Death by Facial and Skull Injuries of a Motorcyclist Wearing a Full-Face Helmet: Case Report and Literature Review

We describe a case of death by facial and skull fractures with brain injuries of a motorcyclist wearing a full-face helmet. A 40-year-old man driving a high-powered motorcycle crashed violently into the rear of a stopped car. The main results from the autopsy revealed the deformation of the left orbito-zygomatic and fronto-temporoparietal regions corresponding to bone fractures with laceration at the left temporal lobe. The CT scan of the helmet revealed the detachment of the energy-absorbing liner. Moreover an impact speed of 93 Km/h resulted from the analysis of accident dynamics. We analysed the literature regarding the effectiveness of full-face helmets in reducing the risk of fatality and we sought the factors that may have deleted the protection offered. The lesions causing death were due to high speed and probably the inadequacy of the helmet

Supply chain management as a competitive advantage in the Spanish grocery sector

Adversarial relationships have long dominated business relationships, but Supply Chain Management (SCM) entails a new perspective. SCM requires a movement away from arms-length relationships toward partnership style relations. SCM involves integration, co-ordination and collaboration across organisations and throughout the supply chain. It means that SCM requires internal (intraorganisational) and external (interorganisational) integration. This paper analyses the relationship between internal and external integration processes, their effect on firms’ performance and their contribution to the achievement of a competitive advantage. Performance improvements are analysed through costs, stock out and lead time reductions. And, the achievement of a better competitive position is measured by comparing the firm’s performance with its competitors’ performance. To analyse this, an empirical study has been conducted in the Spanish grocery sector.Supply chain management, logistics integration processes, Internal and externalintegration, competitive advantage, logistics performance

Logistics-production, logistics-marketing and external integration: Their impact on performance

Highly competitive environments are leading companies to implement Supply Chain Management (SCM) to improve performance and gain a competitive advantage. SCM involves integration, co-ordination and collaboration across organisations and throughout the supply chain. It means that SCM requires internal (intraorganisational) and external (interorganisational) integration. This paper examines the Logistics-Production and Logistics- Marketing interfaces and their relation with the external integration process. The study also investigates the causal impact of these internal and external relationships on the company’s logistical service performance. To analyse this, an empirical study was conducted in the Spanish Fast Moving Consumer Goods (FMCG) sector.Logistics integration processes, internal and external integration, logistics performance

Peculiar and Unusual Drowning in Waste Oil from Motor Vehicles: Case Report

Drowning is one of the most frequent causes of accidental or suicidal death, and more rarely it is associated with a homicide. Cases of drowning in water or in the sea are common. The authors report an unusual and peculiar case of drowning, that of a woman who accidentally fell inside a collection tank of waste oil of motor vehicles

In vitro genotoxic and epigenotoxic effects of occupational exposure to nanofibres

ABSTRACT - In recent years, human exposure to nanofibres (i.e., fibres with diameters < 100 nm) has considerably increased due to their incorporation in a wide range of consumer products. As such, there is a growing concern that the distinctive physicochemical characteristics of nanofibres may lead to adverse human health effects, mainly by their inhalation in occupational settings. Several toxicological studies have indicated that some nanofibres, such as the MWCNT-7, display in vitro toxicity and induce pulmonary inflammation, fibrosis, granulomas and carcinogenesis in vivo. Others, like cellulose nanofibrills (CNF), seem biocompatible and promising for biomedical applications. Thus, the genotoxic effects of nanofibres must be deeply studied to identify their possible hazard, and new “omics” methodologies can uncover their underlying mechanisms of action. Moreover, distinctive genomic or epigenomic expression profiles may be biomarkers of occupational exposure to nanofibres. In this work, the two above-mentioned nanofibres are analyzed in vitro, and the toxic effects of MWCNT-7 compared to those of crocidolite asbestos. Cytotoxicity and genotoxicity were investigated through conventional assays, and the differentially expressed microRNA (DE miRNA) in alveolar epithelial cells exposed to MWCNT-7 or crocidolite identified by next-generation sequencing. The overall results demonstrate that MWCNT-7 is cytotoxic, genotoxic and immunotoxic. Notably, it induced nucleoplasmic bridges in alveolar cells, possibly due to its resemblance with the microtubules and physical interference with the mitotic spindle. Different viabilities and micronucleus frequencies were observed in alveolar cells when using a conventional monoculture or a co-culture of these cells with macrophages, which may be related to their epithelial-mesenchymal transition and consequent increase of cell resistance to apoptosis. Regarding CNF, at low concentrations it stimulates cell proliferation, whereas at higher ones it is moderately toxic. Although no immunotoxicity and no significant DNA damage were detected, low CNF doses induced micronucleus. Concerning the epigenotoxic study, several DE miRNA were identified in alveolar cells exposed to MWCNT-7 or crocidolite, and a unique set was identified for each exposure. Both materials caused common changes in pathways related to cell metabolism, cell growth and death, cell-to-cell communication, protein processing, and signal transduction. Other functional pathways were distinctively identified for each material that sugest particular mechanisms of action. Since most are cancer related, a network of DE miRNA and target cancer genes was constructed, highlighting the carcinogenic potential of both materials.RESUMO - Nos últimos anos, a exposição humana a nanofibras (i.e., fibras com diâmetros <100 nm) tem vindo a aumentar, devido à sua incorporação em vários produtos para consumo humano. Como tal, a preocupação de que as características singulares das nanofibras possam ter efeitos adversos na saúde humana tem-se intensificado, particularmente por inalação em contexto ocupacional. Diversos estudos toxicológicos indicam que certas nanofibras, como o MWCNT-7, têm toxicidade in vitro e induzem inflamação pulmonar, fibrose, granulomas e carcinogénese in vivo. Outras, como a celulose nanofibrilar (CNF), aparentam biocompatibilidade e são prometedoras para aplicações biomédicas. Desta forma, é essencial aprofundar o estudo sobre a sua genotoxicidade para conhecer a sua perigosidade. Neste contexto, as metodologias “ómicas” permitem compreender os mecanismos de ação das nanofibras e, além disso, os perfis genómicos ou epigenómicos podem ser úteis como biomarcadores de exposição ocupacional. Neste trabalho, as nanofibras acima citadas são analisadas in vitro, sendo o MWCNT-7 comparado à crocidolite (amianto). A citotoxicidade e genotoxicidade são analisadas pelos ensaios convencionais, sendo ainda identificados quais os microRNA diferencialmente expressos (miRNA DE) nas células alveolares expostas ao MWCNT-7 ou à crocidolite, por sequenciação de nova geração. Os resultados globais indicam que o MWCNT-7 é citotóxico, genotóxico e imunotóxico. De realçar a indução de pontes nucleoplásmicas nas células alveolares, provavelmente relacionadas com a semelhança do MWCNT-7 aos microtúbulos e interferência com o fuso mitótico. A diferente viabilidade e frequência de micronúcleos nas células alveolares em monocultura ou co-cultura com macrófagos pode estar relacionada com a sua transição epitelial-mesenquimal e aumento da resistência à apoptose. Quanto à CNF, observouse proliferação celular nas doses baixas e citotoxicidade moderada nas doses mais elevadas. Embora não se tenham detetado danos significativos no DNA ou imunotoxicidade, foram induzidos micronúcleos nas doses baixas. No que respeita ao estudo de epigenotoxicidade, foi identificado um conjunto único de miRNA DE nas células expostas ao MWCNT-7 ou à crocidolite. Ambos os materiais causaram as mesmas alterações em vias de metabolismo celular, crescimento e morte celular, comunicação célula-a-célula, processamento proteíco e transdução de sinal. Outras vias distintamente alteradas sugerem mecanismos de acção específicos. Uma vez que a maioria está associada a cancro, foi construída uma rede entre miRNAs DE e genes alvo associados a cancro que realça o potential carcinogénico de ambos os materiais

Evaluating the Maximization-Maximization approach to measure default probabilities on structural credit risk models

This thesis implements the Maximization-Maximization (MM) algorithm proposed by Forte and Lovreta (2012), where in the first step the expected assets rate of return and the asset volatility are estimated applying the Maximum Likelihood technique. As the firm’s assets value is not observable, the observed equity values are treated as transformed data in order to derive the log-likelihood function. In a second step, the default barrier is estimated according to the interests of shareholders, corresponding to the optimal level considered for the firm to default, and as the one that maximizes their participation. Using a sample of fifty-five companies and a time period for the estimation of one year, our results prove that estimating the expected rate of return is hard and does not provide statistically significant results, as it is dependent and highly correlated to the observed equity values. The results for the five-year default probabilities computed were most of them equal to zero or too high.Esta tese implementa o algoritmo Maximization-Maximization (MM) proposto por Forte e Lovreta (2012), em que no primeiro passo, o retorno esperado dos ativos e a volatilidade destes são estimados aplicando a técnica da Máxima Verosimilhança. Como o valor dos ativos da empresa não é observável, os valores do capital próprio são tratados como dados transformados de forma a derivar a função log-likelihood. Num segundo passo, a barreira de incumprimento é estimada de acordo com os interesses dos acionistas, correspondendo ao nível ótimo considerado para a empresa entrar em incumprimento, bem como àquela que maximiza a participação destes. Usando uma amostra de cinquenta e cinco empresas e um período de tempo de um ano para a estimação, os nossos resultados mostram que estimar a taxa de retorno esperado dos ativos é difícil e não fornece resultados estatisticamente significativos, por ser dependente e fortemente correlacionado com os valores do capital próprio. Os resultados das probabilidades de incumprimento a cinco anos calculadas foram na maioria igual a zero ou demasiado altas

Development of Models for On-line Diagnostic and Energy Assessment Analysis of PV Power Plants: The Study Case of 1 MW Sicilian PV Plant

Abstract For photovoltaic (PV) power plants, every kilowatt-hour is important, because only kilowatt-hours that are fed into the grid are remunerated. A plant's operator can only adopt prompt measures to eliminate operational faults when these are immediately signaled. In fact, just reading the feed-in meter each month is not sufficient to promptly recognize faults and to avoid the loss of yields. Many inverters record the most important operational data, automatically evaluate the data and, in case of a fault, send the operator notifications via email or text message. However, it only allows obvious faults to be recorded. On the other hand, continuous, absolute and comparative measurements are necessary to ensure the maximum efficiency and availability. Based on real time and historical data, a technical plant manager should inform the operators of any fault which occurs or even take independent measures to rectify it. In this context, suitable models are developed and applied to a 1 MW power plant where a SCADA, Supervisory Control And Data Acquisition, has been installed and operational data are available on a Web page. In order to evaluate the performance of the PV system, firstly the daily corrected Performance ratio has been evaluated. Then, different approaches to estimate the AC and the DC power of the PV plant have been developed. Basing on the difference between the measured and the estimated power, a statistical approach is proposed; it allows to define suitable thresholds on the AC and DC power in order to individuate a fault when occurs. The experimental results show the effectiveness of the proposed approach

Nonclinical assessment of the potential for herb-drug interactions between herbal extracts present in weight loss supplements and lamotrigine

Plants have been and still continue to be one of the most important sources of active ingredients. Actually, plants are still the backbone of modern pharmacopoeias and remain as a source of new drug candidates. The use of medicinal plants or plant-based medicinal products is also increasing in many developed countries as an alternative and complementary form for the treatment of diseases. Thus, the concomitant use of plants and conventional medications is emerging as a common practice in patients with hypertension, diabetes, epilepsy, depression, and oncological diseases, as well as in people with obesity and being overweight. Recently, obesity and epilepsy have been related as comorbid conditions with a high prevalence, particularly in patients with refractory epilepsy and under polytherapy. Treatment of patients with epilepsy should, therefore, take into account that the presence of comorbid conditions may compromise the efficacy and safety of antiepileptic drugs, which constitute the main therapeutic approach in epilepsy. Lamotrigine (LTG) is a well-tolerated antiepileptic drug widely used in epilepsy; however, it has a narrow therapeutic range and a considerable interindividual variability in its pharmacokinetics. Therefore, the focus of research addressed in this thesis was the nonclinical assessment of the potential for herb-drug interactions between herbal extracts present in weight loss supplements and LTG, using the rat as whole animal model. After optimization and validation of selective, precise and accurate bioanalytical methods for the quantification of LTG in human samples (plasma and saliva) and in rat samples (plasma and brain), the conditions for proceeding with nonclinical studies were met. Therefore, then a number of nonclinical studies were performed in adult male Wistar rats with the main objective of evaluating the effects of standardized extracts of Paullinia cupana (guarana), Garcinia cambogia (malabar tamarind), Citrus aurantium (bitter orange) and Fucus vesiculosus (bladderwrack) on the kinetics of LTG. To this end, at least two independent pharmacokinetic studies were carried out to evaluate the effects of each herbal extract on the pharmacokinetics of LTG; the first study aimed to evaluate the effects after the co-administration of the extract and LTG, and the second one aimed to evaluate the effects of a 14-day pre-treatment period with the extract on the pharmacokinetics of LTG subsequently administered on the 15th day. Globally, the results of the pharmacokinetic studies involving the four herbal extracts pointed out that P. cupana extract is the one that has higher potential to interact with LTG, while G. cambogia, C. aurantium and F. vesiculosus extracts had minor or no effects on LTG pharmacokinetics. The co-administration of P. cupana extract and LTG caused, in particular, a significant decrease in the peak plasma drug concentration (Cmax) and in the extent of systemic exposure to LTG over the first 24 h (AUC0-24). Based on the findings achieved in these nonclinical studies, an important pharmacokinetic interaction between P. cupana extract and LTG was herein described for the first time, which potentially may have clinical impact in patients treated with LTG. Moreover, the repeated administration of the tested herbal extracts during a 14-day period did not have relevant effects on the body weight gain of rats, which raises doubts about their effectiveness in reducing body weight. So, in conclusion, the nonclinical assessment of herb-drug interactions is of utmost importance to anticipate the potential effects of herbal preparations in the pharmacokinetics of narrow therapeutic index drugs like LTG, constituting these data the starting point for further confirmation and investigation of the relevance of these interactions at a clinical level.As plantas têm sido, e continuarão ainda a ser, uma das fontes mais importantes de princípios ativos. Na realidade, as plantas constituem ainda a “espinha dorsal” das farmacopeias modernas e continuam a ser uma fonte de novos candidatos a fármacos. A utilização de plantas medicinais ou de preparações medicinais à base de plantas está também a aumentar em muitos países desenvolvidos como uma forma alternativa e complementar para o tratamento de doenças. Por conseguinte, o uso concomitante de plantas e medicamentos convencionais é uma prática comum em doentes com hipertensão, diabetes, epilepsia, depressão e doenças oncológicas, assim como em pessoas com obesidade e excesso de peso. Recentemente, a obesidade e a epilepsia têm sido consideradas comorbilidades com uma elevada prevalência, particularmente em doentes com epilepsia refratária e polimedicados. O tratamento de doentes com epilepsia deve, portanto, ter em consideração que a presença de comorbilidades pode comprometer a eficácia e a segurança dos fármacos antiepiléticos, os quais constituem a principal estratégia terapêutica na epilepsia. A lamotrigina (LTG) é um fármaco antiepilético bem tolerado e amplamente utilizado na epilepsia, mas que apresenta uma margem terapêutica estreita e uma variabilidade interindividual considerável na sua farmacocinética. Por isso, o foco de investigação considerado nesta tese foi a avaliação não-clínica do potencial de interação entre extratos de plantas presentes em suplementos à base de plantas para emagrecimento e a LTG, usando o rato como modelo animal. Após a otimização e a validação de métodos bioanalíticos seletivos, precisos e exatos para a quantificação da LTG em amostras humanas (plasma e saliva) e em amostras de rato (plasma e cérebro), as condições para prosseguir com os estudos não-clínicos estavam reunidas. Portanto, de seguida, um conjunto de estudos não-clínicos foi realizado em ratos Wistar machos adultos com o objetivo principal de avaliar os efeitos de extratos padronizados de Paullinia cupana (guaraná), de Garcinia cambogia (tamarindo de Malabar), de Citrus aurantium (laranja-amarga) e de Fucus vesiculosus (bodelha) na cinética da LTG. Para tal, pelo menos dois estudos farmacocinéticos independentes foram realizados para avaliar os efeitos de cada extrato na farmacocinética da LTG; o primeiro estudo teve como objetivo avaliar os efeitos após a coadministração do extrato e da LTG, e o segundo estudo foi realizado para avaliar os efeitos de um período de pré-tratamento de 14 dias com cada extrato na farmacocinética da LTG administrada subsequentemente ao 15º dia. Globalmente, os resultados dos estudos farmacocinéticos envolvendo os quatro extratos de plantas revelaram que o extrato de P. cupana é aquele que tem maior potencial para interagir com a LTG, enquanto que os extratos de G. cambogia, C. aurantium e F. vesiculosus tiveram poucos ou nenhuns efeitos na farmacocinética da LTG. A coadministração do extrato de P. cupana e LTG causou, em particular, um decréscimo significativo da concentração plasmática máxima (Cmax) e da extensão de exposição sistémica à LTG nas primeiras 24 h (AUC0-24). Com base nos resultados obtidos nestes estudos não-clínicos, uma interação farmacocinética importante entre o extrato de P. cupana e a LTG foi aqui descrita pela primeira vez, a qual potencialmente pode ter impacto clínico em doentes tratados com a LTG. Além disso, a administração repetida dos extratos testados durante um período de 14 dias não teve efeitos relevantes sobre o ganho de peso corporal dos ratos, o que levanta dúvidas sobre a eficácia deles na redução do peso corporal. Assim, em conclusão, a avaliação não-clínica de interações planta-fármaco é de extrema importância para antecipar os efeitos potenciais de preparações à base de plantas na farmacocinética de fármacos de índice terapêutico estreito como a LTG, constituindo esses dados o ponto de partida para confirmação posterior e investigação da relevância dessas interações a nível clínico.UID/Multi/00709/201

Immunohistochemical detection of early myocardial infarction: a systematic review

The postmortem diagnosis of early myocardial infarction is a challenge for forensic pathologists because the routine histology is neither specific. Many authors have suggested the use of the immunohistochemistry to fill the gaps in the histological diagnosis of early myocardial infarction. This review aims to analyse advances of immunohistochemical detection of early cardiac damage due to ischaemia. To this purpose, we reviewed experimental studies that investigated immunohistochemical markers and their estimated timing of expression. The review was performed according to specific inclusion and exclusion criteria, and a total of 23 studies assessing the immunohistochemical markers for the diagnosis and timing of early myocardial infarction were identified. The literature review highlights that the analysed markers are complement components, others being inflammatory mediators, cardiac cell proteins, plasma proteins, stress or hypoxia-induced factors and proteins associated with heart failure. All studies demonstrate the effectiveness of the tested markers in the early detection of myocardial infarction in both animal and human samples

Virtual and Augmented Reality: New Frontiers for Clinical Psychology

In the last decades, the applied approach for the use of virtual reality (VR) and augmented reality (AR) on clinical and health psychology has grown exponentially. These technologies have been used to treat several mental disorders, for example, phobias, stress-related disorders, depression, eating disorders, and chronic pain. The importance of VR/AR for the mental health field comes from three main concepts: (1) VR/AR as an imaginal technology, people can feel “as if they are” in a reality that does not exist in external world; (2) VR/AR as an embodied technology, the experience to feel user’s body inside the virtual environment; and (3) VR/AR as connectivity technology, the “end of geography’. In this chapter, we explore the opportunities provided by VR/AR as technologies to improve people’s quality of life and to discuss new frontiers for their application in mental health and psychological well-being promotion