Variation in coumarin 7-hydroxylase activity associated with genetic polymorphism of cytochrome P450 2A6 and the body status of iron stores in adult Thai males and females

The relationships between catalytic activity of cytochrome P450 2A6 (CYP2A6), polymorphism of CYP2A6 gene, gender and levels of body iron stores were analysed in a sample group of 202 apparently healthy Thais, aged 1947 years. Eleven individuals were found to have high activity of CYP2A6, judged by the relatively large amounts (11.2-14.6 mg) of 7-hydroyxcoumarin (7-OHC) excreted 3 h following administration of 15 mg of coumarin. Ten individuals, however, did not excrete any 7-OHC. Of these 10, four were found to have no CYP2A6 gene (whole gene deletion; CYP2A6*4 allele). The frequency of the CYP2A6 alleles; *1A, *1B and *4 in the whole sample group was 52, 40 and 8% while the frequency of the CYP2A6 gene types; *1A/* 1A, *1A/* 1B, *1B/* 1B, *1A/* 4, *1BI* 4, *4/* 4 was 29, 41, 16, 7, 5 and 2%. Subjects having CYP2A6* 1A/* 1B gene-type group were found to have higher rates of coumarin 7-hydroxylation compared with those of the CYP2A6* 1B/* 1B and CYP2A6* 1A/* 4 gene types. The inter-individual variability in CYP2A6 catalytic activity was therefore attributed in part to the CYP2A6 genetic polymorphism. Variation in CYP2A6 activity in this sample group was not associated with gender but, interestingly, it did show an inverse association with plasma ferritin; an indicator of body iron stores. Higher rates of coumarin 7-hydroxylation were found in individuals with low body iron stores (plasma ferritin < 20 μg/l) compared with subjects having normal body iron store status. Subjects (n = 16) with iron overload (plasma ferritin > 300 mug/l) also tended to have elevated rates of coumarin 7-hydroxylation. These results suggest an increased CYP2A6 expression in subjects who have excessive body iron stores. Further investigations into the underlying factors that may lead to increased expression of CYP2A6 in association with abnormal body iron stores are currently in progress in our laboratory. Pharmacogenetics 12:241-249 (C) 2002 Lippincott Williams Wilkins.

Variabilidade introduzida pelo operador no processamento dos estudos Gated-SPECT do miocárdio

Introdução – Os estudos Gated – Single Photon Emission Computed Tomography (SPECT) são uma das técnicas de imagiologia cardíaca que mais evoluiu nas últimas décadas. Para a análise das imagens obtidas, a utilização de softwares de quantificação leva a um aumento da reprodutibilidade e exatidão das interpretações. O objetivo deste estudo consiste em avaliar, em estudos Gated-SPECT, a variabilidade intra e interoperador de parâmetros quantitativos de função e perfusão do miocárdio, obtidos com os softwares Quantitative Gated SPECT (QGS) e Quantitative Perfusion SPECT (QPS). Material e métodos – Recorreu-se a uma amostra não probabilística por conveniência de 52 pacientes, que realizaram estudos Gated-SPECT do miocárdio por razões clínicas e que integravam a base de dados da estação de processamento da Xeleris da ESTeSL. Os cinquenta e dois estudos foram divididos em dois grupos distintos: Grupo I (GI) de 17 pacientes com imagens com perfusão do miocárdio normal; Grupo II (GII) de 35 pacientes que apresentavam defeito de perfusão nas imagens Gated-SPECT. Todos os estudos foram processados 5 vezes por 4 operadores independentes (com experiência de 3 anos em Serviços de Medicina Nuclear com casuística média de 15 exames/semana de estudos Gated-SPECT). Para a avaliação da variabilidade intra e interoperador foi utilizado o teste estatístico de Friedman, considerando α=0,01. Resultados e discussão – Para todos os parâmetros avaliados, os respectivos valores de p não traduziram diferenças estatisticamente significativas (p>α). Assim, não foi verificada variabilidade intra ou interoperador significativa no processamento dos estudos Gated-SPECT do miocárdio. Conclusão – Os softwares QGS e QPS são reprodutíveis na quantificação dos parâmetros de função e perfusão avaliados, não existindo variabilidade introduzida pelo operador.

Estudo comparativo entre criança com e sem joelhos valgos praticantes de hóquei em patins utilizando diferentes sistemas de análise

O presente estudo tem como objetivo comparar experimentalmente duas crianças praticantes de Hóquei em Patins, uma normal e uma com a patologia dos joelhos valgos, avaliando qualitativamente as diferenças posturais, estáticas e dinâmicas, decorrentes da utilização dos patins específicos desta modalidade, através do sistema de análise da Força de Reação do Solo (FRS), de Eletromiografia (EMG), de captura de movimento, e de modelação e simulação. Para atingir o objetivo definiu-se um protocolo de ensaios com as seguintes tarefas: repouso com e sem patins, marcha, corrida, deslizar com os dois pés apoiados e deslizar com o pé esquerdo levantado. No repouso avaliou-se a variação do ponto de aplicação da FRS da criança normal e patológica, com e sem patins. Ainda na tarefa de repouso avaliou-se também as componentes médio-lateral, antero-posterior individualmente e a componente vertical da FRS, juntamente com a atividade muscular dos músculos Gastrocnémio Medial (GM), Recto Femoral (RF), Vasto Medial (VM), Vasto Lateral (VL), Bicípete Femoral (BF), Semitendinoso (ST), Tensor da Fascia Lata (TFL), Gastrocnémio Lateral (GL), de forma a comparar os valores de intensidade de FRS e da atividade muscular dos diferentes instantes de tempo desta tarefa. Para as restantes tarefas apenas se avaliou individualmente as componentes médio-lateral e antero-posterior da FRS e a componente vertical da FRS juntamente com a atividade muscular dos referidos músculos, salientando as diferenças evidentes entre as curvas da criança normal e as curvas da criança patológica durante os diferentes instantes do movimento. Todas as tarefas referidas, exceto a tarefa de repouso com patins, foram ainda simuladas recorrendo a modelos músculo-esqueléticos. A partir destas simulações do movimento obtiveram-se os ângulos articulares e efetuou-se a respetiva análise. No final dos resultados obtidos apresentou-se uma tabela de resumo com o cálculo dos coeficientes de variação de cada grandeza, exceto nos gráficos da posição no espaço da FRS, onde se constatou que existe uma grande variabilidade inter-individuo em cada tarefa. A análise dos resultados de cada tarefa permite concluir que a utilização de patins pode trazer uma maior ativação muscular para a criança patológica, embora se verifique instabilidade articular. Apesar dessa instabilidade pode-se inferir que, uma maior ativação muscular decorrente da utilização de patins, tal como acontece na prática do hóquei em patins, pode trazer uma melhoria, a longo prazo, na estabilidade da articulação do joelho e na sustentação corporal, proporcionada pelo fortalecimento muscular.

Polycyclic aromatic hydrocarbons in commercial squids from different geographical origins: levels and risks for human consumption

The concentrations of 18 polycyclic aromatic hydrocarbons (PAHs) were determined in five commercially valuable squid species from different geographical origins (Atlantic, Indic and Pacific Oceans). Out of the 18 quantified PAHs (the 16 PAHs considered by US EPA as priority pollutants, dibenzo(a,l)pyrene and benzo(j)fluoranthene) only dibenz(a,h)anthracene was not detected. The total concentrations of PAHs varied by a factor of more than 100-fold, from 0.22 (Loligo gahi) to 60.9 lg/kg ww (Loligo reynaudii). Intraand inter-specific variability of PAH levels was statistically assessed. Nine carcinogenic (probable/possible) PAHs accounted for 1% (L. reynaudii) to 26% (Loligo opalescens) of the total PAHs content being the main contributors naphthalene (in Loligo duvaucelii, L. reynaudii and Loligo vulgaris species), chrysene (in L. opalescens) and indeno(1,2,3-cd)pyrene (in L. gahi). PAHs source analysis indicated that four of the five zones of capture of the different squid species are significantly affected by both petrogenic and pyrolytic sources. Assessment of the target carcinogenic risks, established by the US EPA, suggested that L. gahi (Atlantic Ocean) and L. opalescens (from Pacific Ocean) may pose additional risks for consumers, if not eaten in moderation, derived from benzo(a)pyrene ingestion.

Climatology of the Iberia coastal low-level wind jet: weather research forecasting model high-resolution results

Coastal low-level jets (CLLJ) are a low-tropospheric wind feature driven by the pressure gradient produced by a sharp contrast between high temperatures over land and lower temperatures over the sea. This contrast between the cold ocean and the warm land in the summer is intensified by the impact of the coastal parallel winds on the ocean generating upwelling currents, sharpening the temperature gradient close to the coast and giving rise to strong baroclinic structures at the coast. During summertime, the Iberian Peninsula is often under the effect of the Azores High and of a thermal low pressure system inland, leading to a seasonal wind, in the west coast, called the Nortada (northerly wind). This study presents a regional climatology of the CLLJ off the west coast of the Iberian Peninsula, based on a 9km resolution downscaling dataset, produced using the Weather Research and Forecasting (WRF) mesoscale model, forced by 19 years of ERA-Interim reanalysis (1989-2007). The simulation results show that the jet hourly frequency of occurrence in the summer is above 30% and decreases to about 10% during spring and autumn. The monthly frequencies of occurrence can reach higher values, around 40% in summer months, and reveal large inter-annual variability in all three seasons. In the summer, at a daily base, the CLLJ is present in almost 70% of the days. The CLLJ wind direction is mostly from north-northeasterly and occurs more persistently in three areas where the interaction of the jet flow with local capes and headlands is more pronounced. The coastal jets in this area occur at heights between 300 and 400 m, and its speed has a mean around 15 m/s, reaching maximum speeds of 25 m/s.

ECG signals for biometric applications: are we there yet?

The potential of the electrocardiographic (ECG) signal as a biometric trait has been ascertained in the literature over the past decade. The inherent characteristics of the ECG make it an interesting biometric modality, given its universality, intrinsic aliveness detection, continuous availability, and inbuilt hidden nature. These properties enable the development of novel applications, where non-intrusive and continuous authentication are critical factors. Examples include, among others, electronic trading platforms, the gaming industry, and the auto industry, in particular for car sharing programs and fleet management solutions. However, there are still some challenges to overcome in order to make the ECG a widely accepted biometric. In particular, the questions of uniqueness (inter-subject variability) and permanence over time (intra-subject variability) are still largely unanswered. In this paper we focus on the uniqueness question, presenting a preliminary study of our biometric recognition system, testing it on a database encompassing 618 subjects. We also performed tests with subsets of this population. The results reinforce that the ECG is a viable trait for biometrics, having obtained an Equal Error Rate of 9.01% and an Error of Identification of 15.64% for the entire test population.

Optimisation of paediatrics computed radiography for full spine curvature measurements using a phantom: a pilot study

Aim: Optimise a set of exposure factors, with the lowest effective dose, to delineate spinal curvature with the modified Cobb method in a full spine using computed radiography (CR) for a 5-year-old paediatric anthropomorphic phantom. Methods: Images were acquired by varying a set of parameters: positions (antero-posterior (AP), posteroanterior (PA) and lateral), kilo-voltage peak (kVp) (66-90), source-to-image distance (SID) (150 to 200cm), broad focus and the use of a grid (grid in/out) to analyse the impact on E and image quality (IQ). IQ was analysed applying two approaches: objective [contrast-to-noise-ratio/(CNR] and perceptual, using 5 observers. Monte-Carlo modelling was used for dose estimation. Cohen’s Kappa coefficient was used to calculate inter-observer-variability. The angle was measured using Cobb’s method on lateral projections under different imaging conditions. Results: PA promoted the lowest effective dose (0.013 mSv) compared to AP (0.048 mSv) and lateral (0.025 mSv). The exposure parameters that allowed lower dose were 200cm SID, 90 kVp, broad focus and grid out for paediatrics using an Agfa CR system. Thirty-seven images were assessed for IQ and thirty-two were classified adequate. Cobb angle measurements varied between 16°±2.9 and 19.9°±0.9. Conclusion: Cobb angle measurements can be performed using the lowest dose with a low contrast-tonoise ratio. The variation on measurements for this was ±2.9° and this is within the range of acceptable clinical error without impact on clinical diagnosis. Further work is recommended on improvement to the sample size and a more robust perceptual IQ assessment protocol for observers.

Influência da experiência profissional e da função visual do operador no processamento semiautomático da cintigrafia de perfusão do miocárdio: variabilidade intra e interoperador na determinação dos parâmetros quantitativos

Introdução – A cintigrafia de perfusão do miocárdio (CPM) desempenha um importante papel no diagnóstico, avaliação e seguimento de pacientes com doença arterial coronária, sendo o seu processamento realizado maioritariamente de forma semiautomática. Uma vez que o desempenho dos técnicos de medicina nuclear (TMN) pode ser afetado por fatores individuais e ambientais, diferentes profissionais que processem os mesmos dados poderão obter diferentes estimativas dos parâmetros quantitativos (PQ). Objetivo – Avaliar a influência da experiência profissional e da função visual no processamento semiautomático da CPM. Analisar a variabilidade intra e interoperador na determinação dos PQ funcionais e de perfusão. Metodologia – Selecionou-se uma amostra de 20 TMN divididos em dois grupos, de acordo com a sua experiência no software Quantitative Gated SPECTTM: Grupo A (GA) – TMN ≥600h de experiência e Grupo B (GB) – TMN sem experiência. Submeteram-se os TMN a uma avaliação ortóptica e ao processamento de 21 CPM, cinco vezes, não consecutivas. Considerou-se uma visão alterada quando pelo menos um parâmetro da função visual se encontrava anormal. Para avaliar a repetibilidade e a reprodutibilidade recorreu-se à determinação dos coeficientes de variação, %. Na comparação dos PQ entre operadores, e para a análise do desempenho entre o GA e GB, aplicou-se o Teste de Friedman e de Wilcoxon, respetivamente, considerando o processamento das mesmas CPM. Para a comparação de TMN com visão normal e alterada na determinação dos PQ utilizou-se o Teste Mann-Whitney e para avaliar a influência da visão para cada PQ recorreu-se ao coeficiente de associação ETA. Diferenças estatisticamente significativas foram assumidas ao nível de significância de 5%. Resultados e Discussão – Verificou-se uma reduzida variabilidade intra (<6,59%) e inter (<5,07%) operador. O GB demonstrou ser o mais discrepante na determinação dos PQ, sendo a parede septal (PS) o único PQ que apresentou diferenças estatisticamente significativas (zw=-2,051, p=0,040), em detrimento do GA. No que se refere à influência da função visual foram detetadas diferenças estatisticamente significativas apenas na fração de ejeção do ventrículo esquerdo (FEVE) (U=11,5, p=0,012) entre TMN com visão normal e alterada, contribuindo a visão em 33,99% para a sua variação. Denotaram-se mais diferenças nos PQ obtidos em TMN que apresentam uma maior incidência de sintomatologia ocular e uma visão binocular diminuída. A FEVE demonstrou ser o parâmetro mais consistente entre operadores (1,86%). Conclusão – A CPM apresenta-se como uma técnica repetível e reprodutível, independente do operador. Verificou-se influência da experiência profissional e da função visual no processamento semiautomático da CPM, nos PQ PS e FEVE, respetivamente.

Functional brain perfusion evaluation with Arterial Spin Labeling at 3 Tesla

Dissertation submitted in Faculdade de Ciências e Tecnologia of Universidade Nova de Lisboa for the degree of Master of Biomedical Engineering

Segmentação de imagens fetais com potencial para desenvolvimento de ferramentas de apoio ao diagnóstico

Programa Doutoral em Engenharia Eletrónica e de Computadores

A network approach to brain aging through multimodal neuroimaging

Tese de Doutoramento em Ciências da Saúde.

Population dynamics of 0-group flounder (Platichthys flesus L.) in Galway Bay, West of Ireland and the value of flounder from shore angling tourism in Ireland

The economic value of flounder from shore angling around Ireland was assessed. Flounder catches from shore angling tournaments around Ireland were related to domestic and overseas shore angling expenditure in order to determine an economic value for the species. Temporal trends in flounder angling catches, and specimen (trophy) flounder reports were also investigated. Flounder was found to be the most caught shore angling species in competitions around Ireland constituting roughly one third of the shore angling competition catch although this did vary by area. The total value of flounder from shore angling tourism was estimated to be of the order of €8.4 million. No significant temporal trends in flounder angling catches and specimen reports were found. Thus there is no evidence from the current study for any decline in flounder stocks. The population dynamics of 0-group flounder during the early benthic stage was investigated at estuarine sites in Galway Bay, west of Ireland. Information was analysed from the March to June sampling period over five years (2002 to 2006). Spatial and temporal variations in settlement and population length structure were analysed between beach and river habitats and sites. Settlement of flounder began from late March to early May of each year, most commonly in April. Peak settlement was usually in April or early May. Settlement was recorded earlier than elsewhere, although most commonly was similar to the southern part of the UK and northern France. Settlement was generally later in tidal rivers than on sandy beaches. Abundance of 0-group flounder in Galway Bay did not exhibit significant inter -annual variability. 0-group flounder were observed in dense aggregations of up to 105 m'2, which were patchy in distribution. Highest densities of 0-group flounder were recorded in limnetic and oligohaline areas as compared with the lower densities in polyhaline and to a lesser extent mesohaline areas. Measurements to of salinity allowed the classification of beaches, and tidal river sections near the mouth, into a salinity based scheme for length comparisons. Beaches were classified as polyhaline,the lower section of rivers as mesohaline, and the middle and upper sections as oligohaline. Over the March to June sampling period 0-group flounder utilised different sections at different length ranges and were significantly larger in more upstream sections. During initial settlement in April, 0-group flounder of 8-10 mm (standard length, SL) were present in abundance on polyhaline sandy beaches. By about 10mm (SL), flounder were present in all polyhaline, mesohaline and (oligohaline) sections. 0-group flounder became absent or in insignificant numbers in polyhaline and mesohaline sections in a matter of weeks after first appearance. From April to June, 0-group flounder of 12-30mm (SL) were found in more upstream locations in the oligohaline sections. About one month (May or June) after initial settlement, 0-group flounder became absent from the oligohaline sections. Concurrently, flounder start to reappear in mesohaline and polyhaline areas at approximately 30mm (SL) in June. The results indicate 0-group flounder in the early benthic stage are associated with low salinity areas, but as they grow, this association diminishes. Results strongly suggest that migration of 0-group flounder between habitats takes place during the early benthic phase.

Внутригодовой ход аэрозольной оптической толщи атмосферы в г. Тбилиси

წარმოდგენილია ატმოსფეროში აეროზოლების ოპტიკური სისქის (AOD) სნაშუალოთვიური მნიშვნელობების შიდაწლიური სვლა დროის სხვადასხვა პერიოდისთვის (1931-1990 წწ.). ნაჩვენებია, რომ AOD საშუალოთვიური მნიშვნელობების შიდაწლიური სვლა, გასაშუალოების პერიოდზე დამოუკიდებლად, გამოისახება მეშვიდე ხარისხის პოლინომით.

Treball de camp a una colònia de xatrac comú (sterna hirundo) en Alemanya

Estudio elaborado a partir de una estancia en el Institut fur Vogelforschung. El objeto de la estancia fue participar en la campaña de campo en la colonia de Charrán común (Sterna hirundo) situada en Wilhelmshaven (Alemania), entre los meses de mayo y agosto de 2005. Esta participación se llevó a cabo bajo la dirección del Prof. Dr. Peter H. Becker y junto a su equipo. Se participó en la recogida rutinaria de datos de la colonia así como en distintas técnicas relacionadas con el presente proyecto, como el marcaje de pollos, su observación directa desde escondites y la recogida de distintas muestras biológicas. El objetivo principal era continuar con la obtención de datos para el trabajo de investigación sobre la influencia de la calidad y la condición parental en la manipulación adaptativa de la razón de sexos y la asignación por sexos. La obtención de datos se basa en la implantación de transponders en pollos, que permiten la identificación de cada charrán de por vida. La combinación de esta información con la observación directa de cebas hace de la colonia un lugar excepcional, lo que permite conocer los factores que influyen en las tendencias que existan. Sin embargo, el objetivo específico de la campaña se centraba en investigar la variabilidad individual de la respuesta inmune en los pollos de charrán en relación a un número de atributos de los propios pollos (sexo, tamaño, tasa de crecimiento, proteínas en plasma, hematocrito, carga parasitaria, carotenos en plasma, isótopos de las plumas), de los padres (fecha y tamaño de puesta, calidad parental) y de las condiciones de cría (orden de eclosión, densidad de la sub-colonia). Los resultados de estos datos obtenidos durante la campaña respaldan que existe una influencia de la condición nutricional y la calidad parental en la respuesta immune de los pollos, debida probablemente a un esfuerzo reproductivo diferencial.

Quantifying consistency of Event Related Potentials across subjects based on single-trial topographic analysis

Introduction: Non-invasive brain imaging techniques often contrast experimental conditions across a cohort of participants, obfuscating distinctions in individual performance and brain mechanisms that are better characterised by the inter-trial variability. To overcome such limitations, we developed topographic analysis methods for single-trial EEG data [1]. So far this was typically based on time-frequency analysis of single-electrode data or single independent components. The method's efficacy is demonstrated for event-related responses to environmental sounds, hitherto studied at an average event-related potential (ERP) level. Methods: Nine healthy subjects participated to the experiment. Auditory meaningful sounds of common objects were used for a target detection task [2]. On each block, subjects were asked to discriminate target sounds, which were living or man-made auditory objects. Continuous 64-channel EEG was acquired during the task. Two datasets were considered for each subject including single-trial of the two conditions, living and man-made. The analysis comprised two steps. In the first part, a mixture of Gaussians analysis [3] provided representative topographies for each subject. In the second step, conditional probabilities for each Gaussian provided statistical inference on the structure of these topographies across trials, time, and experimental conditions. Similar analysis was conducted at group-level. Results: Results show that the occurrence of each map is structured in time and consistent across trials both at the single-subject and at group level. Conducting separate analyses of ERPs at single-subject and group levels, we could quantify the consistency of identified topographies and their time course of activation within and across participants as well as experimental conditions. A general agreement was found with previous analysis at average ERP level. Conclusions: This novel approach to single-trial analysis promises to have impact on several domains. In clinical research, it gives the possibility to statistically evaluate single-subject data, an essential tool for analysing patients with specific deficits and impairments and their deviation from normative standards. In cognitive neuroscience, it provides a novel tool for understanding behaviour and brain activity interdependencies at both single-subject and at group levels. In basic neurophysiology, it provides a new representation of ERPs and promises to cast light on the mechanisms of its generation and inter-individual variability.