Trauma-induced coagulopathy (TIC) is a recently described condition which traditionally has been diagnosed by the common coagulation tests (CCTs) such as prothrombin time/international normalized ratio (PT/INR), activated partial thromboplastin time (aPTT), platelet count, and fibrinogen levels. The varying sensitivity and specificity of these CCTs have led trauma coagulation researchers and clinicians to use Viscoelastic Tests (VET) such as Thromboelastography (TEG) to provide Targeted Thromboelastographic Hemostatic and Adjunctive Therapy (TTHAT) in a goal directed fashion to those trauma patients in need of hemostatic resuscitation. This review describes the utility of VETs, in particular, TEG, to provide TTHAT in trauma and acquired non-trauma-induced coagulopathy.

Förekomsten av psykisk ohälsa bland ensamagerande våldsverkare i Sverige studerades genom en tematisk analys på textdokument. Trettiofem av 70 ensamagerande våldsverkare valdes ut genom ett systematiskt slumpmässigt urval. Textdokumenten innehåller sekretessbelagd information ifrån Polismyndighetens system. Av de undersökta ensamagerande våldsverkarna hade 43 % en psykiatrisk diagnos och tecken på psykisk ohälsa fanns hos 34 %. Resultatet går i linje med internationell forskning som visar att ungefär 40 % av ensamagerande våldsverkare innehar en psykiatrisk diagnos. Sammanfattningsvis i aktuell studie uppvisade 77 % av de ensamagerande våldsverkarna tecken på psykisk ohälsa vilket kan indikera att antalet med psykiatriska diagnoser i studien kan ha underskattats. Således visade studien att psykisk ohälsa är en viktig riskfaktor för våld och Polismyndigheten behöver samverka med andra samhällsaktörer för att kunna förebygga, förhindra och upptäcka brottslighet från ensamagerande våldsverkare. / The frequency of mental illness among lone actors in Sweden were studied through a thematic analysis on textual documents. Thirty-five of 70 lone actors were chosen with a systematic randomized method. The textual documents contain closed source data from The Swedish Police Authority. Of the studied lone actors 43 % had a mental disorder and signs of mental illness were observed in 34 %. The findings are consistent with previous international research that shows that approximately 40 % of lone actors have a mental disorder. In summary current study outlines that 77 % of lone actors in Sweden show signs of mental illness which can indicate that the quantity of mental disorders could have been underestimated. Finally mental illness appears to be an important risk factor for violence and The Swedish Police Authority needs to cooperate with other social actors to be able to prevent and discover violent crimes from future lone actors.

Influenza is a severe disease in humans and animals, causing upwards of 40,000 deaths every year in America alone. Influenza A virus (IAV) also causes periodic pandemics every 10 to 50 years, killing millions of people. Despite this, very few effective therapies are available. All strains of IAV are prone to developing resistance to antibodies due to the high mutation rate in the viral genome. Because of this mutation rate, a yearly vaccine must be generated before every flu season, and efficacy varies year to year. IAV has also mutated to escape several of the clinically-approved small molecule inhibitors. A therapeutic agent that targets a highly conserved region of the virus could bypass resistance and also be effective against multiple strains of IAV. IAV attachment is mediated by many individually weak hemagglutinin–sialic acid interactions that all together make a strong attachment to a host cell. Polymerized sialic acid analogs can recreate these interactions and block infection. However, they are not ideal therapeutics due to solubility issues and in vivo toxicity. We used liposomes as a novel means for delivery of the sialic acid-containing glycan, sialylneolacto-N-tetraose c (LSTc). LSTcbearing decoy liposomes form multivalent, polymer-like interactions with IAV. Decoy liposomes competitively bind IAV in hemagglutination inhibition assays and inhibit infection of target cells in a dose-dependent manner. LSTc decoy liposomes co-localize with IAV, while control liposomes do not. Inhibition is specific, as inhibition of Sendai virus and respiratory syncytial virus is not observed. In contrast, monovalent LSTc does not bind IAV or inhibit infectivity. LSTc decoy liposomes prevent the spread of IAV during multiple rounds of replication in vitro and extend survival of mice challenged with a lethal dose of virus. Considering the conservation of the hemagglutinin binding pocket and the ability of decoy liposomes to form high-avidity interactions with IAV hemagglutinin, our decoy liposomes have potential as a new therapeutic agent against emerging strains.

Les essais cliniques de phase I en cancérologie permettent d’identifier la dose optimale (DO), définie comme la dose maximale tolérée (DMT). Les approches conventionnelles de recherche de dose reposent uniquement sur les événements de toxicité observés au cours du premier cycle de traitement. Le développement des thérapies moléculaires ciblées (TMC), habituellement administrées sur de longues périodes, a remis en question cet objectif. Considérer uniquement le premier cycle de traitement n’est pas suffisant. De plus, comme l'activité n'augmente pas nécessairement de façon monotone avec la dose, la toxicité et l'activité doivent être prises en compte pour identifier la DO. Récemment, les biomarqueurs continus sont de plus en plus utilisés pour mesurer l'activité.L’objectif de cette thèse était de proposer et d'évaluer des designs adaptatifs pour identifier la DO. Nous avons développé deux designs de recherche de dose, basés sur une modélisation conjointe des mesures longitudinales de l'activité des biomarqueurs et de la première toxicité dose-limitante (DLT), avec un effet aléatoire partagé. En utilisant des propriétés de distribution normales asymétriques, l'estimation reposait sur la vraisemblance sans approximation ce qui est une propriété importante dans le cas de petits échantillons qui sont souvent disponibles dans ces essais. La DMT est associée à un certain risque cumulé de DLT sur un nombre prédéfini de cycles de traitement. La DO a été définie comme la dose la moins toxique parmi les doses actives, sous la contrainte de ne pas dépasser la DMT. Le second design étendait cette approche pour les cas d’une relation dose-activité qui pouvait atteindre un plateau. Un modèle à changement de pente a été implémenté. Nous avons évalué les performances des designs avec des études de simulations en étudiant plusieurs scénarios et divers degrés d'erreur de spécification des modèles.Finalement, nous avons effectué une analyse de 27 études des TMCs de phase I, en tant que monothérapie. Les études ont été réalisées par l'Institut National du Cancer. L'objectif principal était d'estimer le risque par cycle et l’incidence cumulative de la toxicité sévère, jusqu’à six cycles. Les analyses ont été effectuées séparément pour différents sous-groupes de doses, ainsi que pour les toxicités hématologiques et non-hématologiques. / Conventional dose-finding approaches in oncology of phase I clinical trials aim to identify the optimal dose (OD) defined as the maximum tolerated dose (MTD), based on the toxicity events observed during the first treatment cycle. The constant development of molecularly targeted agents (MTAs), usually administered in chronic schedules, has challenged this objective. Not only, the outcomes after the first cycle are of importance, but also activity does not necessarily increase monotonically with dose. Therefore, both toxicity and activity should be considered for the identification of the OD. Lately, continuous biomarkers are used more and more to monitor activity. The aim of this thesis was to propose and evaluate adaptive designs for the identification of the OD. We developed two dose-finding designs, based on a joint modeling of longitudinal continuous biomarker activity measurements and time to first dose limiting toxicity (DLT), with a shared random effect, using skewed normal distribution properties. Estimation relied on likelihood that did not require approximation, an important property in the context of small sample sizes, typical of phase I/II trials. We addressed the important case of missing at random data that stem from unacceptable toxicity, lack of activity and rapid deterioration of phase I patients. The MTD was associated to some cumulative risk of DLT over a predefined number of treatment cycles. The OD was defined as the lowest dose within a range of active doses, under the constraint of not exceeding the MTD. The second design extended this approach for cases of a dose-activity relationship that could reach a plateau. A change point model was implemented. The performance of the approaches was evaluated through simulation studies, investigating a wide range of scenarios and various degrees of data misspecification. As a last part, we performed an analysis of 27 phase I studies of MTAs, as monotherapy, conducted by the National Cancer Institut. The primary focus was to estimate the per-cycle risk and the cumulative incidence function of severe toxicity, over up to six cycles. Analyses were performed separately for different dose subgroups, as well as for hematologic and non-hematologic toxicities.

Parce qu’il favorise l’initiation précoce du traitement qui limite la morbi-mortalité et les transmissions secondaires, le dépistage du VIH est essentiel au contrôle de l’épidémie. En France, plusieurs milliers de personnes ignorent encore leur séropositivité et un quart des diagnostics du VIH est tardif. La participation infirmière au dépistage du VIH suscite un vif intérêt car elle permet d’élargir les acteurs impliqués. Nous avons suggéré à partir d’une revue de littérature systématique que, dans les pays à épidémie concentrée du VIH comme la France, les Etats Unis ou le Royaume Uni, les infirmiers pouvaient renforcer l’offre et la réalisation du dépistage du VIH. Dans ces pays, les autorités de santé ont préconisé un dépistage généralisé (non ciblé) du VIH dans les structures de santé non spécialisées. En raison de son efficacité modeste et de la charge de travail associée, cette recommandation a progressivement été remise en cause. L’étude DICI-VIH a été conçue pour explorer un nouveau mode, ciblé, de dépistage du VIH par les infirmiers dans les services d’urgences d’Ile-de-France, une région à forte prévalence. Nous avons montré, à l’aide d’un essai à large échelle randomisé en cluster et crossover en deux périodes, que ce mode de dépistage constitue une approche intéressante. En optimisant l’utilisation des ressources consacrées au dépistage dans les services d’urgences, cette stratégie ciblant un nombre limité de patients est réalisable et efficace pour identifier les personnes qui ne connaitraient pas leur séropositivité et, de plus, son coût est limité. Ces résultats fournissent de nouvelles données permettant l’adaptation des stratégies de dépistage du VIH proposées dans les régions où l’épidémie est concentrée. Ils participent également à l’évaluation de l’implication infirmière dans les programmes de dépistage. / Screening is essential to controlling the HIV epidemic as it ensures early treatment initiation, which limits morbidity, mortality and secondary transmission. In France, thousands of individuals remain unaware of their HIV status and a quarter of diagnoses occur at a late stage of infection. Nurse participation in HIV screening is widely discussed as a means by which to get a greater number of actors involved. Through a systematic review we suggested that, in countries with concentrated epidemics such as France, the United States and the United Kingdom, nurses could increase the number of screening tests being offered and performed. In these countries, Health authorities have recommended non-targeted systematic HIV screening in non-specialized health care settings. While this recommendation has gradually been questioned due to its limited effectiveness and associated increased workload, the DICI-VIH trial was designed to explore a new targeted method of HIV screening, performed by nurses in the Emergency Departments of the Paris metropolitan area, where HIV prevalence is high. A large-scale trial with a cluster-randomized two-period crossover design showed that this screening strategy is a compelling approach. By limiting the use of resources allocated to screening in Emergency Departments and by targeting a limited number of patients, this strategy is shown to be feasible and effective in identifying individuals who are unaware of their HIV status. It is also associated with limited costs. These results contribute new data to the discussion on how to best adapt HIV screening strategies in contexts where the epidemic is concentrated and to the evaluation of the contribution of the nursing profession to screening programs.

A standard Neurofeedback approach to mitigate the working memory decline in some fragile groups (elderly, subjects affected by stroke or Alzheimer's disease) can be suboptimal for some patients. The goal of this research is to investigate which visual stimulus (among colour, geometrical shape, direction, and symbol) is the most suited for each of the six healthy participants and which brain areas are the most discriminative, during the maintenance of a presented stimulus in a retro-cue-based working memory experiment. In order to identify the most discriminative stimulus, the single-trial classification accuracies of some Support Vector Machines, trained on the theta, alpha and beta electroencephalography power bands, have been compared; while, in order to identify the most involved brain regions, three machine learning feature reduction techniques have been explored: the first based on a massive univariate analysis, the second based on multivariate filtering and wrapping, and the last one based on Frequency-based Common Spatial Pattern. The results have shown that the univariate approach, more than the others, managed to clearly identify for each participant at least one preferential type of stimulus and a brain region of discriminative electrodes during the maintenance of the stimulus. These promising results can be interpreted as a further step to optimize the Neurofeedback working memory enhancement through a personalised approach.

Targeted sanctions have become increasingly utilized as conflict management tool to safeguard global peace and security. In recent years, there have been a global push to utilize this tool to specifically address conflict-related sexual violence (CRSV). Yet, there is a dearth in research on how the imposition of targeted sanctions effect the prevalence of CRSV. This thesis aims to contribute to this alarmingly understudied relationship between targeted sanctions and CRSV by investigating the following research question: what impact do targeted sanctions have on the perpetration of CRSV by rebel groups? Thus, I employ a structured, focused comparison of the Revolutionary United Front (RUF) in Sierra Leone and the Lord’s Resistance Army (LRA) in Uganda to test a theoretical theory which argues that targeted sanctions may increase the prevalence of CRSV perpetrated by the targeted rebel group. The empirical findings give partial support to both the proposed hypothesis and the theorized ‘selective incentive’ casual mechanism. However, the findings also suggest less effective sanctions may result in the hypothesized increase in wartime sexual violence perpetrated by the targeted actor, while more effective, debilitating sanctions may a decrease alongside other interventions.

This  research  emphasizes  the role  of  social  media  in  customer  acquisition  retention.Furthermore, it investigates insights that have the potential to benefit tech startups inshaping  their  strategies  and  effectively  allocating  resources  to  achieve  consistentcommunication with their customer base. The field of research is particularly relevant dueto the research gap present in the literature that does not investigate how technologystartups should approach the initial acquisition and retention of the user base, consideringthe limited resources available to these newborn organizations. The research providesinsights into customers' perceptions of brands and companies on social media platforms.It offers intuitions on how to enhance customer trust through these platforms and whichare the preferred way of interaction between customers and companies both on and offsocial media.The study was performed using qualitative and quantitative primary data with the purposeof gaining a deep understanding of the research topic. However, the focus has been puton the quantitative data aiming to create objective and generalizable  results, seekingunbiased findings.The  results  of  the research  showed  how important it  is  to  have  an  effective CRM(Customer Relationship  Management) system as well as  being able to identify  theaudience, understanding, therefore, the communication method that best fit the chosentarget, with the aim of interacting with them in the expected and preferred way, beingthus one step closer on achieving customer retention and acquisition.

The purpose of this study was to determine if there was a relationship between level of funding and achievement of school systems in Tennessee based on the standards of the No Child Left Behind Act (NCLB) of 2001. This study focused on Tennessee school systems and their adequate yearly progress (AYP) status of "targeted" or "good standing" from 2007 through 2009. Federal, state, and local funding, as well as per-pupil expenditure, average teacher salary, and number of students, were used as variables. All data were gathered from the Tennessee Department of Education website. The researcher performed 6 independent samples t-tests and one chi square analysis. The study showed significant differences in the means of federal, state, and local funding levels between targeted systems and systems in good standing. Targeted systems received more federal, state, and local funding than systems in good standing from 2007 through 2009. The study showed no significant difference in mean per-pupil expenditures between targeted systems and systems in good standing. The study showed a significant difference in the mean teacher salaries. Targeted systems had higher teacher salaries than systems in good standing from 2007 through 2009. The study also showed a significant difference in the mean number of students between targeted systems and systems in good standing. Targeted systems had more students than systems in good standing. The findings indicate that targeted systems are receiving as much funding as systems in good standing. To help control for the number of students in each system, the two groups (targeted and in good standing) were compared using per-pupil federal, state and local dollars. The analysis indicated no significant difference between targeted systems and systems in good standing for federal money. The analysis did indicate a significant difference between the two groups for state and local money. However, for state money systems in good standing had the higher mean and for local money, targeted systems had the higher mean. Mean per-pupil expenditures were relatively equal between targeted systems and systems in good standing. System size, based on the number of students, showed a significant relationship with the NCLB status of a system. The mean number of students in targeted systems was more than 3 times as large as systems in good standing (17,656 to 5,284). Also, a group of systems with over 4,445 students had over 5 times the number of targeted systems than a group of systems with fewer than 2,094 students.

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