Systematic review of genetic risk score in coronary heart disease and other diseases

In order to better take advantage of the abundant results from large-scale genomic association studies, investigators are turning to a genetic risk score (GRS) method in order to combine the information from common modest-effect risk alleles into an efficient risk assessment statistic. The statistical properties of these GRSs are poorly understood. As a first step toward a better understanding of GRSs, a systematic analysis of recent investigations using a GRS was undertaken. GRS studies were searched in the areas of coronary heart disease (CHD), cancer, and other common diseases using bibliographic databases and by hand-searching reference lists and journals. Twenty-one independent case-control studies, cohort studies, and simulation studies (12 in CHD, 9 in other diseases) were identified. The underlying statistical assumptions of the GRS using the experience of the Framingham risk score were investigated. Improvements in the construction of a GRS guided by the concept of composite indicators are discussed. The GRS will be a promising risk assessment tool to improve prediction and diagnosis of common diseases.^

Predictors of Contralateral Breast Cancer in BRCA Negative Women

Breast cancer is the most common cancer diagnosis and second leading cause of death in women. Risk factors associated with breast cancer include: increased age, alcohol consumption, cigarette smoking, white race, physical inactivity, benign breast conditions, reproductive and hormonal factors, dietary factors, and family history. Hereditary breast and ovarian cancer syndrome (HBOC) is caused by mutations in the BRCA1 and BRCA2 genes. Women carrying a mutation in these genes are at an increased risk to develop a second breast cancer. Contralateral breast cancer is the most common second primary cancer in patients treated for a first breast cancer. Other risk factors for developing contralateral breast cancer include a strong family history of breast cancer, age of onset of first primary breast cancer, and if the first primary was a lobular carcinoma, which has an increased risk of being bilateral. A retrospective chart review was performed on a select cohort of women in an IRB approved database at MD Anderson Cancer Center. The final cohort contained 572 women who tested negative for a BRCA1 or BRCA2 mutation, had their primary invasive breast cancer diagnosed under the age of 50, and had a BRCAPro risk assessment number over 10%. Of the 572 women, 97 women developed contralateral breast cancer. A number of predictors of contralateral breast cancer were looked at between the two groups. Using univariable Cox Proportional Hazard model, thirteen statistically interesting risk factors were found, defined as having a p-value under 0.2. Multivariable stepwise Cox Proportional Hazard model found four statistically significant variables out of the thirteen found in the univariable analysis. In our study population, the incidence of contralateral breast cancer was 17%. Four statistically significant variables were identified. Undergoing a prophylactic mastectomy was found to reduce the risk of developing contralateral breast cancer, while not having a prophylactic mastecomy, a young age at primary diagnosis, having a positive estrogen receptor status of the primary tumor, and having a family history of breast cancer increased a woman’s risk to develop contralateral breast cancer.

Contribution to the Analysis, Design and Assessment of Compact Antenna Test Ranges At Millimeter Wavelengths - Contribución al Análisis, Diseño y Caracterización de Sistemas de Medida de Antenas en Rango Compacto para Frecuencias Milimétricas

This Doctoral Thesis entitled Contribution to the analysis, design and assessment of compact antenna test ranges at millimeter wavelengths aims to deepen the knowledge of a particular antenna measurement system: the compact range, operating in the frequency bands of millimeter wavelengths. The thesis has been developed at Radiation Group (GR), an antenna laboratory which belongs to the Signals, Systems and Radiocommunications department (SSR), from Technical University of Madrid (UPM). The Radiation Group owns an extensive experience on antenna measurements, running at present four facilities which operate in different configurations: Gregorian compact antenna test range, spherical near field, planar near field and semianechoic arch system. The research work performed in line with this thesis contributes the knowledge of the first measurement configuration at higher frequencies, beyond the microwaves region where Radiation Group features customer-level performance. To reach this high level purpose, a set of scientific tasks were sequentially carried out. Those are succinctly described in the subsequent paragraphs. A first step dealed with the State of Art review. The study of scientific literature dealed with the analysis of measurement practices in compact antenna test ranges in addition with the particularities of millimeter wavelength technologies. Joint study of both fields of knowledge converged, when this measurement facilities are of interest, in a series of technological challenges which become serious bottlenecks at different stages: analysis, design and assessment. Thirdly after the overview study, focus was set on Electromagnetic analysis algorithms. These formulations allow to approach certain electromagnetic features of interest, such as field distribution phase or stray signal analysis of particular structures when they interact with electromagnetic waves sources. Properly operated, a CATR facility features electromagnetic waves collimation optics which are large, in terms of wavelengths. Accordingly, the electromagnetic analysis tasks introduce an extense number of mathematic unknowns which grow with frequency, following different polynomic order laws depending on the used algorithmia. In particular, the optics configuration which was of our interest consisted on the reflection type serrated edge collimator. The analysis of these devices requires a flexible handling of almost arbitrary scattering geometries, becoming this flexibility the nucleus of the algorithmia’s ability to perform the subsequent design tasks. This thesis’ contribution to this field of knowledge consisted on reaching a formulation which was powerful at the same time when dealing with various analysis geometries and computationally speaking. Two algorithmia were developed. While based on the same principle of hybridization, they reached different order Physics performance at the cost of the computational efficiency. Inter-comparison of their CATR design capabilities was performed, reaching both qualitative as well as quantitative conclusions on their scope. In third place, interest was shifted from analysis - design tasks towards range assessment. Millimetre wavelengths imply strict mechanical tolerances and fine setup adjustment. In addition, the large number of unknowns issue already faced in the analysis stage appears as well in the on chamber field probing stage. Natural decrease of dynamic range available by semiconductor millimeter waves sources requires in addition larger integration times at each probing point. These peculiarities increase exponentially the difficulty of performing assessment processes in CATR facilities beyond microwaves. The bottleneck becomes so tight that it compromises the range characterization beyond a certain limit frequency which typically lies on the lowest segment of millimeter wavelength frequencies. However the value of range assessment moves, on the contrary, towards the highest segment. This thesis contributes this technological scenario developing quiet zone probing techniques which achieves substantial data reduction ratii. Collaterally, it increases the robustness of the results to noise, which is a virtual rise of the setup’s available dynamic range. In fourth place, the environmental sensitivity of millimeter wavelengths issue was approached. It is well known the drifts of electromagnetic experiments due to the dependance of the re sults with respect to the surrounding environment. This feature relegates many industrial practices of microwave frequencies to the experimental stage, at millimeter wavelengths. In particular, evolution of the atmosphere within acceptable conditioning bounds redounds in drift phenomena which completely mask the experimental results. The contribution of this thesis on this aspect consists on modeling electrically the indoor atmosphere existing in a CATR, as a function of environmental variables which affect the range’s performance. A simple model was developed, being able to handle high level phenomena, such as feed - probe phase drift as a function of low level magnitudes easy to be sampled: relative humidity and temperature. With this model, environmental compensation can be performed and chamber conditioning is automatically extended towards higher frequencies. Therefore, the purpose of this thesis is to go further into the knowledge of millimetre wavelengths involving compact antenna test ranges. This knowledge is dosified through the sequential stages of a CATR conception, form early low level electromagnetic analysis towards the assessment of an operative facility, stages for each one of which nowadays bottleneck phenomena exist and seriously compromise the antenna measurement practices at millimeter wavelengths.

A Methodological model to assist the optimization and risk management of mining investment decisions

Identifying, quantifying, and minimizing technical risks associated with investment decisions is a key challenge for mineral industry decision makers and investors. However, risk analysis in most bankable mine feasibility studies are based on the stochastic modelling of project “Net Present Value” (NPV)which, in most cases, fails to provide decision makers with a truly comprehensive analysis of risks associated with technical and management uncertainty and, as a result, are of little use for risk management and project optimization. This paper presents a value-chain risk management approach where project risk is evaluated for each step of the project lifecycle, from exploration to mine closure, and risk management is performed as a part of a stepwise value-added optimization process.

A modelling language for the resilience assessment of networked systems of systems

Systems of Systems (SoS) present challenging features and existing tools result often inadequate for their analysis, especially for heteregeneous networked infrastructures. Most accident scenarios in networked systems cannot be addressed by a simplistic black or white (i.e. functioning or failed) approach. Slow deviations from nominal operation conditions may cause degraded behaviours that suddenly end up into unexpected malfunctioning, with large portions of the network affected. In this paper,we present a language for modelling networked SoS. The language makes it possible to represent interdependencies of various natures, e.g. technical, organizational and human. The representation of interdependencies is based on control relationships that exchange physical quantities and related information. The language also makes it possible the identification of accident scenarios, by representing the propagation of failure events throughout the network. The results can be used for assessing the effectiveness of those mechanisms and measures that contribute to the overall resilience, both in qualitative and quantitative terms. The presented modelling methodology is general enough to be applied in combination with already existing system analysis techniques, such as risk assessment, dependability and performance evaluation

Estrategias innovadoras para la gestión del riesgo de sequía en sistemas ganaderos extensivos

La vulnerabilidad de los sistemas ganaderos de pastoreo pone en evidencia la necesidad de herramientas para evaluar y mitigar los efectos de la sequía. El avance en la teledetección ha despertado el interés por explotar potenciales aplicaciones, y está dando lugar a un intenso desarrollo de innovaciones en distintos campos. Una de estas áreas es la gestión del riesgo climático, en donde la utilización de índices de vegetación permite la evaluación de la sequía. En esta investigación, se analiza el impacto de la sequía y se evalúa el potencial de nuevas tecnologías como la teledetección para la gestión del riesgo de sequía en sistemas de ganadería extensiva. Para ello, se desarrollan tres aplicaciones: (i) evaluar el impacto económico de la sequía en una explotación ganadera extensiva de la dehesa de Andalucía, (ii) elaborar mapas de vulnerabilidad a la sequía en pastos de Chile y (iii) diseñar y evaluar el potencial de un seguro indexado para sequía en pastos en la región de Coquimbo en Chile. En la primera aplicación, se diseña un modelo dinámico y estocástico que integra aspectos climáticos, ecológicos, agronómicos y socioeconómicos para evaluar el riesgo de sequía. El modelo simula una explotación ganadera tipo de la dehesa de Andalucía para el período 1999-2010. El método de Análisis Histórico y la simulación de MonteCarlo se utilizan para identificar los principales factores de riesgo de la explotación, entre los que destacan, los periodos de inicios del verano e inicios de invierno. Los resultados muestran la existencia de un desfase temporal entre el riesgo climático y riesgo económico, teniendo este último un periodo de duración más extenso en el tiempo. También, revelan que la intensidad, frecuencia y duración son tres atributos cruciales que determinan el impacto económico de la sequía. La estrategia de reducción de la carga ganadera permite aminorar el riesgo, pero conlleva una disminución en el margen bruto de la explotación. La segunda aplicación está dedicada a la elaboración de mapas de vulnerabilidad a la sequia en pastos de Chile. Para ello, se propone y desarrolla un índice de riesgo económico (IRESP) sencillo de interpretar y replicable, que integra factores de riesgo y estrategias de adaptación para obtener una medida del Valor en Riesgo, es decir, la máxima pérdida esperada en un año con un nivel de significación del 5%.La representación espacial del IRESP pone en evidencia patrones espaciales y diferencias significativas en la vulnerabilidad a la sequía a lo largo de Chile. Además, refleja que la vulnerabilidad no siempre esta correlacionada con el riesgo climático y demuestra la importancia de considerar las estrategias de adaptación. Las medidas de autocorrelación espacial revelan que el riesgo sistémico es considerablemente mayor en el sur que en el resto de zonas. Los resultados demuestran que el IRESP transmite información pertinente y, que los mapas de vulnerabilidad pueden ser una herramienta útil en el diseño de políticas y toma de decisiones para la gestión del riesgo de sequía. La tercera aplicación evalúa el potencial de un seguro indexado para sequía en pastos en la región de Coquimbo en Chile. Para lo cual, se desarrolla un modelo estocástico para estimar la prima actuarialmente justa del seguro y se proponen y evalúan pautas alternativas para mejorar el diseño del contrato. Se aborda el riesgo base, el principal problema de los seguros indexados identificado en la literatura y, que está referido a la correlación imperfecta del índice con las pérdidas de la explotación. Para ello, se sigue un enfoque bayesiano que permite evaluar el impacto en el riesgo base de las pautas de diseño propuestas: i) una zonificación por clúster que considera aspectos espacio-temporales, ii) un período de garantía acotado a los ciclos fenológicos del pasto y iii) umbral de garantía. Los resultados muestran que tanto la zonificación como el periodo de garantía reducen el riesgo base considerablemente. Sin embargo, el umbral de garantía tiene un efecto ambiguo sobre el riesgo base. Por otra parte, la zonificación por clúster contribuye a aminorar el riesgo sistémico que enfrentan las aseguradoras. Estos resultados han puesto de manifiesto que un buen diseño de contrato puede tener un doble dividendo, por un lado aumentar su utilidad y, por otro, reducir el coste del seguro. Un diseño de contrato eficiente junto con los avances en la teledetección y un adecuado marco institucional son los pilares básicos para el buen funcionamiento de un programa de seguro. Las nuevas tecnologías ofrecen un importante potencial para la innovación en la gestión del riesgo climático. Los avances en este campo pueden proporcionar importantes beneficios sociales en los países en desarrollo y regiones vulnerables, donde las herramientas para gestionar eficazmente los riesgos sistémicos como la sequía pueden ser de gran ayuda para el desarrollo. The vulnerability of grazing livestock systems highlights the need for tools to assess and mitigate the adverse impact of drought. The recent and rapid progress in remote sensing has awakened an interest for tapping into potential applications, triggering intensive efforts to develop innovations in a number of spheres. One of these areas is climate risk management, where the use of vegetation indices facilitates assessment of drought. This research analyzes drought impacts and evaluates the potential of new technologies such as remote sensing to manage drought risk in extensive livestock systems. Three essays in drought risk management are developed to: (i) assess the economic impact of drought on a livestock farm in the Andalusian Dehesa, (ii) build drought vulnerability maps in Chilean grazing lands, and (iii) design and evaluate the potential of an index insurance policy to address the risk of drought in grazing lands in Coquimbo, Chile. In the first essay, a dynamic and stochastic farm model is designed combining climate, agronomic, socio-economic and ecological aspects to assess drought risk. The model is developed to simulate a representative livestock farm in the Dehesa of Andalusia for the time period 1999-2010. Burn analysis and MonteCarlo simulation methods are used to identify the significance of various risk sources at the farm. Most notably, early summer and early winter are identified as periods of peak risk. Moreover, there is a significant time lag between climate and economic risk and this later last longer than the former. It is shown that intensity, frequency and duration of the drought are three crucial attributes that shape the economic impact of drought. Sensitivity analysis is conducted to assess the sustainability of farm management strategies and demonstrates that lowering the stocking rate reduces farmer exposure to drought risk but entails a reduction in the expected gross margin. The second essay, mapping drought vulnerability in Chilean grazing lands, proposes and builds an index of economic risk (IRESP) that is replicable and simple to interpret. This methodology integrates risk factors and adaptation strategies to deliver information on Value at Risk, maximum expected losses at 5% significance level. Mapping IRESP provides evidence about spatial patterns and significant differences in drought vulnerability across Chilean grazing lands. Spatial autocorrelation measures reveal that systemic risk is considerably larger in the South as compared to Northern or Central Regions. Furthermore, it is shown that vulnerability is not necessarily correlated with climate risk and that adaptation strategies do matter. These results show that IRESP conveys relevant information and that vulnerability maps may be useful tools to assess policy design and decision-making in drought risk management. The third essay develops a stochastic model to estimate the actuarially fair premium and evaluates the potential of an indexed insurance policy to manage drought risk in Coquimbo, a relevant livestock farming region of Chile. Basis risk refers to the imperfect correlation of the index and farmer loses and is identified in the literature as a main limitation of index insurance. A Bayesian approach is proposed to assess the impact on basis risk of alternative guidelines in contract design: i) A cluster zoning that considers space-time aspects, ii) A guarantee period bounded to fit phenological cycles, and iii) the triggering index threshold. Results show that both the proposed zoning and guarantee period considerably reduces basis risk. However, the triggering index threshold has an ambiguous effect on basis risk. On the other hand, cluster zoning contributes to ameliorate systemic risk faced by the insurer. These results highlighted that adequate contract design is important and may result in double dividend. On the one hand, increasing farmers’ utility and, secondly, reducing the cost of insurance. An efficient contract design coupled with advances in remote sensing and an appropriate institutional framework are the basis for an efficient operation of an insurance program. The new technologies offer significant potential for innovation in climate risk managements. Progress in this field is capturing increasing attention and may provide important social gains in developing countries and vulnerable regions where the tools to efficiently manage systemic risks, such as drought, may be a means to foster development.

Efficient algorithms for dynamic probabilistic safety assessment. An application to convex damage domain.

The design of nuclear power plant has to follow a number of regulations aimed at limiting the risks inherent in this type of installation. The goal is to prevent and to limit the consequences of any possible incident that might threaten the public or the environment. To verify that the safety requirements are met a safety assessment process is followed. Safety analysis is as key component of a safety assessment, which incorporates both probabilistic and deterministic approaches. The deterministic approach attempts to ensure that the various situations, and in particular accidents, that are considered to be plausible, have been taken into account, and that the monitoring systems and engineered safety and safeguard systems will be capable of ensuring the safety goals. On the other hand, probabilistic safety analysis tries to demonstrate that the safety requirements are met for potential accidents both within and beyond the design basis, thus identifying vulnerabilities not necessarily accessible through deterministic safety analysis alone. Probabilistic safety assessment (PSA) methodology is widely used in the nuclear industry and is especially effective in comprehensive assessment of the measures needed to prevent accidents with small probability but severe consequences. Still, the trend towards a risk informed regulation (RIR) demanded a more extended use of risk assessment techniques with a significant need to further extend PSA’s scope and quality. Here is where the theory of stimulated dynamics (TSD) intervenes, as it is the mathematical foundation of the integrated safety assessment (ISA) methodology developed by the CSN(Consejo de Seguridad Nuclear) branch of Modelling and Simulation (MOSI). Such methodology attempts to extend classical PSA including accident dynamic analysis, an assessment of the damage associated to the transients and a computation of the damage frequency. The application of this ISA methodology requires a computational framework called SCAIS (Simulation Code System for Integrated Safety Assessment). SCAIS provides accident dynamic analysis support through simulation of nuclear accident sequences and operating procedures. Furthermore, it includes probabilistic quantification of fault trees and sequences; and integration and statistic treatment of risk metrics. SCAIS comprehensively implies an intensive use of code coupling techniques to join typical thermal hydraulic analysis, severe accident and probability calculation codes. The integration of accident simulation in the risk assessment process and thus requiring the use of complex nuclear plant models is what makes it so powerful, yet at the cost of an enormous increase in complexity. As the complexity of the process is primarily focused on such accident simulation codes, the question of whether it is possible to reduce the number of required simulation arises, which will be the focus of the present work. This document presents the work done on the investigation of more efficient techniques applied to the process of risk assessment inside the mentioned ISA methodology. Therefore such techniques will have the primary goal of decreasing the number of simulation needed for an adequate estimation of the damage probability. As the methodology and tools are relatively recent, there is not much work done inside this line of investigation, making it a quite difficult but necessary task, and because of time limitations the scope of the work had to be reduced. Therefore, some assumptions were made to work in simplified scenarios best suited for an initial approximation to the problem. The following section tries to explain in detail the process followed to design and test the developed techniques. Then, the next section introduces the general concepts and formulae of the TSD theory which are at the core of the risk assessment process. Afterwards a description of the simulation framework requirements and design is given. Followed by an introduction to the developed techniques, giving full detail of its mathematical background and its procedures. Later, the test case used is described and result from the application of the techniques is shown. Finally the conclusions are presented and future lines of work are exposed.

Spatial and temporal variations of trace element distribution in soils and street dust of an industrial town in NW Spain: 15 years of study

Extensive spatial and temporal surveys, over 15 years, have been conducted in soil in urban parks and street dusts in one of the most polluted cities in western Europe, Avilés (NW Spain). The first survey was carried out in 1996, and since then monitoring has been undertaken every five years. Whilst the sampling site is a relatively small town, industrial activities (mainly the steel industry and Zn and Al metallurgy) and other less significant urban sources, such as traffic, strongly affect the load of heavy metals in the urban aerosol. Elemental tracers have been used to characterise the influence of these sources on the composition of soil and dust. Although PM10 has decreased over these years as a result of environmental measures undertaken in the city, some of the “industrial” elements still remain in concentrations of concern for example, up to 4.6% and 0.5% of Zn in dust and soil, respectively. Spatial trends in metals such as Zn and Cd clearly reflect sources from the processing industries. The concentrations of these elements across Europe have reduced over time, however the most recent results from Avilés revealed an upward trend in concentration for Zn, Cd, Hg and As. A risk assessment of the soil highlighted As as an element of concern since its cancer risk in adults was more than double the value above which regulatory agencies deem it to be unacceptable. If children were considered to be the receptors, then the risk nearly doubles from this element.

Assessment of damage domains of the High-Temperature Engineering Test Reactor (HTTR)

This paper presents an assessment analysis of damage domains of the 30 MWth prototype High-Temperature Engineering Test Reactor (HTTR) operated by the Japan Atomic Energy Agency (JAEA). For this purpose, an in-house deterministic risk assessment computational tool was developed based on the Theory of Stimulated Dynamics (TSD). To illustrate the methodology and applicability of the developed modelling approach, assessment results of a control rod (CR) withdrawal accident during subcritical conditions are presented and compared with those obtained by the JAEA.

Desarrollo de un Modelo de Gestión de Riesgos Operacionales basado en las Directrices del Comité de Basilea

La presente investigación tiene como objetivo principal diseñar un Modelo de Gestión de Riesgos Operacionales (MGRO) según las Directrices de los Acuerdos II y III del Comité de Supervisión Bancaria de Basilea del Banco de Pagos Internacionales (CSBB-BPI). Se considera importante realizar un estudio sobre este tema dado que son los riesgos operacionales (OpR) los responsables en gran medida de las últimas crisis financieras mundiales y por la dificultad para detectarlos en las organizaciones. Se ha planteado un modelo de gestión subdividido en dos vías de influencias. La primera acoge el paradigma holístico en el que se considera que hay múltiples maneras de percibir un proceso cíclico, así como las herramientas para observar, conocer y entender el objeto o sujeto percibido. La segunda vía la representa el paradigma totalizante, en el que se obtienen datos tanto cualitativos como cuantitativos, los cuales son complementarios entre si. Por otra parte, este trabajo plantea el diseño de un programa informático de OpR Cualitativo, que ha sido diseñado para determinar la raíz de los riesgos en las organizaciones y su Valor en Riesgo Operacional (OpVaR) basado en el método del indicador básico. Aplicando el ciclo holístico al caso de estudio, se obtuvo el siguiente diseño de investigación: no experimental, univariable, transversal descriptiva, contemporánea, retrospectiva, de fuente mixta, cualitativa (fenomenológica y etnográfica) y cuantitativa (descriptiva y analítica). La toma de decisiones y recolección de información se realizó en dos fases en la unidad de estudio. En la primera se tomó en cuenta la totalidad de la empresa Corpoelec-EDELCA, en la que se presentó un universo estadístico de 4271 personas, una población de 2390 personas y una unidad de muestreo de 87 personas. Se repitió el proceso en una segunda fase, para la Central Hidroeléctrica Simón Bolívar, y se determinó un segundo universo estadístico de 300 trabajadores, una población de 191 personas y una muestra de 58 profesionales. Como fuentes de recolección de información se utilizaron fuentes primarias y secundarias. Para recabar la información primaria se realizaron observaciones directas, dos encuestas para detectar las áreas y procesos con mayor nivel de riesgos y se diseñó un cuestionario combinado con otra encuesta (ad hoc) para establecer las estimaciones de frecuencia y severidad de pérdidas operacionales. La información de fuentes secundarias se extrajo de las bases de datos de Corpoelec-EDELCA, de la IEA, del Banco Mundial, del CSBB-BPI, de la UPM y de la UC at Berkeley, entre otras. Se establecieron las distribuciones de frecuencia y de severidad de pérdidas operacionales como las variables independientes y el OpVaR como la variable dependiente. No se realizó ningún tipo de seguimiento o control a las variables bajo análisis, ya que se consideraron estas para un instante especifico y solo se determinan con la finalidad de establecer la existencia y valoración puntual de los OpR en la unidad de estudio. El análisis cualitativo planteado en el MGRO, permitió detectar que en la unidad de investigación, el 67% de los OpR detectados provienen de dos fuentes principales: procesos (32%) y eventos externos (35%). Adicionalmente, la validación del MGRO en Corpoelec-EDELCA, permitió detectar que el 63% de los OpR en la organización provienen de tres categorías principales, siendo los fraudes externos los presentes con mayor regularidad y severidad de pérdidas en la organización. La exposición al riesgo se determinó fundamentándose en la adaptación del concepto de OpVaR que generalmente se utiliza para series temporales y que en el caso de estudio presenta la primicia de aplicarlo a datos cualitativos transformados con la escala Likert. La posibilidad de utilizar distribuciones de probabilidad típicas para datos cuantitativos en distribuciones de frecuencia y severidad de pérdidas con datos de origen cualitativo fueron analizadas. Para el 64% de los OpR estudiados se obtuvo que la frecuencia tiene un comportamiento semejante al de la distribución de probabilidad de Poisson y en un 55% de los casos para la severidad de pérdidas se obtuvo a las log-normal como las distribuciones de probabilidad más comunes, con lo que se concluyó que los enfoques sugeridos por el BCBS-BIS para series de tiempo son aplicables a los datos cualitativos. Obtenidas las distribuciones de frecuencia y severidad de pérdidas, se convolucionaron estas implementando el método de Montecarlo, con lo que se obtuvieron los enfoques de distribuciones de pérdidas (LDA) para cada uno de los OpR. El OpVaR se dedujo como lo sugiere el CSBB-BPI del percentil 99,9 o 99% de cada una de las LDA, obteniéndose que los OpR presentan un comportamiento similar al sistema financiero, resultando como los de mayor peligrosidad los que se ubican con baja frecuencia y alto impacto, por su dificultad para ser detectados y monitoreados. Finalmente, se considera que el MGRO permitirá a los agentes del mercado y sus grupos de interés conocer con efectividad, fiabilidad y eficiencia el status de sus entidades, lo que reducirá la incertidumbre de sus inversiones y les permitirá establecer una nueva cultura de gestión en sus organizaciones. ABSTRACT This research has as main objective the design of a Model for Operational Risk Management (MORM) according to the guidelines of Accords II and III of the Basel Committee on Banking Supervision of the Bank for International Settlements (BCBS- BIS). It is considered important to conduct a study on this issue since operational risks (OpR) are largely responsible for the recent world financial crisis and due to the difficulty in detecting them in organizations. A management model has been designed which is divided into two way of influences. The first supports the holistic paradigm in which it is considered that there are multiple ways of perceiving a cyclical process and contains the tools to observe, know and understand the subject or object perceived. The second way is the totalizing paradigm, in which both qualitative and quantitative data are obtained, which are complementary to each other. Moreover, this paper presents the design of qualitative OpR software which is designed to determine the root of risks in organizations and their Operational Value at Risk (OpVaR) based on the basic indicator approach. Applying the holistic cycle to the case study, the following research design was obtained: non- experimental, univariate, descriptive cross-sectional, contemporary, retrospective, mixed-source, qualitative (phenomenological and ethnographic) and quantitative (descriptive and analytical). Decision making and data collection was conducted in two phases in the study unit. The first took into account the totality of the Corpoelec-EDELCA company, which presented a statistical universe of 4271 individuals, a population of 2390 individuals and a sampling unit of 87 individuals. The process was repeated in a second phase to the Simon Bolivar Hydroelectric Power Plant, and a second statistical universe of 300 workers, a population of 191 people and a sample of 58 professionals was determined. As sources of information gathering primary and secondary sources were used. To obtain the primary information direct observations were conducted and two surveys to identify the areas and processes with higher risks were designed. A questionnaire was combined with an ad hoc survey to establish estimates of frequency and severity of operational losses was also considered. The secondary information was extracted from the databases of Corpoelec-EDELCA, IEA, the World Bank, the BCBS-BIS, UPM and UC at Berkeley, among others. The operational loss frequency distributions and the operational loss severity distributions were established as the independent variables and OpVaR as the dependent variable. No monitoring or control of the variables under analysis was performed, as these were considered for a specific time and are determined only for the purpose of establishing the existence and timely assessment of the OpR in the study unit. Qualitative analysis raised in the MORM made it possible to detect that in the research unit, 67% of detected OpR come from two main sources: external processes (32%) and external events (35%). Additionally, validation of the MORM in Corpoelec-EDELCA, enabled to estimate that 63% of OpR in the organization come from three main categories, with external fraud being present more regularly and greater severity of losses in the organization. Risk exposure is determined basing on adapting the concept of OpVaR generally used for time series and in the case study it presents the advantage of applying it to qualitative data transformed with the Likert scale. The possibility of using typical probability distributions for quantitative data in loss frequency and loss severity distributions with data of qualitative origin were analyzed. For the 64% of OpR studied it was found that the frequency has a similar behavior to that of the Poisson probability distribution and 55% of the cases for loss severity it was found that the log-normal were the most common probability distributions. It was concluded that the approach suggested by the BCBS-BIS for time series can be applied to qualitative data. Once obtained the distributions of loss frequency and severity have been obtained they were subjected to convolution implementing the Monte Carlo method. Thus the loss distribution approaches (LDA) were obtained for each of the OpR. The OpVaR was derived as suggested by the BCBS-BIS 99.9 percentile or 99% of each of the LDA. It was determined that the OpR exhibits a similar behavior to the financial system, being the most dangerous those with low frequency and high impact for their difficulty in being detected and monitored. Finally, it is considered that the MORM will allows market players and their stakeholders to know with effectiveness, efficiency and reliability the status of their entities, which will reduce the uncertainty of their investments and enable them to establish a new management culture in their organizations.

A aplicação do Gerenciamento de Riscos nas PMEs na cidade de São Bernardo do Campo

Este estudo analisa a utilização do gerenciamento de riscos em algumas Empresas de Pequeno e Médio Porte (PMEs) na cidade de São Bernardo do Campo. A análise do risco empresarial possui uma crescente importância e ela pode contribuir fortemente para a continuidade dos negócios. A capacidade para gerenciar os riscos do negócio em relação ás inevitáveis incertezas e com uma valorização futura dos resultados é um fator substancial de vantagem competitiva. Este processo de geração de valor providencia a disciplina e ferramentas de administração dos riscos empresariais permitindo a criação de valor para sua organização. As Metodologias de Análise de Risco, em sua maioria, são aplicadas para grandes corporações. Uma das motivações desse trabalho é verificar o grau de utilidade dessas metodologias para as empresas PMEs escolhidas para a pesquisa em São Bernardo do Campo. O estudo é desenvolvido por meio de pesquisas bibliográficas e pesquisa exploratória nas empresas escolhidas. Após as pesquisas, foi feita uma análise qualitativa utilizando o método de estudo de casos. Finalmente, conclui-se que as empresas pesquisadas de São Bernardo do Campo, podem obter vantagens significativas ao implantar metodologias de gerenciamento de risco. Todas as empresas pesquisadas possuem mais de dez anos e consideram importante controlar a continuidade de seus negócios.

A aplicação do Gerenciamento de Riscos nas PMEs na cidade de São Bernardo do Campo

Este estudo analisa a utilização do gerenciamento de riscos em algumas Empresas de Pequeno e Médio Porte (PMEs) na cidade de São Bernardo do Campo. A análise do risco empresarial possui uma crescente importância e ela pode contribuir fortemente para a continuidade dos negócios. A capacidade para gerenciar os riscos do negócio em relação ás inevitáveis incertezas e com uma valorização futura dos resultados é um fator substancial de vantagem competitiva. Este processo de geração de valor providencia a disciplina e ferramentas de administração dos riscos empresariais permitindo a criação de valor para sua organização. As Metodologias de Análise de Risco, em sua maioria, são aplicadas para grandes corporações. Uma das motivações desse trabalho é verificar o grau de utilidade dessas metodologias para as empresas PMEs escolhidas para a pesquisa em São Bernardo do Campo. O estudo é desenvolvido por meio de pesquisas bibliográficas e pesquisa exploratória nas empresas escolhidas. Após as pesquisas, foi feita uma análise qualitativa utilizando o método de estudo de casos. Finalmente, conclui-se que as empresas pesquisadas de São Bernardo do Campo, podem obter vantagens significativas ao implantar metodologias de gerenciamento de risco. Todas as empresas pesquisadas possuem mais de dez anos e consideram importante controlar a continuidade de seus negócios.

UMA ANÁLISE DA RELAÇÃO ENTRE VARIÁVEIS MACROECONÔMICAS E O COMPORTAMENTO DAS AÇÕES DE MAIOR LIQUIDEZ DO ÍNDICE IBOVESPA

As ações de maior liquidez do índice IBOVESPA, refletem o comportamento das ações de um modo geral, bem como a relação das variáveis macroeconômicas em seu comportamento e estão entre as mais negociadas no mercado de capitais brasileiro. Desta forma, pode-se entender que há reflexos de fatores que impactam as empresas de maior liquidez que definem o comportamento das variáveis macroeconômicas e que o inverso também é uma verdade, oscilações nos fatores macroeconômicos também afetam as ações de maior liquidez, como IPCA, PIB, SELIC e Taxa de Câmbio. O estudo propõe uma análise da relação existente entre variáveis macroeconômicas e o comportamento das ações de maior liquidez do índice IBOVESPA, corroborando com estudos que buscam entender a influência de fatores macroeconômicos sobre o preço de ações e contribuindo empiricamente com a formação de portfólios de investimento. O trabalho abrangeu o período de 2008 a 2014. Os resultados concluíram que a formação de carteiras, visando a proteção do capital investido, deve conter ativos com correlação negativa em relação às variáveis estudadas, o que torna possível a composição de uma carteira com risco reduzido.

Intermediate hosts of Toxoplasma gondii and food safety:epidemiology, genetics and parasite survival in meat-producing animals in Italy

Toxoplasma gondii is a coccidian parasite with a global distribution. The definitive host is the cat (and other felids). All warm-blooded animals can act as intermediate hosts, including humans. Sexual reproduction (gametogony) takes place in the final host and oocysts are released in the environment, where they then sporulate to become infective. In intermediate hosts the cycle is extra-intestinal and results in the formation of tachyzoites and bradyzoites. Tachyzoites represent the invasive and proliferative stage and on entering a cell it multiplies asexually by endodyogeny. Bradyzoites within tissue cysts are the latent form. T. gondii is a food-borne parasite causing toxoplasmosis, which can occur in both animals and humans. Infection in humans is asymptomatic in more than 80% of cases in Europe and North-America. In the remaining cases patients present fever, cervical lymphadenopathy and other non-specific clinical signs. Nevertheless, toxoplasmosis is life threatening if it occurs in immunocompromised subjects. The main organs involved are brain (toxoplasmic encephalitis), heart (myocarditis), lungs (pulmonary toxoplasmosis), eyes, pancreas and parasite can be isolated from these tissues. Another aspect is congenital toxoplasmosis that may occur in pregnant women and the severity of the consequences depends on the stage of pregnancy when maternal infection occurs. Acute toxoplasmosis in developing foetuses may result in blindness, deformation, mental retardation or even death. The European Food Safety Authority (EFSA), in recent reports on zoonoses, highlighted that an increasing numbers of animals resulted infected with T. gondii in EU (reported by the European Member States for pigs, sheep, goats, hunted wild boar and hunted deer, in 2011 and 2012). In addition, high prevalence values have been detected in cats, cattle and dogs, as well as several other animal species, indicating the wide distribution of the parasite among different animal and wildlife species. The main route of transmission is consumption of food and water contaminated with sporulated oocysts. However, infection through the ingestion of meat contaminated with tissue cysts is frequent. Finally, although less frequent, other food products contaminated with tachyzoites such as milk, may also pose a risk. The importance of this parasite as a risk for human health was recently highlighted by EFSA’s opinion on modernization of meat inspection, where Toxoplasma gondii was identified as a relevant hazard to be addressed in revised meat inspection systems for pigs, sheep, goats, farmed wild boar and farmed deer (Call for proposals -GP/EFSA/BIOHAZ/2013/01). The risk of infection is more highly associated to animals reared outside, also in free-range or organic farms, where biohazard measure are less strict than in large scale, industrial farms. Here, animals are kept under strict biosecurity measures, including barriers, which inhibit access by cats, thus making soil contamination by oocysts nearly impossible. A growing demand by the consumer for organic products, coming from free-range livestock, in respect of animal-welfare, and the desire for the best quality of derived products, have all led to an increase in the farming of free-range animals. The risk of Toxoplasma gondii infection increases when animals have access to environment and the absence of data in Italy, together with need for in depth study of both the prevalence and genotypes of Toxoplasma gondii present in our country were the main reasons for the development of this thesis project. A total of 152 animals have been analyzed, including 21 free-range pigs (Suino Nero race), 24 transhumant Cornigliese sheep, 77 free-range chickens and 21 wild animals. Serology (on meat juice) and identification of T. gondii DNA through PCR was performed on all samples, except for wild animals (no serology). An in-vitro test was also applied with the aim to find an alternative and valid method to bioassay, actually the gold standard. Meat samples were digested and seeded onto Vero cells, checked every day and a RT-PCR protocol was used to determine an eventual increase in the amount of DNA, demonstrating the viability of the parasite. Several samples were alos genetically characterized using a PCR-RFLP protocol to define the major genotypes diffused in the geographical area studied. Within the context of a project promoted by Istituto Zooprofilattico of Pavia and Brescia (Italy), experimentally infected pigs were also analyzed. One of the aims was to verify if the production process of cured “Prosciutto di Parma” is able to kill the parasite. Our contribution included the digestion and seeding of homogenates on Vero cells and applying the Elisa test on meat juice. This thesis project has highlighted widespread diffusion of T. gondii in the geographical area taken into account. Pigs, sheep, chickens and wild animals showed high prevalence of infection. The data obtained with serology were 95.2%, 70.8%, 36.4%, respectively, indicating the spread of the parasite among numerous animal species. For wild animals, the average value of parasite infection determined through PCR was 44.8%. Meat juice serology appears to be a very useful, rapid and sensitive method for screening carcasses at slaughterhouse and for marketing “Toxo-free” meat. The results obtained on fresh pork meat (derived from experimentally infected pigs) before (on serum) and after (on meat juice) slaughter showed a good concordance. The free-range farming put in evidence a marked risk for meat-producing animals and as a consequence also for the consumer. Genotyping revealed the diffusion of Type-II and in a lower percentage of Type-III. In pigs is predominant the Type-II profile, while in wildlife is more diffused a Type-III and mixed profiles (mainly Type-II/III). The mixed genotypes (Type-II/III) could be explained by the presence of mixed infections. Free-range farming and the contact with wildlife could facilitate the spread of the parasite and the generation of new and atypical strains, with unknown consequences on human health. The curing process employed in this study appears to produce hams that do not pose a serious concern to human health and therefore could be marketed and consumed without significant health risk. Little is known about the diffusion and genotypes of T. gondii in wild animals; further studies on the way in which new and mixed genotypes may be introduced into the domestic cycle should be very interesting, also with the use of NGS techniques, more rapid and sensitive than PCR-RFLP. Furthermore wildlife can become a valuable indicator of environmental contamination with T. gondii oocysts. Other future perspectives regarding pigs include the expansion of the number of free-range animals and farms and for Cornigliese sheep the evaluation of other food products as raw milk and cheeses. It should be interesting to proceed with the validation of an ELISA test for infection in chickens, using both serum and meat juice on a larger number of animals and the same should be done also for wildlife (at the moment no ELISA tests are available and MAT is the reference method for them). Results related to Parma ham do not suggest a concerning risk for consumers. However, further studies are needed to complete the risk assessment and the analysis of other products cured using technological processes other than those investigated in the present study. For example, it could be interesting to analyze products such as salami, produced with pig meat all over the Italian country, with very different recipes, also in domestic and rural contexts, characterized by a very short period of curing (1 to 6 months). Toxoplasma gondii is one of the most diffuse food-borne parasites globally. Public health safety, improved animal production and protection of endangered livestock species are all important goals of research into reliable diagnostic tools for this infection. Future studies into the epidemiology, parasite survival and genotypes of T. gondii in meat producing animals should continue to be a research priority.