Les Plus Anciens Mastodontes Tetralophodontes (Langhien inférieur Vb), évolution et remarques sur la Tetralophodontie

This study deals with mastodont teeth found near Lisbon in Lower Langhian (lower Middle Miocene) fluviatile, feldspathic sands (Vb division). Conclusions are as follows: 1. Tetralophodont molars (even if at a still primitive stade of the tetralophodont condition) do exist at least since lower Langhian times, and not only since late Middle Miocene as was previously known. 2. Tri- and tetralophodont structures may (and indeed do) coexist in the same individual: such examples do not correspond to transitional forms, but instead to a mosaic of juxtaposed characters (however this does not mean there are no transitional forms in other instances). 3. So these structures coexisted in a population not yet genetically separated beyond fertile cross-breeding, i.e. beyond species' level. 4. Origin of the tetralophodont molar was due to some mutation (s). but without crossing species, limits and even more genus'ones. 5. At this times probably soon after the first appearance of tetralophodont mutants, animals with such characters were a small but significant minority among the population (17% if account is taken on D4's: only 2% after M2's). 6. There was not then any direct and clear correlation between number of lophs (transversal crests) and tooth size, even if the increase of such number goes along with length's increase. 7. Dimensions (length in special) in tetralophodont teeth tend to exceed those in «normal» trilophodont teeth, this being particularly clear in D4, even if there is no clear distinction: the situation is quite the same, maybe less marked, with the M2. 8. According to the preceding conclusions there are no reasons to segregate different taxa among such mastodont population on the grounds of the presence in D4, M1 and M2 of 3 or 4 crests (this character being regarded as diagnostic of the genus Tetralophodon). 9. On the contrary, if any natural (in biological sense) classification is disregarded and a morphological parataxonomy is adopted there should be considered both Gomphotherium angustidens and Tetralophodon sp.: however this is absolutely not our opinion.

Notes sur la géologie et la paleontology du Miocène de Lisbonne; (XX) les plus anciens mastodontes tetralophodontes (Langhien inférieur Vb), évolution et remarques sur la tetralophodontie

This study deals with mastodont teeth found near Lisbon in Lower Langhian (lower Middle Miocene) fluviatile, feldspathic sands (Vb division). Conclusions are as follows: 1. Tetralophodont molars (even if at a still primitive stade of the tetralophodont condition) do exist at least since lower Langhian times, and not only since late Middle Miocene as was previously known. 2. Tri- and tetralophodont structures may (and indeed do) coexist in the same individual: such examples do not correspond to transitional forms, but instead to a mosaic of juxtaposed characters (however this does not mean there are no transitional forms in other instances). 3. So these structures coexisted in a population not yet geneticaliy separated beyond fertile cross-breeding, i.e. beyond species'level. 4. Origin of the tetralophodont molar was due to some mutation (s). but without crossing species, limits and even more genus' ones. 5. At this times probably soon after the first appearance of tetralophodont mutants, animals with such characters were a small but signifiant minority among the population (17% if account is taken on D4's: only 2% after M2's). 6. There was not then any direct and clear correlation between number of lophs (transversal crests) and tooth size, even if the increase of such number goes along with length's increase. 7. Dimensions (length in special) in tetralophodont teeth tend to exceed those in «normal» trilophodont teeth, this being particularly clear in D4, even if there is no clear distinction: the situation is quite the same, maybe less marked, with the M2. 8. According to the preceding conclusions there are no reasons to segregate different taxa among such mastodont population on the grounds of the presence in D4, M1 and M2 of 3 or 4 crests (this character being regarded as diagnostic of the genus Tetralophodon). 9. On the contrary, if any natural (in biological sense) classification is disregarded and a morphological parataxonomy is adopted there should be considered both Gomphotherium angustidens and Tetralophodon sp.: however this is absolutely not our opinion.

Vertébrés du Miocène moyen de Amor (Leiria) - importance stratigraphique

Some outcrops in the western part of Leiria's diapir yielded continental fossils in five points near Amor village (mammals, other vertebrata, and gastropoda). This is most significant as it is the first locality where miocene age could undoubtedly been ascribed to formations northwards the Iberian Central Chain and Nazare's accident. Mammalian fauna comprises 18 taxa. A new cricetid species, Fahlbuschia freudenthali n. sp. is described. This fauna allows to date fossil-bearing units from Upper Orleanian, MN5 mammal zone, that may be correlated to Upper Langhian marine stage. As the fauna is quite varied, it is possible to recognize the main characters of environment and of climatic conditions. It may probably be assumed that at the time the climate was of mediterranean type, generally warmer than today.

Biogeographic and palaeoclimatic relationships of the Middle Pliocene ichthyofauna of the Samoggia Torrent (Bologna, Italy)

New Middle Pliocene ichthyofauna (2.4-2.2 Ma) from central-eastern Italy (Samoggia Torrent, Bologna) are described. These ichthyolites were found in a rather thin laminated layer that was deposited after the 2.4 Ma climatic crisis. The origin of this deposit, in which 31 taxa have been classified, is to be related to anoxic events on a regional and, probably, supraregional scale. This ichthyofaunistic association, which consists of living genera, is characterized by a clearcut predominance of mesopelagic species. The palaeoclimatic characters of these ichthyofauna indicate subtropical-type waters, while from a palaeobiogeographic point of view there is a close relationship with the present-day Atlantic-Mediterranean bioprovince. The Samoggia deposit has yielded six taxa that are absent or only occasionally present in the Mediterranean: one of these, Spratelloides gracilis, is exclusive of the Indo-Pacific bioprovince.

Cork stoppers industry: defining appropriate mould colonization

Aims: The main aims of this work were the study of cork slabs moulds colonization and the evaluation of the moulds diversity during cork processing steps, in different cork stoppers factories. Simultaneously, it was envisaged to perform an evaluation of the air quality. Methods and Results: Moulds were isolated and identified from cork slabs and cork samples in four cork stoppers factories. The identification was based on morphological characters and microscopic observation of the reproductive structures. Airborne spore dispersion was assessed using a two stage Andersen sampler. It was observed that Chrysonilia sitophila was always present on cork slabs during the maturing period, but mould diversity appeared to be associated to the different factory configurations and processing steps. Conclusions: Spatial separation of the different steps of the process, including physical separation of the maturation step, is essential to guarantee high air quality and appropriate cork slabs colonization, i.e. C. sitophila dominance. The sorting and cutting of the edges of cork slabs after boiling and before the maturing step is also recommended. Significance and Impact of the Study: This study is very important for the cork stopper industry as it gives clear indications on how to keep high quality manufacturing standards and how to avoid occupational health problems.

Cork stoppers industry: defining appropriate mould colonization

Aims: The main aims of this work were the study of cork slabs moulds colonization and the evaluation of the moulds diversity during cork processing steps, in different cork stoppers factories. Simultaneously, it was envisaged to perform an evaluation of the air quality. Methods and Results: Moulds were isolated and identified from cork slabs and cork samples in four cork stoppers factories. The identification was based on morphological characters and microscopic observation of the reproductive structures. Airborne spore dispersion was assessed using a two stage Andersen sampler. It was observed that Chrysonilia sitophila was always present on cork slabs during the maturing period, but mould diversity appeared to be associated to the different factory configurations and processing steps. Conclusions: Spatial separation of the different steps of the process, including physical separation of the maturation step, is essential to guarantee high air quality and appropriate cork slabs colonization, i.e. C. sitophila dominance. The sorting and cutting of the edges of cork slabs after boiling and before the maturing step is also recommended. Significance and Impact of the Study: This study is very important for the cork stopper industry as it gives clear indications on how to keep high quality manufacturing standards and how to avoid occupational health problems.

Biogeographic and palaeoclimatic relationships of the Middle Pliocene ichthyofauna of the Samoggia Torrent (Bologna, Italy)*

New Middle Pliocene ichthyofauna (2.4-2.2 Ma) from central-eastern Italy (Samoggia Torrent, Bologna) are described. These ichthyolites were found in a rather thin laminated layer that was deposited after the 2.4 Ma climatic crisis. The origin of this deposit, in which 31 taxa have been classified, is to be related to anoxic events on a regional and, probably, supraregional scale. This ichthyofaunistic association, which consists of living genera, is characterized by a clearcut predominance of mesopelagic species. The palaeoclimatic characters of these ichthyofauna indicate subtropical-type waters, while from a palaeobiogeographic point of view there is a close relationship with the present-day Atlantic-Mediterranean bioprovince. The Samoggia deposit has yielded six taxa that are absent or only occasionally present in the Mediterranean: one of these, Spratelloides gracilis, is exclusive of the Indo-Pacific bioprovince.

The last Anthracothere Brachyodus onoideus (Mammalia, Artiodactyla) from westernmost Europe and its extinction

This paper deals with B. onoideus specimens from Portugal. This species occurs in the Lisbon area (in the upper part of the lower Miocene, ca.18 to 17.6 Ma) in a very accurate stratigraphic framing (age, lithostratigraphic, climatic and palaeoecologic control being most complete). Some mandibular dental size variation, sex characters, functional interpretation, ecology and predation, chemical corrosion, and extinction are discussed.

Abordagem farmacoepidemiológica da terapêutica no idoso: um ensaio em meio hospitalar

Introdução: O envelhecimento demográfico e o aumento da esperança de vida, criam condições para uma maior incidência de doenças degenerativas. Vários aspectos críticos envolvem a medicação no idoso, tais como: polimedicação frequente, com risco acrescido de ocorrência de reacções adversas, relacionadas com interacções medicamentosas e eventual medicação desaconselhada, em que o risco pode ser superior ao benefício. Estes aspectos são particularmente críticos no idoso hospitalizado. Objectivo: Este estudo teve como objectivo estimar a prevalência da polimedicação em idosos hospitalizados e analisar a medicação considerada inadequada nesta população. Participantes e metodologia: Seguiu-se um modelo retrospectivo descritivo transversal, reportando-se os dados a um período de um ano e meio, incidindo sobre o último internamento. A natureza da medicação, foi analisada de acordo com o Formulário Terapêutico Nacional, Resumo das Caracteristicas do Medicamento e com critérios de Beers-2002.Englobou 100 idosos (>65 anos) utentes do Hospital Cuf Descobertas, em regime de internamento. Os dados pessoais e clínicos e respectivo mapa farmacoterapêutico, foram introduzidos em base de dados construída para este estudo, em Access 2003 SP2. Procedeu-se à analise estatística (SPSS 13,0), descritiva, com cálculo de medidas de tendência central; análise univariada para todas as variáveis relevantes e análise bi-variada para quantificar a prevalência da polimedicação por sexo e grupo etário. Resultados:Dos doentes estudados (65-98 anos), maioritariamente femininos, 7 apresentavam 4 patologias em simultâneo, 13:3 patologias, 27:2 patologias e 30:1 patologia. Em 23 não se verificou qualquer patologia crónica. A hipertensão (n=49:27,5%) e a patologia cardiovascular (n=41:23%) foram as mais frequentemente encontradas na amostra em estudo sendo as de menor frequência a patologia reumática (n=1:0,56%), a osteoporose e os problemas psíquicos (n=2:1,12%. A prevalência de polimedicação foi de 84% e nº de medicamentos prescrito em simultâneo variou entre 2 e 23.Não se observou associação entre a polimedicação, a idade: e o sexo. Em apenas um caso foi identificado um medicamento desaconselhado em função do diagnóstico (metoclopramida:Parkinson), e independentemente do diagnóstico a amiodariona foi o mais frequente (25%), hidroxizina (22%), ticlopidina (2%) e cetorolac (1%). Conclusões: A polimedicação é um fenómeno muito frequente nos idosos hospitalizados; o número de medicamentos envolvidos pode ser elevado e a prevalência de medicamentos que requerem uma ponderação sobre o risco/benefício no idoso, indicia a vantagem da revisão da terapêutica, impondo-se a implementação de estratégias informativas sobre os mesmos. Background: The demographic aging and expansion of life expectancy create conditions for increased occurrence of degenerative illnesses. Several critical aspects involve the medication of the elderly, such as: frequent polipharmacy with increased occurrence of adverse drug reactions, related to medication interactions and inappropriate prescribing, in which the benefits can be inferior to the risks.These aspects are particularly critical in the hospitalized elderly. Aim: This study aimed to estimate the prevalence of polipharmacy in hospitalized elderly and to analyze the medication considered inappropriate in this population. Participants and Methodology: A cross sectional model was followed, in which the data used relate to a period of a year and a half, focussing on the last hospitalization. The nature of the medication was analysed according to National Therapeutic Formulary, Drug Characteristics Summary and according to Beers-2002.It considered 100 elderly (>65 years) hospitalized at Hospital Cuf Descobertas. The personal and clinical data and the corresponding pharmacotherapeutic registration were introduced in a database created for this study in Access 2003 SP2. Descriptive statistics was calculated trough SPSS 13,0,.Exploraty analysis consisted in measures of average and spread for all variable considered relevant and univariate and bivariate analysis to quantify the prevalence of polipharmacy by sex and age and to relate polipharmacy with inappropriate medication. Results: Of the patients studied (65-98 years), the majority were women, 7 presented 4 pathologies, 13:3 pathologies, 27:2 pathologies and 30:1 pathology. In 23 patients there was any chronic pathology. Hypertension (n=49:27,5%) and cardiovascular disease (n=41:23%) were the most frequent disease in our study, and the minimal values were observed in rheumatism (n=1:0,56%), osteoporosis and psychic disorders (n=2:1,12%. The prevalence of polipharmacy was of 84% and the amount of medication simultaneously prescribed varied between 2 and 23.No association was observed between polipharmacy and age or gender. In only one case inappropriate medication was identified concerning diagnosis (metoclopramid: Parkinson), and independent of diagnosis the amiodaron was the most frequent (25%), hydroxyzin (22%), ticlopidin (2%). and ketorolac (1%). Conclusions: Polipharmacy is very prevalent among elderly people admitted to the hospital; the number of inappropriate medication can also be very high and this evidence should be collected in order to accomplish good drug use reviews and informative strategies in the hospital setting.

Burrows-wheeler transform in secondary memory

Master’s Thesis in Computer Engineering

The visual image in Epiphanic Short History

The visual image is a fundamental component of epiphany, stressing its immediacy and vividness, corresponding to the enargeia of the traditional ekphrasis and also playing with cultural and social meanings. Morris Beja in his seminal book Epiphany in the Modern Novel, draws our attention to the distinction made by Joyce between the epiphany originated in a common object, in a discourse or gesture and the one arising in “a memorable phase of the mind itself”. This type materializes in the “dream-epiphany” and in the epiphany based in memory. On the other hand, Robert Langbaum in his study of the epiphanic mode, suggests that the category of “visionary epiphany” could account for the modern effect of an internally glowing vision like Blake’s “The Tyger”, which projects the vitality of a real tyger. The short story, whose length renders it a fitting genre for the use of different types of epiphany, has dealt with the impact of the visual image in this technique, to convey different effects and different aesthetic aims. This paper will present some examples of this occurrence in short stories of authors in whose work epiphany is a fundamental concept and literary technique: Walter Pater, Joseph Conrad, K. Mansfield, Clarice Lispector. Pater’s “imaginary portraits” concentrate on “priviledged moments” of the lives of the characters depicting their impressions through pictorial language; Conrad tries to show “moments of awakening” that can be remembered by the eye; Mansfield suggests that epiphany, the “glimpse”, should replace plot as an internal ordering principle of her impressionist short-stories; in C. Lispector the visualization of some situations is so aggressive that it causes nausea and a radical revelation on the protagonist’s.

Biological predictors of survival in limphoma and mechanisms underlying follicular lymphoma transformaion into diffuse large B cell lymphoma (vol I e II)

RESUMO: Os biomarcadores tumorais permitem identificar os doentes com maior risco de recorrência da doença, predizer a resposta tumoral à terapêutica e, finalmente, definir candidatos a novos alvos terapêuticos. Novos biomarcadores são especialmente necessários na abordagem clínica dos linfomas. Actualmente, esses tumores são diagnosticados através de uma combinação de características morfológicas, fenotípicas e moleculares, mas o prognóstico e o planeamento terapêutico estão quase exclusivamente dependentes de características clínicas. Estes factores clínicos são, na maioria dos linfomas, insuficientes numa proporção significativa dos doentes, em particular, aqueles com pior prognóstico. O linfoma folicular (LF) é, globalmente, o segundo subtipo mais comum de linfoma. É tipicamente uma doença indolente com uma sobrevida média entre os 8 e 12 anos, mas é geralmente fatal quando se transforma num linfoma agressivo de alto grau, habitualmente o linfoma difuso de grandes células B (LDGCB). Morfologicamente e funcionalmente, as células do LF recapitulam as células normais do centro germinativo na sua dependência de sobrevivência do microambiente não-tumoral, especialmente das células do sistema imunológico. Biomarcadores preditivos de transformação não existem pelo que um melhor conhecimento da biologia intrínseca de progressão do LF poderá revelar novos candidatos. Nesta tese descrevo duas abordagens distintas para a descoberta de novos biomarcadores. A primeira, o estudo da expressão global de genes ('genomics') obtidos por técnicas de alto rendimento que analisam todo o genoma humano sequenciado, permitindo identificar novas anomalias genéticas que possam representar mecanismos biológicos importantes de transformação. São descritos novos genes e alterações genómicas associados à transformação do LF, sendo especialmente relevantes as relacionadas com os eventos iniciais de transformação em LDGCB. A segunda, baseou-se em várias hipóteses centradas no microambiente do LF, rico em vários tipos de células nãomalignas. Os estudos imunoarquitectural de macrófagos, células T regulatórias e densidade de microvasos efectuado em biopsias de diagnóstico de doentes com LF tratados uniformemente correlacionaram-se significativamente, e independentemente dos critérios clínicos, com a evolução clínica e, mais importante, com o risco de transformação em LDGCB. Nesta tese, foram preferencialmente utilizadas (e optimizadas) técnicas que permitam o uso de amostras fixadas em parafina e formalina (FFPET). Estas são facilmente acessíveis a partir das biopsias de diagnóstico de rotina presentes nos arquivos de todos os departamentos de patologia, facilitando uma transição rápida dos novos marcadores para a prática clínica. Embora o FL fosse o tema principal da tese, os novos achados permitiram estender facilmente hipóteses semelhantes a outros subtipos de linfoma. Assim, são propostos e validados vários biomarcadores promissores e relacionados com o microambiente não tumoral, sobretudo dependentes das células do sistema imunológico, como contribuintes importantes para a biologia dos linfomas. Estes sugerem novas opções para a abordagem clínica destas doenças e, eventualmente, novos alvos terapêuticos.------------- ABSTRACT: Cancer biomarkers provide an opportunity to identify those patients most at risk for disease recurrence, predict which tumours will respond to different therapeutic approaches and ultimately define candidate biomarkers that may serve as targets for personalized therapy. New biomarkers are especially needed in the management of lymphoid cancers. At present, these tumours are diagnosed using a combination of morphologic, phenotypic and molecular features but prognosis and overall survival are mostly dependent on clinical characteristics. In most lymphoma types, these imprecisely assess a significant proportion of patients, in particular, those with very poor outcomes. Follicular lymphoma (FL) is the second most common lymphoma subtype worldwide. It is typically an indolent disease with current median survivals in the range of 8-12 years, but is usually fatal when it transforms into an aggressive high-grade lymphoma, characteristically Diffuse Large B Cell Lymphoma (DLBCL). Morphologically and functionally it recapitulates the normal cells of the germinal center with its survival dependency on non-malignant immune and immunerelated cells. Informative markers of transformation related to the intrinsic biology of FL progression are needed. Within this thesis two separate approaches to biomarker discovery were employed. The first was to study the global expression of genes (‘genomics’) obtained using high-throughput, wholegenome-wide approaches that offered the possibility for discovery of new genetic abnormalities that might represent the important biological mechanisms of transformation. Gene signatures associated with early events of transformation were found. Another approach relied on hypothesis-driven concepts focusing upon the microenvironment, rich in several non-malignant cell types. The immunoarchitectural studies of macrophages, regulatory T cells and microvessel density on diagnostic biopsies of uniformly treated FL patients significantly predicted clinical outcome and, importantly, also informed on the risk of transformation. Techniques that enabled the use of routine formalin fixed paraffin embedded diagnostic specimens from the pathology department archives were preferentially used in this thesis with the goal of fulfilling a rapid bench-to-beside” translation for these new findings. Although FL was the main subject of the thesis the new findings and hypotheses allowed easy transition into other lymphoma types. Several promising biomarkers were proposed and validated including the implication of several non-neoplastic immune cells as important contributors to lymphoma biology, opening new options for better treatment planning and eventually new therapeutic targets and candidate therapeutics.

Épica e guerra

Dizia Hegel, mergulhado no Volksgeist romântico, que a situação que mais convém à poesia épica é a que é caracterizada pelos «conflitos do estado de guerra» (1979, IV: 117). Hegel referia-se à luta travada entre «totalidades nacionais». Nem sempre foi assim. A Ilíada, fons et origo do epos ocidental, sobrepõe a iniciativa individual a qualquer autoridade centralizada. «They (the homeric characters) were egoists and individualists. An epic warrior must not be cribbed and cabined by responsibility to the common welfare; [...] bis greatness must arise from perfect freedom» (Routh 1971, I: 48). Segundo Wemer Jaeger, Tirteu, o poeta que cantou a areté espartana, «precisou apenas de transferir para a realidade das guerras messénicas o poderoso ethos que anima as cenas homéricas» (1979: 111). A vida acaba por imitar arte.

Changing environmental behaviors through smartphone-based augmented experiences

Dissertação para obtenção do Grau de Mestrado em Engenharia de Informática

Homogneous time resolved fluorescence: a new technique for detection and quantifications of infliximab in autoimmune patients

RESUMO:As terapias biológicas revolucionaram o tratamento das doenças autoimunes nos últimos anos. Tipicamente têm como alvos mediadores importantes no mecanismo das doenças. Os antagonistas do fator de necrose tumoral-α (TNF-α) são um grupo de agentes biológicos muito prescrito, pois estão indicados no tratamento de doenças imuno-mediadas comuns, tais como artrite reumatoide, artrite idiopática juvenil, artrite psoriática, espondilite anquilosante, doença de Crohn e colite ulcerosa. Com o uso frequente de inibidores do TNF-α, tem-se tornado evidente que estes agentes têm um potencial imunogénico importante, que pode comprometer o prognóstico a longo prazo dos doentes cronicamente tratados. A produção de anticorpos anti-fármaco parece causar falência terapêutica secundária em muitos doentes. Um dos efeitos dos anticorpos anti-fármaco é o aumento da eliminação do fármaco. A eliminação do fármaco, por sua vez, varia entre indivíduos, refletindo diferentes perfis farmacocinéticos. A determinação dos níveis séricos mínimos do agente anti-TNF-α é assim muito informativa e pode auxiliar nas decisões terapêuticas. Contudo, os testes imunológicos para determinar as concentrações séricas do fármaco não estão facilmente disponíveis na prática clínica. De forma a investigar uma nova técnica potencialmente fidedigna e prática para a deteção e quantificação dos agentes biológicos anti-TNF-α, foi testada a técnica por HTRF (homogeneous time-resolved fluorescence resonance energy transfer) para a determinação de concentrações séricas de infliximab. Apesar de apresentar algumas limitações relacionadas com as condições de leitura da fluorescência, esta técnica provou obter resultados próximos das concentrações obtidas por ELISA (enzyme-linked immunosorbent assay) bridging. Adicionalmente, tem a vantagem de ser de execução muito mais fácil e rápida. Deste modo, a técnica por HTRF poderá ser otimizada e tornar-se uma valiosa ferramenta laboratorial para orientar as decisões terapêuticas em doentes autoimunes com falência da terapêutica anti-TNF-α.--------- ABSTRACT: Biologic therapies revolutionized the treatment of autoimmune diseases in the last years. Typically, they target important disease mediators. Tumor necrosis factor-alpha (TNF-α) antagonists constitute a very prescribed group of biologic agents as they are indicated for the treatment of common immune-mediated diseases, such as rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease and ulcerative colitis. With the increasing use of TNF-α inhibitors it has been noticed that they have an important immunogenic potential that can compromise long-term outcomes in chronically treated patients. The production of anti-drug antibodies seems to cause secondary therapeutic failure in many patients. One of the effects of anti-drug antibodies is the enhancement of drug clearance. Drug clearance, in turn, varies among individuals, reflecting different pharmacokinetic profiles. Determination of serum anti-TNF-α drug trough levels is though very informative and could support treatment decisions. However, immunologic assays to determine drug serum concentrations are not readily available in clinical practice. In order to investigate a potentially reliable and practical new technique for detection and quantification of anti-TNF-α biologic agents, homogeneous time-resolved fluorescence resonance energy transfer (HTRF) technique was tested for determination of serum infliximab concentrations. Although presenting some limitations related with fluorescence reading conditions, this technique proved to give results close to the concentrations obtained by the widely used bridging enzyme-linked immunosorbent assay (ELISA). In addition, it has the advantage of being much easier and faster to perform. Thus, HTRF technique can be optimized and become a valuable laboratorial tool to guide treatment decisions in autoimmune patients with anti-TNF-α therapy failure.