Corneal topography reinterpretation through separate analysis of the projected rings

Póster presentado en SPIE Photonics Europe, Brussels, 16-19 April 2012.

Revisiting youden’s index as a useful measure of the misclassification error in meta-analysis of diagnostic studies

The paper considers meta-analysis of diagnostic studies that use a continuous score for classification of study participants into healthy or diseased groups. Classification is often done on the basis of a threshold or cut-off value, which might vary between studies. Consequently, conventional meta-analysis methodology focusing solely on separate analysis of sensitivity and specificity might be confounded by a potentially unknown variation of the cut-off value. To cope with this phenomena it is suggested to use, instead, an overall estimate of the misclassification error previously suggested and used as Youden’s index and; furthermore, it is argued that this index is less prone to between-study variation of cut-off values. A simple Mantel–Haenszel estimator as a summary measure of the overall misclassification error is suggested, which adjusts for a potential study effect. The measure of the misclassification error based on Youden’s index is advantageous in that it easily allows an extension to a likelihood approach, which is then able to cope with unobserved heterogeneity via a nonparametric mixture model. All methods are illustrated at hand of an example on a diagnostic meta-analysis on duplex doppler ultrasound, with angiography as the standard for stroke prevention.

Revisiting Youden's index as a useful measure of the misclassification error in meta-analysis of diagnostic studies

The paper considers meta-analysis of diagnostic studies that use a continuous Score for classification of study participants into healthy, or diseased groups. Classification is often done on the basis of a threshold or cut-off value, which might vary between Studies. Consequently, conventional meta-analysis methodology focusing solely on separate analysis of sensitivity and specificity might he confounded by a potentially unknown variation of the cut-off Value. To cope with this phenomena it is suggested to use, instead an overall estimate of the misclassification error previously suggested and used as Youden's index and; furthermore, it is argued that this index is less prone to between-study variation of cut-off values. A simple Mantel-Haenszel estimator as a summary measure of the overall misclassification error is suggested, which adjusts for a potential study effect. The measure of the misclassification error based on Youden's index is advantageous in that it easily allows an extension to a likelihood approach, which is then able to cope with unobserved heterogeneity via a nonparametric mixture model. All methods are illustrated at hand of an example on a diagnostic meta-analysis on duplex doppler ultrasound, with angiography as the standard for stroke prevention.

In situ analysis and structural elucidation of sainfoin (Onobrychis viciifolia) tannins for high-throughput germplasm screening

A rapid thiolytic degradation and cleanup procedure was developed for analyzing tannins directly in chlorophyll-containing sainfoin (Onobrychis viciifolia) plants. The technique proved suitable for complex tannin mixtures containing catechin, epicatechin, gallocatechin, and epigallocatechin flavan-3-ol units. The reaction time was standardized at 60 min to minimize the loss of structural information as a result of epimerization and degradation of terminal flavan-3-ol units. The results were evaluated by separate analysis of extractable and unextractable tannins, which accounted for 63.6−113.7% of the in situ plant tannins. It is of note that 70% aqueous acetone extracted tannins with a lower mean degree of polymerization (mDP) than was found for tannins analyzed in situ. Extractable tannins had between 4 and 29 lower mDP values. The method was validated by comparing results from individual and mixed sample sets. The tannin composition of different sainfoin accessions covered a range of mDP values from 16 to 83, procyanidin/prodelphinidin (PC/PD) ratios from 19.2/80.8 to 45.6/54.4, and cis/trans ratios from 74.1/25.9 to 88.0/12.0. This is the first high-throughput screening method that is suitable for analyzing condensed tannin contents and structural composition directly in green plant tissue.

Improving the analysis of road pricing acceptability surveys by using hybrid models

Several international studies have analyzed the acceptability of road pricing schemes by means of an attitude survey in combination with the results of a stated choice experiment using both a descriptive analysis and a discrete-choice model with binary choice (?accept? or ?not accept? the toll). However, the use of hybrid discrete choice models constitutes an innovative alternative for integrating subjective attitudes and perceptions deriving from the survey of attitudes with the more objective variables from the stated choice experiment. This paper analyzes the results of applying these models to measure the acceptability of interurban road pricing among different groups of stakeholders (road freight and passenger operators, highway concessionaires, and associations of private car users) with qualitatively significant opinions on road pricing measures. Our results show that hybrid models are better suited to explaining the acceptability of a road pricing scheme by different groups of stakeholders than a separate analysis of the survey of attitudes and a discrete-choice model applied on a stated choice experiment. A particular finding was that the strong psycho-social latent variable of the perception of fairness explains the rejection or acceptance of a toll scheme by road stakeholders.

Fatores associados à capacidade para o trabalho de trabalhadores do Setor Elétrico

O Setor Elétrico passou por recente processo de reestruturação produtiva com reflexos nas condições e organização do trabalho, podendo comprometer a capacidade para o trabalho. Este estudo objetivou avaliar fatores associados à capacidade para o trabalho junto a 475 trabalhadores de uma empresa do Setor Elétrico no Estado de São Paulo, Brasil. Neste estudo transversal foi realizada análise descritiva e análise de regressão linear múltipla. A média do Índice de Capacidade para o Trabalho (ICT) foi de 41,8 pontos (escala de 7,0 a 49,0 pontos). A análise múltipla mostrou que os fatores que melhor explicaram a variabilidade do ICT foram estresse no trabalho (p < 0,001) e saúde física (p < 0,001 em todas as dimensões). Em outra análise, excluídas as dimensões da saúde, as variáveis associadas ao ICT foram estresse no trabalho (p < 0,001), local de trabalho (p = 0,022), prática de atividade física (p = 0,001), consumo de álcool (p = 0,012) e índice de massa corporal (p < 0,001). Os resultados identificaram aspectos a serem considerados no desenvolvimento de medidas visando a preservação da capacidade para o trabalho, com ênfase no controle do estresse no trabalho e na promoção da saúde.

Comparison of the Use of Tympanic and Extratympanic Electrodes for Electrocochleography

Objectives: To determine the differences between tympanic and extratympanic electrodes regarding recording technique, comfort and ease of execution of the exam, and quality of auditory potential tracings. Study Design: Prospective cross-section investigation. Methods: Determination of the summation potential/action potential (SP/AP) ratio by electrocochleography (EchoG) using tympanic and extratympanic electrodes and separate analysis of SP and AP regarding the amplitude recorded. Results: Twenty-three subjects (15 men and 8 women; mean age: 33.17 years) with normal tonal threshold audiometry were evaluated. EchoG analysis revealed no significant difference between the two tympanic electrodes. Eleven of the 23 subjects reported discomfort with the insertion of the tympanic electrode even with the use of topical xylocaine, whereas no complaints of discomfort were reported with the use of the extratympanic electrode. Conclusions: Both electrodes were effective for EchoG evaluation, but the extratympanic one was easier to insert and did not cause discomfort. However, the tympanic electrode produced tracings of greater amplitude and of better reproducibility. Laryngoscope, 119:563-566, 2009

A technique to assess small-scale heterogeneity of chemical properties in soil aggregates

A new method is presented which allows the separation of the soil aggregate exterior from the aggregate core. The method employs a combination of aggregate freezing with rapid separation of aggregate exteriors using ultrasonic energy. The factors influencing the thickness of the removed aggregate surface layer include water content of the aggregate prior to freezing, temperature difference between that of the frozen aggregate and that of the liquid it is submerged in during sonification, sonification time and energy, and the type of the immersion liquid. The success of the method and the thickness of the removed aggregate surface were examined using barium ( Ba2+) as a tracer. Barium ( as BaCl2) is rapidly absorbed by soil and is present at only very low levels in natural soils. Surface layers of 0.2 - 0.4 cm thickness were successfully removed from aggregates of 1 - 4 cm diameter. Two examples are given from soils in northern NSW to demonstrate the occurrence of small- scale heterogeneity in soil chemical properties. Compared with the surface fraction, a 4 - 7% higher calcium concentration was found in the core fraction of a clay loam soil ( Dermosol). Conversely, on a cracking clay soil ( Vertosol), atrazine concentration was around 15 times greater in the aggregate surface fractions compared with core fractions. Compared with the traditional estimation of soil chemical properties on homogenised bulk soil samples, it is suggested that separate analysis of aggregate surface and core fractions could provide useful additional information on the relationships between soil properties and environmental responses.

Evaluation of parasitological examination, kDNA polymerase chain reaction and rK39-based immunochromatography for the diagnosis of visceral leishmaniasis in seropositive dogs from the screening-culling program in Brazil

Introduction Dogs play a primary role in the zoonotic cycle of visceral leishmaniasis (VL). Therefore, the accurate diagnosis of infected dogs, primarily asymptomatic dogs, is crucial to the efficiency of VL control programs. Methods We investigated the agreement of four diagnostic tests for canine visceral leishmaniasis (CVL): parasite detection, either after myeloculture or by direct microscopic examination of tissue imprints; kinetoplast-deoxyribonucleic acid-polymerase chain reaction (kDNA-PCR); and an immunochromatographic test (ICT). An enzyme-linked immunosorbent assay (ELISA) and an indirect immunofluorescence test (IFAT), both of which were adopted as part of the screening-culling program in Brazil, were used as reference tests. Our sample set consisted of 44 seropositive dogs, 25 of which were clinically asymptomatic and 19 were symptomatic for CVL according to ELISA-IFAT. Results The highest and lowest test co-positivities were observed for ICT (77.3%) and myeloculture (58.1%), respectively. When analyzed together, the overall percentage of co-positive tests was significantly higher for the symptomatic group compared to the asymptomatic group. However, only ICT was significantly different based on the results of a separate analysis per test for each group of dogs. The majority (93.8%) of animals exhibited at least one positive test result, with an average of 2.66 positive tests per dog. Half of the symptomatic dogs tested positive for all four tests administered. Conclusions The variability between test results reinforces the need for more efficient and reliable methods to accurately diagnose canine VL, particularly in asymptomatic animals.

Predição precoce de risco de Pré-eclâmpsia na doença hipertensiva e diabetes na gravidez: Papel de fatores angiogénicos

RESUMO: A pré-eclâmpsia tem elevada morbi-mortalidade materna e perinatal. A sua etiologia multi-fatorial tem sido objeto de investigação, não sendo ainda totalmente conhecida. Não se conhece também a razão da diferente suscetibilidade individual e das diferentes expressões da doença. A hipertensão crónica e a diabetes são fatores de risco reconhecidos, e o adiamento da maternidade contribui para que estas duas patologias sejam atualmente mais prevalentes entre as mulheres grávidas. Uma vez que o seu quadro fisiopatológico precede em meses o quadro clínico, tem-se investigado a possibilidade de serem encontrados marcadores precoces e indicadores de risco. Em Portugal, os estudos relativos à hipertensão na gravidez são escassos, bem como a investigação sobre fatores de risco e marcadores para a mesma. No sentido de avaliar possíveis marcadores de risco para o desenvolvimento de préeclâmpsia ou complicações hipertensivas foi colhida, para esta dissertação, uma amostra de 1215 mulheres que frequentaram a consulta de Hipertensão ou de Diabetes na gravidez de um centro terciário, entre 2004 e 2013. Optou-se pela realização de três estudos independentes, abrangendo os dois primeiros um leque temporal de 9 e de 2 anos respetivamente. O primeiro, centrado na hipertensão, pesquisou, em 521 mulheres com hipertensão na presente ou em anterior gravidez, fatores de risco capazes de influenciar a progressão para pré-eclâmpsia. O segundo, direcionado para a diabetes gestacional, considerou uma amostra de 334 grávidas, parte das quais tinha também hipertensão crónica e procurou identificar fatores que contribuíram para o aparecimento de complicações hipertensivas. O terceiro estudo, realizado em 2012 e 2013, em três coortes de grávidas com hipertensão crónica, com diabetes gestacional, e sem estas patologias - procurou avaliar no 1º trimestre o comportamento de dois marcadores placentares obtidos no 1º trimestre - proteína plasmática A associada à gravidez (PAPP-A) e o fator de crescimento placentar (PlGF) - e o seu papel, quer como bio-marcadores isolados, quer em associação aos fatores de risco encontrados nos anteriores estudos, na construção de um modelo preditivo de préeclâmpsia. No primeiro estudo, a nuliparidade, a hipertensão gestacional, a fluxometria das artérias uterinas com IP superiores ao P95 entre as 20-22 semanas e a existência de restrição de crescimento fetal, foram os fatores que contribuíram para a construção de um modelo preditivo de pré-eclâmpsia. No segundo estudo, a coexistência de diabetes e hipertensão crónica agravou o prognóstico, associando-se as complicações hipertensivas à multiparidade, obesidade, idade materna e etnia negra. No terceiro estudo verificou-se uma redução da PlGf e da PAPP-A no 1º trimestre nas duas primeiras coortes, comparativamente à coorte sem patologia; na análise separada de cada coorte, quando se verificaram complicações hipertensivas ou pré-eclâmpsia, as concentrações de PlGf e PAPP-A também foram inferiores. Contudo, na elaboração de um modelo preditivo de pré-eclâmpsia, em conjunto com marcadores encontrados, apenas a PlGf pode ser integrada no modelo preditivo, o que se verificou na coorte com hipertensão crónica. Os marcadores bioquímicos em estudo tiveram valores inferiores nas coortes com patologia hipertensiva, demonstrando uma deficiente produção destas proteínas placentares nestas situações, podendo ser importante a sua pesquisa. Contudo, neste estudo, apenas na coorte de hipertensão crónica a PlGf teve participação como fator de risco, na construção de um modelo preditivo de pré-eclâmpsia.--------------------------------------------------------------------------------------------------ABSTRACT: Preeclampsia is associated with a great maternal and perinatal morbimortality. Its multifactorial etiology has been under investigation and is still insufficiently understood. The reason why there are differences in individual susceptibility and differences in expressions of the disease is still unknown. Chronic hypertension and diabetes are known risk factors for preeclampsia and maternity delay contributes to the great prevalence of these pathologies among pregnant women. As the physiopathological signs antedate by months the clinical course of the disease, early risk factors and biological markers are object of clinical research. In Portugal, scarce clinical studies were devoted to hypertension in pregnancy and to risk factors and markers of this pathology. This dissertation inquires 1215 pregnant women who were treated for hypertension or diabetes in a tertiary care center between 2004 and 2013, in order to find risk markers for hypertensive complications or preeclampsia. We conducted three independent studies for this purpose. In the first one we investigated which risk factors could influence the progression to preeclampsia in 521 pregnant women with present or past history of hypertension. The second one was conducted to find what factors were associated to hypertensive complications, with a sample of 334 pregnant women with gestational diabetes, some also with chronic hypertension, addressing the identification of the factors contributing to hypertensive complications. The third study was conducted between 2012 and 2013 with three cohorts of pregnant women, with chronic hypertension, gestational diabetes, and in the third one, pregnant women had a low risk pregnancy. The objective of the study was to evaluate the behavior of two placental markers – PAPP-A and PlGf – obtained in the first trimester, and the role of these markers as isolated biomarkers or in association with other risk factors, in order to define a predictive model of early preeclampsia. In the first study, nuliparity, gestational hypertension, uterine arteries doppler with PI above P95 between 20-22 weeks of gestation and the presence of fetal growth restriction were the markers involved in a predictive model for preeclampsia. In the second study the cohort with the coexistence of diabetes and hypertension had registered worse result and hypertensive complications were associated to multiparity, obesity, maternal age and black ethnicity. In the third study there was a reduction of the PlGf and a PAPP-A concentration for the first trimester in the two first cohorts comparatively to the low risk cohort; the separate analysis of each cohort showed that plGf and PAPP-A concentrations were reduced when hypertensive complications appeared. However, when trying to find a preeclampsia predictive model, only plGf gave significant results for being considered in the model and this was only possible in the chronic hypertension cohort. The biochemical markers investigated in this study were reduced in the cohorts when high blood pressure complications occurred, showing a defective production of these placenta proteins, and suggesting that they should be investigated as first trimester biomarkers. Nevertheless, for this research, in the cohort of chronic hypertension only PlGf had a significant result, when multivariate analysis of all the risk factors was considered for the construction of a preeclampsia predictive model.

Joint modelling of longitudinal and survival data on breast cancer

Tese de Doutoramento em Ciências (Especialidade em Matemática)

Association of adiposity genetic variants with menarche timing in 92,105 women of European descent.

Obesity is of global health concern. There are well-described inverse relationships between female pubertal timing and obesity. Recent genome-wide association studies of age at menarche identified several obesity-related variants. Using data from the ReproGen Consortium, we employed meta-analytical techniques to estimate the associations of 95 a priori and recently identified obesity-related (body mass index (weight (kg)/height (m)(2)), waist circumference, and waist:hip ratio) single-nucleotide polymorphisms (SNPs) with age at menarche in 92,116 women of European descent from 38 studies (1970-2010), in order to estimate associations between genetic variants associated with central or overall adiposity and pubertal timing in girls. Investigators in each study performed a separate analysis of associations between the selected SNPs and age at menarche (ages 9-17 years) using linear regression models and adjusting for birth year, site (as appropriate), and population stratification. Heterogeneity of effect-measure estimates was investigated using meta-regression. Six novel associations of body mass index loci with age at menarche were identified, and 11 adiposity loci previously reported to be associated with age at menarche were confirmed, but none of the central adiposity variants individually showed significant associations. These findings suggest complex genetic relationships between menarche and overall obesity, and to a lesser extent central obesity, in normal processes of growth and development.

Activity and exploratory behavior after lesions of the medial entorhinal cortex in the woodmouse (Apodemus sylvaticus).

The effects of bilateral electrolytic lesions of the entorhinal cortex were studied in male adult woodmice. Experiments were designed to allow separate analysis of the basal activity level and exploratory behavior. Activity recording was conducted in three situations: (a) 24-hr wheel running in the home cage pre- and postoperatively; (b) 24-hr activity composition in a large enclosure over 4 days, 5 to 9 days postoperatively; and (c) sequence and duration of visits in a residential plus maze 11 to 14 days postoperatively. Medial entorhinal cortex lesion involving the para- and presubiculum increased the 24-hr amount of movements in the enclosure (b) without increasing wheel running in any situation (a or b). This lesion also enhanced the locomotor reactivity to being introduced into the plus maze and impaired exploratory behavior. This last effect was equally apparent when the whole situation was new or when part of the familiar maze was modified. Lesioned woodmice did notice the new element but did not show active focalization of their behavior on that element. Data showed that lesion induced hyperactivity and changes of exploratory behavior were not necessarily associated. Novelty detection was performed but it is not clear now on what information this discrimination was based.

Soft tissue sarcomas of the trunk wall (STS-TW): a study of 343 patients from the French Sarcoma Group (FSG) database.

BACKGROUND: Soft tissue sarcomas of the trunk wall (STS-TW) are usually studied together with soft tissue sarcomas of other locations. We report a study on STS-TW forming part of the French Sarcoma Group database. PATIENTS AND METHODS: Three hundred and forty-three adults were included. We carried out univariate and multivariate analysis for overall survival (OS), metastasis-free survival (MFS) and local recurrence-free survival (LRFS). RESULTS: Tumor locations were as follows: thoracic wall, 82.5%; abdominal wall, 12.3% and pelvic wall, 5.2%. Median tumor size was 6.0 cm. The most frequent tumor types were unclassified sarcoma (27.7%) and myogenic sarcoma (19.2%). A total of 44.6% of cases were grade 3. In all, 21.9% of patients had a previous medical history of radiotherapy (PHR). Median follow-up was 7.6 years. The 5-year OS, MFS and LRFS rates were 60.4%, 68.9% and 58.4%, respectively. Multivariate analysis retained PHR and grade for predicting LRFS and PHR, size and grade as prognostic factors of MFS. Factors influencing OS were age, size, PHR, depth, grade and surgical margins. The predictive factors of incomplete response were PHR, size and T3. CONCLUSIONS: Our results suggest similar classical prognostic factors as compared with sarcomas of other locations. However, a separate analysis of STS-TW revealed a significant poor prognosis subgroup of patients with PHR.

Evidence of chemical reactions in the hydroxyapatite laser ablation plume with a water atmosphere

The expansion dynamics of the ablation plume generated by KrF laser irradiation of hydroxyapatite targets in a 0.1 mbar water atmosphere has been studied by fast intensified charge coupled device imaging with the aid of optical bandpass filters. The aim of the filters is to isolate the emission of a single species, which allows separate analysis of its expansion. Images obtained without a filter revealed two emissive components in the plume, which expand at different velocities for delay times of up to 1.1 ¿s. The dynamics of the first component is similar to that of a spherical shock wave, whereas the second component, smaller than the first, expands at constant velocity. Images obtained through a 520 nm filter show that the luminous intensity distribution and evolution of emissive atomic calcium is almost identical to those of the first component of the total emission and that there is no contribution from this species to the emission from the second component of the plume. The analysis through a 780 nm filter reveals that atomic oxygen partially diffuses into the water atmosphere and that there is a contribution from this species to the emission from the second component. The last species studied here, calcium oxide, was analyzed by means of a 600 nm filter. The images revealed an intensity pattern more complex than those from the atomic species. Calcium oxide also contributes to the emission from the second component. Finally, all the experiments were repeated in a Ne atmosphere. Comparison of the images revealed chemical reactions between the first component of the plume and the water atmosphere.