Joint modelling of longitudinal and survival data on breast cancer

Tese de Doutoramento em Ciências (Especialidade em Matemática)

Assessing the suitability of the minimum capture size and protection regimes in the gooseneck barnacle shellfishery

The suitability of a total-length-based, minimum capture-size and different protection regimes was investigated for the gooseneck barnacle Pollicipes pollicipes shellfishery in N Spain. For this analysis, individuals that were collected from 10 sites under different fishery protection regimes (permanently open, seasonally closed, and permanently closed) were used. First, we applied a non-parametric regression model to explore the relationship between the capitulum Rostro-Tergum (RT) size and the Total Length (TL). Important heteroskedastic disturbances were detected for this relationship, demon- strating a high variability of TL with respect to RT. This result substantiates the unsuitability of a TL-based minimum size by means of a mathematical model. Due to these disturbances, an alternative growth- based minimum capture size of 26.3 mm RT (23 mm RC) was estimated using the first derivative of a Kernel-based non-parametric regression model for the relationship between RT and dry weight. For this purpose, data from the permanently protected area were used to avoid bias due to the fishery. Second, the size-frequency distribution similarity was computed using a MDS analysis for the studied sites to evaluate the effectiveness of the protection regimes. The results of this analysis indicated a positive effect of the permanent protection, while the effect of the seasonal closure was not detected. This result needs to be interpreted with caution because the current harvesting based on a potentially unsuitable mini- mum capture size may dampen the efficacy of the seasonal protection regime.

Establishing the prevalence of hypertension. Influence of sampling criteria

OBJECTIVE: To compare the prevalence of systemic hypertension in two different populations: a representative sample of the adult urban population of Porto Alegre, and individuals who sought blood pressure measurement in a hypertension prevention and control campaign. METHODS: A cross-sectional study was carried out involving a representative sample of the adult urban population of Porto Alegre and a population sample obtained from a hypertension prevention and control campaign, which included all the individuals who sought the blood pressure assessment unit at the Hospital das Clínicas in Porto Alegre. The following parameters were investigated: history of hypertension, use of antihypertensive drugs, age, and sex. Adjustments for age and sex in the prevalence rates were performed to make them comparable. RESULTS: Hypertension prevalence, defined as values > or = 160/95mmHg or treatment with antihypertensive drugs, was higher in the campaign sample (42%) as compared with the population sample (24%). Among those who were aware of their hypertensive condition and were under medication, 54% of the campaign sample and 62% of the representative population sample maintained their pressure levels <160/90mmHg. CONCLUSION: Prevalence rates of hypertension differed a lot in the campaign sample and in the representative population sample, showing that the sampling criterion may influence assessment of risk factors and bias the association between risk factors and health aggravations.

Anxiety and depression symptoms in women and men from early pregnancy to 3-months postpartum: parity differences and effects

This study aimed to investigate both anxiety and depression symptoms from early pregnancy to 3-months postpartum, comparing women and men and first and second-time parents. Methods: A sample of 260 Portuguese couples (N=520), first or second-time parents, recruited in an Obstetrics Out-patients Unit, filled in the State-Anxiety Inventory (STAI-S) and the Edinburgh Post-Natal Depression Scale (EPDS) at the 1st, 2nd and 3rd pregnancy trimesters, childbirth, and 3-months postpartum. Results: A decrease in anxiety and depression symptoms from early pregnancy to 3-months postpartum was found in both women and men, as well as in first and second-time parents. Men presented less anxiety and depression symptoms than women, but the same pattern of symptoms over time. Second-time parents showed more anxiety and depression symptoms than first-time parents and a different pattern of symptoms over time: an increase in anxiety and depression symptoms from the 3rd trimester to childbirth was observed in first-time parents versus a decrease in second-time parents. Limitations: The voluntary nature of the participation may have lead to a selection bias; women and men who agreed to participate could be those who presented fewer anxiety and depression symptoms. Moreover, the use of self-report symptom measures does not give us the level of possible disorder in participants. Conclusions: Anxiety and depression symptoms diminish from pregnancy to the postpartum period in all parents. Patterns of anxiety and depression symptoms from early pregnancy to 3-months postpartum are similar in women and men, but somewhat different in first and second time parents. Second-time parents should also be considered while studying and intervening during pregnancy and the postpartum.

Avaliação da dosagem direta do colesterol-LDL em amostras de sangue de 10.664 pacientes em comparação com o uso da fórmula de Friedewald

OBJETIVO: Avaliar a dosagem direta do colesterol LDL (LDL-C) por um método homogêneo, em comparação com a estimativa pela fórmula de Friedewald, em uma grande população heterogênea. MÉTODOS: As dosagens do colesterol total (ColT) e dos triglicerídeos (Trig) foram realizadas por métodos enzimáticos tradicionais. As dosagens do HDL-C e do LDL-C foram realizadas por métodos diretos, sem precipitação, e a estimativa da fração LDL-C calculada pela fórmula de Friedewald. RESULTADOS: Por análise de regressão linear, os dois métodos apresentaram coeficientes de correlação extremamente significativos (p<0,001). Entretanto, a fórmula de Friedewald apresentou um bias positivo em relação ao método direto, mais pronunciado com níveis de ColT > 201 mg/dL. Este bias positivo também ocorreu com relação a níveis de Trig < 150 mg/dL. Com níveis de Trig entre 151-200 mg/dL e entre 201-300 mg/dL, não foi observado bias entre os dois métodos. Por outro lado, com níveis de Trig entre 301-400 mg/dL, este bias da fórmula de Friedewald tornou-se negativo. CONCLUSÃO: Foi possível demonstrar que a fórmula de Friedewald não apresenta um desempenho homogêneo para a estimativa do LDL-C em amostras com diferentes níveis de Trig, em comparação com o método direto, podendo causar dúvidas na classificação quanto ao risco de desenvolver doença arterial coronariana.

Ireland’s understudied flatfish: reproduction, age and growth of the dab Limanda limanda (L.) in Irish coastal waters

In Ireland, although flatfish form a valuable fishery, little is known about the smallest, the dab Limanda limanda. In this study, a variety of parameters of reproductive development, including ovarian phase description, gonadosomatic index (GSI), hepatosomatic index (HSI), relative condition (Kn) and oocyte size were analysed to provide information on the dab’s reproductive cycle and spawning periods. Sampling were collected monthly over an 18-month period using bottom trawls of the Irish coastline. A six phase macroscopic guide was developed for both sexes of dab, and verified using histology. In comparisons of macroscopic and microscopic phases, there was high agreement in the proposed female guide (86%), with males demonstratively lower (62%). No significant bias was observed between the the two reproductive methods. When the male macroscopic guide was examined, misclassification was high in phase 5 and phase 5 (41%), with 96% of misclassification occurring in adjacent phases. The sampled population was primarily composed of females, with ratios of females to males 1:0.6, although the predominance of females was less noticeable during the reproductive season. Oocyte growth in dab follows asynchronous development, and spawn over a protracted period indicating a batch spawning strategy. Spawning occurred mainly in early spring, with total regeneration of gonads by May. The length at which 50% of the population was reproductively mature was identified as 14cm and 17cm, for male and female dab, respectively. Precision and bias in age determinations using whole otoliths to age dab was investigated using six age readers from various institutions. Low levels of precision were obtained (CV: 10-23%) inferring the need for an alternative methodology. Precision and bias was influence by the level of experience of the reader, with ageing error attributed to interpretative differences and difficulty in edge determination. Sectioned otolith age determinations were subsequently compared to whole otolith age determinations using two age readers experienced in dab ageing. Although increased precision was observed in whole otoliths from previous estimates (CV=0%, 0% APE), sectioned otoliths were used for growth models. This was based on multinominal logistic regression on age length keys developed using both ageing methods. Biological data (length and age) for both sexes was applied to four growth models, where the Akaike criterion and Multi model Inference indicated the logistic model as having the best fit to the collected data. In general, female dab attained a longer length then males, with growth rates significantly different between the two sexes. Length weight relationships between the two sexes were also significantly different.

Untersuchungen zur ionenstromangepassten Prozessführung und zu Verfahrensvarianten im gepulsten Vakuumbogen-Beschichtungsprozess

Vacuum arc, deposition, ion current, plasma properties, power electronics, bias voltage

Estudo comparativo entre métodos de contrôle quantitativo da produção leiteira

This paper deals with the estimation of milk production by means of weekly, biweekly, bimonthly observations and also by method known as 6-5-8, where one observation is taken at the 6th week of lactation, another at 5th month and a third one at the 8th month. The data studied were obtained from 72 lactations of the Holstein Friesian breed of the "Escola Superior de Agricultura "Luiz de Queiroz" (Piracicaba), S. Paulo, Brazil), being 6 calvings on each month of year and also 12 first calvings, 12 second calvings, and so on, up to the sixth. The authors criticize the use of "maximum error" to be found in papers dealing with this subject, and also the use of mean deviation. The former is completely supersed and unadvisable and latter, although equivalent, to a certain extent, to the usual standard deviation, has only 87,6% of its efficiency, according to KENDALL (9, pp. 130-131, 10, pp. 6-7). The data obtained were compared with the actual production, obtained by daily control and the deviations observed were studied. Their means and standard deviations are given on the table IV. Inspite of BOX's recent results (11) showing that with equal numbers in all classes a certain inequality of varinces is not important, the autors separated the methods, before carrying out the analysis of variance, thus avoiding to put together methods with too different standard deviations. We compared the three first methods, to begin with (Table VI). Then we carried out the analysis with the four first methods. (Table VII). Finally we compared the two last methods. (Table VIII). These analysis of variance compare the arithmetic means of the deviations by the methods studied, and this is equivalent to compare their biases. So we conclude tht season of calving and order of calving do not effect the biases, and the methods themselves do not differ from this view point, with the exception of method 6-5-8. Another method of attack, maybe preferrable, would be to compare the estimates of the biases with their expected mean under the null hypothesis (zero) by the t-test. We have: 1) Weekley control: t = x - 0/c(x) = 8,59 - 0/ = 1,56 2) Biweekly control: t = 11,20 - 0/6,21= 1,80 3) Monthly control: t = 7,17 - 0/9,48 = 0,76 4) Bimonthly control: t = - 4,66 - 0/17,56 = -0,26 5) Method 6-5-8 t = 144,89 - 0/22,41 = 6,46*** We denote above by three asterisks, significance the 0,1% level of probability. In this way we should conclude that the weekly, biweekly, monthly and bimonthly methods of control may be assumed to be unbiased. The 6-5-8 method is proved to be positively biased, and here the bias equals 5,9% of the mean milk production. The precision of the methods studied may be judged by their standard deviations, or by intervals covering, with a certain probability (95% for example), the deviation x corresponding to an estimate obtained by cne of the methods studied. Since the difference x - x, where x is the mean of the 72 deviations obtained for each method, has a t distribution with mean zero and estimate of standard deviation. s(x - x) = √1+ 1/72 . s = 1.007. s , and the limit of t for the 5% probability, level with 71 degrees of freedom is 1.99, then the interval to be considered is given by x ± 1.99 x 1.007 s = x ± 2.00. s The intervals thus calculated are given on the table IX.

On the design of peer punishment experiments

We discuss how technologies of peer punishment might bias the results that are observed in experiments. A crucial parameter is the “fine-to-fee” ratio, which describes by how much the punished subjects income is reduced relatively to the fee the punishing subject has to pay to inflict punishment. We show that a punishment technology commonly used in experiments embeds a variable fine-to-fee ratio and show that it confounds the empirical findings about why, whom, and how much subjects punish.

Human capital in growth regressions: how much difference does data quality make? An update and further results

We construct estimates of educational attainment for a sample of OECD countries using previously unexploited sources. We follow a heuristic approach to obtain plausible time profiles for attainment levels by removing sharp breaks in the data that seem to reflect changes in classification criteria. We then construct indicators of the information content of our series and a number of previously available data sets and examine their performance in several growth specifications. We find a clear positive correlation between data quality and the size and significance of human capital coefficients in growth regressions. Using an extension of the classical errors in variables model, we construct a set of meta-estimates of the coefficient of years of schooling in an aggregate Cobb-Douglas production function. Our results suggest that, after correcting for measurement error bias, the value of this parameter is well above 0.50.

The Social contract with endogenous sentiments

Moral values infuence individual behavior and social interactions. A specially signif- cant instance is the case of moral values concerning work e¤ort. Individuals determine what they take to be proper behaviour and judge the others, and themselves, accordingly. They increase their esteem -and self-esteem- for those who perform in excess of the standard and decrease their esteem for those who work less. These changes in self-esteem result from the self-regulatory emotions of guilt or pride extensively studied in Social Psychology. We examine the interactions between sentiments, individual behaviour and the social contract in a model of rational voting over redistribution where individual self-esteem and relative es-teem for others are endogenously determined. Individuals di¤er in their productivities. The desired extent of redistribution depends both on individual income and on individual attitudes toward others. We characterize the politico-economic equilibria in which sentiments, labor supply and redistribution are simultaneously determined. The model has two types of equilibria. In "cohesive" equilibria, all individuals conform to the standard of proper behav- iour, income inequality is low and social esteem is not biased toward any particular type. Under these conditions equilibrium redistribution increases in response to larger inequality. In a "clustered" equilibrium skilled workers work above the mean while unskilled workers work below. In such an equilibrium, income inequality is large and sentiments are biased in favor of the industrious. As inequality increases, this bias may eventually overtake the egoistic demand for greater taxation and equilibrium redistribution decreases. The type of equilibrium that emerges crucially depends on inequality. We contrast the predictions of the model with data on inequality, redistribution, work values and attitudes toward work and toward the poor for a set of OECD countries.

Modeling sequencing errors by combining Hidden Markov models.

Among the largest resources for biological sequence data is the large amount of expressed sequence tags (ESTs) available in public and proprietary databases. ESTs provide information on transcripts but for technical reasons they often contain sequencing errors. Therefore, when analyzing EST sequences computationally, such errors must be taken into account. Earlier attempts to model error prone coding regions have shown good performance in detecting and predicting these while correcting sequencing errors using codon usage frequencies. In the research presented here, we improve the detection of translation start and stop sites by integrating a more complex mRNA model with codon usage bias based error correction into one hidden Markov model (HMM), thus generalizing this error correction approach to more complex HMMs. We show that our method maintains the performance in detecting coding sequences.

Addressing Sea Surface Salinity retrieval at different spatial resolution. Feasibility study using OCCAM data within SEPS simulator and L2 processor tools

Projecte de recerca elaborat a partir d’una estada a la National Oceanography Centre of Southampton (NOCS), Gran Bretanya, entre maig i juliol del 2006. La possibilitat d’obtenir una estimació precissa de la salinitat marina (SSS) és important per a investigar i predir l’extensió del fenòmen del canvi climàtic. La missió Soil Moisture and Ocean Salinity (SMOS) va ser seleccionada per l’Agència Espacial Europea (ESA) per a obtenir mapes de salinitat de la superfície marina a escala global i amb un temps de revisita petit. Abans del llençament de SMOS es preveu l’anàlisi de la variabilitat horitzontal de la SSS i del potencial de les dades recuperades a partir de mesures de SMOS per a reproduir comportaments oceanogràfics coneguts. L’objectiu de tot plegat és emplenar el buit existent entre les fonts de dades d’entrada/auxiliars fiables i les eines desenvolupades per a simular i processar les dades adquirides segons la configuració de SMOS. El SMOS End-to-end Performance Simulator (SEPS) és un simulador adhoc desenvolupat per la Universitat Politècnica de Catalunya (UPC) per a generar dades segons la configuració de SMOS. Es va utilitzar dades d’entrada a SEPS procedents del projecte Ocean Circulation and Climate Advanced Modeling (OCCAM), utilitzat al NOCS, a diferents resolucions espacials. Modificant SEPS per a poder fer servir com a entrada les dades OCCAM es van obtenir dades de temperatura de brillantor simulades durant un mes amb diferents observacions ascendents que cobrien la zona seleccionada. Les tasques realitzades durant l’estada a NOCS tenien la finalitat de proporcionar una tècnica fiable per a realitzar la calibració externa i per tant cancel•lar el bias, una metodologia per a promitjar temporalment les diferents adquisicions durant les observacions ascendents, i determinar la millor configuració de la funció de cost abans d’explotar i investigar les posibiltats de les dades SEPS/OCCAM per a derivar la SSS recuperada amb patrons d’alta resolució.

A Multicenter Randomized Clinical Trial of Primary Anastomosis or Hartmann's Procedure for Perforated Left Colonic Diverticulitis With Purulent or Fecal Peritonitis.

OBJECTIVES: : To evaluate the outcome after Hartmann's procedure (HP) versus primary anastomosis (PA) with diverting ileostomy for perforated left-sided diverticulitis. BACKGROUND: : The surgical management of left-sided colonic perforation with purulent or fecal peritonitis remains controversial. PA with ileostomy seems to be superior to HP; however, results in the literature are affected by a significant selection bias. No randomized clinical trial has yet compared the 2 procedures. METHODS: : Sixty-two patients with acute left-sided colonic perforation (Hinchey III and IV) from 4 centers were randomized to HP (n = 30) and to PA (with diverting ileostomy, n = 32), with a planned stoma reversal operation after 3 months in both groups. Data were analyzed on an intention-to-treat basis. The primary end point was the overall complication rate. The study was discontinued following an interim analysis that found significant differences of relevant secondary end points as well as a decreasing accrual rate (NCT01233713). RESULTS: : Patient demographics were equally distributed in both groups (Hinchey III: 76% vs 75% and Hinchey IV: 24% vs 25%, for HP vs PA, respectively). The overall complication rate for both resection and stoma reversal operations was comparable (80% vs 84%, P = 0.813). Although the outcome after the initial colon resection did not show any significant differences (mortality 13% vs 9% and morbidity 67% vs 75% in HP vs PA), the stoma reversal rate after PA with diverting ileostomy was higher (90% vs 57%, P = 0.005) and serious complications (Grades IIIb-IV: 0% vs 20%, P = 0.046), operating time (73 minutes vs 183 minutes, P < 0.001), hospital stay (6 days vs 9 days, P = 0.016), and lower in-hospital costs (US $16,717 vs US $24,014) were significantly reduced in the PA group. CONCLUSIONS: : This is the first randomized clinical trial favoring PA with diverting ileostomy over HP in patients with perforated diverticulitis.

Perinatal choline supplementation reveals a dissociation between two types of spatial strategies.

Choline supplementation improving memory functions in rodents is assumed to increase the synthesis and release of acetylcholine in the brain. We have found that a combined pre- and postnatal supplementation results in long-lasting facilitation of spatial memory in juvenile rats when training was conducted in presence of a local salient cue. The present work was aimed at analysing the effects of peri- and postnatal choline supplementation on spatial abilities of naive adult rats. Rats given a perinatal choline supplementation were trained in various cued procedures of the Morris navigation task when aged 5 months. The treatment had a specific effect of reducing the escape latency of the rats when the platform was at a fixed position in space and surrounded by a suspended cue. This effect was associated with an increased spatial bias when the cue and platform were removed. In this condition, the control rats showed impaired spatial discrimination following the removal of the target cue, most likely due to an overshadowing of the distant environmental cues. This impairment was not observed in the treated rats. Further training with the suspended cue at unpredictable places in the pool revealed longer escape latencies in the control than in the treated rats suggesting that this procedure induced a selective perturbation of the normal but not of the treated rats. A special probe trial with the cue at an irrelevant position and no escape platform revealed a significant bias of the control rats toward the cue and of the treated rats toward the uncued spatial escape position. This behavioural dissociation suggests that a salient cue associated with the target induces an alternative "non spatial" guidance strategy in normal rats, with the risk of overshadowing of the more distant spatial cues. In this condition, the choline supplementation facilities a spatial reliance on the cue, that is an overall facilitation of learning a set of spatial relations between several visual cues. As a consequence, the improved escape in presence of the cue is associated with a stronger memory of the spatial position following disappearance of the cue. This and previous observations suggest that a specific spatial attention process relies on the buffering of highly salient visual cues.to facilitate integration of their relative position in the environment.