Growth and Characterization of some Bio-material Crystals

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In Silico and In Vitro Investigation into the Next Generation of New Psychoactive Substances

New Psychoactive Substances (NPS) were designed to be legal alternatives to existing established recreational drugs. They have fast become a very popular and up until 2016, NPS were legal, cheap and freely accessible via the internet and high street “head shops”. The rapid expansion in the number of these drugs has reached epidemic proportions, whereby hundreds of NPS have been developed and sold within the last five-year period. As NPS are synthesized in clandestine laboratories there is little to no control in the manufacture, dosage and packaging of these drugs. The public health risks posed by these drugs are therefore far-reaching. Fatalities and severe adverse reactions associated with these compounds have become an ongoing challenge to healthcare services, primarily because these drugs have not previously been abused and therefore there is little pharmacological information available regarding NPS. There are a number of different biological receptors that are implicated in the effects of NPS and the mechanism of action for the majority of these drugs is still largely unknown. It is of great importance to try and establish an understanding of how various classes of NPS interact on a molecular level. In this thesis, structure-based and ligand-based in Silico methodologies were employed to gain a better understanding of how NPS may interact with monoamine transporters (MAT). Key findings included both molecular docking studies and a number of robust and predictive QSAR models for the dopamine and serotonin transporters provided insight into how promiscuity of NPS between the different MAT isoforms could arise. In addition, pharmacophore models were generated to identify chemical entities that were structurally dissimilar to known existing NPS that had the potential to interact with the cannabinoid 1 receptor (CB1) and hence were hypothesised could elicit similar biological responses to known potent synthetic cannabinoids. Thirteen of these compounds were identified and carried forward for in vitro and ex vivo analyses, where preliminary results have shown that two compounds activate the CB1 receptor. Further optimisation of these compounds could yield a novel SC scaffold that was previously unseen. Additionally, the compounds identified and the methodology employed in the generation of these new chemical scaffolds could be used to guide Early Warning Systems (EWS) and facilitate law enforcement with respect to emergent NPS

Mining the Medical and Patent Literature to Support Healthcare and Pharmacovigilance

Recent advancements in healthcare practices and the increasing use of information technology in the medical domain has lead to the rapid generation of free-text data in forms of scientific articles, e-health records, patents, and document inventories. This has urged the development of sophisticated information retrieval and information extraction technologies. A fundamental requirement for the automatic processing of biomedical text is the identification of information carrying units such as the concepts or named entities. In this context, this work focuses on the identification of medical disorders (such as diseases and adverse effects) which denote an important category of concepts in the medical text. Two methodologies were investigated in this regard and they are dictionary-based and machine learning-based approaches. Futhermore, the capabilities of the concept recognition techniques were systematically exploited to build a semantic search platform for the retrieval of e-health records and patents. The system facilitates conventional text search as well as semantic and ontological searches. Performance of the adapted retrieval platform for e-health records and patents was evaluated within open assessment challenges (i.e. TRECMED and TRECCHEM respectively) wherein the system was best rated in comparison to several other competing information retrieval platforms. Finally, from the medico-pharma perspective, a strategy for the identification of adverse drug events from medical case reports was developed. Qualitative evaluation as well as an expert validation of the developed system's performance showed robust results. In conclusion, this thesis presents approaches for efficient information retrieval and information extraction from various biomedical literature sources in the support of healthcare and pharmacovigilance. The applied strategies have potential to enhance the literature-searches performed by biomedical, healthcare, and patent professionals. The applied strategies have potential to enhance the literature-searches performed by biomedical, healthcare, and patent professionals. This can promote the literature-based knowledge discovery, improve the safety and effectiveness of medical practices, and drive the research and development in medical and healthcare arena

Novel Analytical Methods in Food Analysis

This reprint provides information on the novel analytical methods used to address challenges occurring at academic, regulatory, and commercial level. All topics covered include information on the basic principles, procedures, advantages, limitations, and applications. Integration of biological reagents, (nano)materials, technologies, and physical principles (spectroscopy and spectrometry) are discussed. This reprint is ideal for professionals of the food industry, regulatory bodies, as well as researchers

Developmental neurocognitive pathway of psychosis proneness and the impact of cannabis use

Cette thèse fait la promotion d’une nouvelle approche ciblant le risque de psychose qui consiste à identifier les enfants et les jeunes adolescents de la communauté appartenant à différentes trajectoires développementales d’expériences psychotiques. Une identification très précoce du risque de psychose chez des jeunes de la communauté pourrait ainsi diminuer la période où les symptômes cliniques ne sont pas traités, mais aurait également le potentiel de prévenir efficacement l’émergence de symptômes avérés, et ce, si les facteurs de risque sont identifiés. Étant donné que la consommation de cannabis s’avère un important facteur de risque de la psychose et le contexte actuel où les états en sont à réviser leurs politiques de réglementation du cannabis, il s’avère primordial de mieux comprendre comment la consommation peut mener à la psychose chez les individus vulnérables. Tout d’abord, j’ai investigué la séquence temporelle entre la consommation de cannabis et les expériences psychotiques chez une population de 4000 adolescents, suivis pendant 4 ans, au moment de l’adolescence où les deux phénomènes s’initient. Ensuite, j’ai examiné, chez des adolescents suivant une trajectoire de vulnérabilité, le rôle d’un moins bon fonctionnement cognitif ainsi que celui d’une exacerbation des symptômes anxieux et dépressifs comme médiateurs du lien entre cannabis et risque de psychose. Enfin, j’ai investigué la présence de marqueurs neurocognitifs précoces (fonctionnels et structurels) qui seraient associés à l’émergence de symptômes psychotiques chez des adolescents, et exploré si la consommation de cannabis pourrait modérer l’ampleur de ces marqueurs. Les données proviennent de deux cohortes longitudinales suivant des adolescents de la population générale, l’étude Co-Venture (n=4000, âgés de 12 ans, suivis annuellement pendant 4 ans) et l’étude de neuroimagerie IMAGEN (n=2200, âgés de 14 ans, suivis pendant 2 ans), ainsi qu’un sous-échantillon de l’étude Co-Venture ayant complété des mesures de neuroimagerie (n=151, âgés de 12 ans, suivis annuellement pendant 4 ans). Les résultats ont montré que la consommation de cannabis précédait systématiquement l’augmentation des expériences psychotiques, et non l’inverse. Chez les jeunes suivant une trajectoire de vulnérabilité, la relation entre la consommation de cannabis et le risque de psychose était davantage expliquée par une augmentation des symptômes de dépression et d’anxiété. Une réduction du volume de l’hippocampe et de l’amygdale en combinaison avec une hyperactivité de ces mêmes régions en réponse à des expressions neutres étaient tous associés à l’émergence de symptômes psychotiques. Or, la consommation de cannabis n’a pas exacerbé les altérations structurelles observées chez les adolescents rapportant des expériences psychotiques. Ces résultats ont mis en évidence le rôle primordial d’un hyperfonctionnement du système limbique pouvant mener à l’attribution aberrante d’une importance émotionnelle aux stimuli de l’environnement, et ce, chez des adolescents vulnérables. Il semble que le mécanisme par lequel la consommation de cannabis mène à l’émergence de symptômes cliniques passe par son influence sur les symptômes de dépression et d’anxiété ainsi que leurs mécanismes neuronaux sous-jacents d’une hypersensibilité au stress. Enfin, de par ces résultats, cette thèse permet de contribuer au développement de nouvelles interventions visant à réduire la demande de cannabis chez des adolescents vulnérables.Following the worldwide initiative on intervening early in clinical high-risk individuals for psychosis, this thesis promotes a novel approach to identify those at risk for psychosis by studying children and adolescents from the community who report different trajectories of subclinical psychosis symptoms (i.e., psychotic-like experiences) without the confounds of iatrogenic effects such as major social and cognitive impairments. Early identification from this approach may not only reduce harm by shortening the duration of untreated symptoms, but may also have the capacity to prevent the emergence of clinically validated symptoms, particularly if early risk factors can be identified. Considering the long-standing notion that cannabis misuse is an important risk factor for psychosis and that jurisdictions around the world are currently revising their cannabis regulatory policies, there is a need to better understand how cannabis use may lead to psychosis in vulnerable youths. This thesis examined different mechanisms that may explain the complex relationship between cannabis use and psychosis risk. I first explored the temporal sequence between cannabis use and self-reported psychotic-like experiences in a population-based sample of 4000 adolescents, over a 4-year period when both phenomena have their onset. Second, in vulnerable youths, I investigated the role of impaired cognitive functioning as well as increased affective and anxious symptoms as mediators of the cannabis-to-psychosis relationship. And third, I explored the presence of early neurocognitive markers (both functional and structural) associated with the emergence of psychotic symptoms, and how cannabis use moderates these markers. Two longitudinal cohorts from the general population, the Co-Venture Study (n=4000, aged 12 years old, followed annually for 4 years) and the neuroimaging IMAGEN Study (n=2200, aged 14 years old, followed for 2 years), as well as the neuroimaging subsample from the Co-Venture Study (n=151, aged 12 years old, followed annually for 4 years) were used. It was found that an increase in cannabis use always preceded an increase in reported psychotic-like experiences throughout adolescence, but an increase in psychotic-like experiences rarely predicted an increase in cannabis use. Then, in vulnerable adolescents, the cannabis-to-psychosis risk relationship was better explained by increases in depression and anxiety symptoms relative to changes in cognitive functioning. It was demonstrated that reduced hippocampus and amygdala volumes, combined with hyperactivity of the same regions during neutral cues processing were associated with the emergence of psychotic symptoms in young adolescents reporting psychotic-like experiences. However, cannabis use did not exacerbate the structural alterations observed in youths with psychotic-like experiences. These findings have improved our understanding of the relationship between cannabis use and vulnerability to psychosis. They have also highlighted the important role of an impaired limbic network leading to an aberrant emotional salience attribution in vulnerable adolescents. Although cannabis use did not exacerbate brain structural alterations observed in vulnerable youths, it appears that cannabis will more likely interfere with depression and/or anxiety symptoms and their associated brain mechanisms underlying vulnerability to stress in the path towards psychosis risk. This thesis may inform the development of new evidence-based interventions that reduce demand for cannabis among vulnerable youths

Target and Non-Target Approaches for Food Authenticity and Traceability

Over the last few years, the subject of food authenticity and food fraud has received increasing attention from consumers and other stakeholders, such as government agencies and policymakers, control labs, producers, industry, and the research community. Among the different approaches aiming to identify, tackle, and/or deter fraudulent practices in the agri-food sector, the development of new, fast, and accurate methodologies to evaluate food authenticity is of major importance. This book, entitled “Target and Non-Target Approaches for Food Authenticity and Traceability”, gathers original research and review papers focusing on the development and application of both targeted and non-targeted methodologies applied to verify food authenticity and traceability. The contributions regard different foods, among which some are frequently considered as the most prone to adulteration, such as olive oil, honey, meat, and fish. This book is intended for readers aiming to enrich their knowledge through reading contemporary and multidisciplinary papers on the topic of food authentication

Decision Support Systems

Decision support systems (DSS) have evolved over the past four decades from theoretical concepts into real world computerized applications. DSS architecture contains three key components: knowledge base, computerized model, and user interface. DSS simulate cognitive decision-making functions of humans based on artificial intelligence methodologies (including expert systems, data mining, machine learning, connectionism, logistical reasoning, etc.) in order to perform decision support functions. The applications of DSS cover many domains, ranging from aviation monitoring, transportation safety, clinical diagnosis, weather forecast, business management to internet search strategy. By combining knowledge bases with inference rules, DSS are able to provide suggestions to end users to improve decisions and outcomes. This book is written as a textbook so that it can be used in formal courses examining decision support systems. It may be used by both undergraduate and graduate students from diverse computer-related fields. It will also be of value to established professionals as a text for self-study or for reference