Métodos de estadística espacial para evaluar la influencia de factores medioambientales sobre la incidencia y mortalidad por cáncer

Los objetivos de la tesis son: 1.- Estudiar la relación entre la incidencia y mortalidad por cáncer y los factores medioambientales, en particular la contaminación atmosférica, controlando por factores socioeconómicos. 2.- Utilizar aquellos métodos de estadística espacial apropiados para cada tipo de diseño. 3.- Distinguir en los modelos las diferentes fuentes de extra-variabilidad espacial. 4.- Controlar el problema de exceso de ceros inherente a alguna de las neoplasias de interés medioambientales. Conclusiones: - Tanto la incidencia como la mortalidad de las neoplasias, presentaron dos fuentes de extravariación. La extravariaicón espacial, por la que unidades vecinas tienden a presentar razones de incidencia/mortalidad similares, y la heterogeneidad no espacial. En general la extravariabilidad espacial ha resultado ser mucho mayor que la no espacial. - Para suavizar las RIE/RME correspondientes a variables con un porcentaje de ceros superior al40-50% debe utilizarse un modelo que capture este comportamiento. - El mejor modelo en términos de ajuste para recoger el exceso de ceros en las variables de interés ha resultado ser el modelo mixto de riesgo relativo. - Las RIE/RME suavizadas presentan un patrón geográfico claro sólo en algunas neoplasias de interés medioambiental. - Parte de la variabilidad remanente en las RIE/RME suavizadas pudo ser explicada mediante la introducción de variables explicativas, en particular la contaminación atmosférica y variables socioeconómicas. -Como los contaminantes atmosféricos fueron observados en un diseño geoestadístico y las neoplasias de interés mediambiental lo fueron en un diseño en rejilla se modelizó la superficie de exposición. - El efecto del contaminante en cada municipio/sección censal se aproximó introduciendo en el modelo el valor promedio en cada área y la variabilidad intra-área. - El efecto del contaminante se consideró aleatorio, en el sentido de que podría ser diferente en cada una de las áreas. - Las condiciones socioeconómicas fueron otra de las variables que redujeron la variabilidad remanente en las RIE/RME suavizadas. -Las variables explicativas observadas con un diseño en rejilla, como el índice de privación, se introdujeron en el modelo como efectos fijos. - El efecto de la privación sobre la incidencia y/o mortalidad por cáncer de tráquea, bronquios y pulmón, controlando por contaminantes atmosféricos, fue mayor en las mujeres que en los hombres. -Altas concentraciones de contaminantes atmosféricos aumentan el riesgo de padecer neoplasias de interés medioambiental, controlando por condiciones socioeconómicas.

Evolution in software systems: foundations of the SPE classification scheme

The SPE taxonomy of evolving software systems, first proposed by Lehman in 1980, is re-examined in this work. The primary concepts of software evolution are related to generic theories of evolution, particularly Dawkins' concept of a replicator, to the hermeneutic tradition in philosophy and to Kuhn's concept of paradigm. These concepts provide the foundations that are needed for understanding the phenomenon of software evolution and for refining the definitions of the SPE categories. In particular, this work argues that a software system should be defined as of type P if its controlling stakeholders have made a strategic decision that the system must comply with a single paradigm in its representation of domain knowledge. The proposed refinement of SPE is expected to provide a more productive basis for developing testable hypotheses and models about possible differences in the evolution of E- and P-type systems than is provided by the original scheme. Copyright (C) 2005 John Wiley & Sons, Ltd.

SPARC Data Initiative: Comparison of water vapor climatologies from international satellite limb sounders

Within the SPARC Data Initiative, the first comprehensive assessment of the quality of 13 water vapor products from 11 limb-viewing satellite instruments (LIMS, SAGE II, UARS-MLS, HALOE, POAM III, SMR, SAGE III, MIPAS, SCIAMACHY, ACE-FTS, and Aura-MLS) obtained within the time period 1978-2010 has been performed. Each instrument's water vapor profile measurements were compiled into monthly zonal mean time series on a common latitude-pressure grid. These time series serve as basis for the "climatological" validation approach used within the project. The evaluations include comparisons of monthly or annual zonal mean cross sections and seasonal cycles in the tropical and extratropical upper troposphere and lower stratosphere averaged over one or more years, comparisons of interannual variability, and a study of the time evolution of physical features in water vapor such as the tropical tape recorder and polar vortex dehydration. Our knowledge of the atmospheric mean state in water vapor is best in the lower and middle stratosphere of the tropics and midlatitudes, with a relative uncertainty of. 2-6% (as quantified by the standard deviation of the instruments' multiannual means). The uncertainty increases toward the polar regions (+/- 10-15%), the mesosphere (+/- 15%), and the upper troposphere/lower stratosphere below 100 hPa (+/- 30-50%), where sampling issues add uncertainty due to large gradients and high natural variability in water vapor. The minimum found in multiannual (1998-2008) mean water vapor in the tropical lower stratosphere is 3.5 ppmv (+/- 14%), with slightly larger uncertainties for monthly mean values. The frequently used HALOE water vapor data set shows consistently lower values than most other data sets throughout the atmosphere, with increasing deviations from the multi-instrument mean below 100 hPa in both the tropics and extratropics. The knowledge gained from these comparisons and regarding the quality of the individual data sets in different regions of the atmosphere will help to improve model-measurement comparisons (e.g., for diagnostics such as the tropical tape recorder or seasonal cycles), data merging activities, and studies of climate variability.

SPARC Data Initiative: A comparison of ozone climatologies from international satellite limb sounders

A comprehensive quality assessment of the ozone products from 18 limb-viewing satellite instruments is provided by means of a detailed intercomparison. The ozone climatologies in form of monthly zonal mean time series covering the upper troposphere to lower mesosphere are obtained from LIMS, SAGE I/II/III, UARS-MLS, HALOE, POAM II/III, SMR, OSIRIS, MIPAS, GOMOS, SCIAMACHY, ACE-FTS, ACE-MAESTRO, Aura-MLS, HIRDLS, and SMILES within 1978–2010. The intercomparisons focus on mean biases of annual zonal mean fields, interannual variability, and seasonal cycles. Additionally, the physical consistency of the data is tested through diagnostics of the quasi-biennial oscillation and Antarctic ozone hole. The comprehensive evaluations reveal that the uncertainty in our knowledge of the atmospheric ozone mean state is smallest in the tropical and midlatitude middle stratosphere with a 1σ multi-instrument spread of less than ±5%. While the overall agreement among the climatological data sets is very good for large parts of the stratosphere, individual discrepancies have been identified, including unrealistic month-to-month fluctuations, large biases in particular atmospheric regions, or inconsistencies in the seasonal cycle. Notable differences between the data sets exist in the tropical lower stratosphere (with a spread of ±30%) and at high latitudes (±15%). In particular, large relative differences are identified in the Antarctic during the time of the ozone hole, with a spread between the monthly zonal mean fields of ±50%. The evaluations provide guidance on what data sets are the most reliable for applications such as studies of ozone variability, model-measurement comparisons, detection of long-term trends, and data-merging activities.

Lojalitet eller kriminalitet? : Ransoneringsbrottsligheten i Sandviken/Högbo under åren 1939-1949.

Syftet med uppsatsen är att undersöka omfattningen av och karaktären på ransoneringsbrottsligheten i Sandviken/Högbo under åren 1939-1949 samt myndigheternas försök att stävja denna brottslighet. Det ska främst uppnås genom att studera den rannsakade ransonerings-brottsligheten som det framkommer i domböckerna.Materialet som använts i undersökningen är domböcker för Gästriklands östra domsaga, protokoll från Högbo kommuns och Sandvikens köpings kristidsnämnd, ett klipparkiv med pressklipp från lokaltidningarna samt ett brottmålsdiarium för Sandvikens distrikt.Resultatet är att det föll 119 st fällande domar för ransoneringsbrott i Sandviken/Högbo under de undersökta åren, de flesta sakfällda brotten begicks under åren 1944-45. Den övervägande delen av brotten handlade om olika varubrott, i regel olaga försäljning/köp av ransonerade varor. De varor som framförallt drabbades av olika brott var olika former av livsmedel, främst smör. De som framförallt begick ransoneringsbrotten var personer som på något sätt hanterade ransonerade varor eller ransoneringskuponger i sitt yrke. Påföljderna för ransoneringsbrotten var i regel dagsböter, vilka oftast låg på två normala dagslöner, varvid det märktes att myndigheterna försökte stävja denna brottslighet. Endast fem personer dömdes till fängelse eller straffarbete under de undersökta åren. Karaktären på brottsligheten var att den främst verkade drivas av vinstintressen eller bekvämlighet.

Seasonal changes in daily metabolic patterns of tegu lizards (Tupinambis merianae) placed in the cold (17 degrees C) and dark

Oxygen consumption rate was measured continuously in young tegu lizards Tupinambis merianae exposed to 4 d at 25 degrees C followed by 7-10 d at 17 degrees C in constant dark at five different times of the year. Under these conditions, circadian rhythms in the rate of oxygen consumption persisted for anywhere from 1 d to the entire 2 wk in different individuals in all seasons except the winter. We also saw a progressive decline in standard oxygen consumption rate (at highly variable rates in different individuals) to a very low rate that was seasonally independent (ranging from 19.1 +/- 6.2 to 27.7 +/- 0.2 mL kg(-1) h(-1) across seasons). Although this degree of reduction appeared to take longer to invoke when starting from higher metabolic rates, tegu lizards reduced their metabolism to the low rates seen in winter dormancy at all times of the year when given sufficient time in the cold and dark. In the spring and summer, tegus reduced their standard metabolic rate (SMR) by 80%-90% over the experimental run, but only roughly 20%-30% of the total fall was due to the reduction in temperature; 70%-80% of the total fall occurred at constant temperature. By autumn, when the starting SMR on the first night at 25 degrees C was already reduced by 59%-81% (early and late autumn, respectively) from peak summer values, virtually all of the fall (63%-83%) in metabolism was due to the reduction in temperature. This suggests that the temperature-independent reduction of metabolism was already in place by autumn before the tegus had entered winter dormancy.

Characterization, inclusion mode, phase-solubility and in vitro release studies of inclusion binary complexes with cyclodextrins and meglumine using sulfamerazine as model drug

In order to investigate the effect on the aqueous solubility and release rate of sulfamerazine (SMR) as model drug, inclusion complexes with beta-cyclodextrin (beta CD), methyl-beta-cyclodextrin (M beta CD) and hydroxypropyl-beta-cyclodextrin (HP beta CD) and a binary system with meglumine (MEG) were developed. The formation of 1: 1 inclusion complexes of SMR with the CDs and a SMR: MEG binary system in solution and in solid state was revealed by phase solubility studies (PSS), nuclear magnetic resonance (NMR), Fourier-transform infrared spectroscopy (FT-IR), thermal analysis and X-Ray diffractometry (XRD) studies. The CDs solubilization of SMR could be improved by ionization of the drug molecule through pH adjustments. The higher apparent stability constants of SMR:CDs complexes were obtained in pH 2.00, demonstrating that CDs present more affinity for the unionized drug. The best approach for SMR solubility enhancement results from the combination of MEG and pH adjustment, with a 34-fold increment and a S-max of 54.8 mg/ml. The permeability of the drug was reduced due to the presence of beta CD, M beta CD, HP beta CD and MEG when used as solubilizers. The study then suggests interesting applications of CD or MEG complexes for modulating the release rate of SMR through semipermeable membranes.

Effects of Lactobacillus Probiotic, P22 Bacteriophage and Salmonella Typhimurium on the Heterophilic Burst Activity of Broiler Chickens

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Solubility and release modulation effect of sulfamerazine ternary complexes with cyclodextrins and meglumine

This study investigated the effect on solubility and release of ternary complexes of sulfamerazine (SMR) with beta-(beta CD), methyl-(M beta CD) and hydroxypropyl-P-cyclodextrin (HP beta CD) using meglumine (MEG) as the ternary component. The combination of MEG with M beta CD resulted the best approach, with an increased effect (29-fold) of the aqueous solubility of SMR. The mode of inclusion was supported by 2D NMR, which indicated that real ternary complexes were formed between SMR, MEG and M beta CD or HP beta CD. Solid state analysis was performed using Fourier-transform infrared spectroscopy (FT IR), differential scanning calorimetry (DSC) and powder X-ray diffraction (XRD), which demonstrated that different interactions occurred among SMR, MEG and M beta CD or HP beta CD in the ternary lyophilized systems. The ternary complexes with beta CD and M beta CD produced an additional retention effect on the release of SMR compared to the corresponding binary complexes, implying that they were clearly superior in terms of solubility and release modulation. (C) 2014 Elsevier B.V. All rights reserved.

Development and characterization of a biocompatible soybean oil-based microemulsion for the delivery of poorly water-soluble drugs

The aim of this work was the development and characterization of a biocompatible microemulsion (ME) containing soybean oil (O), phosphatidylcholine/sodium oleate/Eumulgin®HRE40 as the surfactant mixture (S) and water or buffer solution as the aqueous phase (W), for oral delivery of the poorly water-soluble drugs sulfamerazine (SMR) and indomethacin (INM). A wide range of combinations to obtain clear oil-in-water (o/w) ME was observed from pseudo-ternary phase diagrams, which was greater after the incorporation of both drugs, suggesting that they acted as stabilizers. Drug partition studies indicated a lower affinity of the drugs for the oil domain when they were ionized and with increased temperature, explained by the fact that both drugs were introduced inside the oil domain, determined by nuclear magnetic resonance. High concentrations of SMR and INM were able to be incorporated (22.0 and 62.3 mg/mL, respectively). The ME obtained presented an average droplet size of 100 nm and a negative surface charge. A significant increase in the release of SMR was observed with the ME with the highest percentage of O, because of the solubilizing properties of the ME. Also, a small retention effect was observed for INM, which may be explained by the differences in the partitioning properties of the drugs. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:3535-3543, 2015.

Catalysts for H2 production

The research of new catalysts for the hydrogen production described in this thesis was inserted within a collaboration of Department of Industrial Chemistry and Materials of University of Bologna and Air Liquide (Centre de Recherche Claude-Delorme, Paris). The aim of the work was focused on the study of new materials, active and stable in the hydrogen production from methane, using either a new process, the catalytic partial oxidation (CPO), or a enhanced well-established process, the steam methane reforming (SMR). Two types of catalytic materials were examined: 1) Bulk catalysts, i.e. non-supported materials, in which the active metals (Ni and/or Rh) are stabilized inside oxidic matrix, obtained from perovskite type compounds (PVK) and from hydrotalcite type precursors (HT); 2) Structured catalysts, i.e. catalysts supported on materials having high thermal conductivity (SiC and metallic foams). As regards the catalytic partial oxidation, the effect of the metal (Ni and/or Rh), the role of the metal/matrix ratio and the matrix formulation of innovative catalysts obtained from hydrotalcite type precursors and from perovskites were examined. In addition, about steam reforming process, the study was carried out first on commercial type catalysts, examining the deactivation in industrial conditions, the role of the operating conditions and the activity of different type of catalysts. Then, innovative materials bulk (PVK and HT) and structured catalysts (SiC and metallic foam) were studied and a new preparation method was developed.

Multiple testing in spatial epidemiology: a Bayesian approach

In this work we aim to propose a new approach for preliminary epidemiological studies on Standardized Mortality Ratios (SMR) collected in many spatial regions. A preliminary study on SMRs aims to formulate hypotheses to be investigated via individual epidemiological studies that avoid bias carried on by aggregated analyses. Starting from collecting disease counts and calculating expected disease counts by means of reference population disease rates, in each area an SMR is derived as the MLE under the Poisson assumption on each observation. Such estimators have high standard errors in small areas, i.e. where the expected count is low either because of the low population underlying the area or the rarity of the disease under study. Disease mapping models and other techniques for screening disease rates among the map aiming to detect anomalies and possible high-risk areas have been proposed in literature according to the classic and the Bayesian paradigm. Our proposal is approaching this issue by a decision-oriented method, which focus on multiple testing control, without however leaving the preliminary study perspective that an analysis on SMR indicators is asked to. We implement the control of the FDR, a quantity largely used to address multiple comparisons problems in the eld of microarray data analysis but which is not usually employed in disease mapping. Controlling the FDR means providing an estimate of the FDR for a set of rejected null hypotheses. The small areas issue arises diculties in applying traditional methods for FDR estimation, that are usually based only on the p-values knowledge (Benjamini and Hochberg, 1995; Storey, 2003). Tests evaluated by a traditional p-value provide weak power in small areas, where the expected number of disease cases is small. Moreover tests cannot be assumed as independent when spatial correlation between SMRs is expected, neither they are identical distributed when population underlying the map is heterogeneous. The Bayesian paradigm oers a way to overcome the inappropriateness of p-values based methods. Another peculiarity of the present work is to propose a hierarchical full Bayesian model for FDR estimation in testing many null hypothesis of absence of risk.We will use concepts of Bayesian models for disease mapping, referring in particular to the Besag York and Mollié model (1991) often used in practice for its exible prior assumption on the risks distribution across regions. The borrowing of strength between prior and likelihood typical of a hierarchical Bayesian model takes the advantage of evaluating a singular test (i.e. a test in a singular area) by means of all observations in the map under study, rather than just by means of the singular observation. This allows to improve the power test in small areas and addressing more appropriately the spatial correlation issue that suggests that relative risks are closer in spatially contiguous regions. The proposed model aims to estimate the FDR by means of the MCMC estimated posterior probabilities b i's of the null hypothesis (absence of risk) for each area. An estimate of the expected FDR conditional on data (\FDR) can be calculated in any set of b i's relative to areas declared at high-risk (where thenull hypothesis is rejected) by averaging the b i's themselves. The\FDR can be used to provide an easy decision rule for selecting high-risk areas, i.e. selecting as many as possible areas such that the\FDR is non-lower than a prexed value; we call them\FDR based decision (or selection) rules. The sensitivity and specicity of such rule depend on the accuracy of the FDR estimate, the over-estimation of FDR causing a loss of power and the under-estimation of FDR producing a loss of specicity. Moreover, our model has the interesting feature of still being able to provide an estimate of relative risk values as in the Besag York and Mollié model (1991). A simulation study to evaluate the model performance in FDR estimation accuracy, sensitivity and specificity of the decision rule, and goodness of estimation of relative risks, was set up. We chose a real map from which we generated several spatial scenarios whose counts of disease vary according to the spatial correlation degree, the size areas, the number of areas where the null hypothesis is true and the risk level in the latter areas. In summarizing simulation results we will always consider the FDR estimation in sets constituted by all b i's selected lower than a threshold t. We will show graphs of the\FDR and the true FDR (known by simulation) plotted against a threshold t to assess the FDR estimation. Varying the threshold we can learn which FDR values can be accurately estimated by the practitioner willing to apply the model (by the closeness between\FDR and true FDR). By plotting the calculated sensitivity and specicity (both known by simulation) vs the\FDR we can check the sensitivity and specicity of the corresponding\FDR based decision rules. For investigating the over-smoothing level of relative risk estimates we will compare box-plots of such estimates in high-risk areas (known by simulation), obtained by both our model and the classic Besag York Mollié model. All the summary tools are worked out for all simulated scenarios (in total 54 scenarios). Results show that FDR is well estimated (in the worst case we get an overestimation, hence a conservative FDR control) in small areas, low risk levels and spatially correlated risks scenarios, that are our primary aims. In such scenarios we have good estimates of the FDR for all values less or equal than 0.10. The sensitivity of\FDR based decision rules is generally low but specicity is high. In such scenario the use of\FDR = 0:05 or\FDR = 0:10 based selection rule can be suggested. In cases where the number of true alternative hypotheses (number of true high-risk areas) is small, also FDR = 0:15 values are well estimated, and \FDR = 0:15 based decision rules gains power maintaining an high specicity. On the other hand, in non-small areas and non-small risk level scenarios the FDR is under-estimated unless for very small values of it (much lower than 0.05); this resulting in a loss of specicity of a\FDR = 0:05 based decision rule. In such scenario\FDR = 0:05 or, even worse,\FDR = 0:1 based decision rules cannot be suggested because the true FDR is actually much higher. As regards the relative risk estimation, our model achieves almost the same results of the classic Besag York Molliè model. For this reason, our model is interesting for its ability to perform both the estimation of relative risk values and the FDR control, except for non-small areas and large risk level scenarios. A case of study is nally presented to show how the method can be used in epidemiology.

Studio preliminare di un sistema di monitoraggio e controllo del traffico di superficie nell’area di manovra dell’aeroporto di Fiumicino

Questo lavoro ha analizzato il modulo di localizzazione ed identificazione dei mezzi circolanti in area di manovra e la tecnologia da impiegare per ottenere lo scambio dei dati tra le unità imbarcate ed il server centrale. L’attività è stata svolta in collaborazione con ADR-Aeroporti di Roma, gestore aeroportuale di Fiumicino. L’obiettivo è quello di ottenere, in tempo reale, la conoscenza della posizione e della traiettoria di tutti i mezzi circolanti in area di manovra per creare un sistema automatizzato di monitoraggio, in grado di controllare sia eventuali invasioni delle piste e dei raccordi principali sia rischi di potenziali collisioni tra velivoli e mezzi, garantendo la minima separazione richiesta dalle normative e fornendo agli operatori l’indicazione del rischio rilevato. La prima parte della tesi espone lo scenario europeo per quanto riguarda le tecnologie utilizzate per la sorveglianza di velivoli in area di manovra, la seconda descrive la tecnologia più diffusa e promettente a livello internazionale, proposta per l’aeroporto di Fiumicino, mentre nella terza parte tale tecnologia viene analizzata e sviluppata appunto per lo scenario preso in considerazione.

Severe Accident Simulation of Small Modular Reactors

Since the Three Mile Island Unit 2 (TMI-2), accident in 1979 which led to the meltdown of about one half of the reactor core and to limited releases of radioactive materials to the environment, an important international effort has been made on severe accident research. The present work aims to investigate the behaviour of a Small Modular Reactor during severe accident conditions. In order to perform these analyses, a SMR has been studied for the European reference severe accident analysis code ASTEC, developed by IRSN and GRS. In the thesis will be described in detail the IRIS Small Modular Reactor; the reference reactor chosen to develop the ASTEC input deck. The IRIS model was developed in the framework of a research collaboration with the IRSN development team. In the thesis will be described systematically the creation of the ASTEC IRIS input deck: the nodalization scheme adopted, the solution used to simulate the passive safety systems and the strong interaction between the reactor vessel and the containment. The ASTEC SMR model will be tested against the RELAP-GOTHIC coupled code model, with respect to a Design Basis Accident, to evaluate the capability of the ASTEC code on reproducing correctly the behaviour of the nuclear system. Once the model has been validated, a severe accident scenario will be simulated and the obtained results along with the nuclear system response will be analysed.

Mortality from road traffic accidents in Switzerland: longitudinal and spatial analyses

Road traffic accidents (RTA) are an important cause of premature death. We examined socio-demographic and geographical determinants of RTA mortality in Switzerland by linking 2000 census data to RTA mortality records 2000-2005 (ICD-10 codes V00-V99). Data from 5.5 million residents aged 18-94 years, 1744 study areas, and 1620 RTA deaths were analyzed, including 978 deaths (60.4%) in motor vehicle occupants, 254 (15.7%) in motorcyclists, 107 (6.6%) in cyclists, and 259 (16.0%) in pedestrians. Weibull survival models and Bayesian methods were used to calculate hazard ratios (HR), and standardized mortality ratios (SMR) across study areas. Adjusted HR comparing women with men ranged from 0.04 (95% CI 0.02-0.07) in motorcyclists to 0.43 (95% CI 0.32-0.56) in pedestrians. There was a u-shaped relationship with age in motor vehicle occupants and motorcyclists. In cyclists and pedestrians, mortality increased after age 55 years. Mortality was higher in individuals with primary education (HR 1.53; 95% CI 1.29-1.81), and higher in single (HR 1.24; 95% CI 1.05-1.46), widowed (HR 1.31; 95% CI 1.05-1.65) and divorced individuals (HR 1.62; 95% CI 1.33-1.97), compared to persons with tertiary education or married persons. The association with education was particularly strong for pedestrians (HR 1.87; 95% CI 1.20-2.91). RTA mortality increased with decreasing population density of study areas for motor vehicle occupants (test for trend p<0.0001) and motorcyclists (p=0.0021) but not for cyclists (p=0.39) or pedestrians (p=0.29). SMR standardized for socio-demographic and geographical variables ranged from 82 to 190. Prevention efforts should aim to reduce inequities across socio-demographic and educational groups, and across geographical areas, with interventions targeted at high-risk groups and areas, and different traffic users, including pedestrians.