Familial Hypercholesterolemia in Portugal: analysis of biomarkers

Aims of the study: 1) Cardiovascular risk assessment of a cohort of children with a clinical diagnosis of FH; 2) Identification of biomarkers to distinguish between monogenic and polygenic/environmental dyslipidemia in clinical settings; 3) Clinical criteria improvement to identify FH children.

Functional genomics of Familial Hypercholesterolemia

Main Aim of the study: to identify the cause of the dyslipidaemia in patients with a clinical phenotype of Familial Hypercholesterolaemia (FH).

Functional genomics of Familial Hypercholesterolemia

Main aim of the Portuguese Family Hypercholesterolemia study: to identify the cause of the dyslipidaemia in patients with a clinical phenotype of Familial Hypercholesterolaemia (FH).

Classificação e Análise de Fatores Humanos nos Acidentes e Incidentes na Força Aérea

A aviação, enquanto elemento crucial na aproximação entre culturas, povos e esforços de guerra, atravessa atualmente um período de elevada valorização e consequente evolução da sua componente de Segurança de Voo (SV). A larga maioria das ocorrências aeronáuticas resultam de falhas humanas, isto é, são grandemente oriundas de erros na interface homem-máquina. Tal facto, alerta para a pertinência da criação, e posterior aplicação, de um sistema cada vez mais eficaz de análise e classificação das causas das ocorrências. A Força Aérea (FA) recorre, desde 1999, ao anexo F do RFA 330-1 para proceder à classificação das causas das ocorrências, o qual, face às necessidades atuais – frequentemente aventadas por quem proximamente lida com esta área – poderá beneficiar com um trabalho periódico de estudo e reformulação, catalisador de um processo de análise e de classificação cada vez mais ajustado às exigências da realidade envolvente. A presente dissertação propõe uma abordagem de classificação e análise de Fatores Humanos (FH) adaptada ao contexto da FA, a qual se convencionou designar por abordagem HFACS adaptada à FA. Para tal, utilizou-se uma metodologia essencialmente qualitativa, recorrendo a entrevistas semiestruturadas a Oficiais e Civis da FA com experiência direta e indireta nesta área. A abordagem HFACS adaptada, neste estudo, à FA, revelou-se como uma resposta adequada às necessidades atuais, quer em termos de pressupostos teórico-práticos, quer no plano fundamentalmente prático, também aqui operacionalizado através do seu teste a quatro relatórios de ocorrências reais.

Konstruierte Landschaften

Die zentrale Forschungsaufgabe der Dissertation „Die Landschaften der Inseln Rügen, Hiddensee und Vilm in ihrer Bedeutung für die Landschaftsmalerei zwischen dem 18. und 21.Jahrhundert als Beitrag für die Landschaftsplanung“ ist die Beweisführung einer persistenten Landschaftsmalerei mit einem Fokus auf bestimmte Orte und Landschaftstypologien. Ferner war bisher unbeantwortet, ob es in dem Zeitraum vom Aufkommen der ersten Landschaftsgemälde im 18. Jahrhundert bis zur Gegenwart zu einer Verschiebung des künstlerischen Interesses für bestimmte Landschaftsausschnitte gekommen ist.Zudem soll die Frage beantwortet werden, ob sich im Laufe der Epochen Motive änderten und es Gründe für die Auswahl und Darstellung der spezifisch wahrgenommenen Landschaft gab. In dieser Arbeit wird der Suche nach einer kollektiven Landschaft nachgegangen. In Anlehnung an Konzepte zum kollektiven Gedächtnis von Maurice Halbwachs (1939) wird es neben individuellen Deutungsmustern auch kulturelle Bedingungen und/oder Übereinkünfte geben, weshalb bestimmte Motive und Orte von den Landschaftsmalern bevorzugt wurden. Bevorzugung wird hier verstanden, als die bewusste Auseinandersetzung im künstlerischen Schaffen mit Objekten im Raum, die in ihrer Gesamtheit als Landschaft wahrgenommen werden. Auf den Inseln Rügen, Hiddensee und Vilm konnten über 60 Malerorte nachgewiesen werden, die persistent Grundlage für die Erschaffung von Landschaftsgemälden gaben. Diese "malerischen" Orte sollten in der kommunalen Landschaftsplanung mehr Berücksichtigung finden.

The impact and control of malignant catarrhal fever in Tanzania

Malignant Catarrhal Fever (MCF), an often-lethal infectious disease, presents as a variable complex of lesions in susceptible ungulate species. The disease is caused by a -herpesvirus following transmission from an inapparent carrier host. Two major epidemiological forms exist: wildebeest-associated MCF (WA-MCF), in which the virus is transmitted to susceptible species by wildebeest calves less than approximately four months of age, and sheepassociated MCF (SA-MCF) in which the virus is spread by sheep (primarily adolescents). Due to the lack of an in-vitro propagation system for the causative agent of the more economically significant SA-MCF, and with the expectation that cross-protective immunity may be provided, vaccine development has focused on the more easily propagated alcelaphine herpesvirus-1 (AlHV-1) that causes WA-MCF. In 2008 a direct viral challenge trial showed that a novel vaccine, employing an attenuated AlHV-1 (atAlHV-1) `C5000 virus strain, protected British Friesian-Holstein (FH) cattle against an intranasal challenge with virulent AlHV-1 `C5000 virus. For cattle keeping people living near wildebeest calving areas in sub-Saharan Africa an effective vaccine would have value as it would release them from the costly annual disease avoidance strategy of having to move their herds away from the oncoming wildebeest. On the other hand, an effective vaccine will release herd owners from the need to avoid MCF, allowing them to graze their cattle alongside wildebeest on the highly nutritious pastures of the calving areas. As such conservationists have raised concerns that the development of a vaccine might lead to detrimental grazing competition. The principle objective of this study was to test the novel vaccine on Tanzanian shorthorn zebu cross cattle (SZC).We did this firstly using a natural challenge field trial (Chapter Two) which demonstrated that immunisation with the atAlHV-1 vaccine was well tolerated and induced an oro-nasopharyngeal AlHV-1-specific and -neutralising antibody response. This resulted in an immunity in SZC cattle that was partially protective and reduced naturally transmitted infection by 56%. We also demonstrated that non-fatal infections occurred with a much higher frequency than previously thought. Because the calculated efficacy of the vaccine was less than that seen in British FH cattle we wanted to determine whether host factors, particular to SZC cattle, had impacted the outcomes of the field trial. To do this we repeated the 2008 direct viral challenge trial using SZC cattle (Chapter Four). During this trial we also investigated whether the recombinant bacterial flagellin monomer (FliC), when used as an adjuvant, might improve the vaccine’s efficacy. The findings from this trial indicated that direct challenge with pathogenic AlHV-1 is effective at inducing MCF in SZC cattle and that FliC is not an appropriate adjuvant for this vaccine. Furthermore, with less control group cattle dying of MCF than expected we speculate that SZC cattle may have a degree of resistance to MCF that affords them protection from infection and developing fatal disease. In Chapter Three we investigated aspects of the epidemiology of MCF, specifically whether wildebeest placenta, long implicated by Maasai cattle owners as a source of MCF, might play a role in viral transmission. Additionally, through comparative sequence analysis, at two specific genes (A9.5 and ORF50) of wild-type and atAlHV-1, we investigated whether the `C5000 strain, the source of which was taken from Africa more than 40 years ago, was appropriate for vaccine development. The detection of AlHV-1 virus in approximately 50% of placentae indicated that infection can occur in-utero and that this tissue might play a role in disease transmission. And, despite describing three new alleles of the A9.5 gene (supporting previous evidence that this gene is polymorphic and encodes a secretory protein with interleukin-4 as the major homologue), the observation that the most frequently detected haplotypes, in both wild-type and attenuated AlHV-1, were identical suggests that AlHV-1 has a slow molecular clock and that the attenuated strain was appropriate for vaccine development. In Chapter Five we present the first quantitative assessment of the annual MCF avoidance costs that Maasai pastoralists incur. In particular we estimated that as a result of MCF avoidance 64% of the total daily milk yield during the MCF season was not available to be used by the 81% of the family unit remaining at the permanent boma. This represents an upper-bound loss of approximately 8% of a household0s annual income. Despite these considerable losses we concluded that, given an incidence of fatal MCF in cattle living in wildebeest calving areas of 5% to 10%, if herd owners were to stop trying to avoid MCF by allowing their cattle to graze alongside wildebeest, any gains made through increased availability of milk, improved body condition and reduced energy demands would be offset by an increase in MCF-incidence. With the development of an effective vaccine, however, this alternative strategy might become optimal. The overall conclusion we draw therefore is that, despite the substantial costs incurred each year avoiding MCF, the partial protection afforded by the novel vaccine strategy is not sufficient to warrant a wholesale change in disease avoidance strategy. Nonetheless, even the partial protection provided by this vaccine could be of value to protect animals that cannot be moved, for example where some of the herd remain at the boma to provide milk or where land-use changes make traditional disease avoidance difficult. Furthermore, the vaccine may offer a feasible solution to some of the current land-use challenges and conflicts, providing a degree of protection to valuable livestock where avoidance strategies are not possible, but with less risk of precipitating the potentially damaging environmental consequences, such as overgrazing of highly nutritious seasonal pastures, that might result if herd owners decide they no longer need to avoid wildebeest.

Evaluación de las propiedades clinimétricas de la escala POSAS y su aplicación en pacientes de la Fundación del Quemado en Bogotá

•Objetivos: Se tradujo, adaptó y evaluaron las propiedades clinimétricas de la escala POSAS en pacientes con cicatrices hipertróficas (CHT) y queloides (CQ) cómo secuelas de quemadura, que fueron manejados con Z plastias en la Fundación del Quemado en Bogotá (Colombia), entre Junio de 2015 a Abril de 2016. •Métodos: Estudio de evaluación de las propiedades clinimétricas de una escala. Se hizo una traducción y adaptación transcultural siguiendo el método de traducción-retrotraducción. Se aplicó el instrumento adaptado a cincuenta y dos pacientes (n=52) antes y después de la intervención quirúrgica. Se evaluó la validez, confiabilidad, sensibilidad al cambio y la utilidad de la escala. •Resultados: Se hallaron diferencias significativas en los puntajes obtenidos del Observador y del Paciente, antes y después de la intervención quirúrgica (p<0.000); a excepción de prurito. La escala POSAS demostró ser altamente confiable para la Escala del Observador y del Paciente (α = 0.912 y 0.765). Hubo alta correlación en las evaluaciones de dos observadores para las variables ordinales de la Escala del Observador (r>0.6). La concordancia entre las evaluaciones de dos observadores para las variables categóricas de la Escala del Paciente fue buena para la evaluación antes de la intervención para pigmentación y relieve (κ>0.61). Se demostró que el instrumento es capaz de detectar cambios clínicos en el tiempo (p<0.0000), a excepción de prurito (p= 0.271). •Conclusiones: La escala POSAS demostró ser un instrumento válido, confiable y útil para evaluar la calidad de la cicatriz en pacientes con CHT y CQ cómo secuelas de quemadura.

Impedancias basales registradas durante la denervación renal por radiofrecuencia en pacientes con hipertensión arterial resistente

Objetivo: Determinar diferencias en las impedancias basales registradas durante los procedimientos de denervación renal por radiofrecuencia de los pacientes sometidos a este procedimiento en la Fundación Cardioinfantil de Bogotá durante los años 2012 a 2015. Materiales y métodos: Estudio observacional, analítico de corte retrospectivo, donde se analizaron todas las impedancias basales medidas durante los procedimientos de denervación renal, buscando diferencias significativas entre los segmentos de las arterias intervenidas, estratificados en proximal, medio distal y superior, lateral, inferior u ostial. Con seguimiento a los pacientes a tres, seis y doce meses en cuanto a presión arterial de consultorio. Resultados: Se evaluaron 150 puntos de denervación renal exitosos, correspondientes a 23 arterias renales de 11 procedimientos. La mediana de edad fue 56 años. Al realizar un modelo de regresión lineal no se encontró ninguna diferencia estadísticamente significativa entre las impedancias de ninguno de los segmentos de las arterias ni sitios anatómicos. Se documentó disminución de presión arterial sistólica a tres meses, seis meses y doce meses de 14 mmHg (RIQ 10-33mmHg), 21 mmHg (RIQ 12-42mmHg) y 19 mmHg (RIQ 11-42 mmHg) respectivamente

Cáncer gástrico en pacientes de Méderi – Hospital Universitario Mayor entre los años 2011 - 2014

Introducción: El cáncer gástrico es uno de los más frecuentes a nivel mundial y Colombia se sitúa entre los países de mayor incidencia en este tipo de patología. Objetivo: Describir las características epidemiológicas, clínicas, el tratamiento administrado y los desenlaces inmediatos de los pacientes con diagnóstico de cáncer gástrico atendidos en el Hospital Universitario Mayor de Bogotá entre los años 2011 y 2014. Metodología: Se realizó un estudio observacional descriptivo con diagnóstico de cáncer gástrico. Se realizaron análisis univariados por medio de proporciones para las variables cualitativas y medidas de tendencia central para las variables cuantitativas según la distribución. Resultados: Un total de 189 pacientes fueron analizados. El dolor fue el síntoma más frecuente en los pacientes (30.7%) y el principal signo encontrado fue una masa palpable en abdomen (9,5%). Los pacientes fueron sometidos a diferentes abordajes terapéuticos, la mayoría recibieron manejo paliativo no quirúrgico (52.9%) y la opción quirúrgica más usada en los pacientes fue la gastrectomía total (20.6%), y la subtotal (16,4) seguidas de quimioterapia y/o radiación perioperatoria. Los pacientes que sobrevivieron a los 2 años fueron 7,4% del total. Conclusiones: El registro de los pacientes con cáncer gástrico es bueno en el Méderi-Hospital Universitario Mayor es bueno y permite caracterizar los pacientes, la presentación de la patología y los resultados del tratamiento que concuerdan con los presentados en contextos similares en la literatura.

Data-driven multivariate flood hazard modeling

The present Dissertation shows how recent statistical analysis tools and open datasets can be exploited to improve modelling accuracy in two distinct yet interconnected domains of flood hazard (FH) assessment. In the first Part, unsupervised artificial neural networks are employed as regional models for sub-daily rainfall extremes. The models aim to learn a robust relation to estimate locally the parameters of Gumbel distributions of extreme rainfall depths for any sub-daily duration (1-24h). The predictions depend on twenty morphoclimatic descriptors. A large study area in north-central Italy is adopted, where 2238 annual maximum series are available. Validation is performed over an independent set of 100 gauges. Our results show that multivariate ANNs may remarkably improve the estimation of percentiles relative to the benchmark approach from the literature, where Gumbel parameters depend on mean annual precipitation. Finally, we show that the very nature of the proposed ANN models makes them suitable for interpolating predicted sub-daily rainfall quantiles across space and time-aggregation intervals. In the second Part, decision trees are used to combine a selected blend of input geomorphic descriptors for predicting FH. Relative to existing DEM-based approaches, this method is innovative, as it relies on the combination of three characteristics: (1) simple multivariate models, (2) a set of exclusively DEM-based descriptors as input, and (3) an existing FH map as reference information. First, the methods are applied to northern Italy, represented with the MERIT DEM (∼90m resolution), and second, to the whole of Italy, represented with the EU-DEM (25m resolution). The results show that multivariate approaches may (a) significantly enhance flood-prone areas delineation relative to a selected univariate one, (b) provide accurate predictions of expected inundation depths, (c) produce encouraging results in extrapolation, (d) complete the information of imperfect reference maps, and (e) conveniently convert binary maps into continuous representation of FH.

Operazioni di assemblaggio automatizzato tramite robot antropomorfo e visione artificiale

Obiettivo dello studio condotto è l’implementazione di cicli di operazioni per l’assemblaggio automatizzato di componenti che costituiscono un sistema di trasporto a catena presente in alcune macchine automatiche. L’automazione del processo, fino ad oggi svolto manualmente, prevede l’utilizzo di un robot e, per il controllo di quest’ultimo, di un sistema di visione artificiale. L’attività di tirocinio associata alla tesi di laurea, che ha incluso una parte sperimentale oltre alla scrittura degli algoritmi di controllo del robot, è stata svolta all’interno del laboratorio TAILOR (Technology and Automation for Industry LabORatory) presso Siropack Italia S.r.l dove è presente una cella dotata di robot antropomorfo (Mitsubishi Electric) e di sistema di visione artificiale con camere 2D (Omron). La presenza di quest’ultimo è risultata strategica in termini di possibilità di adattare il montaggio anche a diversi posizionamenti degli oggetti all’interno dello spazio di lavoro, fermo restando che gli stessi risultassero appoggiati su una superficie piana. In primo luogo, affinché fosse garantita la ripetibilità del processo, sono state testate le prestazioni del sistema di visione tramite opportuna calibrazione della camera e del sistema di illuminazione ad esso collegata, al fine di ottenere un’acquisizione delle immagini che fosse sufficientemente robusta e risoluta mediante lo sfruttamento del software di elaborazione Omron FH Vision System. Un’opportuna programmazione della traiettoria del robot in ambiente di simulazione RT Toolbox 3, software integrato nel sistema di controllo del robot Mitsubishi Electric, ha infine consentito le regolari operazioni di assemblaggio, garantendo un processo affidabile ed, allo stesso tempo, adattabile ad ambienti eventualmente non strutturati in cui esso si trova ad operare.