FEAR (Wilson 2008). The DEA package performs some models of data envelopment analysis presented in Cooper et al. (2007). FEAR is a software package for computing nonparametric efficiency estimates and testing hypotheses in frontier models. FEAR implements the bootstrap methods described in Simar and Wilson (2000). PAR is a software framework using a portfolio of models for efficiency estimation and also providing results explanation functionality. PAR framework has been developed to distinguish between efficient and inefficient observations and to explicitly advise the producers about possibilities for production optimisation. PAR framework offers several R functions for a reasonable interpretation of the data analysis results and text presentation of the obtained information. The output of an efficiency study with PAR software is self-explanatory. We are applying PAR framework to estimate the efficiency of the agricultural system in Azores (Mendes et al. 2009). All Azorean farms will be clustered into homogeneous groups according to their efficiency measurements to define clusters of "good" practices and cluster of "less good" practices. This makes PAR appropriate to support public policies in agriculture sector in Azores.

Para os fins deste ensaio, defino desenvolvimento como a criação de condições tendentes à promoção do ser humano em sua integridade. É, portanto, um processo plus o sucesso resultante...

Copyright © 2013 Springer Netherlands. Superefficiency is an important extension of DEA that overcomes some limitations of the traditional models, specifically allowing ranking of efficient units and a unique set of weights for those units. Weights restriction is a well-known technique in the DEA field. When those techniques are applied, weights cluster around its new limits, making its evaluation dependent of its levels. This chapter introduces a new approach to weights adjustment by goal programming techniques, avoiding the imposition of hard restrictions that can even lead to unfeasibility. This method results in models that are more flexible.

Copyright © 2013 Springer Netherlands. In this concluding chapter the editors make some important remarks on the importance and conclusions of the book as a whole, focusing on its importance, relevance and adequacy to an extended audience of researchers in the efficiency analysis in the agricultural and environment fields.

Copyright © 2013 Springer Netherlands. Data Envelopment Analysis (DEA) is a popular non-parametric method used to measure efficiency. It uses linear programming to identify points on a convex hull defined by the inputs and outputs of the most efficient Decision Making Units (DMUs). Two critical elements account for the strength of the DEA approach: (1) no a priori structure is placed on the production process of the firm, and (2) the models can yield a measure of efficiency even with a very small number of data points. The first point is particularly important because the measure of efficiency is based upon the best practice of the DMUs at any of the levels of output observed. Data envelopment analysis measures efficiency and is very sensitive to the choice of variables for two reasons: the number of efficient DMUs is directly related to the number of variables, and the selection of the variables greatly affects the measure of efficiency when the number of DMUs is few and/or when the number of explanatory variables needed to compute the measure of efficiency is too large. Our approach advises which variables should be included in a DEA model. Hence, a variable selection method is presented for the deterministic DEA approach. First, a definition of different measures of efficiency and the various DEA models used to measure efficiency is provided, and then a variable selection method is proposed. The Azorean agricultural system is used as an example to illustrate the method.

Extracting knowledge from data is the major objective of any data analysis process, including the ones developed in several sciences as statistics and quantitative methods, data base \ data warehouse and data mining. From the latter disciplines the data mining is the most ambitious because intends to analyse and extract knowledge from massive often badly structured data with many specific objectives. It is also used for relational data base data, network data, text data, log file data, and data in many other forms. In this way, is no surprise that a myriad of applications and methodologies have been and are being developed and applied for data analysis functions, where CRISP-DM (cross industry standard process for data mining) and SEMMA (sample, explore, modify, model, assessment) are two examples. The need for a roadmap is, therefore, highly recognised in the field and almost every software company has established their own process model.

A secção UAciência é coordenada pelo Professor Universitário Armindo Rodrigues. O iFarm e um serviço inovador que oferece uma experiencia interativa na Internet, e proporciona a oportunidade de produzir géneros alimentares com base nos conceitos de agricultura biológica e alimentação saudável. E uma ideia que surgiu num projeto transversal, impulsionado e estimulado na 1a edição da Pós-Graduação em Tecnologias Web (P3W em http://p3w.uac.pt), da Universidade dos Acores. A P3W assume que as competências em Informática são fatores potenciadores de sucesso pessoal e profissional num mundo globalizado de forte inspiração tecnológica. […]. info:eu-repo/semantics/publishedVersion

15th Portuguese Conference on Artificial Inteligence - EPIA 2011. Lisboa, Faculdade de Ciências da Universidade de Lisboa, 10-13 Outubro 2011. A paremiologic (study of proverbs) case is presented as a part of a wider project, based on data collected by thousands of interviews made to people from Azores, and involving a set of twenty-two thousand Portuguese proverbs, where we searched for the minimum information needed to identify the birthplace island of an interviewee. The concept of birthplace was extended for all respondents that have lived in any locations more than 5 years, unintentionally introducing inconsistencies in the data classification task. The rough sets differ from classical sets by their ability to deal with inconsistent data. A parallel approach to data reduction is given by the logical analysis of data (LAD). LAD handicaps, like the inability to cope with the contradiction and the limited number of classification classes, will be overcome in this version of Logical Analysis of Inconsistent Data (LAID).

Given the large amount of data provided by the Web 2.0, there is a pressing need to obtain new metrics to better understand the network structure; how their communities are organized and the way they evolve over time. Complex network and graph mining metrics are essentially based on low complexity computational procedures like the diameter of the graph, clustering coefficient and the degree distribution of the nodes. The connected communities in the social networks have, essentially, been studied in two contexts: global metrics like the clustering coefficient and the node groups, such as the graph partitions and clique communities.

Workshop "Modelos de Apoio à Decisão na Agricultura e Ambiente". Universidade dos Açores, Angra do Heroísmo, Ilha Terceira, Açores, 16 de Setembro de 2011. Data Envelopment Analysis (DEA) is becoming an increasingly popular management tool for decision support related to efficiency comparisons. The task of the DEA is to evaluate the relative performance of units of a system. Is not a problem solution technique but an important problem analysis method based in mathematical programming with some similarities with Multiple Criteria Decision Analysis (MCDA). DEA makes it possible to identify efficient and inefficient units in a framework where results are considered in their particular context. The units to be assessed should be relatively homogeneous and were originally called Decision Making Units (DMUs). It is an extreme point method that compares each DMU with the "best" DMUs. The “Productivity Analysis with R” (PAR) framework establishes a user - friendly data envelopment analysis environment with special emphasis on variable selection and aggregation, and summarization and interpretation of the results. PAR framework has been developed to distinguish between efficient and inefficient observations of performances and to advise explicitly for producers’ possibilities to optimize their production. In this work we will apply PAR to farms in Terceira Island, with a small data set of 30 farms. This data set includes 14 input variables and 4 output variables. With PAR was possible to conclude that 4 farms are scale – efficient and the others are scale inefficiency due to decreasing returns to scale or increasing returns to scale. This implies that either the dairy farm is too big (the number of cows is too large) or to small and that the farmer can improve the productivity of inputs and hence reduce unit costs by reducing or increasing the dimension of the farm.

Neste trabalho identificam-se as causas responsáveis por variações no consumo horário de energia com base na identificação de padrões e relações entre os dados de consumo e várias variáveis climatéricas. Para tal utilizam-se técnicas de data mining, nomeadamente a metodologia CRISP-DM e software de data warehouse MS SQL Server. Assim, foi possível verificar que as variáveis climatéricas têm influência muito significativa na produção de energia eléctrica, tendo sido possível prever os consumos de 2007 com um erro absoluto médio de 1,4 MW. Identificam-se ainda vários padrões no comportamento do consumo ou produção de energia eléctrica, nem todos espectáveis face ao conhecimento actual de domínio. info:eu-repo/semantics/publishedVersion

14º Congresso da APDIO, 7 a 9 de Setembro de 2009, Faculdade de Ciências e Tecnologia - Caparica. Na análise de redes sociais, uma k-clique é a relaxação de uma clique, i.e., uma k-clique é um quase sub-grafo completo. Um k-clique num grafo é um sub-grafo onde a distancia entre quaisquer par de vértices não é maior que k. A visualização de um pequeno número de vértices é fácil de obter. Contudo, quando o número de vértices aumenta a visualização torna-se incompreensível. Nesta comunicação, propomos uma nova abordagem na extracção de conhecimento em grafos, utilizando k-cliques. O conceito que clique relaxado é estendido para todo o grafo, de forma a ter uma visão geral, ao cobrir a rede com k-cliques. Sequências de coberturas de k-cliques são apresentadas combinando o conceito dos "pequenos mundos" com estruturas com coesão. Resultados computacionais e exemplos são apresentados. ABSTRACT: In social network analysis, a k-clique is a relaxed clique, i.e., a k-clique is a quasi-complete sub-graph. A k-clique in a graph is a sub-graph where the distance between any two vertices is no greater than k. The visualization of a small number of vertices can be easy to perform in a graph. However, when the number of vertices and edges increases the visualization becomes incomprehensible. In this paper, we propose a new graph mining approach based on k-cliques. The concept of relaxed clique is extended to whole the graph, to achieve a general view, by covering the network with k-cliques. The sequence of k-clique covers is presented, combining small world concepts with community structure components. Computational results and examples are presented.

O projecto descrito tem o objectivo de apoiar decisões de investimento em infraestruturas de comunicação na Electricidade Dos Açores (EDA), a empresa responsável pela geração, transporte e venda de corrente eléctrica na Região Autónoma dos Açores. A decisão imediata a apoiar consistia em saber se as comunicações entre ilhas deveriam passar para tecnologias Voice over IP (VoIP), um serviço actualmente contratado em regime de outsourcing. Foi estabelecido um projecto de business intelligence, usando tecnologias OLAP do Microsoft SQL Server, para ler e pré-processar os ficheiros CSV de grande dimensão, combinar esses dados com bases de dados existentes e apresentar os resultados sobre a forma de cubos multidimensionais. Posteriormente, implementaram-se igualmente algoritmos de data mining, integrando na metodologia CRISP-DM as duas técnicas utilizadas. Construindo vários modelos foi possível, além de apoiar a decisão pretendida, identificar situações ineficientes e mesmo fraudulentas. Os modelos construídos foram ainda disponibilizados aos decisores estratégicos e de controlo, assim como toda a estrutura de reutilização, manutenção e realimentação que suporta o OLAP e os modelos de data mining., Revista de Ciências da Computação, v. 3 (2008)

3ª Conferência Ibérica de Sistemas e Tecnologias de Informação (CISTI 2008), 19 a 21 de Junho de 2008, organizada pela Universidad de Vigo. Este artigo descreve um Sistema de Apoio à Decisão capaz de fornecer informação precisa e de qualidade sobre as comunicações na Electricidade Dos Açores (EDA). A decisão imediata a apoiar consistia em saber se as comunicações entre ilhas deveriam passar para tecnologias Voice over IP (VoIP), um serviço actualmente contratado a uma empresa de comunicações externa. Num projecto de business intelligence e usando tecnologias Microsoft SQL server, o sistema lê e pré-processa ficheiros CSV de grande dimensão, recebidas da empresa de comunicações, combina esses dados com bases de dados existentes e apresenta os resultados sobre a forma de cubos multidimensionais. Posteriormente, este trabalho foi integrado num projecto de data minig, usando a metodologia CRISP-DM, tendo sido possível além de apoiar a decisão pretendida identificar situações ineficientes e mesmo de utilização fraudulenta de equipamentos de comunicação. Vários modelos foram construídos e disponibilizados a diferentes decisores para apoiar decisões estratégicas e de controlo.

Copyright © 2006 The authors. Elsevier B.V. All rights reserved. This work is part of a supermarket chain expansion study and is intended to cluster the existent outlets in order to support the evaluation of outlet performance and new outlet site location. To overcome the curse of dimensionality (a large number of attributes for a very small number of existing outlets) experts' knowledge is considered in the clustering process. Three alternative approaches are compared for this end, the experts being required to: (1) a priori: provide values for perceived dissimilarities between pairs of outlets; (2) a posteriori: evaluate results from alternative regression trees; (3) interactively: help to select base variables and evaluate results from alternative dendrograms. The later approach provided the best results according to the marketing experts.

Publicado originalmente em "Advances in Doctoral Research in Management", Volume 1, pp. 171-195, Fevereiro de 2006. ISBN 978-981-256-044-5 (Hardcover). This work is part of a dissertation that addresses the supermarket site assessment problem. We propose a 3-steps method for stores' site evaluation. (The 1st step yields the constitution of analogue groups of existent supermarkets, using a clustering procedure. On the 2nd step we use classification trees to classify new stores into specific analogue groups. Finally, on the 3rd step, we build a linear regression model to forecast new sites’ sales, based on several predictor variables, including dummy variables referred to analogue groups). In order to deal with demographic and competition data related to each supermarket, we use neighborhood delimitation techniques. Three alternative delimitation techniques and two aggregation procedures are compared. Results are evaluated based on the proportion of sales turnover variance that the alternative predictors are able to explain. (As a result, we select one aggregation procedure, although we conclude that none of the delimitation models: shortest path polygons and multiplicative weighted Voronoi diagrams, first and second order, present similar performance). Finally, we compare the relative importance of spatial data predictors in site assessment evaluation, using Dominance Analysis. As a result, the relevance of spatial analysis predictors clearly emerges being only dominated by the "trade area".

"Na edição do passado mês de Agosto da prestigiada revista Wired, o seu fundador e actual chefe de redacção, Kevin Kelly, previa que daqui a três milénios o desenvolvimento da Internet será considerado um dos momentos-chave da história da Humanidade, à semelhança do aparecimento das grandes religiões! Exagero? Ninguém sabe. No ano da comemoração do 10º aniversário do fim da participação do governo dos Estados Unidos, através da National Science Foundation, na administração dos nomes no domínio de nível .org e da entrada da Netscape para o Nasdaq, é interessante recordar algumas ideias que estão relacionadas com a invenção da Internet tal como a conhecemos hoje. […]."

Copyright © 2004 Instituto Português de Administração de Marketing (IPAM – The Marketing School). Neste artigo apresentam-se os resultados obtidos na tipificação de lojas de retalho alimentar de pequena dimensão. O objectivo da tipificação prende-se não só com a realização futura de acções de marketing mas também com a previsão de vendas por métodos de analogia. Ainda que se tenha recolhido muita informação resultante de inquéritos a clientes, bases de dados sobre concorrência, demografia do INE e por observação directa das lojas e localizações, o reduzido número de lojas existentes dificulta a avaliação interna das tipificações obtidas. Assim, sugerem-se e aplicam-se diferentes técnicas de validação interna e externa para construção dos agrupamentos de lojas com utilização de conhecimentos de especialistas. Os métodos apresentados de integração de conhecimento dos especialistas a priori apresentam bons resultados. No entanto, conclui-se pela melhor qualidade das soluções resultantes da integração dos especialistas a posteriori, verificando-se que variação intra-grupos das vendas anuais é menor segundo esta abordagem. ABSTRACT: In this article we use several clustering and classification tecniches to define types of food stores of small dimension. The objective for this is to support the future accomplishment of marketing actions and also to fore cast sales by analogy methods. Although we had picked up a lot of data by means of inquiries, existing data bases on competition, demography, and direct observation of the stores and its locations, the few existing stores makes internal validation of obtained clusters very difficult. Thus, we suggest here several different techniques of external and internal validation with the explicit or inplicit use of knowledge of specia lists. The suggested a priori methods of specialists knowledge integration present good results. However, we found better quality in the resulting solutions for the knowledge integration a posteriori, as the calculated intra-grupes variaction of the annual sales happen to be smaller.

Background: T-cell activation, the key event in the development of acute allograft rejection, depends on co-stimulatory signals delivered by antigen-presenting cells (APC). APC-derived cytokines may provide co-stimulation and modulate alloimmune reaction. We have studied cytokine synthesis by fine-needle aspiration biopsy (FNAB) culture and we found significant differences for interleukin (IL)-2, IL-6, IL-10, M-CSF and IL-1ra on comparing acute rejection versus stable kidney transplant patients. We report our findings on FNAB cultures synthesis of IL-7, IL-15, IL-16, IL-17, IL-18 and RANTES (regulated upon activation, normal T-cell expressed and secreted), all potential modulators of anti-graft reaction. Patients and Methods: Kidney transplants (KTX) treated with CsA-AZA-Pred from the beginning, were divided into four groups. Group I: day 7 post-KTX, stable; II: day 7 post-KTX, 6.5 ± 5.5 days before acute rejection; III: first day of acute rejection; IV: day 14 post-KTX, stable. Patients from I and IV remained rejection-free for the first 6 months, at least. All rejection episodes were confirmed by classical core renal biopsy. FNAB samples were cultured according to our published methodology and culture supernatants were collected at 48 h and analysed by ELISA for IL-7, IL-15, IL-16, IL-17, IL-18 and RANTES. Results: Group III synthesized significantly higher amounts of IL-7, IL-16 and IL-18 than stable patients (groups I and IV). RANTES production did not show significant differences among the four groups. We did not find any trace of IL-15. Conclusions: IL-18 may play the activation role that has been attributed to IL-12 which previously, we did not find to correlate significantly with acute rejection in KTX. IL-16 seems to play an activation role rather than an inhibition of anti-graft reaction. We confirm that RANTES is not significantly associated with acute rejection in KTX.

Background/Aims: Growth of T cell lines from kidney graft biopsy specimens that suppress the antidonor response, either directly or through a soluble factor, both specific and nonspecific to donor, has been reported. Fine-needle aspiration biopsy sample cultures synthesize a large array of cytokines/chemokines with significant differences between stable versus acute rejection transplants. We hypothesize that the products of such cultures may be endowed with antidonor response modulation abilities in kidney transplantation. Methods: From 46 patients, 21 rejection free (group A) and 25 developing 28 acute rejection crises (group B), samples were obtained on days 7 and 30 after transplantation in group A and on day 7 and on acute rejection day in group B. The supernatants obtained after 48 h of culture were studied for IL-1 receptor antagonist, IL-4, IL-4 soluble receptor alpha, IL-12, IL-13, IFN-γ, TGF-β1, TGF-β2, GM-CSF, and PGE2 and for their effects on mixed lymphocyte reactions, donor-recipient and recipient-third-party combinations. At the end, analysis by flow cytometry of donor-recipient cultures complemented the analysis done before cultures. Results: Day 7 supernatants from group A specifically and significantly inhibited the antidonor response; supernatants from group B nonspecifically stimulated the antidonor response. The IL-1 receptor antagonist production was significantly higher by day 7 in group A, and the PGE2 production was significantly higher in group B. Flow cytometry analysis did not disclose significant differences between inhibited versus stimulated antidonor responses. Conclusions: Cultures of aspiration biopsy samples done early after transplantation in rejection-free patients produce soluble suppression-specific antidonor response factor(s), not present in cultures from biopsy specimens taken before and during rejection. This was associated with IL-1 receptor antagonist synthesis.

The new immunosuppressive drug Rapamycin (Rapa) is endowed with a mechanism of action that is distinct from that of calcineurin inhibitors. It has been claimed that Rapa does not significantly modulate either the cytokine expression or the transcription of several growth factors in mitogen-activated T cells. Previously, we reported that fine-needle aspiration biopsy (FNAB) sample cultures synthesize a large array of cytokines, and some of them may be powerful predictors of acute rejection in renal transplants. We hypothesized that Rapa may induce significant changes on cytokine production by FNAB sample cultures and on serum cytokine receptors when compared to other immunosuppressive drugs.Kidney transplants treated with CsA-Rapa-Pred (Rapa group) were compared with transplants treated with CsA-mycophenolate mofetil-Pred (MMF group). They were studied on day 7 posttransplantation, and they remained rejection free for at least the first 6 months. FNAB samples were cultured and the supernatants were collected at 48 hr of incubation and analyzed by ELISA for interleukin 1 receptor antagonist (IL-1ra), IL-2, IL-6, IL-10, IL-18, monocyte chemotactic protein 1 (MCP-1), soluble tumor necrosis factor I, and transforming growth factor (TGF)-beta(1). The soluble receptors for IL-1, IL-2, IL-6, and tumor necrosis factor alpha, together with IL-2 and IL-18 were also measured in serum.Significant differences were observed when comparing Rapa with the MMF group. IL-18 and TGF-beta(1) synthesis were up-regulated, whereas IL-6 and MCP-1 were down-regulated in FNAB sample cultures. The Rapa group showed a significant down-regulation of each cytokine receptor and of IL-2 in serum.Rapa was associated with a decreased synthesis of primarily monocyte-derived cytokines and enhanced production of TGF-beta(1), which in an appropriate cytokine milieu may promote allograft tolerance. The down-regulation of cytokine receptors and IL-2 may be associated with a depressed immune response towards the kidney allograft.

Background. The new cyclosporin (CsA) formulation, Neoral®, has different pharmacokinetics compared with Sandimmune® (SIM). Larger area under the curve (AUC) values with equivalent trough blood values are reached when Neoral is administered at equivalent doses to SIM. Previously, we showed a great diagnostic reliability when using cytofluorometric analysis from fine-needle aspiration biopsy (FNAB) samples. We investigated possible changes brought about by Neoral on lymphocyte subsets and the repercussions on the activation score cut-off for acute rejection, defined under SIM treatment. Methods. Of 63 patients that received SIM, 40 remained rejection-free and 23 suffered one episode of rejection. Of 52 patients that received Neoral, 38 remained rejection-free. Peripheral blood lymphocytes (PBL) and lymphocytes from FNAB taken on days 7 and 14 post-transplantation and on the first day of acute rejection were analysed by flow cytometry. Results. Trough blood CsA levels were not different between SIM and Neoral treatments. Among rejection-free patients, a significant down-regulation of CD3DR and of CD8DR expression on both graft-infiltrating lymphocytes (GIL) and PBL, and significant up-regulation of naive T cells on GIL were observed with Neoral. These changes were followed by a significant down-regulation of the activation score with Neoral. Conversely, within the acute rejection group, the activation score was significantly higher with Neoral than with SIM. The activation score performed equally well in Neoral transplants compared with what we had reported with SIM. Conclusions. Our study indicates that Neoral elicits stronger immunosuppressive effects in stable patients, which eventually should translate into better clinical efficiency. However, when acute rejection supervenes, the treatment breakthrough seems stronger with Neoral. Cytofluorometric studies from FNAB samples showed that diagnostic reliability was maintained at a high level under Neoral therapy.

of cytokine production: Th0 cells (IL-2, IL-4, IFN-c, Methods. Fifty-six adult cadaver kidney transplants lymphotoxin), Th1 (IL-2, IFN-c, lymphotoxin) and were subdivided into 21 stable patients (group A), 22 Th2 (IL-4, IL-5, IL-6, IL-10). Th0 is the common suVering acute rejection (group B), 10 with chronic precursor to both Th1 and Th2 [2,3]. The cytokine rejection (group C ) and three with CMV disease milieu at the time of antigenic stimulation can greatly (group D). Fine-needle aspiration biopsies were cul- influence the development of Th1 and Th2 subsets as tured and their supernatants analysed for IL-2, IL-4, there is no Th0 commitment to either subset [3]. Th1 IL-10 and IFN-c. maturation requires IL-12/IFN-c while Th2 needs IL-4 Results. Group A produced small amounts of both [4]. Several groups have presented data linking a Th1 IL-2 and IL-10 while group B synthetized significantly cytokine pattern to allograft rejection and Th2 cytokine higher IL-2 and significantly lower IL-10 amounts than to transplant tolerance [5‐12]. However, others have group A. Group B produced significantly more IL-2 reported conflicting results [13‐15], which suggests than A on day 7 post-transplantation, several days that the Th1/Th2 paradigm may not be suYcient to before rejection supervened. Group C produced IL-10 fully explain the mechanisms underlying allograft rejecand very low amount of IL-2. Group D produced both tion and tolerance. IL-2 and IL-10. We did not find any IL-4, and IFN-c The measurements of cytokines from renal transwas present in a few samples. For IL-2, sensitivity, plant patients either in peripheral blood or in urine specificity, negative and positive predictive values for have produced variable results, with some pointing to acute rejection were 100, 87.2, 94.7 and 83.3%, their potential use in the diagnosis of renal graft respectively. rejection [16,17], and others failing to reproduce these Conclusions. Cytokine analysis in fine-needle aspira- findings [18,19]. tion biopsy cultures supernatants is a very useful Fine-needle aspiration biopsy (FNAB) is a reliable immunological screening method for kidney trans- and safe diagnostic tool for the immunologic monplants. IL-2 synthesis on day 7 post-transplantation itoring of kidney transplants [20‐22]. Previously we reliably predicted the risk of impending acute rejection have shown that FNAB cell cultures have significant during the first weeks. The cytokine pattern suggests diVerent proliferative abilities whether they come from that acute rejection is associated with Th1, stable stable kidney transplant patients or from acute patients with Th0/Th2, and chronic rejection with Th2 rejecting patients [23]. We hypothesized that patterns. these diVerent proliferative responses could reflect discriminant cytokines patterns of production, following our previous report on chemokines synthesis by FNAB cell cultures [24], which could help both

Background. Peripheral blood lymphocyte (PBL) analysis by flow cytometry has been inconsistently reported as an adjunctive method for diagnosing acute kidney transplant rejection. However, there is good evidence that lymphocytes infiltrating renal grafts differ from those found at the peripheral level. We hypothesized that the study of aspiration biopsy samples in conjunction with PBL by flow cytometry would enable us to diagnose acute rejection crisis reliably. Methods. Lymphocytes from PBL and aspiration biopsies of kidney transplant patients were analyzed. Fifty-one stable patients, rejection-free for the first 6 months, were studied on day 7 and day 30 after transplantation and were compared with 32 patients with 40 acute rejection episodes. Results. Significant differences were observed for several lymphocyte subpopulations on aspiration biopsy samples comparing stable patients with rejection patients. In contrast, PBL analysis was not helpful in differentiating the two groups of patients. By combining the expression of several activation markers inside the graft with CD3DR and CD3CD25 aspiration biopsy to peripheral blood ratios, we obtained very good values for sensitivity and specificity-83.9% and 90.5%, respectively. The positive predictive value for rejection among dysfunctional grafts reached 85.8%. Conclusions. Flow cytometry study of aspiration biopsy samples of kidney transplant patients is a reliable and powerful method to diagnose acute rejection episodes, although it is needed to consider several lymphocyte phenotypes; cytofluorometric analysis of PBL is important because it provides graft-infiltrating cell to peripheral blood lymphocyte ratios. This safe and rapid test may significantly improve the management of kidney transplant patients.

Background Monocytes-macrophages are found within kidney allografts during the first days after surgery, where they perform "housekeeping" tasks, participate in postreperfusion injury, and act as antigen-presenting cells, as well as become involved in the effector phase of acute rejection. They also seem to play a prominent role in chronic rejection. We quantified their presence in fine-needle aspiration biopsies and studied the growth factors that, we hypothesized, would mark the different implications of the presence of monocytes-macrophages. Methods Fine-needle aspiration biopsies were obtained from 56 adult renal transplants and analyzed for CD14+ using the alkaline phosphatase-anti-alkaline phosphatase procedure. Thirty-three patients were studied on the production of interleukin (IL)-1 receptor antagonist (IL-1ra), IL-6, IL-8, macrophage colony-stimulating factor, monocyte chemotactic protein 1, and macrophage inflammatory protein 1alpha by aspiration biopsies cultures using enzyme-linked immunosorbent assay techniques. Results CD14+ cells were present at significantly higher numbers in steroid-resistant acute rejections but also during the first days after surgery, especially if acute tubular necrosis was present. We found a significantly higher production of IL-1ra by rejection-free patients compared with acutely rejecting patients, and this difference was already established on day 7 after surgery (10+/-10.5 days before rejection). Conclusions Monocytes-macrophages are present at higher numbers in aspiration biopsies of kidney transplant patients suffering either acute tubular necrosis or steroid-resistant rejections, but they are present during the first days after transplant in stable patients, too. The production of IL-1ra is significantly up-regulated in stable patients, which suggests that monocytes-macrophages may constitute an early key factor in the down-regulation of the anti-allograft immune response.

Graft-infiltrating cells (GIC) have been studied in heart, lung, and liver transplants and have been shown to have greater proliferative ability when taken from rejecting allografts. Our aim was to study GIC harvested by fine-needle aspiration biopsy (FNAB) in renal transplant recipients.93 adult patients entered the study. The FNABs were done on the 7th, 14th, and 30th day after transplantation in stable cases and whenever a rejection crisis supervened.The proliferation responses of GIC were significantly higher in rejection than in stable cases during the 1st month after transplantation. The sensitivity for rejection was 96.4%, the specificity 91.3%, the negative predictive value 98.7%, and the positive predictive value was 93.3% among dysfunctioning grafts.The study of the proliferative capacity of graft-infiltrating cells in renal transplants is a safe and very useful immunologic monitoring tool, and it could improve the FNAB diagnostic accuracy.

Using a 27 gauge hypodermic needle, bone marrow is aspirated from a lumbar vertebra into 0.1 ml of Hanks' salt solution. The aspirate is kept well mixed in 1% sodium citrate for 15 min, centrifuged, and the cell pellet fixed for 30 min in Clarke's 3:1 ethanol-acetic fixative. After removal of the fixative the cells are suspended in 0.05-0.1 ml of 60% acetic acid, centrifuged and resuspended in 0.03 ml of this fixative. Chromosome preparations are made by spreading the suspension on a slide heated to 60 C.